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Dashjamts G, Ganzorig AE, Tsedendorj Y, Dondov G, Nergui O, Badamjav T, Huang CF, Liang PC, Lonjid T, Batsaikhan B, Dai CY. Post-Treatment Occurrence of Serum Cryoglobulinemia in Chronic Hepatitis C Patients. Diagnostics (Basel) 2024; 14:1188. [PMID: 38893714 PMCID: PMC11171999 DOI: 10.3390/diagnostics14111188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/21/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND Persistent cryoglobulinemia after the completion of antiviral treatment is an important consideration of clinical management in chronic hepatitis C patients. We aimed to investigate the occurrence of serum cryoglobulinemia in chronic hepatitis C patients without cryoglobulinemia at the initiation of antiviral treatment. METHODS In total, 776 patients without cryoglobulinemia were assessed for serum cryoglobulinemia after the completion of anti-HCV treatment. Serum cryoglobulinemia precipitation was assessed upon both the initiation and the completion of the treatment and analyzed for the clinical laboratory factors associated with chronic hepatitis C. RESULTS One hundred eighteen (118) patients were checked for serum cryo-precipitation after the completion of the treatment, and eight patients (4.6%) were positive for serum cryoglobulinemia. The patients who tested positive for cryoglobulinemia included a higher proportion of liver cirrhosis patients (4/50%, p = 0.033) and other organ cancer patients (5/62.5%, p = 0.006) than patients who showed no signs of cryoglobulinemia after treatment. In a multivariate analysis, liver cirrhosis (odds ratio [OR]-17.86, 95% confidence interval [95% CI]-1.79-177.35, p = 0.014) and other organ cancer (OR-25.17 95% CI-2.59-244.23, p = 0.005) were independently and significantly associated with positive cryoglobulinemia 3 months after antiviral treatment. CONCLUSIONS Three months after the antiviral DAA therapy had concluded, eight patients tested positive for cryoglobulinemia, representing a 6.7% prevalence. Liver cirrhosis and other organ cancer were independently and significantly associated with positive cryoglobulinemia after antiviral treatment. Further investigation into the causes of positive cryoglobulinemia after DAA antiviral therapy is warranted.
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Affiliation(s)
- Gantogtokh Dashjamts
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
| | - Amin-Erdene Ganzorig
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
| | - Yumchinsuren Tsedendorj
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
| | - Ganchimeg Dondov
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
| | - Otgongerel Nergui
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
| | - Tegshjargal Badamjav
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
- Department of Biological Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010031, China
| | - Chung-Feng Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Po-Cheng Liang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Tulgaa Lonjid
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
| | - Batbold Batsaikhan
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (G.D.); (O.N.); (T.B.); (T.L.)
- Department of Health Research, Graduate School, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Ph.D. Program in Environmental and Occupational Medicine, Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
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Geographic Transmission and Epidemic History of HIV-1 CRF01_AE, CRF07_BC, and HCV Subtype-6w among Taiwanese Persons Who Inject Drugs. Viruses 2022; 14:v14102142. [PMID: 36298695 PMCID: PMC9610456 DOI: 10.3390/v14102142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/19/2022] [Accepted: 09/25/2022] [Indexed: 11/30/2022] Open
Abstract
Persons who inject drugs (PWID) and their risk-related behaviors (e.g., unprotected sex and sharing needles/syringes/other injection equipment) have caused severe public health problems, especially in the rapid spread of HIV-1 and HCV. Here, we reconstructed the epidemic history of HIV-1 circulating recombinant form (CRF) 01_AE, CRF07_BC, and HCV subtype-6w among Taiwanese PWID. The timescales were estimated using phylogenetic and Bayesian coalescent analyses. The results revealed that CRF01_AE started to circulate in the Taiwanese PWID population in central Taiwan at 1992.5 (95% credible region: 1988.8–1995.9) and spread to other regions of Taiwan, while CRF07_BC was first identified in southern Taiwan at 2000.0 (95% CR: 1997.8–2002.2) and then spread northward to central-northern Taiwan. All HCV-6 strains were from Asia (that is, China, Myanmar, Taiwan, and Vietnam) and originated in 1928.1 (95% CR: 1890.2–1966.0). Furthermore, subtype-6w isolates from different regions of Taiwan appeared to share a common source that existed in the mid-1990s (95% CR: 1985.0–2001.8) or thereabouts. The routes of drug trafficking and the resulting high prevalence of HIV-1/HCV co-infections among PWID might have contributed to the virus transmission and promoted its spread worldwide. Long-term monitoring and policy implementation in at-risk populations would be useful for disease control.
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Batsaikhan B, Huang CI, Yeh ML, Huang CF, Lin YH, Liang PC, Hsieh MY, Lin YC, Huang JF, Chuang WL, Lee JC, Yu ML, Kuo HT, Dai CY. Persistent cryoglobulinemia after antiviral treatment is associated with advanced fibrosis in chronic hepatitis C patients. PLoS One 2022; 17:e0268180. [PMID: 35560166 PMCID: PMC9106159 DOI: 10.1371/journal.pone.0268180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 04/24/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients and analyze the associated factors of persistent cryoglobulinemia. METHODS Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy. RESULTS Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio [OR]- 4.13, 95% Confidence Interval [95% CI]- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy. CONCLUSIONS The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance.
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Affiliation(s)
- Batbold Batsaikhan
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Ching-I. Huang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Ching Lin
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jin-Ching Lee
- Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chia-Yen Dai
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Professional Studies, National Pingtung University of Science and Technology, Pingtung, Taiwan
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Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin. Viruses 2021; 13:v13030475. [PMID: 33799370 PMCID: PMC8000314 DOI: 10.3390/v13030475] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/24/2021] [Accepted: 03/11/2021] [Indexed: 12/12/2022] Open
Abstract
This retrospective cohort study aims to investigate interferon (IFN)-associated retinopathy incidence in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon (PegIFN) plus ribavirin (RBV). We selected 1688 patients undergoing PegIFN/RBV therapy for HCV (HCV-treated cohort), 3376 patients not receiving HCV treatment (HCV-untreated cohort) and 16,880 controls without HCV (non-HCV cohort) from the Taiwan Longitudinal Health Insurance Database. The patients were frequency-matched by age, sex, and index date at a 1:2:10 ratio, and followed up until the end of 2013. Cox proportional hazard regression models were used to compare the incidences of any retinal vascular events, including subtypes, among the three cohorts. Compared with the non-HCV cohort, the HCV-treated cohort had a significantly increased risk of retinopathy (hazard ratio (HR) = 4.98, 95% confidence interval (CI): 2.02–12.3). The risk was particularly prominent for retinal hemorrhage (HR = 12.7, 95% CI: 3.78–42.9). When the HCV-untreated cohort was used as the reference, the aforementioned HRs increased to 9.02 (95% CI: 3.04–26.8) and 32.3 (95% CI: 3.94–265), respectively. This study suggested that PegIFN/RBV therapy significantly increased the risk of retinal hemorrhage but not retinal vascular occlusions in the HCV-treated cohort.
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Lin CP, Liang PC, Huang CI, Yeh ML, Hsu PY, Hsu CT, Wei YJ, Liu TW, Hsieh MY, Hou NJ, Jang TY, Lin YH, Wang CW, Lin ZY, Chen SC, Huang CF, Huang JF, Dai CY, Chuang WL, Yu ML. Concordance of SVR12, SVR24 and SVR durability in Taiwanese chronic hepatitis C patients with direct-acting antivirals. PLoS One 2021; 16:e0245479. [PMID: 33539408 PMCID: PMC7861540 DOI: 10.1371/journal.pone.0245479] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 01/03/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND/AIMS Undetectable HCV RNA 12 weeks after the end of treatment (SVR12) has been the valid efficacy endpoint in the era of direct-acting antivirals (DAAs). Its concordance with SVR4 and SVR24 and long-term durability is unknown in Taiwanese chronic hepatitis C (CHC) patients. METHODS A total of 1080 CHC patients who received all-oral DAAs and an achieved end-of-treatment virological response (EOTVR), defined as undetectable HCV RNA at the end of therapy, were consecutively enrolled. HCV RNA was monitored 4, 12, and 24 weeks after EOT. Patients who achieved SVR24, defined as undetectable HCV RNA 24 weeks after EOT, were followed annually for assessing SVR durability. RESULTS Eleven (1.02%) patients experienced HCV RNA reappearance after EOT. The most frequent timing of RNA reappearance was observed at SVR4 (n = 7), followed by SVR12 (n = 3) and SVR 24 (n = 1). The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 in predicting SVR12 were 99.7% and 100%, respectively, whereas the PPV and NPV of SVR12 in predicting SVR24 were 99.9% and 100%, respectively. Pyrosequencing confirmed delayed relapse rather than reinfection for the patient who had detectable HCV RNA at SVR24. Among 978 patients who achieved SVR24, after a median follow-up period of 17.3±8.2 months, the SVR durability is 100% up to a 4-year follow-up. CONCLUSION Achievement of SVR12 provides excellent durability of HCV seroclearance after DAA therapy. On-demand HCV RNA beyond SVR12 should be recommended for patients with unexplainable abnormal liver function or high-risk behaviors.
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Affiliation(s)
- Chuan-Pin Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Ting Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Ta-Wei Liu
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Tyng-Yuang Jang
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Ping-Tung, Taiwan
| | - Yi-Hung Lin
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Chih-Wen Wang
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
- Insitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Center For Intelligent Drug Systems and Smart Bio-devices (IDSB) and Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
- Center for Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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The epidemiological profile of chronic hepatitis C with advanced hepatic fibrosis regarding virus genotype in Taiwan: A nationwide study. J Formos Med Assoc 2021; 120:1444-1451. [PMID: 33516585 DOI: 10.1016/j.jfma.2021.01.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 11/19/2020] [Accepted: 01/06/2021] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND/PURPOSE This study aims at investigating the epidemiological profile of chronic hepatitis C (CHC) regarding hepatitis C virus (HCV) genotype in Taiwan. METHODS A total of 29,087 CHC patients with advanced fibrosis who received direct-acting antivirals (DAAs) therapy under Taiwan's National Health Insurance (NHI) during 2017-2018 were recruited. The HCV genotype distribution and its association with patients' demographic factors including age, gender, and geographical areas were examined. RESULTS The most common genotypes were 1b (59.5%) and 2 (30.1%) with characteristics of older age (mean ± standard deviation (SD): 66.5 ± 10.7 years and 67.3 ± 10.9 years) and female gender predominant (57.1% and 59.4%), which were associated with iatrogenic infection decades ago. Most of patients with genotype 1a (5.9%) and 6 (3.7%) infection were relatively younger (59.2 ± 12.0 years and 60.0 ± 13.8 years) and male gender predominant (59.1% and 61.1%), except Liujia and Liuying districts in southern Taiwan. The youngest group (53.2 ± 11.8 years) and most male gender predominant (74.3%) was genotype 3 (0.37%). These genotypes with characteristics of being younger and male gender predominant were highly related to injection drug use in recent years. The number of genotype 4 patients were extremely rare (n = 25) and efficacy of genotype-4-specific-DAA was significantly poorer than non-genotype-4-specific DAA (P value = 0.0411). CONCLUSION The significant differences in demographic characteristics among CHC patients with different HCV genotypes found in this study suggest HCV genotype was highly associated with transmission pattern and may be used as a reference for HCV control.
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Alezzi ZMM, Abd El Rehim AY, Fathallah WF, Alamrani MA, Othman FH. Factors Affecting the Virological Response Among Chronic Hepatitis C Virus Patients in Yemen. J Interferon Cytokine Res 2019; 38:38-44. [PMID: 29328881 DOI: 10.1089/jir.2017.0098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is increasingly seen as a major public health problem, threat, and concern worldwide. In Yemen about 1.7% of the population is infected with chronic hepatitis C. This study aimed to detect the predictors for response to pegylated interferon and ribavirin (Peg-IFN/RBV) in chronic HCV Yemeni patients. The study was conducted on 100 patients with chronic HCV who received Peg-IFN/RBV in the 48th Military Hospital in Sana'a Yemen, from 2011 to 2013. All patients were subjected to complete history taking, thorough clinical examinations, routine laboratory investigation, and abdominal ultrasonography. The HCV RNA was assessed at week 72 of treatment to detect whether the patient achieved sustained virological response (SVR). The SVR was achieved in 64% of the samples. Age above 40, Khat chewing, and obesity were the sociodemographic factors that predict good response for Peg-IFN/RBV combined therapy. Platelet count, alpha feto-protein (AFP), aspartate transaminase (AST), and alanine transaminase (ALT) levels were the basic laboratory investigations that gave favorable response. Significant predictors of sustained response included: older than 40 years (OR = 0.136, P = 0.042), Khat chewer (OR = 0.016, P = 0.008), body mass index (BMI) (OR = 0.055, P = 0.029) and increase in fasting blood glucose (OR = 0.925, P = 0.004), alkaline phosphatase (OR = 0.969, P = 0.001), total and bilirubin (OR = 0.058, P = 0.017), AST (OR = 1.033, P = 0.002), and albumin (OR = 6.490, P = 0.021). Studying the independent variables of response, we revealed that male gender, BMI, ALT >40, AFP >10, viremia >600, and hemoglobin and thyroid stimulating hormone (TSH) levels are variables associated with failure of end of treatment response (ETR) and SVR.
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Affiliation(s)
| | - Ayman Yosry Abd El Rehim
- 2 Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University , Cairo, Egypt
| | - Waleed Fouad Fathallah
- 2 Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University , Cairo, Egypt
| | | | - Fouad Hezam Othman
- 3 Department of Community Medicine, Faculty of Medicine & Health Sciences, Taiz University , Taiz, Yemen
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Tai CM, Yen YC, Bair MJ, Tseng CH, Chang TT, Huang CF, Yeh ML, Dai CY, Chuang WL, Yu ML, Huang JF. Integrated care for methadone maintenance patients with hepatitis C virus infection. Kaohsiung J Med Sci 2019; 35:501-507. [PMID: 31087764 DOI: 10.1002/kjm2.12086] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 04/29/2019] [Indexed: 01/14/2023] Open
Abstract
The majority of patients undergoing methadone maintenance treatment (MMT) are neither examined nor treated for hepatitis C virus (HCV) infection. We aimed to evaluate an integrated referral model in the management of HCV among MMT patients. This retrospective study included 390 HCV-infected MMT patients between April 2015 and May 2017. Patients who tested positive for HCV antibodies were referred to a liver clinic by MMT case managers or psychiatrists. Patients who agreed to receive anti-HCV treatment were treated with pegylated interferon and ribavirin. The rate of patient engagement at a liver clinic increased from 14.1% to 58.2% after integrated care. Multiple logistic regression analysis showed that higher education level (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.01-2.60) and elevated ALT level (OR, 4.30; 95% CI, 2.70-6.85) were independently associated with patients who accepted referral. Active drug use (OR, 0.52; 95% CI, 0.31-0.85) was inversely associated with referral acceptance. Of the 112 patients who met the criteria for anti-HCV therapy, 66 (58.9%) were treated with pegylated interferon and ribavirin. Finally, the rate of treatment completion and sustained virological response (SVR) was 65.2% and 54.5%, respectively, among the 66 patients. Treatment completion (OR, 39.67; 95% CI, 7.80-201.62) was found to be the only independent factor associated with SVR achievement. Although integrated care by psychiatrists and hepatologists significantly increased the rates of engagement and acceptance of antiviral treatment for HCV-infected MMT patients, only a minority of MMT patients achieved successful treatment.
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Affiliation(s)
- Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yung-Chieh Yen
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Department of Psychiatry, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Cheng-Hao Tseng
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ting-Ting Chang
- Department of Psychiatry, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, and Lipid Science and Aging Research Center, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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9
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Liu CH, Yu ML, Peng CY, Hsieh TY, Huang YH, Su WW, Cheng PN, Lin CL, Lo CC, Chen CY, Chen JJ, Ma Q, Brooks-Rooney C, Kao JH. Real-world anti-viral treatment decisions among chronic hepatitis C patients in Taiwan: The INITIATE study. J Formos Med Assoc 2019; 118:1014-1023. [PMID: 30448077 DOI: 10.1016/j.jfma.2018.10.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 08/27/2018] [Accepted: 10/30/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/PURPOSE While direct-acting antiviral regimens have been approved for chronic hepatitis C (CHC) patients in Taiwan, reimbursement is limited to certain populations. Thus, pegylated interferon plus ribavirin (PEG-IFN/RBV) remains the standard of care for many patients. The aim of this study was to investigate the percentage of CHC patients who were recommended and willing to receive PEG-IFN/RBV, and to identify reasons why patients were not recommended or unwilling to receive treatment. METHODS 822 Taiwanese CHC patients were enrolled from May-August 2016 in this cross-sectional study. PEG-IFN/RBV recommendation and patient willingness to receive treatment were evaluated through surveys. Patient characteristics associated with treatment recommendation and willingness were assessed. RESULTS 311 (37.8%) patients were recommended PEG-IFN/RBV while 102 (12.4%) were willing to follow treatment recommendation. Rates of recommendation and willingness were lower in treatment-experienced, hepatitis C virus genotype 1 (GT1) and cirrhotic patients, and those treated in Northern Taiwan. Multivariate analyses found factors such as prior treatment experience, GT1, cirrhosis and low hemoglobin levels to be associated with lower recommendation rates while advanced age, GT1 and low baseline viral loads were associated with lower willingness rates. Physicians' top reasons for not recommending PEG-IFN/RBV included the wish to wait for better treatment options (60.3%), prior treatment failure (21.3%) and patients' advanced age (20.9%). Patients were unwilling to receive treatment mainly due to concerns about side effects (91.4%), the wish to wait for better treatment options (71.3%) and inconvenience (25.4%). CONCLUSION A minority of Taiwanese CHC patients were recommended PEG-IFN/RBV, of which few were willing to receive treatment.
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Affiliation(s)
- Chen-Hua Liu
- National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Department of Internal Medicine, School of Medicine, China Medical University, Taichung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Centre, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Taipei City Hospital - Renai Branch, Taipei, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan
| | - Jyh-Jou Chen
- Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan
| | - Qian Ma
- Costello Medical Singapore Pte Ltd, Singapore
| | | | - Jia-Horng Kao
- National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
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Rattanavipapong W, Anothaisintawee T, Teerawattananon Y. Revisiting policy on chronic HCV treatment under the Thai Universal Health Coverage: An economic evaluation and budget impact analysis. PLoS One 2018; 13:e0193112. [PMID: 29466415 PMCID: PMC5821370 DOI: 10.1371/journal.pone.0193112] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 02/05/2018] [Indexed: 12/15/2022] Open
Abstract
Thailand is encountering challenges to introduce the high-cost sofosbuvir for chronic hepatitis C treatment as part of the Universal Health Care's benefit package. This study was conducted in respond to policy demand from the Thai government to assess the value for money and budget impact of introducing sofosbuvir-based regimens in the tax-based health insurance scheme. The Markov model was constructed to assess costs and benefits of the four treatment options that include: (i) current practice-peginterferon alfa (PEG) and ribavirin (RBV) for 24 weeks in genotype 3 and 48 weeks for other genotypes; (ii) Sofosbuvir plus peginterferon alfa and ribavirin (SOF+PEG-RBV) for 12 weeks; (iii) Sofosbuvir and daclatasvir (SOF+DCV) for 12 weeks; (iv) Sofosbuvir and ledipasvir (SOF+LDV) for 12 weeks for non-3 genotypes and SOF+PEG-RBV for 12 weeks for genotype 3 infection. Given that policy options (ii) and (iii) are for pan-genotypic infection, the cost of genotype testing was applied only for policy options (i) and (iv). Results reveal that all sofosbuvir-based regimens had greater quality adjusted life years (QALY) gains compared with the current treatment, therefore associated with lower lifetime costs and more favourable health outcomes. Additionally, among the three regimens of sofosbuvir, SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype are the most cost-effective treatment option with the threshold of 160,000 THB per QALY gained. The results of this study had been used in policy discussion which resulted in the recent inclusion of SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype in the Thailand's benefit package.
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Affiliation(s)
- Waranya Rattanavipapong
- Health Intervention and Technology Assessment Program (HITAP), Department of Health, Ministry of Public Health, Nonthaburi, Thailand
| | - Thunyarat Anothaisintawee
- Health Intervention and Technology Assessment Program (HITAP), Department of Health, Ministry of Public Health, Nonthaburi, Thailand
- Department of Family Medicine, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand
| | - Yot Teerawattananon
- Health Intervention and Technology Assessment Program (HITAP), Department of Health, Ministry of Public Health, Nonthaburi, Thailand
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11
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Liang PC, Lin PC, Huang CI, Huang CF, Yeh ML, Zeng YS, Hsu WY, Hsieh MY, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Chiou SS, Yu ML. The treatment outcome and impact on blood transfusion demand of Peg-interferon/ribavirin in thalassemic patients with chronic hepatitis C. J Formos Med Assoc 2018; 117:14-23. [PMID: 29097076 DOI: 10.1016/j.jfma.2017.10.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Revised: 07/29/2017] [Accepted: 10/13/2017] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND/AIMS Hepatitis C virus (HCV) prevails in patients with thalassemia. We aimed to investigate the efficacy, safety, and impact on red blood cells (RBC) transfusion demand of pegylated interferon (Peg-IFN)/ribavirin therapy in thalassemic patients with HCV. METHODS This retrospective study included 18 thalassemic patients (16 with HCV-1b, one HCV-1b/2b, and one HCV-2b) and 54 consecutive sex- and genotype-matched controls. Patients with HCV-2, or HCV-1 or mixed HCV-1/2 with lower viral loads plus rapid virological response (RVR) received 24-week Peg-IFN/ribavirin; whereas HCV-1 or mixed HCV-1/2 with higher viral loads or without RVR received 48-week regimens. RESULTS The rates of RVR, complete early virological response, and sustained virological response (SVR) in thalassemic patients were 72.2% (13/18), 94.1% (16/17), and 77.8% (14/18), which resembled those of controls (63.0%, 94.4%, and 81.5%, respectively). RVR was the only significant factor associated with SVR in thalassemic group, and was the strongest predictor for SVR among both groups (OR/95% CI = 14.7/2.20-98.6), followed by male gender and lower viral loads. More proportion of interleukin-28B-TT carriage were observed among thalassemic patients with SVR versus non-SVR (78.6% vs. 50.0%). Thalassemic patients experienced significantly less 80/80/80 adherence, more ribavirin reduction and serious adverse events than controls. Notably, there was a decreased post-treatment RBC transfusion demand versus baseline in thalassemic patients with SVR (5.21 vs. 5.64 units/month, p = 0.05), but not in those without SVR (6.33 vs. 6.56 units/month, p = 0.54). CONCLUSION Peg-IFN/ribavirin was effective and tolerable for thalassemic HCV patients. Successful antiviral therapy might have extra benefit of reducing the post-treatment transfusion demand.
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Affiliation(s)
- Po-Cheng Liang
- Graduate Institute of Clinical Medicine College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chin Lin
- Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Special Hematologic Disease Service Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Graduate Institute of Clinical Medicine College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Sheng Zeng
- Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Special Hematologic Disease Service Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Yi Hsu
- Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Special Hematologic Disease Service Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shyh-Shin Chiou
- Graduate Institute of Clinical Medicine College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Special Hematologic Disease Service Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Taiwan; Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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12
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Liu TW, Tsai PC, Huang CI, Tsai YS, Wang SC, Ko YM, Lin CC, Chen KY, Liang PC, Lin YH, Hsieh MY, Hou NJ, Huang CF, Yeh ML, Lin ZY, Chen SC, Dai CY, Chuang WL, Huang JF, Yu ML. Identification of treatment-experienced hepatitis C patients with poor cost-effectiveness of pegylated interferon plus ribavirin from a real-world cohort. J Formos Med Assoc 2018; 117:54-62. [PMID: 28389143 DOI: 10.1016/j.jfma.2017.02.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 02/21/2017] [Accepted: 02/23/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/PURPOSE Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. METHODS A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. RESULTS We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. CONCLUSION In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.
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Affiliation(s)
- Ta-Wei Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shu-Chi Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Min Ko
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-Chih Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Kuan-Yu Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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Huang CF, Yu ML. Treating hepatitis C in the elderly: pharmacotherapeutic considerations and developments. Expert Opin Pharmacother 2017; 18:1867-1874. [PMID: 29086615 DOI: 10.1080/14656566.2017.1400010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 10/30/2017] [Indexed: 12/17/2022]
Abstract
The seroprevalence of hepatitis C virus (HCV) infection tends to be higher in the elderly than in younger populations. Meanwhile, age per sec is an unfavorable determinant that has an impact on liver-related outcomes. Geriatric chronic hepatitis C (CHC) patients would be viewed as a special population and have an urgent need for viral eradication. Areas covered: The antivirals for CHC have evolved from interferon (IFN)-based therapyto interferon-free DAAs. The treatment strategy, in terms of its clinical efficacy and drug safety, in the elderly is presented. Expert opinion: In the previous IFN era, the sustained virological response (SVR) rate of the elderly was lower. More unfavorable safety concerns attributing to the underlying liver disease severity and extra-hepatic presentations further compromised the treatment efficacy. In the IFN-free DAA era, data showing similar SVR rates and safety profiles between the elderly and their counterparts have been demonstrated. Notably, aging is an unfavorable factor for fibrosis regression and HCC development even after HCV eradication. The extent of the improvement of extra-hepatic manifestations in the elderly with SVR is also unclear. The long-term benefits of viral eradication by DAAs in the elderly await further explorations.
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Affiliation(s)
- Chung-Feng Huang
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan
- b Faculty of Internal Medicine, School of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- c Department of Occupational Medicine, Kaohsiung Medical University Hospital , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Ming-Lung Yu
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan
- b Faculty of Internal Medicine, School of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- d Institute of Biomedical Sciences , National Sun Yat-Sen University , Kaohsiung , Taiwan
- e Liver Center, Division of Gastroenterology , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA
- f College of Biological Science and Technology , National Chiao Tung University , Hsin-Chu , Taiwan
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Huang JF, Ko YM, Huang CF, Yeh ML, Dai CY, Hsieh MH, Huang CI, Yang HL, Wang SC, Lin ZY, Chen SC, Yu ML, Chuang WL. 25-Hydroxy vitamin D suppresses hepatitis C virus replication and contributes to rapid virological response of treatment efficacy. Hepatol Res 2017; 47:1383-1389. [PMID: 28225575 DOI: 10.1111/hepr.12878] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Revised: 01/16/2017] [Accepted: 02/20/2017] [Indexed: 12/15/2022]
Abstract
AIM 25-Hydroxy vitamin D (Vit D) plays a role in treatment outcomes in chronic hepatitis C virus (HCV) infection. We aimed to clarify whether HCV replication is inhibited by Vit D in HCV replicon cells. Clinical implication was assessed for rapid virological response (RVR) and sustained virological response (SVR) among those patients receiving antiviral therapy. METHODS Cell survival and viral loads were observed in Con1 (genotype 1b) and J6/JFH (genotype 2a) cells treated with different doses of Vit D. Three groups of patients with different treatment responses were recruited to assess their Vit D levels: group A, RVR-/SVR-; group B, RVR+/SVR-; and group C, RVR+/SVR+. RESULTS The viral load of Con1 cells decreased by 69%, 80%, and 86% following treatment with 1 μM, 5 μM, and 10 μM Vit D, respectively (P < 0.0001). In J6/JFH cells, it decreased by 12%, 55%, and 80.5% following treatment with 1 μM, 5 μM, and 10 μM Vit D, respectively (P < 0.0001). There was a significant increase of Vit D between chronic hepatitis C groups, ranging from 4.4 ± 5.6 ng/mL in group A (n = 44), to 17.2 ± 11.6 ng/mL in group B (n = 44), and 32.5 ± 37.5 ng/mL of group C (n = 44) (P < 0.001). Advanced fibrosis (odds ratio = 0.13, 95% confidence interval = 0.04-0.41, P < 0.001) and Vit D deficiency (<10 ng/mL) (odds ratio = 0.11, 95% confidence interval = 0.03-0.43, P = 0.001) were predictive of SVR in the multivariate regression analysis. CONCLUSION Vitamin D decreases HCV replication and also contributes to early treatment viral kinetics.
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Affiliation(s)
- Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Min Ko
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hua-Ling Yang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shu-Chi Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Chern Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Annual Change in FIB-4, but not in APRI, was a Strong Predictor for Liver Disease Progression in Chinese Patients with Chronic Hepatitis C. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.57250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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16
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Tsai PC, Liu TW, Yu ML. Reply to "cost effectiveness of hepatitis C treatments: Need for a comprehensive evaluation". Kaohsiung J Med Sci 2017; 33:586. [PMID: 29050678 DOI: 10.1016/j.kjms.2017.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 06/02/2017] [Indexed: 11/22/2022] Open
Affiliation(s)
- Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ta-Wei Liu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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17
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Sghaier I, Mouelhi L, Ghazoueni E, Brochot E, Almawi WY, Yacoubi-Loueslati B. Role of TLRs and IL-6 in the outcome of chronic hepatitis C treatment in Tunisian population. Cytokine 2017; 99:297-304. [PMID: 28823914 DOI: 10.1016/j.cyto.2017.08.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 07/25/2017] [Accepted: 08/12/2017] [Indexed: 12/13/2022]
Abstract
OBJECTIVES TLRs are one of the most studied families of pathogen recognition receptors (PRRs) and play a pivotal role during HCV infection. The binding of ligands to TLRs on antigen presenting cells (APCs) leads to secretion of inflammatory cytokines, such as IL6, and induction of the acquired immunity response. Therefore, it has become necessarily to harness the TLRs properties' on therapeutically tools to enhance the HCV treatment response. Herein, we investigated the association between TLR3, TLR4 variants and nine IL-6 polymorphisms, and response to anti-viral treatment during HCV infection. METHODS Study subjects comprised 120 patients infected with HCV-1b and treated with Peg-IFN/RBV. Genotyping of nine IL-6 variants were done by real -time PCR and genotyping of TLRs polymorphisms were done by RFLP-PCR. RESULTS High frequency of TLR3 rs3775290 C/C genotype and TLR4 rs4986790 A/A genotype were noticed among patients with sustained viral response compared to Non-responder patients. The genetic association of TLR3 and TLR4 variants was evidenced by the improvement in the kinetics of viral load decline, with superiority of TLR3 compared to TLR4. Among, nine polymorphisms studied on IL-6 only rs1800796, rs2069845 and rs1880242 were associated with sustained viral response. Our study reports also that the common favourable IL-28B variant is essential for TLR-activated antiviral protection. CONCLUSION TLR3 and TLR4 are involved in the pathogenesis of viral infections. TLR3 may be better suited than TLR4 to activate anti-viral program. Moreover, we propose that the Th2 cytokine, IL-6, constitutes a determinant of the outcome of therapy in HCV patients.
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Affiliation(s)
- Ikram Sghaier
- University of Tunis El Manar, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092, Tunisia.
| | - Leila Mouelhi
- Charles Nicolle Hospital, Hepato-Gastro-Enterology Department, Tunis, Tunisia
| | | | - Etienne Brochot
- Department of Virology, Amiens University Medical Centre, Amiens, France; Virology Research Unit, EA 4294, Jules Verne University of Picardie, Amiens, France
| | - Wassim Y Almawi
- University of Tunis El Manar, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092, Tunisia
| | - Besma Yacoubi-Loueslati
- University of Tunis El Manar, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092, Tunisia
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18
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Huang Y, Li MH, Hou M, Xie Y. Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals. Hepatobiliary Pancreat Dis Int 2017; 16:470-479. [PMID: 28992878 DOI: 10.1016/s1499-3872(17)60044-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 06/23/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.
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Affiliation(s)
- Yan Huang
- Shanghai Roche Pharmaceuticals Ltd., Shanghai 201203, Beijing, China
| | - Ming-Hui Li
- Liver Disease Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Min Hou
- Shanghai Roche Pharmaceuticals Ltd., Shanghai 201203, Beijing, China
| | - Yao Xie
- Liver Disease Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
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19
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Cheng CH, Lin CC, Chen HL, Lin IT, Wu CH, Lee YK, Wong MW, Bair MJ. High frequencies of a favorable IL-28B rs8099917 polymorphism and the clinical implications in patients with HCV in one multiracial area of Taiwan. Kaohsiung J Med Sci 2017; 33:510-515. [PMID: 28962822 DOI: 10.1016/j.kjms.2017.06.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 05/14/2017] [Accepted: 06/02/2017] [Indexed: 12/25/2022] Open
Abstract
There is a strong association between hepatitis C virus (HCV) treatment efficacy and the interleukin (IL)-28B gene. However, the IL-28B variant's distribution and potential role in the therapeutic response are not well established in Taitung, a racially diverse county in Taiwan. Here, we investigated the distribution pattern of IL-28B rs8099917 and its influence on treatment efficacy. In this retrospective study, we enrolled 180 patients who had been treated with pegylated-interferon plus ribavirin. Patients' general information, virological characteristics, IL-28B status, laboratory results, treatment course, and outcome were analyzed. Of the patients enrolled, 56.7% were male, with a mean age of 54.11 years. A total of 24.4% of the population were indigenous people. The majority of patients had the favorable IL-28B polymorphism (rs8099917 TT/TG/GG: 94.4%/5.6%/0%). The proportion of patients with the TT genotype seemed to be higher in indigenous patients. The rate of sustained virological response (SVR) among included patients was 73.0%. Univariate analysis showed that genotype non-1, patients achieved rapid virological response (RVR), lower body mass index (BMI), and lower baseline HCV viral load were significantly associated with SVR. Multivariate analysis revealed that BMI <25 and RVR are the independent predictor of success treatment. In conclusion, the favorable IL-28B rs8099917 polymorphism occurs in high frequency in this multiracial area, which might be important to help guide physicians and patients in their future clinical decisions.
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Affiliation(s)
- Chun-Han Cheng
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - Ching-Chung Lin
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Huan-Lin Chen
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - I-Tsung Lin
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - Chia-Hsien Wu
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - Yuan-Kai Lee
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - Ming-Wun Wong
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan; Mackay Medical College, New Taipei, Taiwan.
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20
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Yu ML. Hepatitis C treatment from "response-guided" to "resource-guided" therapy in the transition era from interferon-containing to interferon-free regimens. J Gastroenterol Hepatol 2017; 32:1436-1442. [PMID: 28124463 DOI: 10.1111/jgh.13747] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 01/17/2017] [Accepted: 01/22/2017] [Indexed: 12/13/2022]
Abstract
Peginterferon/ribavirin has been the standard-of-care for chronic hepatitis C virus (HCV) infections: 48 weeks for genotype 1 or 4 (HCV-1/4) and 24 weeks for HCV-2/3. Response-guided therapy recommended shorter 24- and 16-week regimens for HCV-1 with lower baseline viral loads (< 400 000-800 000 IU/mL) and rapid virological response (RVR, undetectable HCV RNA at week 4) and HCV-2/3 with RVR, respectively; and extending to 72 and 48 weeks for HCV-1 slower responders and HCV-2 non-RVR patients, respectively, to improve the efficacy. The progress of directly acting antivirals (DAA), moving from interferon-containing regimens in 2011 to interferon-free regimens in 2013, has greatly improved the treatment success. Interferon-containing regimens include boceprevir or telaprevir or simeprevir or daclatasvir plus peginterferon/ribavirin, 24-48 weeks, for HCV-1 or 4. However, adding these DAA has no benefit for HCV-1 with lower baseline viral loads/RVR. Instead, 12-week sofosbuvir plus peginterferon/ribavirin attained sustained virological response rates of > 90% for HCV-1/3-6. Interferon-free regimens include two main categories: NS5B nucleotide inhibitor (sofosbuvir)-based regimens and NS3/4A inhibitor/NS5A inhibitor-based regimens (daclatasvir/asunaprevir, paritaprevir/r/ombitasvir/dasabuvir and grazoprevir/elbasvir). About 8-24 weeks interferon-free regimens could achieve sustained virological response rates of 82-99% for corresponding HCV genotypes. Although the newly DAA interferon-free regimens have high efficacy and safety, the huge budget impact increases the treatment barriers. The current recommendation should, therefore, base on the availability, indication, and cost-effectiveness in the transition era of DAA. Based on the concept of "resource-guided therapy," peginterferon/ribavirin might be applied for easy-to-treat interferon-eligible patients in resource-constrained areas. Prioritizing patients for interferon-free regimens according to "time-degenerative factors" (age and fibrosis) is justified before the regimens becoming available and affordable.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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21
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Lee MH, Huang CF, Lai HC, Lin CY, Dai CY, Liu CJ, Wang JH, Huang JF, Su WP, Yang HC, Kee KM, Yeh ML, Chuang PH, Hsu SJ, Huang CI, Kao JT, Chen CC, Chen SH, Jeng WJ, Yang HI, Yuan Y, Lu SN, Sheen IS, Liu CH, Peng CY, Kao JH, Yu ML, Chuang WL, Chen CJ. Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients. Sci Rep 2017; 7:3718. [PMID: 28623331 PMCID: PMC5473811 DOI: 10.1038/s41598-017-02313-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 04/10/2017] [Indexed: 12/23/2022] Open
Abstract
This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004-2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22-0.63) for those without cirrhosis and 0.54 (0.31-0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Pang Su
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Chih Yang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kwong-Ming Kee
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Heng Chuang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jung-Ta Kao
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Sheng-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Juei Jeng
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol Myers-Squibb, Princeton, NJ, USA
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
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22
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Tsai PC, Liu TW, Tsai YS, Ko YM, Chen KY, Lin CC, Huang CI, Liang PC, Lin YH, Hsieh MY, Hou NJ, Huang CF, Yeh ML, Lin ZY, Chen SC, Dai CY, Chuang WL, Huang JF, Yu ML. Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database. Medicine (Baltimore) 2017; 96:e6984. [PMID: 28562549 PMCID: PMC5459714 DOI: 10.1097/md.0000000000006984] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Revised: 04/05/2017] [Accepted: 04/19/2017] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. METHODS A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. RESULTS The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. CONCLUSION We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.
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Affiliation(s)
- Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Ta-Wei Liu
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Yu-Min Ko
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Kuan-Yu Chen
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Ching-Chih Lin
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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Lo AOS, Chan HLY, Wong VWS, Wong GLH. Cost-effectiveness of the highly effective direct-acting antivirals in the treatment of chronic hepatitis C in Hong Kong. J Gastroenterol Hepatol 2017; 32:1071-1078. [PMID: 28449343 DOI: 10.1111/jgh.13638] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 10/11/2016] [Accepted: 10/30/2016] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND AIM In Asia-Pacific where cost is a major concern, peginterferon plus ribavirin (PR) often remain as the standard of care in chronic hepatitis C (CHC) treatment, while the direct-acting antivirals (DAAs) are commonly recommended as retreatment. Newer DAAs can achieve a sustained virological response (SVR) of nearly 100% with pan-genotypic coverage, that is "Highly Effective DAAs." We aimed to investigate the most desirable cost range for the Highly Effective DAAs using Hong Kong as an example. METHODS Markov modeling was performed using PR as the reference strategy. The cost-effectiveness of the Highly Effective DAAs was compared with sofosbuvir-PR (first-line and rescue) and boceprevir-PR therapies. A 50-year-old genotype 1b hepatitis C virus (HCV) infected treatment-naïve patient with METAVIR F3 was used as the base case scenario to reflect the commonest HCV genotype in Hong Kong. RESULTS The use of PR would incur a lifetime cost of US$35,854 and effectiveness of 14.85 quality-adjusted life-year (QALY). Sofosbuvir-PR as first-line treatment was dominated by other regimes. If Sofosbuvir-PR rescue therapy was used, the drug cost of Highly Effective DAAs should be set below US$43,553, with a cost-effectiveness ratio (CER) of US$3035/QALY compared with PR. In regions where Boceprevir-PR was still used as first-line therapy, the desirable drug cost of Highly Effective DAAs would be below US$56,985 to achieve a CER of US$5427/QALY. CONCLUSIONS The most desirable costs of the Highly Effective DAAs would be below US$43,553 if Sofosbuvir-PR rescue therapy is used and below US$56,985 if Boceprevir-PR therapy is used.
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Affiliation(s)
- Angeline Oi-Shan Lo
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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First Week HCV RNA Level Under the Pegylated Interferon and Ribavirin Treatment Predicts Sustained Virological Response. Am J Ther 2017; 23:e1612-e1618. [PMID: 25933139 DOI: 10.1097/mjt.0000000000000279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
This study was planned to investigate whether the decrease in the hepatitis C virus (HCV) RNA levels at the first week of combined pegylated interferon and ribavirin treatment of naive genotype 1 patients with HCV was predicting sustained virologic response (SVR). Fifty-two patients were enrolled into the study. HCV RNA levels were measured at the baseline, first, fourth, and 12th weeks of treatment. Thirty-four patients achieved SVR, which basal, first week, and fourth week HCV RNA levels were log 5.57, log 3.65, and log 1.92, respectively. Eighteen patients could not achieve SVR, which basal, first week, and fourth week HCV RNA levels were log 6.22, log 5.45, and log 3.84, respectively (P < 0.05). Patients were distributed in 2 groups according to the amount of decrease in HCV RNA levels at the first week as less or more than 1.5 log. There were 20 patients with ≥1.5 log decrease in the HCV RNA levels at the first week. They were named as patients with very rapid virologic response (VRVR). All patients (100%) with VRVR were achieved SVR. In only 14 (44%) of the 32 patients without VRVR, SVR was achieved. In 16 (84%) of the 19 patients with rapid virologic response and 33 (79%) of the 42 patients with early virologic response, SVR was achieved. A ≥1.5 log decrease (VRVR) in HCV RNA levels of patients with HCV at the first week of combined pegylated interferon and ribavirin treatment predicts SVR very strongly.
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Borba HH, Wiens A, Steimbach LM, Tonin FS, Pedroso MLA, Ivantes CA, Fernandez-Llimos F, Pontarolo R. Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study. Ther Clin Risk Manag 2017; 13:59-64. [PMID: 28138248 PMCID: PMC5237588 DOI: 10.2147/tcrm.s124663] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil. Materials and methods A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR). Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load) on RVR achievement. Results Data were collected from 117 patients with chronic hepatitis C virus (HCV) genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL) and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group). Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir) and the baseline viral load had an influence on the RVR rate (odds ratio [OR] =0.011; 95% confidence interval [CI]: 0.001–0.119; P<0.001/OR =13.004; 95% CI: 1.522–111.115; P=0.019, respectively). Conclusion In this longitudinal multicenter cohort study conducted from the Brazilian perspective, differences were found in the RVR rates, favoring telaprevir over boceprevir for genotype 1 HCV-infected patients. In addition, the baseline viral load was associated with RVR achievement in both evaluated groups. As RVR is also reported in the literature as a predictor of the sustained virological response (SVR), further analyses of RVR as predictor of SVR outcomes should be further evaluated in Brazil.
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Affiliation(s)
- Helena Hl Borba
- Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy
| | - Astrid Wiens
- Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy
| | - Laiza M Steimbach
- Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy
| | - Fernanda S Tonin
- Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy
| | - Maria LA Pedroso
- Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná
| | - Cláudia Ap Ivantes
- Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paraná, Brazil
| | - Fernando Fernandez-Llimos
- Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal
| | - Roberto Pontarolo
- Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy
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26
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Tsai PC, Liu TW, Hsieh MH, Yeh ML, Liang PC, Lin YH, Huang CI, Huang CF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Yu ML. A real-world impact of cost-effectiveness of pegylated interferon/ribavarin regimens on treatment-naïve chronic hepatitis C patients in Taiwan. Kaohsiung J Med Sci 2017; 33:44-49. [PMID: 28088273 DOI: 10.1016/j.kjms.2016.10.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 08/11/2016] [Accepted: 08/15/2016] [Indexed: 02/07/2023] Open
Abstract
Treatments with pegylated interferon/ribavirin (PEG-IFN/RBV) has been standard-of-care in patients with chronic hepatitis C virus (HCV) (CHC) infection and reimbursed in Taiwan. However, the actual cost-effectiveness remains unclear. We aimed to evaluate a real-world cost-effectiveness for CHC patients treated with PEG-IFN/RBV by using a clinical cohort with linkage to the National Health Insurance Research Database of Taiwan. The total and itemized medical-care expenses of outpatient visits of 117 treatment-naïve CHC patients with linkage to the two million sampling of the National Health Insurance Research Database were collected. Four components of costs were assessed, including antiviral agents, nonantiviral agents, laboratory testing and consultation costs. The cost per sustained virological response (SVR) achieved was calculated to evaluate the cost-effectiveness. The average cost per treatment in 117 naïve Taiwanese CHC patients was $4620. With an overall SVR rate of 78.6%, the average cost per SVR was $5878. The average medical-care cost per treatment for 52 Genotype 1 (G1) patients was $5133, including $4420 for antivirals, $380 for nonantivirals, $302 for laboratory, and $78 for consultation, compared to $4209, $3635, $317, $233, and $56 for 65 Genotype 2 (G2) patients. With an SVR rate at 67.3% for G1 and 87.7% for G2 patients, the cost per SVR achieved was significantly higher in G1 patients than those in G2 patients ($7627 vs. $4799, p = 0.001). In the current study, we provided the real-world cost-effectiveness of PEG-IFN/RBV for treatment-naïve CHC patients. The genotype-specific cost-effectiveness could enhance decision-making for policy-makers in the coming era of directly acting antiviral therapy.
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Affiliation(s)
- Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ta-Wei Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Mangia A, De Ledinghen V, Bailly F, Brahm J, Keiss J, Valantinas J, Rasmann N, Messinger D, Tatsch F, Bakalos G, Foster GR. IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study. SPRINGERPLUS 2016; 5:1990. [PMID: 27917361 PMCID: PMC5116020 DOI: 10.1186/s40064-016-3663-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 11/07/2016] [Indexed: 02/07/2023]
Abstract
Background and purpose Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. Methods A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records. Results 2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection. Conclusion This large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-3663-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Alessandra Mangia
- Liver Unit, IRCCS Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, 71013 Italy
| | | | - François Bailly
- Hepatology Unit, Groupe Hospitalier Nord, CHU Lyon, 69004 Lyon, France
| | - Javier Brahm
- Gastroenterology Department, University of Chile Clinical Hospital, Santiago, 8380456 Chile
| | - Jazeps Keiss
- Latvian Centre of Infectious Diseases, LLC Riga East University Hospital, Riga, 1006 Latvia
| | - Jonas Valantinas
- Centre of Hepatology, Gastroenterology and Dietetics, Vilnius University, 08661 Vilnius, Lithuania
| | - Nele Rasmann
- Center for Infectious Diseases, West Tallinn Central Hospital, 10617 Tallinn, Estonia
| | | | - Fernando Tatsch
- Global Medical Affairs, F. Hoffmann-La Roche Ltd, 4074 Basel, Switzerland ; AbbVie, North Chicago, IL USA
| | - Georgios Bakalos
- Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, 4074 Basel, Switzerland
| | - Graham R Foster
- Institute of Cellular and Molecular Sciences, Queen Mary University of London, London, E1 2AT UK
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Kao JH, Tung SY, Lee Y, Thongsawat S, Tanwandee T, Sheen IS, Wu JJ, Li H, Brennan BJ, Zhou J, Le Pogam S, Najera I, Thommes JA, Hill G. Ritonavir-boosted danoprevir plus peginterferon alfa-2a and ribavirin in Asian chronic hepatitis C patients with or without cirrhosis. J Gastroenterol Hepatol 2016; 31:1757-1765. [PMID: 26992248 DOI: 10.1111/jgh.13374] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 03/04/2016] [Accepted: 03/07/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Chronic hepatitis C is an important public health problem in Asia. We evaluated the safety, efficacy, and pharmacokinetics of fixed-dose ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin in treatment-naive Asian patients with chronic hepatitis C virus (HCV) genotype (G)1 infection. METHODS Treatment-naive G1 patients in Taiwan, Thailand, and Korea with serum HCV-RNA level ≥ 105 IU/mL received ritonavir-boosted danoprevir 125/100 mg twice daily plus peginterferon alfa-2a/ribavirin for either 12 (noncirrhotic patients: Arm A, n = 34) or 24 weeks (cirrhotic patients: Arm B, n = 27) in this phase II open-label study. Sustained virologic response was defined as HCV-RNA < 25 IU/mL 12 weeks after end of treatment (SVR12). RESULTS Similar SVR12 rates were achieved in Arms A (88.2%; 95% confidence interval, 73.4-95.3%) and B (88.9%; 71.9-96.2%). Most patients had G1b infection, among whom SVR12 rates in Arms A and B were 96.7% and 91.7%, respectively. The overall SVR12 rate was 94.0% in noncirrhotic Taiwanese patients (100% in the subset of G1b patients). No patients withdrew for safety reasons. Three (11%) cirrhotic patients (Arm B) experienced serious adverse events, none of which was considered to be related to treatment. No Grade 3/4 alanine aminotransferase elevations were reported. The pharmacokinetic properties of danoprevir were broadly overlapping in noncirrhotic and cirrhotic patients both on Days 1 and 14. CONCLUSIONS Ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin produced sustained virologic response rates > 90% after 12 weeks' treatment in noncirrhotic and 24 weeks' treatment in cirrhotic Asian patients with G1b infection and was well tolerated. These regimens are well suited to countries where G1b predominates.
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Affiliation(s)
- Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University and Hospital, Taipei, Taiwan.
| | - Shui-Yi Tung
- Department of Gastroenterology, Chang Gung Memorial Hospital, Chia Yi, Taiwan.,Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Younjae Lee
- Pusan Paik Hospital, Inje University, Pusan, Korea
| | | | | | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | | | - Hui Li
- Roche Product Development, Shanghai, China
| | - Barbara J Brennan
- Roche Translational and Clinical Research Center, New York, New York, USA
| | | | | | - Isabel Najera
- Roche Pharma and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland
| | | | - George Hill
- Genentech, South San Francisco, California, USA
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Lu MY, Huang CI, Hsieh MY, Hsieh TJ, Hsi E, Tsai PC, Tsai YS, Lin CC, Hsieh MH, Liang PC, Lin YH, Hou NJ, Yeh ML, Huang CF, Lin ZY, Chen SC, Huang JF, Chuang WL, Dai CY, Yu ML. Dynamics of PBMC gene expression in hepatitis C virus genotype 1-infected patients during combined peginterferon/ribavirin therapy. Oncotarget 2016; 7:61325-61335. [PMID: 27542257 PMCID: PMC5308654 DOI: 10.18632/oncotarget.11348] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 08/10/2016] [Indexed: 12/29/2022] Open
Abstract
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment. A complete early virologic response (cEVR) was defined as negative HCV RNA at treatment week 12. Forty-three differentially expressed genes identified by Affymetrix microarray were validated by quantitative polymerase chain reaction. Thirteen genes at week 1 and 24 genes at week 4 were upregulated in the SVR group compared with the non-SVR group. We selected 8 target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3, and DDX60) at week 1 as the major components of the predictive model. This predictive model reliably stratified the responders and non-responders at week 1 (AUC = 0.89, p = 0.007 for SVR; AUC = 0.95, p = 0.003 for cEVR), especially among patients carrying the IL28B rs8099917 TT genotype (AUC = 0.89, p = 0.02 for SVR; AUC = 1.0, p = 0.008 for cEVR). The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype.
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Affiliation(s)
- Ming-Ying Lu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tusty-Juan Hsieh
- Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Edward Hsi
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-Chih Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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30
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Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Dokmeci AK, Al-Mahtab M, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Yokosuka O, Lau GKK, Sarin SK. APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing. Hepatol Int 2016; 10:681-701. [PMID: 27229718 PMCID: PMC5003900 DOI: 10.1007/s12072-016-9736-3] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023]
Abstract
The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on "APASL consensus statements and recommendations for management of hepatitis C" in March 2015 to revise the "APASL consensus statements and management algorithms for hepatitis C virus infection" (Hepatol Int 6:409-435, 2012). The working party consisted of expert hepatologists from the Asian-Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review.
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Affiliation(s)
- Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Ming-Lung Yu
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Banha, Egypt
| | | | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geofferey W McCaughan
- Royal Prince Alfred Hospital, Centenary Institute, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - George K K Lau
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Dokmeci AK, Mamun-Al-Mahtab, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Yokosuka O, Lau GKK, Sarin SK. APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int 2016; 10:702-726. [PMID: 27130427 PMCID: PMC5003907 DOI: 10.1007/s12072-016-9717-6] [Citation(s) in RCA: 153] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Accepted: 02/18/2016] [Indexed: 12/18/2022]
Abstract
The Asian-Pacific Association for the Study of the Liver (APASL) convened an international working party on the "APASL consensus statements and recommendation on management of hepatitis C" in March, 2015, in order to revise "APASL consensus statements and management algorithms for hepatitis C virus infection (Hepatol Int 6:409-435, 2012)". The working party consisted of expert hepatologists from the Asian-Pacific region gathered at Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed and debated to draft a revision. Participants of the consensus meeting assessed the quality of cited studies. Finalized recommendations on treatment of hepatitis C are presented in this review.
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Affiliation(s)
- Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-Shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Lai Wei
- Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China
| | - Ming-Lung Yu
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Benha, Egypt
| | | | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun-Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geofferey W McCaughan
- Centenary Institute, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- School of Medicine, University of Queensland, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - George K K Lau
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Chuang WL, Chien RN, Peng CY, Chang TT, Lo GH, Sheen IS, Wang HY, Chen JJ, Yang JC, Knox SJ, Gao B, Garrison KL, Mo H, Pang PS, Hsu YC, Hu TH, Chu CJ, Kao JH. Ledipasvir/sofosbuvir fixed-dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus. J Gastroenterol Hepatol 2016; 31:1323-1329. [PMID: 26841930 DOI: 10.1111/jgh.13305] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Revised: 01/12/2016] [Accepted: 01/24/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. METHODS In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. RESULTS The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. CONCLUSIONS Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
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Affiliation(s)
- Wan-Long Chuang
- Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Rong-Nan Chien
- Liver Research Unit, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan
| | - Cheng-Yuan Peng
- Department of Internal Medicine, School of Medicine, China Medical University, Taichung, Taiwan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Gin-Ho Lo
- Department of Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | - I-Shyan Sheen
- Chang Gung Memorial Hospital and Medical College, Chang Gung University, Taoyuan, Taiwan
| | - Horng-Yuan Wang
- Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Jyh-Jou Chen
- Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan
| | - Jenny C Yang
- Gilead Sciences, Inc., Foster City, California, USA
| | | | - Bing Gao
- Gilead Sciences, Inc., Foster City, California, USA
| | | | - Hongmei Mo
- Gilead Sciences, Inc., Foster City, California, USA
| | | | - Yu-Chun Hsu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Tsung-Hui Hu
- Chang Gung Medical Foundation, Kaohsiung, Taiwan
| | - Chi-Jen Chu
- Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
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Su PY, Yen HH, Hsu YC, Wu SS, Kor CT, Su WW. Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin. Kaohsiung J Med Sci 2016; 32:381-6. [PMID: 27450028 DOI: 10.1016/j.kjms.2016.06.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 05/28/2016] [Accepted: 05/30/2016] [Indexed: 01/28/2023] Open
Abstract
The lower limits of virus detection of hepatitis C virus (HCV) RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4(th) week viral load [rapid virological response (RVR)] in predicting sustained virological response (SVR) in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN) and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4(th) week viral load as follows: undetectable (n = 90) and detectable but not quantifiable (< 12 IU/mL, n = 27). All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA) HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4(th) week viral load, respectively. The between-group difference in SVR was significant (p < 0.001). We determined 4(th) week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002) and a good predictor of SVR [area under the curve (AUC) = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4(th) week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks) with PEG-IFN and ribavirin.
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Affiliation(s)
- Pei-Yuan Su
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan, ROC
| | - Hsu-Heng Yen
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan, ROC
| | - Yu-Chun Hsu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan, ROC
| | - Shun-Sheng Wu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan, ROC
| | - Chew-Teng Kor
- Internal Medicine Research Center, Changhua Christian Hospital, Changhua, Taiwan, ROC
| | - Wei-Wen Su
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan, ROC; School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
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Ren S, Jin Y, Huang Y, Ma L, Liu Y, Meng C, Guan S, Xie L, Chen X. HCV NS3Ag: a reliable and clinically useful predictor of antiviral outcomes in genotype 1b hepatitis C virus-infected patients. Eur J Clin Microbiol Infect Dis 2016; 35:1195-203. [PMID: 27173787 DOI: 10.1007/s10096-016-2653-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 04/18/2016] [Indexed: 11/25/2022]
Abstract
Since hepatitis C virus (HCV) non-structural 3 (NS3) protease inhibitor (PI) combined with pegylated interferon/ribavirin (PR) has been approved for chronic HCV genotype (GT) 1b infection, a reliable and clinically useful predictor combining with serum HCV RNA to predict early virologic response, breakthrough, and relapse is important during HCV antiviral treatment. We evaluated the role of HCV NS3 antigen (HCV NS3Ag) on the prediction of virologic response in patients with HCV GT1b during PR or PR/simeprevir (triple) therapy. Three hundred patients were recruited, and HCV RNA and HCV NS3Ag were tested at baseline and weeks 2, 4, 12, 24, 48, and 72. NS3Ag and HCV RNA were significantly related (r(2) = 0.67) in the whole patient selection. The kinetic pattern of HCV RNA and HCV NS3Ag during triple treatment was similar. HCV NS3Ag levels in the triple group closely followed those of HCV RNA; the r(2) values were 0.756 (baseline), 0.837 (2 weeks), 0.989 (4 weeks), and 0.993 (12 weeks), respectively. For patients treated with PR, the positive and negative predictive values (PPVs and NPVs) for viral response were 96.31 % and 67.19 %, respectively, at week 4 by using the decrease of NS3Ag (dHCV NS3Ag) combined with HCV RNA. At week 12, the PPV was similar at 94.16 %, while the NPV reached 87.26 %. The PPV and NPV for the prediction of relapse and breakthrough were 90.6 % and 76.7 %, respectively. HCV NS3Ag is a valuable marker and could be a supplementary predictor of HCV RNA for the prediction of antiviral response, breakthrough, or relapse during HCV antiviral treatment.
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Affiliation(s)
- S Ren
- Beijing You'an Hospital, Capital Medical University, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China
| | - Y Jin
- Beijing You'an Hospital, Capital Medical University, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China
| | - Y Huang
- Beijing Municipal Liver Diseases Institute, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China
| | - L Ma
- Beijing You'an Hospital, Capital Medical University, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China
| | - Y Liu
- Beijing You'an Hospital, Capital Medical University, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China
| | - C Meng
- Beijing Municipal Liver Diseases Institute, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China
| | - S Guan
- Beijing Municipal Liver Diseases Institute, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China
| | - L Xie
- Beijing Municipal Liver Diseases Institute, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China.
| | - X Chen
- Beijing You'an Hospital, Capital Medical University, No. 8 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, People's Republic of China.
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Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis. Hum Immunol 2016; 77:609-15. [PMID: 27180197 DOI: 10.1016/j.humimm.2016.05.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 05/05/2015] [Accepted: 05/10/2016] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS Many studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors. METHODS We conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model. RESULTS The pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR=4.65, 95% CI=3.36-6.42, P<0.00001) but not in HCV-2/3-infected Caucasian patients (OR=1.44, 95% CI: 0.89-2.33, P=0.13). Conversely, the rs368234815 ΔG/ΔG genotype was significantly linked to treatment failure in Caucasian patients (OR=0.49, 95% CI: 0.38-0.64, P<0.00001), regardless of the HCV genotype. CONCLUSION The results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients.
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Yeh ML, Hsieh MY, Huang CI, Huang CF, Hsieh MH, Huang JF, Dai CY, Chuang WL, Yu ML. Long-term efficacy of Peg-Interferon/Ribavirin with and without Lamivudine therapy for HBeAg-positive hepatitis B and C dual infection. J Gastroenterol Hepatol 2016; 31:835-841. [PMID: 26478984 DOI: 10.1111/jgh.13203] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 09/21/2015] [Accepted: 10/11/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND The optimal therapeutic strategy for hepatitis B virus (HBV) e antigen (HBeAg)-seropositive and hepatitis C virus (HCV) dually infected patients remains unknown. We aimed to elucidate the effectiveness of peginterferon (Peg-IFN)/ribavirin (RBV) with and without lamivudine (LAM) combination therapy in the clinical settings. PATIENTS AND METHODS Nine patients seropositive for HBV surface antigen, HBeAg, antibodies to HCV and HCV RNA for >6 months were treated with Peg-IFN/RBV with (n = 5) and without (n = 4) a 12-month LAM add-on therapy at treatment week 12. The treatment duration of Peg-IFN/RBV was 24 weeks (HCV genotype 1 [HCV-1] with rapid virological response [RVR] or HCV-2) or 48 weeks (HCV-1 without RVR). Primary endpoints included HBeAg loss and HCV-sustained virological response (SVR). RESULTS All of the nine patients had undetectable HCV RNA at treatment weeks 4 and 12 and end-of-Peg-IFN/RBV therapy. However, SVR was achieved in 100% of patients treated with triple therapy, compared with only 50% in those with Peg-IFN/RBV therapy (P = 0.167). The 3-year durability of HCV SVR was 100%. HBeAg loss and HBV DNA <2000 IU/mL at 6 months post-LAM treatment were found in 100% and 40% of patients treated with triple therapy, compared with none of the four patients with Peg-IFN/RBV therapy achieved any HBV responses. Of the five patients with triple therapy, four had persistent HBeAg loss during 3-year follow-up period; one developed HBeAg seroreversion 15 months after treatment. CONCLUSION For HBeAg-positive HBV/HCV dually infected patients, Peg-IFN/RBV was effective for HCV eradication. Add-on LAM might promote HBeAg loss in the clinical setting.
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Affiliation(s)
- Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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Lu MY, Huang CI, Dai CY, Wang SC, Hsieh MY, Hsieh MH, Liang PC, Lin YH, Hou NJ, Yeh ML, Huang CF, Lin ZY, Chen SC, Huang JF, Chuang WL, Yu ML. Elevated on-treatment levels of serum IFN-gamma is associated with treatment failure of peginterferon plus ribavirin therapy for chronic hepatitis C. Sci Rep 2016; 6:22995. [PMID: 26965318 PMCID: PMC4786849 DOI: 10.1038/srep22995] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 02/22/2016] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response.
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Affiliation(s)
- Ming-Ying Lu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Chi Wang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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Liu CJ. Simple predictor for anemia in chronic hepatitis C patients receiving peginterferon plus ribavirin. ADVANCES IN DIGESTIVE MEDICINE 2016. [DOI: 10.1016/j.aidm.2016.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2016; 22:76-139. [PMID: 27044763 PMCID: PMC4825161 DOI: 10.3350/cmh.2016.22.1.76] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 02/22/2016] [Indexed: 12/11/2022] Open
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Chou WW, Huang CF, Yeh ML, Tsai YS, Hsieh MY, Huang CI, Huang JF, Tsai PC, Hsi E, Juo SHH, Tsai WL, Chuang WL, Yu ML, Dai CY. MicroRNA let-7g cooperates with interferon/ribavirin to repress hepatitis C virus replication. J Mol Med (Berl) 2016; 94:311-320. [PMID: 26489607 DOI: 10.1007/s00109-015-1348-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 08/18/2015] [Accepted: 09/21/2015] [Indexed: 01/19/2023]
Abstract
MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.
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Affiliation(s)
- Wen-Wen Chou
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Edward Hsi
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Suh-Hang Hank Juo
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang Ming University, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Broglio KR, Daar ES, Quintana M, Yuan Y, Kalsekar A, Spellberg B, Lewis RJ, Akker DVD, Detry MA, Le T, Berry SM. A meta-analysis platform methodology for determining the comparative effectiveness of antihepatitis C virus regimens. J Comp Eff Res 2016; 4:101-14. [PMID: 25825840 DOI: 10.2217/cer.14.69] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
AIM Many hepatitis C virus regimens are unlikely to be compared head to head. In more difficult to treat populations where there is no standard of care, trials are single arm. We describe a flexible meta-analysis platform in this setting. METHODS Our meta-analysis is literature based. We illustrate our methodology and show how inference can be extended to single-arm trials. RESULTS As an example, in the single arm setting, a regimen with response rates of 84, 72 and 54% in genotype 1a across treatment naive, previous partial responders and previous null responders, respectively, would have 95% probability of superiority to IFN-α + RBV + TPV. CONCLUSION This is a rigorous approach to comparative effectiveness that accounts for varying patient populations and plans for the incorporation of emerging treatments.
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Fu R, Gutfraind A, Brandeau ML. Modeling a dynamic bi-layer contact network of injection drug users and the spread of blood-borne infections. Math Biosci 2016; 273:102-13. [PMID: 26775738 DOI: 10.1016/j.mbs.2016.01.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 11/23/2015] [Accepted: 01/07/2016] [Indexed: 12/19/2022]
Abstract
Injection drug users (IDUs) are at high risk of acquiring and spreading various blood-borne infections including human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) and a number of sexually transmitted infections. These infections can spread among IDUs via risky sexual and needle-sharing contacts. To accurately model the spread of such contagions among IDUs, we build a bi-layer network that captures both types of risky contacts. We present methodology for inferring important model parameters, such as those governing network structure and dynamics, from readily available data sources (e.g., epidemiological surveys). Such a model can be used to evaluate the efficacy of various programs that aim to combat drug addiction and contain blood-borne diseases among IDUs. The model is especially useful for evaluating interventions that exploit the structure of the contact network. To illustrate, we instantiate a network model with data collected by a needle and syringe program in Chicago. We model sexual and needle-sharing contacts and the consequent spread of HIV and HCV. We use the model to evaluate the potential effects of a peer education (PE) program under different targeting strategies. We show that a targeted PE program would avert significantly more HIV and HCV infections than an untargeted program, highlighting the importance of reaching individuals who are centrally located in contact networks when instituting prevention programs.
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Affiliation(s)
- Rui Fu
- Department of Management Science and Engineering, Stanford University, United States.
| | - Alexander Gutfraind
- Division of Epidemiology and Biostatistics, University of Illinois at Chicago, United States
| | - Margaret L Brandeau
- Department of Management Science and Engineering, Stanford University, United States
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Jabłońska J, Pawłowski T, Laskus T, Zalewska M, Inglot M, Osowska S, Perlejewski K, Bukowska-Ośko I, Cortes KC, Pawełczyk A, Ząbek P, Radkowski M. The correlation between pretreatment cytokine expression patterns in peripheral blood mononuclear cells with chronic hepatitis C outcome. BMC Infect Dis 2015; 15:556. [PMID: 26637466 PMCID: PMC4670510 DOI: 10.1186/s12879-015-1305-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 12/01/2015] [Indexed: 12/24/2022] Open
Abstract
Backgroud Cytokine response against hepatitis C virus (HCV) is likely to determine the natural course of infection as well as the outcome of antiviral treatment. However, the role of particular cytokines remains unclear. The current study analyzed activation of cytokine response in chronic hepatitis C patients undergoing standard antiviral treatment. Methods Twenty-two patients were treated with pegylated interferon and ribavirin. Twenty-six different cytokine transcripts were measured quantitatively in peripheral blood mononuclear cells (PBMC) before and after therapy and correlated with therapy outcome as well as with clinical and liver histological data. Results We found that patients who achieved sustained virological response (SVR) showed higher pretreatment cytokine response when compared to subjects in whom therapy was unsuccessful. The differentially expressed factors included IL-8, IL-16, TNF-α, GM-CSF, MCP-2, TGF-β, and IP-10. Serum ALT activity and/or histological grading also positively correlated with the expression of IL-1α, IL-4, IL-6, IL-10, IL-12, IL-15, GM-CSF, M-CSF, MCP-2 and TGF-β. Conclusion Pretreatment activation of the immune system, as reflected by cytokines transcripts upregulation, positively correlates with treatment outcome and closely reflects liver inflammatory activity.
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Affiliation(s)
- Joanna Jabłońska
- Department of Hepatology and Acquired Immunodeficiences, Medical University of Warsaw, Warsaw, Poland.
| | - Tomasz Pawłowski
- Division of Psychotherapy and Psychosomatic Medicine, Wrocław Medical University, Wrocław, Poland.
| | - Tomasz Laskus
- Department of Immunopathology of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Małgorzata Zalewska
- Department of Infectious Diseases, Hepatology and Acquired Immune Deficiences, Wrocław Medical University, Wrocław, Poland.
| | - Małgorzata Inglot
- Department of Infectious Diseases, Hepatology and Acquired Immune Deficiences, Wrocław Medical University, Wrocław, Poland.
| | - Sylwia Osowska
- Department of General Surgery and Clinical Nutrition, Medical University of Warsaw, Warsaw, Poland.
| | - Karol Perlejewski
- Department of Immunopathology of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Iwona Bukowska-Ośko
- Department of Immunopathology of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Kamila Caraballo Cortes
- Department of Immunopathology of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Agnieszka Pawełczyk
- Department of Immunopathology of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Piotr Ząbek
- Municipal Hospital of Infectious Diseases, Warsaw, Poland.
| | - Marek Radkowski
- Department of Immunopathology of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.
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Hiramine S, Furusyo N, Ogawa E, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, Koyanagi T, Kotoh K, Shimoda S, Hayashi J. Importance of virological response in the early stage of telaprevir-based triple therapy for hepatitis C. World J Hepatol 2015; 7:2688-2695. [PMID: 26609346 PMCID: PMC4651913 DOI: 10.4254/wjh.v7.i26.2688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 05/03/2015] [Accepted: 09/07/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy of virological response (VR) to telaprevir (TVR)-based triple therapy in predicting treatment outcome of hepatitis C.
METHODS: This prospective, multicenter study consisted of 253 Japanese patients infected with hepatitis C virus (HCV) genotype 1b. All received 12 wk of TVR in combination with 24 wk of pegylated-interferon-α (IFN-α) and ribavirin. Serum HCV RNA was tested at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. VR was defined as undetectable serum HCV RNA. Sustained virological response (SVR) was VR at 24 wk after the end of treatment and was regarded as a successful outcome.
RESULTS: Of 253 patients, 207 (81.8%) achieved SVR. The positive predictive value of VR for SVR was 100% at week 2, after which it gradually decreased, and was over 85% to week 12. The negative predictive value (NPV) gradually increased, reaching 100% at week 12. The upslope of the NPV showed a large increase from week 4 (40.6%) to week 6 (82.4%). There was a moderate concordance between the SVR and VR at week 6 (kappa coefficient = 0.44), although other VRs had poor concordance to SVR. Multiple logistic regression analysis extracted VR at week 6 (P < 0.0001, OR = 63.8) as an independent factor contributing to SVR. In addition, the interleukin-28B single nucleotide polymorphism and response to previous pegylated-IFN-α and ribavirin therapy were identified as independent factors for SVR.
CONCLUSION: VR at week 6, but not at week 4, is an efficient predictor of both SVR and non-SVR to TVR-based triple therapy.
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Lin CC, Wu CH, Chen HL, Lin IT, Chen MJ, Wang TE, Wang HY, Shih SC, Bair MJ. Hepatitis C treatment outcome in relation to alcohol consumption and racial differences in southeastern Taiwan. J Formos Med Assoc 2015; 114:1069-1075. [PMID: 24767103 DOI: 10.1016/j.jfma.2014.03.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Revised: 03/09/2014] [Accepted: 03/14/2014] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND/PURPOSE Alcohol use may have negative impacts on hepatitis C virus (HCV) treatment due to low adherence, and racial differences can influence HCV sustained virological response (SVR) rate between East Asian and European ancestry. The objective of this study is to confirm the influence of alcohol consumption and racial differences on HCV treatment outcome in aboriginal and nonaboriginal people of southeastern Taiwan. METHODS In this retrospective cohort study, a total of 195 patients were treated with peginterferon-alpha once weekly plus ribavirin for 24 weeks. The efficacy analysis was performed based on the SVR rate for patients who received at least one dose of the study medication or who completed treatment. The endpoints were denoted by virological response rate including the influences of alcohol use, HCV genotype, serum level of HCV virological load, and racial differences. RESULTS No differences were observed in the baseline clinical characteristics between drinkers and nondrinkers, but a significant difference was noted in the body mass index between aboriginal and nonaboriginal populations (28.3 vs. 25.8; p < 0.01). With respect to the SVR rate, no difference was found between drinkers and nondrinkers, and between aboriginal and nonaboriginal people. The treatment efficacy of SVR in the whole group was significantly different between patients with HCV genotype 1 and nongenotype 1 (73.5% vs. 91.2%; p < 0.01). An analysis of the SVR rate in the aboriginal group showed no significant difference between patients with genotype 1 and nongenotype 1 (80.0% vs. 91.3%; p = 0.31). CONCLUSION In southeastern Taiwan, alcohol consumption did not influence the HCV treatment outcome, and the SVR rates were similar between patients with HCV genotype 1 and nongenotype 1 infections in the aboriginal group.
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Affiliation(s)
- Ching-Chung Lin
- Division of Gastroenterology, Department of Internal Medicine and Liver Medical Center, Mackay Memorial Hospital, Taipei, Taiwan; Department of Nursing, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Chia-Hsien Wu
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - Huan-Lin Chen
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - I-Tsung Lin
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
| | - Ming-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine and Liver Medical Center, Mackay Memorial Hospital, Taipei, Taiwan; Department of Nursing, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Tsang-En Wang
- Division of Gastroenterology, Department of Internal Medicine and Liver Medical Center, Mackay Memorial Hospital, Taipei, Taiwan; Department of Nursing, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine and Liver Medical Center, Mackay Memorial Hospital, Taipei, Taiwan; Department of Nursing, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Shou-Chuan Shih
- Division of Gastroenterology, Department of Internal Medicine and Liver Medical Center, Mackay Memorial Hospital, Taipei, Taiwan; Department of Nursing, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan; Department of Nursing, Meiho University, Pingtung, Taiwan; Department of Applied Science, National Taitung University, Taitung, Taiwan.
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Cai Q, Zhang X, Lin C, Shao X, Guan Y, Deng H, Wei M, Huang M, Ren Z, Lu L, Mei Y, Xu M, Zhu J, Shi H, Lin G, Liu Y, Hu F, Luo Q, Lan Y, Guo F, Zhao Z, Gao Z. 24 versus 48 Weeks of Peginterferon Plus Ribavirin in Hepatitis C Virus Genotype 6 Chronically Infected Patients with a Rapid Virological Response: A Non-Inferiority Randomized Controlled Trial. PLoS One 2015; 10:e0140853. [PMID: 26509605 PMCID: PMC4624894 DOI: 10.1371/journal.pone.0140853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Accepted: 09/29/2015] [Indexed: 12/27/2022] Open
Abstract
Objectives The optimal treatment of hepatitis C virus (HCV) genotype 6 is unclear owing to its limited geographic distribution. Because of a high predictive value of rapid virological response (RVR) for sustained virological response (SVR), we conducted an open-label randomized controlled trial to compare 24- and 48-week peginterferon/ribavirin combination therapy for patients with HCV genotype 6 in Southern China who achieved an RVR. Methods and Findings Treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 6 were treated with pegylated interferon α-2a (180 μg/week) and ribavirin (800–1,200 mg, according to weight) for 4 weeks. Patients who achieved an RVR, which was defined as HCV RNA negativity at week 4 (<50 IU), were randomized to receive either an additional 20 or 44 weeks of treatment (24- and 48-week treatment groups, respectively). The primary outcome measure was SVR. From January 2011 to June 2014, 152(152/210, 72.4%) patients with HCV genotype 6a and RVR were randomized 1:1 to the 24- or 48-week treatment group. The SVR rates in the 24- and 48-week groups in the intention-to-treat analysis were 90.8% (69/76) and 88.2% (67/76), respectively; those in the per-protocol analysis were 95.7% (67/70) and 97.0% (64/66), respectively. More patients in the 48-week group had anemia (46.1% vs. 28.9%, P = 0.03), but other adverse events were comparable between the groups. The limitation of the present study was that only patients from Southern China were enrolled which may inhibit the extensive application of the findings. Conclusion Twenty-four weeks of peginterferon/ribavirin combination therapy was non-inferior to 48 weeks in patients with HCV genotype 6a in Southern China who achieved an RVR. Trial Registration ClinicalTrials.gov NCT01263860
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Affiliation(s)
- Qingxian Cai
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiaohong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Chaoshuang Lin
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiaoqiong Shao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yujuan Guan
- Eighth People’s Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Min Wei
- Zhongshan Second People’s Hospital, Zhongshan, Guangdong, China
| | | | - Zefang Ren
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Ling Lu
- Laboratory for Hepatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yongyu Mei
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Min Xu
- Eighth People’s Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Jianyun Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Haiyan Shi
- Eighth People’s Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Guoli Lin
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Ying Liu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Fengyu Hu
- Eighth People’s Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Qiumin Luo
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yun Lan
- Eighth People’s Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Fengxia Guo
- Eighth People’s Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Zhixin Zhao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- * E-mail:
| | - Zhiliang Gao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China
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Liu CH, Huang CF, Liu CJ, Dai CY, Huang JF, Lin JW, Liang CC, Yang SS, Lin CL, Su TH, Yang HC, Chen PJ, Chen DS, Chuang WL, Kao JH, Yu ML. Peginterferon alfa-2a plus Weight-Based or Flat-Dose Ribavirin for Treatment-Naïve Hepatitis C Virus Genotype 2 Rapid Responders: A Randomized Trial. Sci Rep 2015; 5:15255. [PMID: 26469083 PMCID: PMC4606559 DOI: 10.1038/srep15255] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 09/16/2015] [Indexed: 12/31/2022] Open
Abstract
The impact of ribavirin (RBV) dosage on sustained virologic response (SVR) rates remains elusive in hepatitis C virus genotype 2 (HCV-2) rapid responders receiving 16 weeks of peginterferon (Peg-IFN) plus RBV. Treatment-naïve HCV-2 patients with rapid virologic response (RVR) received Peg-IFN alfa-2a 180 μg/week plus weight-based RBV (1,000 or 1,200 mg/day; cut-off body weight: 75 kg) for 6 weeks, and then randomly received Peg-IFN alfa-2a 180 μg/week plus weight-based (1,000 or 1,200 mg/day; n = 247) or flat-dose (800 mg/day; n = 246) RBV for additional 10 weeks. The primary endpoint was SVR24. Patients receiving weight-based and flat-dose RBV therapies had comparable SVR24 rates (93.5% versus 91.9%, P = 0.49). The risk differences (RDs) of SVR24 receiving weight-based and flat-dose RBV arms were 7.1% [95% CI: 0.7% to 13.6%] in males, and -5.8% [95% CI: -12.1% to 0.5%] in females (interaction P = 0.01). The SVR24 rate was higher in males receiving ≥13 mg/kg/day than those receiving <13 mg/kg/day (96.3% versus 85.1%, P = 0.001). In conclusion, Peg-IFN alfa-2a plus weight-based or flat-dose RBV for 16 weeks provides comparable SVR24 rates in treatment-naïve HCV-2 rapid responders. However, males should receive weight-based RBV to achieve a high SVR24 rate.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Chung-Feng Huang
- Institute of Clinical Medicine and Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Yen Dai
- Institute of Clinical Medicine and Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Institute of Clinical Medicine and Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Jou-Wei Lin
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Cheng-Chao Liang
- Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Sheng-Shun Yang
- Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hung-Chih Yang
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Microbiology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Genomics Research Center, Academia Sinica, Taiwan
| | - Wan-Long Chuang
- Institute of Clinical Medicine and Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Lung Yu
- Institute of Clinical Medicine and Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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Yeh ML, Hsieh MY, Huang CI, Huang CF, Hsieh MH, Liang PC, Lin YH, Hou NJ, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Yu ML. Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With Pegylated Interferon Plus Ribavirin: A Randomized Study. Medicine (Baltimore) 2015; 94:e1837. [PMID: 26496327 PMCID: PMC4620800 DOI: 10.1097/md.0000000000001837] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 09/19/2015] [Accepted: 09/23/2015] [Indexed: 12/18/2022] Open
Abstract
We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at treatment week 4) could be applied for active HCV/hepatitis B virus (HBV) dually infected patients, without compromised the treatment efficacy.A total of 203 patients, seropositive of HCV antibody, HCV RNA and HBV surface antigen (HBsAg), and seronegative for HBV e antigen for >6 months, were randomized to receive peginterferon-alpha/ribavirin by either genotype-guided therapy (GGT, n = 102: HCV genotype 1 [HCV-1], 48 weeks; HCV-2/3, 24 weeks) or RGT (n = 101: HCV-1, 48 or 24 weeks if patients with baseline VL <400,000 IU/mL and RVR; HCV-2/3, 24 or 16 weeks if patients with RVR). The primary endpoint was HCV-sustained virological response (SVR).The HCV SVR rate was comparable between the GGT (77.5%, 79/102) and RGT groups (70.3%, 71/101, P = 0.267), either among HCV-1/HBV (69.4% [43/62] vs 63.5% [40/63], P = 0.571) or among HCV-2/3/HBV (90.0% [36/40] vs 81.6% [31/38], P = 0.342) dually infected patients based on intention-to-treat analysis. In HCV-1/HBV dually infected patients, RVR (odds ratio [OR]: 6.05; 95% confidence intervals [CI]: 2.148-17.025, P = 0.001) and lower pretreatment blood glucose levels (OR: 0.97; CI: 0.944-0.989, P = 0.003) were independent predictors of HCV SVR. Although RVR (OR: 10.68; CI: 1.948-58.514, P = 0.006) was the only significant factor associated with HCV SVR in HCV-2/3/HBV dually infected patients. HBsAg loss at 1 year posttreatment was observed in 17 of 185 (9.2%) patients. The rates of discontinuation and adverse events were similar between the 2 groups.RGT with peginterferon-alpha/RBV may be considered for HBeAg-negative HBV/HCV dually infected patients.
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Affiliation(s)
- Ming-Lun Yeh
- From the Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital (M-LYeh, M-YH, C-FH, P-CL, Y-HL, Z-YL, S-CC, J-FH, C-YD, W-LC, M-LYu), Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University (M-LYeh, C-FH, M-HH, Z-YL, S-CC, J-FH, C-YD, W-LC; M-LYu), Institute of Biomedical Sciences, National Sun Yat-Sen University (M-LYu), Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital (C-IH, N-JH), Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University (C-FH), Department of Preventive Medicine, Kaohsiung Medical University Hospital (M-HH), Graduate Institute of Medicine, College of Medicine (M-LYeh, C-YD), Center for Infectious Disease and Cancer Research; and Center for Lipid Science and Aging Research, Kaohsiung Medical University, Kaohsiung, Taiwan (C-YD, W-LC, M-LYu)
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Omata M, Kanda T, Yokosuka O, Crawford D, Al-Mahtab M, Wei L, Ibrahim A, Lau GKK, Sharma BC, Hamid SS, Chuang WL, Dokmeci AK. Features of hepatitis C virus infection, current therapies and ongoing clinical trials in ten Asian Pacific countries. Hepatol Int 2015; 9:486-507. [PMID: 25941137 DOI: 10.1007/s12072-015-9630-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Accepted: 04/06/2015] [Indexed: 02/07/2023]
Abstract
Estimated hepatitis C virus (HCV) infection rates in the general populations were 1.3, 0.9, 0.4-1.0, 14.7, 0.1-0.3, 0.9-1.9, 1.0-2.0, 5, 4.4-8.6 and 0.5-1.3 % in Australia, Bangladesh, Mainland China, Egypt, Hong Kong, India, Japan, Pakistan, Taiwan and Turkey, respectively. The main HCV genotypes (Gs) are G1, G3, G1b, G4, G1b, G3, G1b, G3, G1b and G2, and G1 in Australia, Bangladesh, Mainland China, Egypt, Hong Kong, India, Japan, Pakistan, Taiwan and Turkey, respectively. Of IL28B genotypes, favorable alleles are ~50 % in Australia and Turkey, but 60-70 % in most of the other Asian countries. Peginterferon plus ribavirin is available in all ten Asian Pasific countries. In addition, HCV NS3/4A protease inhibitors with peginterferon plus ribavirin are currently available in several countries. Clinical trials of interferon-free regimens for HCV are ongoing in most of the ten Asian Pacific countries.
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Affiliation(s)
- Masao Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
| | - Darrell Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia.
| | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh.
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Benha, Egypt.
| | - George K K Lau
- Humanity and Health Medical Centre, Hong Kong SAR China Institute of Translational Hepatology and Centre of Liver Fibrosis Diagnosis and Treatment Center, 302 Hospital, Beijing, China.
| | - Barjesh C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India.
| | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan.
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey.
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50
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Yang CC, Tsai WL, Su WW, Huang CF, Cheng PN, Lo CC, Tseng KC, Mo LR, Wang CH, Hsu SJ, Lai HC, Su CW, Liu CJ, Peng CY, Yu ML. Rapid Prediction of Treatment Futility of Boceprevir with Peginterferon-Ribavirin for Taiwanese Treatment Experienced Hepatitis C Virus Genotype 1-Infected Patients. PLoS One 2015; 10:e0137852. [PMID: 26368130 PMCID: PMC4569190 DOI: 10.1371/journal.pone.0137852] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 08/23/2015] [Indexed: 12/30/2022] Open
Abstract
The efficacy and safety of the boceprevir (BOC)-containing triple therapy in Taiwanese treatment-experienced patients remains elusive. After 4 weeks of peginterferon/ribavirin lead-in therapy, patients with cirrhosis or previous null-response received triple therapy for 44 weeks; whereas others received 32 weeks of triple therapy followed by 12 weeks of peginterferon/ribavirin therapy. Patients with HCV RNA > 100 IU/mL at week 12 or with detectable HCV RNA at week 24 of treatment were viewed as futile. A total of 123 patients received treatment. The rates of sustained virological response (SVR) and relapse were 66.7% and 8.9%, respectively by using intention-to-treat analysis. Multivariate analysis revealed that factors associated with SVR included HCV-1b (odds ratio [OR]/ 95% confidence intervals [CI]: 19.23/1.76-525.15, P = 0.01), BOC adherence (7.69/1.55-48.78, P = 0.01), serum albumin (OR/CI:6.25/1.14-40.07, P = 0.03) levels and HCV RNA levels (OR/CI:0.34/0.12-0.79, P = 0.01). Twenty-six (21.1%) patients experienced severe adverse events (SAEs). Multivariate analysis revealed that APRI > 1.5 was the single factor associated with occurring SAEs (OR/CI: 3.77/ 0.97-14.98, P = 0.05). Merging the cut-off values of HCV RNA > 7 log IU/mL at baseline and HCV RNA > 6 log IU/mL at week 4 provided the earliest and best combing viral kinetics in predicting week 12/24 futility with the PPV of 100% and accuracy of 93.5%. HCV-1 treatment experienced Taiwanese patients treated with boceprevir-containing triple therapy in real world had comparable efficacy and safety profiles with those reported in clinical trials. Early viral kinetics before week 4 of treatment highly predicted futility at week 12 or 24 of treatment.
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Affiliation(s)
- Chi-Chieh Yang
- Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine and School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chia-Yi, Taiwan
- Chung-Jen Junior College of Nursing, Health Sciences and Management and School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | - Chun-Hsiang Wang
- Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan
| | - Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun Lin, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Hepatitis Research Center and Department of Internal Medicine National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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