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Khan S, Soni S, Veerapu NS. HCV Replicon Systems: Workhorses of Drug Discovery and Resistance. Front Cell Infect Microbiol 2020; 10:325. [PMID: 32714881 PMCID: PMC7344236 DOI: 10.3389/fcimb.2020.00325] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 05/28/2020] [Indexed: 12/16/2022] Open
Abstract
The development of direct-acting antivirals (DAAs) has revolutionized the state-of-the art treatment of HCV infections, with sustained virologic response rates above 90%. However, viral variants harboring substitutions referred to as resistance-associated substitutions (RASs) may be present in baseline levels and confer resistance to DAAs, thereby posing a major challenge for HCV treatment. HCV replicons have been the primary tools for discovering and evaluating the inhibitory activity of DAAs against viral replication. Interest in replicon systems has further grown as they have become indispensable for discovering genotype-specific and cross-genotype RASs. Here, we review functional replicon systems for HCV, how these replicon systems have contributed to the development of DAAs, and the characteristics and distribution of RASs for DAAs.
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Affiliation(s)
- Shaheen Khan
- Virology Section, Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar, India
| | - Shalini Soni
- Virology Section, Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar, India
| | - Naga Suresh Veerapu
- Virology Section, Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar, India
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Liu X, Chen Y, Wang Y, Dong X, Wang J, Tang J, Sundquist K, Sundquist J, Ji J. Cancer risk in patients with hepatitis C virus infection: a population-based study in Sweden. Cancer Med 2017; 6:1135-1140. [PMID: 28374973 PMCID: PMC5527979 DOI: 10.1002/cam4.988] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 09/26/2016] [Accepted: 11/07/2016] [Indexed: 12/15/2022] Open
Abstract
Increased risks of certain cancers have been observed in patients with hepatitis C virus (HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardized incidence ratios (SIRs) were calculated for subsequent 35 common cancer sites/types between 1990 and 2010 in patients with HCV infection in Sweden. Increased risks were recorded for six cancers. The highest SIR was seen for liver cancer (36.67; 95% CI: 33.20–40.40). The decreased risk was for prostate cancer (0.73; 95% CI: 0.59–0.90) and melanoma (0.50; 95% CI: 0.30–0.79). A significant sex‐difference for cancer was observed only for liver cancer (40.72; 95% CI: 36.36–45.45 for men and 27.21; 95% CI: 21.90–33.41 for women). Also, increased SIRs were noted only for liver cancer during the entire period of follow‐up. HCV infection was associated with an increased incidence of liver cancer and additionally five other types of cancer. Active surveillance of other cancers may be needed in order to be diagnosed at an earlier stage.
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Affiliation(s)
- Xiangdong Liu
- Department of Poliomyelitis, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.,Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | | | - Youxin Wang
- School of Public Health, Capital Medical University, Beijing, China
| | - Xiaohua Dong
- Department of Pharmacology, School of Pharmacy, Hebei North University, Zhangjiakou, China
| | - Junming Wang
- College of Lab Medicine, Hebei North University, Zhangjiakou, China
| | - Jianhua Tang
- Department of Clinical Pharmacology, First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, California
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, California
| | - Jianguang Ji
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
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Barathan M, Mohamed R, Saeidi A, Vadivelu J, Chang LY, Gopal K, Ram MR, Ansari AW, Kamarulzaman A, Velu V, Larsson M, Shankar EM. Increased frequency of late-senescent T cells lacking CD127 in chronic hepatitis C disease. Eur J Clin Invest 2015; 45:466-74. [PMID: 25721991 DOI: 10.1111/eci.12429] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 02/25/2015] [Indexed: 02/01/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) causes persistent disease in ~85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses. MATERIALS AND METHODS We characterized the distinct T-cell phenotypes based on the expression of costimulatory molecules CD28 and CD27, senescence markers PD-1 and CD57, chronic immune activation markers CD38 and HLA-DR, and survival marker CD127 (IL-7R) by flow cytometry following activation of T cells using HCV peptides and phytohemagglutinin. RESULTS HCV-specific CD4+ and CD8+ T cells from chronic HCV (CHC) patients showed increased expression of PD-1. Furthermore, virus-specific CD4+ T cells of CHC-infected subjects displayed relatively increased expression of HLA-DR and CD38 relative to HCV-specific CD8+ T cells. The CD4+ and CD8+ T cells from HCV-infected individuals showed significant increase of late-differentiated T cells suggestive of immunosenescence. In addition, we found that the plasma viral loads positively correlated with the levels of CD57 and PD-1 expressed on T cells. CONCLUSIONS Chronic HCV infection results in increased turnover of late-senescent T cells that lack survival potentials, possibly contributing to viral persistence. Our findings challenge the prominence of senescent T-cell phenotypes in clinical hepatitis C infection.
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Affiliation(s)
- Muttiah Barathan
- Department of Medical Microbiology, Tropical Infectious Disease Research and Education Center (TIDREC), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia
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Huang CI, Huang CF, Huang JF, Dai CY, Yeh ML, Hsieh MY, Lin ZY, Chen SC, Wang LY, Yu ML, Chuang WL. Treatment efficacy of pegylated interferon plus ribavirin therapy in chronic hepatitis C patients with mixed genotype 1/2 infection. J Gastroenterol Hepatol 2014; 29:1012-1018. [PMID: 24325201 DOI: 10.1111/jgh.12467] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/25/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM The treatment efficacy of patients with mixed hepatitis C virus (HCV) genotype 1/genotype 2 (HCV-1/2) remains unknown. We aimed to elucidate the sustained virological response (SVR) rate in patients with HCV-1/2 infection. METHODS One hundred and ten HCV-1/2 patients treated with response-guided peginterferon/ribavirin therapy (24 weeks for patients with a rapid virological response [RVR] and low viral loads; 48 weeks for patients without a RVR or high viral loads) were allocated. Two hundred HCV-1 patients were selected as a historical control. Interleukin-28B (IL-28B) rs8099917 genotype was tested for the association with an SVR. RESULTS The rates of RVR, sustained virologic response (SVR), and relapse rate were 71.8%, 87.3%, and 11.1%, respectively. The SVR rate was significantly higher in patients with an abbreviated regimen as compared with those with 48-week regimen (95.5% vs 75.0%, P = 0.002), and both were similar to the HCV-1 historical control. Stepwise logistic regression analysis revealed that lower baseline viral loads were the single factor predictive of an RVR (odds ratio/95% confidence intervals [OR/CI] of 41.62/9.72-178.19, P < 0.001). The achievement of an RVR was the single best factor predictive of an SVR (OR/CI: 7.5/1.33-42.27, P = 0.02). Nevertheless, an abbreviated regimen became the single factor associated with an SVR if treatment regimen was taken into consideration (OR/CI: 11.0/1.25-96.79, P = 0.03). The SVR rate did not differ between patients with rs8099917 TT and TG/GG genotype (91.7% vs 87.5%, P = 0.63). CONCLUSIONS The treatment efficacy of patients with HCV-1/2 was satisfactory. The role of IL-28B genetic variants in the population with response-guided therapy was limited.
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Affiliation(s)
- Ching-I Huang
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Thong VD, Akkarathamrongsin S, Poovorawan K, Tangkijvanich P, Poovorawan Y. Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and clinical implication. World J Gastroenterol 2014; 20:2927-2940. [PMID: 24659883 PMCID: PMC3961978 DOI: 10.3748/wjg.v20.i11.2927] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 01/06/2014] [Accepted: 01/19/2014] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.
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Marciano S, Gadano AC. How to optimize current treatment of genotype 2 hepatitis C virus infection. Liver Int 2014; 34 Suppl 1:13-7. [PMID: 24373073 DOI: 10.1111/liv.12399] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
The standard of care (SOC) for hepatitis C virus (HCV) genotype 2 is pegylated interferon (PEG-IFN) plus ribavirin (RBV). Even though most patients can be cured with this therapy after 24 weeks, tailoring treatment can improve its safety and efficacy in special populations. Thus, shortening treatment together with a weight-based RBV dosing approach has been considered satisfactory in patients with positive predictors of response. With the development of the direct antiviral agents (DAAs), shorter, better tolerated and more efficient treatments for HCV genotype 2 will become available, including interferon-free regimens. Until these new treatments are released, the decision to treat patients with HCV genotype 2 with currently approved drugs or to wait for future options must be made, taking into account the stage of fibrosis.
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Huang CF, Dai CY, Yeh ML, Huang JF, Huang CI, Hsieh MY, Lin ZY, Chen SC, Wang LY, Juo SHH, Chuang WL, Lin YC, Yu ML. Virological predictors of response to retreatment in hepatitis C genotype 2 infected patients. PLoS One 2013; 8:e58882. [PMID: 23527043 PMCID: PMC3602580 DOI: 10.1371/journal.pone.0058882] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 02/07/2013] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND/AIMS The impact of virological factors and interleukin-28B (IL-28B) genetic variants on retreatment of hepatitis C virus genotype 2 (HCV-2) treatment-experienced patients remains unknown. METHODS On-treatment virological responses and IL-28B rs8099917 genotype were determined in 46 HCV-2 treatment-experienced patients (42 previous relapsers; four previous non-responders) retreated with 24-week peginterferon/ribavirin. RESULTS Forty (87.0%) patients carried the rs8099917 TT genotype and 6 patients (13.0%) carried the TG/GG genotype. The sustained virological response (SVR; seronegativity of HCV RNA throughout 24 weeks of the post-treatment follow-up period) rate was 71.7%. Compared with previous non-responders, previous relapsers had a significantly higher SVR rate (78.6% vs. 0%, P = 0.004) and a lower relapse rate (17.5% vs. 100%, P = 0.04). All the previous non-responders were with the rs8099917 TT genotype. As for those who relapsed, treatment responses, including the rates of rapid virological response (RVR, 80.6% vs. 66.7%, P = 0.59), early virological response (EVR, 97.2% vs. 83.3%, P = 0.27), end-of-treatment virological response (97.2% vs. 83.3%, P = 0.27) and SVR (80.6% vs. 66.7%, P = 0.59) and relapse rate (17.1% vs. 20.0%, P = 1) did not differ significantly between patients with the rs8099917 TT and those with the non-TT genotype. Multivariate analysis revealed that the most important factor predictive of an SVR in the retreatment of HCV-2 was previous relapse; the only factor predictive of an SVR for previous relapsers was the achievement of an EVR. Compared with the achievement of a RVR, the attainment of an EVR was more accurate in predicting an SVR (88% vs. 74%). CONCLUSIONS Peginterferon/ribavirin is effective in the retreatment of HCV-2 relapsers, especially among those who achieved an EVR.
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Affiliation(s)
- Chung-Feng Huang
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Preventive 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
| | - 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
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, 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
| | - Liang-Yen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Suh-Hang Hank Juo
- Department of Medical Genetics, 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
| | - Yi-Ching Lin
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Laboratory Medicine, Kaohsiung Medical University Hospital, 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
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Du B, Jin X, Liu W, Li XK, Yu XY, Zhang SY. Analysis of hepatitis C virus subgenotypes in patients in Heilongjiang province. Shijie Huaren Xiaohua Zazhi 2013; 21:531-536. [DOI: 10.11569/wcjd.v21.i6.531] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze the distribution of different hepatitis C virus (HCV) subgenotypes in Heilongjiang province, China.
METHODS: Serum samples from 1 313 patients with HCV infection, including 627 (47.75%) males and 686 (52.25%) females, were subgenotyped using multiplex nested PCR assay. The associations of HCV subgenotypes with gender, age, viral load, and ALT level were analyzed.
RESULTS: Of 1 313 patients, 927 (70.60%) were successfully subgenotyped. Among typable subgenotypes, 1b+/2a- was found in 388 (41.86%) cases, 2a+/1b- in 318 (34.30%) cases, 1b+2a in 197 (21.25%) cases, and 1a+/2b in 24 (2.59%) cases. The percentage of patients with 2a+/1b- subgenotype was significantly higher in females (37.50%) and patients with HCVRNA of (1.000-9.999) × 104 (54.55%), ALT level >200 (60.87%) or ≤ 40 (41.02%) (all P < 0.05). The percentage of patients with 1b+/2a- subgenotype was significantly lower in patients with HCVRNA of (1.000-9.999) × 104 (24.24%) or ALT level >200 (13.04%) (both P < 0.05).
CONCLUSION: Genotypes 1b and 2a are the most prevalent genotypes in Heilongjiang province. The distribution of different HCV subgenotypes is associated with gender, viral load, and ALT level.
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Abstract
Hepatitis C Virus (HCV) Genotype 2 accounts for 10% of the patients with chronic HCV worldwide. The current standard of care (SOC) in these patients is 24 weeks of Pegylated Interferon (PEG-IFN) plus Ribavirin (RBV), with sustained virological response rates (SVR) of 80-90%. However, there are subgroups of patients with HCV-2, such as those with advanced fibrosis/cirrhosis, in whom SVR rates are still suboptimal, and highly responsive groups in whom SVR rates reach 95%. Treatment optimization is necessary to maximize efficacy in the former group and reduce treatment-related side effects in the latter. Unfortunately, any attempt to modify the duration or dosing of the SOC according to baseline factors has been disappointing and should not be continued at present. On the other hand on-treatment HCV RNA kinetics are fundamental for individualized treatment regimens because achieving negative HCV RNA at week 4 (rapid virological response, RVR) is the key factor when the duration of PEG-IFN/RBV is tailored in HCV-2 patients. Several studies have shown that treatment can be shortened to 16 weeks in HCV-2 patients with a RVR, without increasing the risk of post-treatment relapse, thus increasing tolerance to treatment while reducing healthcare costs. On the other hand, patients who do not achieve a RVR correspond to a population of difficult-to-cure HCV-2 patients who need alternative treatment strategies which are not yet available.
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Affiliation(s)
- Eleonora Grassi
- A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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Hung MY, Hsu KH, Hu WS, Chang NC, Huang CY, Hung MJ, Miyamura T, Maruoka D, Wu S, Tanaka T, Arai M, Mikami S, Fujiwara K, Imazeki F, Yokosuka O. Gender-specific prognosis and risk impact of C-reactive protein, hemoglobin and platelet in the development of coronary spasm. Int J Med Sci 2013; 10:255-64. [PMID: 23372432 PMCID: PMC3558714 DOI: 10.7150/ijms.5383] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2012] [Accepted: 01/09/2013] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Scarce data are available on hemoglobin and platelet in relation to coronary artery spasm (CAS) development. We sought to determine the roles that high-sensitivity C-reactive protein (hs-CRP), hemoglobin and platelet play in CAS patients. METHODS Patients (337 women and 532 men) undergoing coronary angiography with or without CAS but without obstructive coronary artery disease were evaluated during a 12-year period. RESULTS Among women with high hemoglobin levels, the odds ratios (OR) from the lowest (<1 mg/l) to the highest tertiles (>3 mg/l) of hs-CRP were 1.21, 2.15, and 5.93 (p=0.009). In women with low hemoglobin levels, an elevated risk was found from the middle to the highest tertiles of hs-CRP (OR 0.59 to 3.85) (p=0.004). This relationship was not observed in men. In men, platelet count was the most significant risk factor for CAS (p=0.004). The highest likelihood of developing CAS was found among women with the highest hs-CRP tertile and low platelet counts (OR 8.77; 95% confidence interval [CI] 2.20-35.01) and among men with the highest hs-CRP tertile and high platelet counts (OR 4.58; 95% CI 0.48-43.97). Neither hemoglobin level nor platelet count was associated with frequent recurrent angina in both genders with CAS whereas death and myocardial infarction were rare. CONCLUSIONS There are positive interactions among hs-CRP, hemoglobin and platelet in women with this disease, but not in men. While hemoglobin is a modifier in CAS development in women, platelet count is an independent risk factor for men. Both women and men have good prognosis of CAS.
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Affiliation(s)
- Ming-Yow Hung
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Kanda T, Nakamoto S, Nishino T, Takada N, Tsubota A, Kato K, Miyamura T, Maruoka D, Wu S, Tanaka T, Arai M, Mikami S, Fujiwara K, Imazeki F, Yokosuka O. Peginterferon Alfa-2a plus ribavirin in Japanese patients infected with hepatitis C virus genotype 2 who failed previous interferon therapy. Int J Med Sci 2012; 10:43-49. [PMID: 23289004 PMCID: PMC3534876 DOI: 10.7150/ijms.5358] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Accepted: 12/02/2012] [Indexed: 01/07/2023] Open
Abstract
Some patients infected with hepatitis C virus (HCV) genotype 2 could be cured with treatment shorter than 24 weeks using peginterferon plus ribavirin, but there are still treatment-refractory patients. Direct-acting antivirals (DAAs) are not currently available for HCV genotype 2 patients, different from genotype 1 patients, in clinical practice. We investigated 29 HCV genotype 2-infected Japanese patients who had been previously treated and failed to clear HCV. We retreated them with peginterferon alfa-2a plus ribavirin and measured HCV RNA level to assess the efficacy and safety of this treatment in patients who had failed previous therapy. We found that retreatment of HCV genotype 2-infected Japanese patients with peginterferon alfa-2a plus ribavirin for 24-48 weeks led to 60 to 66.6% sustained virological response (SVR) in patients previously treated with (peg-)interferon monotherapy and to 69.9% SVR in relapsers previously treated with peginterferon plus ribavirin. Attention should be paid to certain patients with unique features. Selection of patients according to their previous treatment could lead to optimal therapy in HCV genotype 2 treatment-experienced patients.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
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The race for interferon-free HCV therapies: a snapshot by the spring of 2012. Rev Med Virol 2012; 22:392-411. [DOI: 10.1002/rmv.1727] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Revised: 07/05/2012] [Accepted: 07/13/2012] [Indexed: 12/16/2022]
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