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Li M, Zong Z, Xiong X, Fan J, Zhong H, Liu N, Ye W, Jing J. Ascites re-compensation in HBV-related first decompensated cirrhosis after anti-viral therapy. Front Cell Infect Microbiol 2023; 12:1053608. [PMID: 36710977 PMCID: PMC9878306 DOI: 10.3389/fcimb.2022.1053608] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 12/19/2022] [Indexed: 01/15/2023] Open
Abstract
Effective antiviral therapy can significantly improve the long-term prognosis of HBV-related decompensated patients, and re-compensation may be achieved in part of the patients. To explore the re-compensation of ascites after HBV suppression and the risk factors, the clinical outcomes of 196 consecutive patients with HBV-related first decompensated cirrhosis of ascites treated with nucleos(t)ide analogue (NUC) were analyzed retrospectively. Among these patients, the median serum HBV DNA level was 5.0 (IQR, 3.0-6.0) log10 IU/mL before treatment. Most patients were given NUC with high barrier to resistance including ETV (152), TDF (1) and TAF (1). Initial combination of LAM plus ADV and LdT plus ADV was used in 41 patients and 1 patients, respectively. After NUC treatment, the percentage of patients with ascites regression was 77.6%, 81.4%, 70.5%, 93.8%, 80.8% at 12, 24, 36, 48, 60 months, respectively (P<0.001). The distribution of ascites severity showed that the patients' ascites improved, with the proportion of no ascites and mild ascites gradually increased. The proportion of re-compensation of ascites defined as negative HBV DNA, improved liver function and ascites regression (off diuretics) was 59.7%, 70.0%, 52.3%, 59.4%, 46.2% at 12, 24, 36, 48, 60 months (P<0.001). The rate of ascites regression was higher in viral response (VR) cohort when compared with that in non-VR cohort. Univariate and multivariable analysis showed that level of serum ALT (OR:0.988, 95%CI, p=0.029) and load of serum HBV DNA (OR:0.78895%CI, p=0.044) at baseline were risk factors of re-compensation of ascites. This study demonstrated that antiviral therapy could reverse decompensation of ascites in HBV-related first decompensated cirrhosis and the level of ALT and HBV DNA were risk factors of ascites re-compensation.
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Affiliation(s)
- Mingyu Li
- Department of Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zheng Zong
- Department of Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xinmiao Xiong
- Department of Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jing Fan
- Department of Clinical Research Centre, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Huan Zhong
- Department of Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Na Liu
- Department of Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wei Ye
- Department of Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China,*Correspondence: Wei Ye, ; Jisheng Jing,
| | - Jisheng Jing
- Department of Infectious Diseases, Jurong People’s Hospital, Jiangsu University, Zhenjiang, China,*Correspondence: Wei Ye, ; Jisheng Jing,
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Han S, Qi Y, Xu Y, Wang M, Wang J, Wang J, Yuan M, Jia Y, Ma X, Wang Y, Liu X. lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p. Cancer Cell Int 2021; 21:376. [PMID: 34261460 PMCID: PMC8278695 DOI: 10.1186/s12935-021-02074-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 07/05/2021] [Indexed: 12/24/2022] Open
Abstract
Background Gastric cancer (GC) remains an important cancer worldwide. Further understanding of the molecular mechanisms of gastric carcinogenesis will enhance the diagnosis and treatment of GC. Methods The expression of DLEU2 and ETS2 was analyzed in several GC cell lines using GEPIA online analyze, qRT-PCR and immunohistochemistry. The biological behavior of GC cells was detected by CCK8, clone formation, transwell, wound healing, western blot, and flow cytometry assay. More in-depth mechanisms were studied. Results DLEU2 was significantly up-regulated in GC tissues and cell lines. The expression of DLEU2 was significantly associated with pathological grading and TNM stage of GC patients. Furthermore, knockdown of DLEU2 inhibited the proliferation, migration, and invasion of AGS and MKN-45 cells, while overexpression of DLEU2 promoted the proliferation, migration, and invasion of HGC-27 cells. MiR-30a-5p could directly bind to the 3’ UTR region of ETS2. Moreover, DLEU2 bound to miR-30a-5p through the same binding site, which facilitated the expression of ETS2. Knockdown of DLEU2 reduced the protein level of intracellular ETS2 and inhibited AKT phosphorylation, while overexpression of DLEU2 induced the expression of ETS2 and the phosphorylation of AKT. ETS2 was highly expressed in GC tissues. The expression of ETS2 was significantly associated with age, pathological grading, and TNM stage. ETS2 overexpression promoted cell proliferation and migration of AGS and MKN-45 cells. Furthermore, ETS2 overexpression rescued cell proliferation and migration inhibition induced by DLEU2 down-regulation and miR-30a-5p up-regulation in AGS and MKN-45 cells. Conclusions DLEU2 is a potential molecular target for GC treatment.
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Affiliation(s)
- Shuyi Han
- Jinan Central Hospital Affiliated to Shandong First Medical University, 115 Jie Fang Road, Jinan, 250013, Shandong, People's Republic of China.,Jinan Central Hospital Affiliated to Shandong University, 115 Jie Fang Road, Jinan, 250013, Shandong, P.R. China
| | - Yan Qi
- Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao, Shandong, People's Republic of China
| | - Yihui Xu
- Jinan Central Hospital Affiliated to Shandong First Medical University, 115 Jie Fang Road, Jinan, 250013, Shandong, People's Republic of China
| | - Min Wang
- Jinan Central Hospital Affiliated to Shandong First Medical University, 115 Jie Fang Road, Jinan, 250013, Shandong, People's Republic of China
| | - Jun Wang
- Jinan Central Hospital Affiliated to Shandong First Medical University, 115 Jie Fang Road, Jinan, 250013, Shandong, People's Republic of China
| | - Jing Wang
- Binzhou Medical University, Binzhou, Shandong, People's Republic of China
| | - Mingjie Yuan
- Binzhou Medical University, Binzhou, Shandong, People's Republic of China
| | - Yanfei Jia
- Jinan Central Hospital Affiliated to Shandong First Medical University, 115 Jie Fang Road, Jinan, 250013, Shandong, People's Republic of China
| | - Xiaoli Ma
- Jinan Central Hospital Affiliated to Shandong First Medical University, 115 Jie Fang Road, Jinan, 250013, Shandong, People's Republic of China
| | - Yunshan Wang
- Jinan Central Hospital Affiliated to Shandong First Medical University, 115 Jie Fang Road, Jinan, 250013, Shandong, People's Republic of China
| | - Xiangdong Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated To Shandong University, Jinan, Shandong, People's Republic of China.
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Li FC, Fan YC, Li YK, Wang K. Plasma diamine oxidase level predicts 6-month readmission for patients with hepatitis B virus-related decompensated cirrhosis. Virol J 2019; 16:115. [PMID: 31533748 PMCID: PMC6751599 DOI: 10.1186/s12985-019-1219-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Accepted: 09/05/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS Hepatitis B virus-related decompensated cirrhosis is difficult to cure but has a high readmission rate due to multiple complications. Our aim was to investigate the diagnostic potential value of plasma diamine oxidase (DAO) for 6-month readmission of patients with HBV-related decompensated cirrhosis. METHODS A total of 135 patients with HBV-related decompensated cirrhosis were prospectively collected at the onset of discharge of hospital, and then were followed up for at least 6 months with the readmission as the primary outcome. The plasma DAO level was measured using enzyme linked immunosorbent assay. In addition, 120 age and sex matched patients with HBV-related compensated cirrhosis were included as controls. RESULTS A total of 36 patients (36.7%) with decompensated cirrhosis admitted to hospital during the 6-month follow up. The plasma DAO level of readmission group [21.1 (14.5; 29.0) ng/ml] was significantly higher than that in the non-readmission group [12.7 (9.3; 18.0) ng/mL, P < 0.001]. Multivariate analysis showed that the plasma DAO level (HR = 1.102, P < 0.05) and hepatic encephalopathy (HE) (HR = 5.018, P < 0.05) were independent factors for 6-month readmission of decompensated cirrhosis. DAO level showed higher area under the curve of receiver operating characteristic (AUROC) than HE (0.769 vs. 0.598, P < 0.05) and Child-Pugh-Turcotte (CPT) score (0.769 vs. 0.652, P < 0.05) for predicting 6-month readmission rate, with the best cut-off value as 19.7 ng/mL. Furthermore, plasma DAO level (HR = 1.184, P < 0.05) was an independent factor and has the higher AUROC than CPT score for the onset of recurrent HE (0.905 vs. 0.738, P < 0.05) during the 6-month follow up. CONCLUSIONS Plasma DAO level > 19.7 ng/mL predicts high rate of 6-month readmission in patients with HBV-related decompensated cirrhosis.
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Affiliation(s)
- Feng-Cai Li
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China
- Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China
- Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China
| | - Yue-Kai Li
- Department of Nuclear Medicine, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China
| | - Kai Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China.
- Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China.
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Ando Y, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Hayashi K, Ishikawa T, Nakano I, Hirooka Y, Goto H. Cumulative incidence and risk factors for the development of hepatocellular carcinoma in patients with chronic hepatitis B who achieved sustained disappearance of viremia by nucleos(t)ide analog treatment. Hepatol Res 2018; 48:E240-E251. [PMID: 28865403 DOI: 10.1111/hepr.12976] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 08/25/2017] [Accepted: 08/29/2017] [Indexed: 12/12/2022]
Abstract
AIM Nucleos(t)ide analog (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC). However, some patients who achieve hepatitis B virus (HBV)-DNA disappearance from serum by NA develop HCC. In this study, we investigated the cumulative incidence and risk factors for HCC in patients with chronic hepatitis B (CHB) who achieved sustained disappearance of viremia by NA treatment. METHODS A total of 133 CHB patients (median age, 51 years; 79 men [59%]; 28 with cirrhosis [21%]) who received NA therapy and achieved HBV-DNA disappearance from serum were analyzed retrospectively. We evaluated the cumulative incidence of HCC and risk factors associated with HCC based on data collected at the time of HBV-DNA disappearance. RESULTS Thirteen patients developed HCC during the follow-up period. The 1-, 3-, and 5-year cumulative incidence of HCC was 0.0%, 7.8%, and 11.1%, respectively. In multivariate analysis, advanced age (hazard ratio [HR], 4.601; 95% confidence interval [CI], 1.220-17.351; P = 0.024), liver cirrhosis (HR, 5.563; 95% CI, 1.438-21.519; P = 0.013), and higher HBV core-related antigen (HBcrAg) levels (HR, 13.532; 95% CI, 1.683-108.815; P = 0.014) at the time of HBV-DNA disappearance were significantly associated with the development of HCC. CONCLUSION Our findings indicate the importance of continuous HCC surveillance especially in patients with advanced age, cirrhosis, and/or higher serum levels of HBcrAg, even if they achieve HBV-DNA disappearance.
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Affiliation(s)
- Yusuke Ando
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tetsuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Isao Nakano
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Kawanaka M, Nishino K, Nakamura J, Oka T, Urata N, Goto D, Suehiro M, Kawamoto H, Kudo M, Yamada G. Quantitative Levels of Hepatitis B Virus DNA and Surface Antigen and the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Receiving Long-Term Nucleos(t)ide Analogue Therapy. Liver Cancer 2014; 3:41-52. [PMID: 24804176 PMCID: PMC3995398 DOI: 10.1159/000343857] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Serum levels of hepatitis B virus (HBV) DNA are an important predictor of the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. However, little is known about whether high levels of hepatitis B surface antigen (HBsAg) increase the risk for HCC. METHODS We investigated 167 patients who were treated with nucleos(t)ide analogues (NA) for at least 2 years (median: 5.8 years, range: 2-13.1 years). Relationships between reduced levels of HBsAg and various factors were evaluated. In addition, we evaluated the usefulness of quantitative serum levels of HBV DNA and HBsAg as predictors of HCC development in patients receiving long-term NA therapy. RESULTS HCC developed in 9 of the 167 NA-treated patients. In the 9 patients with HCC, HBV DNA was undetectable (<2.1 log copies/mL), but HBsAg levels were ≥2000 C.O.I. in 7 patients. No maternal transmission, long NA treatment period, HBV DNA levels <3.0 log copies/mL, and reduced hepatitis B e antigen levels during the first 24 weeks of treatment were a significant factor of HBsAg levels <2000 C.O.I.. CONCLUSIONS Hepatocarcinogenesis was observed in patients with high HBsAg levels, despite the negative conversion of HBV DNA as a result of long-term NA therapy. Therefore, to suppress hepatocarcinogenesis, it is important to control not only HBV DNA levels but also HBsAg levels.
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Affiliation(s)
- Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Ken Nishino
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Jun Nakamura
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Takahito Oka
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Noriyo Urata
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Daisuke Goto
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Mitsuhiko Suehiro
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Hirofumi Kawamoto
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan
| | - Gotaro Yamada
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
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Lian JS, Zeng LY, Chen JY, Jia HY, Zhang YM, Xiang DR, Yu L, Hu JH, Lu YF, Zheng L, Li LJ, Yang YD. De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis. World J Gastroenterol 2013; 19:6278-6283. [PMID: 24115827 PMCID: PMC3787360 DOI: 10.3748/wjg.v19.i37.6278] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare efficacy of combined lamivudine (LAM) and adefovir dipivoxil (ADV) therapy with that of entecavir (ETV) monotherapy for hepatitis B virus (HBV)-related decompensated liver cirrhosis.
METHODS: A total of 120 naïve patients with HBV-related decompensated cirrhosis participated in this study. Sixty patients were treated with combined LAM and ADV therapy (LAM + ADV group), while the other 60 were treated with ETV monotherapy (ETV group) for two years. Tests for liver and kidney function, alpha-fetoprotein, HBV serum markers, HBV DNA load, prothrombin time (PT), and ultrasonography or computed tomography scan of the liver were performed every 1 to 3 mo. Repeated measure ANOVA and the χ2 test were performed to compare the efficacy, side effects, and the cumulative survival rates at 48 and 96 wk.
RESULTS: Forty-five patients in each group were observed for 96 wk. No significant differences in HBV DNA negative rates and alanine aminotransferase (ALT) normalization rates at weeks 48 (χ2 = 2.12 and 2.88) and 96 (χ2 = 3.21 and 3.24) between the two groups were observed. Hepatitis B e antigen seroconversion rate in the LAM + ADV group at week 96 was significantly higher in the ETV group (43.5% vs 36.4%, χ2 = 4.09, P < 0.05). Viral breakthrough occurred in 2 cases (4.4%) by week 48 and in 3 cases (6.7%) by week 96 in the LAM + ADV group, and no viral mutation was detected. In the ETV group, viral breakthrough occurred in 1 case (2.2%) at the end of week 96. An increase in albumin (F = 18.9 and 17.3), decrease in total bilirubin and in ALT (F = 16.5, 17.1 and 23.7, 24.8), reduced PT (F = 22.7 and 24.5), and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores (F = 18.5, 17.8, and 24.2, 23.8) were observed in both groups. The cumulative rates of mortality and liver transplantation were 16.7% (10/60) and 18.3% (11/60) in the LAM + ADV and ETV groups, respectively.
CONCLUSION: Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication, improve liver function, and decrease mortality.
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Chan HLY, Chen YC, Gane EJ, Sarin SK, Suh DJ, Piratvisuth T, Prabhakar B, Hwang SG, Choudhuri G, Safadi R, Tanwandee T, Chutaputti A, Yurdaydin C, Bao W, Avila C, Trylesinski A. Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis. J Viral Hepat 2012; 19:732-43. [PMID: 22967105 DOI: 10.1111/j.1365-2893.2012.01600.x] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.
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Affiliation(s)
- H L Y Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
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Tsai N, Jeffers L, Cragin L, Sorensen S, Su W, Rosenblatt L, Tang H, Hebden T, Juday T. Cost-effectiveness of entecavir versus adefovir for the treatment of chronic hepatitis B in patients with decompensated cirrhosis from a third-party US payer perspective. CLINICOECONOMICS AND OUTCOMES RESEARCH 2012; 4:227-35. [PMID: 22977309 PMCID: PMC3430439 DOI: 10.2147/ceor.s31784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Decompensated cirrhosis is a serious clinical complication of chronic hepatitis B (CHB) that places a large economic burden on the US health care system. Although entecavir has been shown to improve health outcomes in a cost-effective manner in mixed populations of CHB patients, the cost-effectiveness of entecavir has not been evaluated in CHB patients with decompensated cirrhosis. METHODS This study assessed the cost-effectiveness of entecavir versus adefovir, from a US payer perspective, in CHB patients with decompensated cirrhosis, using a health-state transition Markov model with four health states: hepatocellular carcinoma (HCC), HCC-free survival, post-liver transplant, and death. The model considered a hypothetical patient population similar to that included in a randomized controlled trial in the target population (ETV-048): predominantly male (74%), Asian (54%), mean age 52 years, hepatic decompensation (Child-Pugh score ≥ seven), hepatitis B e antigen-positive or -negative, treatment-naïve or lamivudine-experienced, and no liver transplant history. Clinical inputs were based on cumulative safety results for ETV-048 and published literature. Costs were obtained from published literature. Costs and outcomes were discounted at 3% per annum. RESULTS For 1000 patients over a 3-year time horizon, predicted overall survival and HCC-free survival were longer with entecavir than with adefovir (2.35 versus 2.30 years and 2.11 versus 2.03 years, respectively). Predicted total health care costs were $889 lower with entecavir than with adefovir ($91,878 versus $92,768). For incremental cost/life-year gained and incremental cost/HCC-free-year gained, entecavir was less costly and more effective than adefovir. Sensitivity analyses found the results to be robust to plausible variations in health-state costs and discount rate. CONCLUSION This analysis suggests that entecavir improves survival outcomes in a cost-saving manner compared with adefovir in CHB patients with hepatic decompensation.
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Affiliation(s)
- Naoky Tsai
- John A Burns School of Medicine, University of Hawaii, Honolulu, HI, USA
| | | | - Lael Cragin
- United BioSource Corporation, Bethesda, MD, USA
| | | | - Wenqing Su
- United BioSource Corporation, Bethesda, MD, USA
| | | | - Hong Tang
- Bristol-Myers Squibb Company, Plainsboro, NJ, USA
| | - Tony Hebden
- Bristol-Myers Squibb Company, Plainsboro, NJ, USA
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Abstract
The management of hepatitis B in liver transplantation has evolved significantly over the past 2 decades. Introduction of hepatitis B immune globulin and subsequently nucleos(t)ide analogues has revolutionized transplantation for hepatitis B virus (HBV), increasing survival for patients transplanted for this indication. With the availability of new and potent antivirals for HBV, the need for liver transplant should continue to decrease in the coming years. Moreover, the newer antivirals with high resistance barriers will allow effective long-term viral prophylaxis and therefore, prevention of recurrence.
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Affiliation(s)
- Corinne Buchanan
- Center for Liver Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Guan R, Lui HF. Treatment of hepatitis B in decompensated liver cirrhosis. Int J Hepatol 2011; 2011:918017. [PMID: 21994876 PMCID: PMC3170850 DOI: 10.4061/2011/918017] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2011] [Accepted: 04/19/2011] [Indexed: 12/12/2022] Open
Abstract
Chronic hepatitis B infection progresses from an asymptomatic persistently infected state to chronic hepatitis, cirrhosis, decompensated liver disease, and/or hepatocellular carcinoma. About 3% of patients with chronic hepatitis develop cirrhosis yearly, and about 5% of individuals with hepatitis B cirrhosis become decompensated annually. The outcome for patients with decompensated cirrhosis is bleak. Lamivudine, the first oral antiviral agent available for hepatitis B treatment is safe and effective and can improve or stabilize liver disease in patients with advanced cirrhosis and viraemia. Viral resistance restricts its prolonged use. Entecavir and tenofovir are newer agents with excellent resistance profile to date. These and some other antiviral agents are being investigated for optimal use in this rather challenging patient group.
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Affiliation(s)
- Richard Guan
- Mount Elizabeth Hospital and Medical Centre, Singapore 228510
| | - Hock Foong Lui
- Gleneagles Hospital and Medical Centre, Singapore 258500
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Abstract
IMPORTANCE OF THE FIELD Successful treatment of chronic hepatitis B (CHB) often requires long-term oral nucleoside/nucleotide agents which can be associated with viral resistance, patient non-compliance and adverse effects. Telbivudine is one of the more potent options available, with a 6.5- to 6.6-log copies/ml hepatitis B DNA reduction at 12 weeks in an early viral kinetic study, a potency comparable to entecavir. It is also one of the few drugs in the treatment of CHB under FDA pregnancy Category B. AREAS COVERED IN THIS REVIEW The efficacy and safety profile of telbivudine in compensated and decompensated CHB patients compared to other agents are discussed. Viral resistance, characteristic adverse effects including elevation in creatine kinase and peripheral neuropathy in telbivudine treatment are reviewed. Infrequent but significant adverse effects of other nucleoside/nucleotide analogs are highlighted. WHAT THE READER WILL GAIN Readers are provided the latest update on the clinical profile of long-term use of telbivudine. TAKE HOME MESSAGE Long-term telbivudine treatment offers effective viral suppression to CHB patients with certain baseline characteristics and on-treatment virologic response. Creatine kinase elevation is not a good predictor of muscle-related adverse effects with nucleoside/nucleotide analogs. But significant myopathy and neuropathy have been reported in a small number of patients receiving telbivudine.
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Affiliation(s)
- David Yiu-Kuen But
- University of Hong Kong, Queen Mary Hospital, Department of Medicine, Pokfulam Road, Hong Kong SAR, China
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12
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Abstract
Hepatitis B virus is a common cause of acute liver failure. It can be especially problematic in patients coinfected with hepatitis C, hepatitis D or human immunodeficiency virus. In addition, immunosuppression-associated hepatitis B reactivation is being increasingly recognized following chemotherapy, biologic therapy, and organ transplantation. This article highlights treatment options in these special populations.
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13
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Abstract
The retrospective scrutiny of studies that were originally designed to assess the antiviral activity of interferon (IFN) and nucleos(t)ide analogues (NUC) suggested reduced incidence of hepatocellular carcinoma (HCC) in responders. The interpretation of these studies, however, is questioned by the heterogeneity of patient referral, adoption of surrogate end-points, lack of control arms and, overall, by the lack of power to capture enough hard end-points of the natural history of hepatitis B, including HCC. Another point of criticism is that above all, IFN studies could have been affected by study enrolment skewed towards patients with less advanced liver disease, who had a better predicted compliance to therapy but a lower risk of developing HCC in the short-term. In my opinion, these constraints coupled with the lack of patient stratification by HCC predictors, make the evaluation of the prophylactic activity of IFN and NUC even more difficult. Overall, while single studies provide some evidence for a reduced HCC incidence in virological responders, particularly in those with moderate liver fibrosis, we still lack confirmation that anti-HBV therapy prevents HCC in patients with an established cirrhosis, too. Finally, tertiary prevention with anti-HBV treatments is controversial, due to the existence of a few, methodologically flawed studies.
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Affiliation(s)
- Massimo Colombo
- First Division of Gastroenterology, Department of Medicine, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Università degli Studi di Milano, Milan, Italy.
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14
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Peck-Radosavljevic M, Deutsch J, Ferenci P, Graziadei I, Hofer H, Holzmann H, Huber WD, Laferl H, Maieron A, Stauber R, Vogel W. [4. Austrian consensus-statement for diagnosis and therapy of hepatitis B 2009]. Wien Klin Wochenschr 2010; 122:280-302. [PMID: 20443069 DOI: 10.1007/s00508-009-1298-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2009] [Accepted: 12/04/2009] [Indexed: 02/07/2023]
Abstract
Hepatitis B is the most common chronic viral infection of the liver. Chronic hepatitis B is estimated to affect at least 350 million people worldwide and is the leading cause of death from liver disease. There have been dramatic developments both in the diagnostic field and in drug treatment of chronic hepatitis B. Today, chronic hepatitis B is a well manageable disease in the vast majority of cases and the main challenge remains the detection of affected patients at an early enough disease stage to prevent end-stage liver disease and its complications. The rapid pace of drug development mandated an update of the Austrian guidelines on the treatment of hepatitis B, which after 1994 and 1998 were now dating back to 2005 in their third version. All chapters from the 3. consensus statement from 2005 were renewed except for the chapter on liver biopsy, which is still valid in its 2005-version. In particular, virologic parameters take now center stage for treatment decisions, HBV-genotyping is now being considered for the choice of treatment, and the oral first line treatment for chronic hepatitis B has been changed. Overall this consensus statement accounts for the major advances in the management of hepatitis B and significantly changes clinical management of patients with hepatitis B in Austria.
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Affiliation(s)
- Markus Peck-Radosavljevic
- Osterreichische Gesellschaft für Gastroenterologie und Hepatologie, Arbeitsgruppe Leber, Wien, Austria.
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15
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Muttil P, Prego C, Garcia-Contreras L, Pulliam B, Fallon JK, Wang C, Hickey AJ, Edwards D. Immunization of guinea pigs with novel hepatitis B antigen as nanoparticle aggregate powders administered by the pulmonary route. AAPS JOURNAL 2010; 12:330-7. [PMID: 20419360 DOI: 10.1208/s12248-010-9192-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2010] [Accepted: 04/01/2010] [Indexed: 12/26/2022]
Abstract
Novel nanoparticle-aggregate formulations containing recombinant hepatitis B surface antigen (rHBsAg) were administered to the lungs of guinea pigs and antibodies generated to this antigen evaluated. Preparations of dry powders of: (a) rHBsAg encapsulated within poly(lactic-co-glycolic acid) (PLGA)/polyethylene glycol (PEG) nanoparticles (antigen nanoparticles, AgN(SD)), (b) rHBsAg in a physical mixture with blank PLGA/PEG nanoparticles (antigen nanoparticle admixture (AgNA(SD)), and (c) rHBsAg encapsulated in PLGA/PEG nanoparticles plus free rHBsAg (antigen nanoparticles and free antigen), were generated by spray drying with leucine. Control groups consisted of alum with adsorbed rHBsAg (AlumAg); reconstituted suspensions of spray-dried rHBsAg-loaded PLGA/PEG nanoparticles with leucine; and rHBsAg-loaded PLGA/PEG nanoparticles (AgN). Control preparations were administered by intramuscular injection; AgN was also spray instilled into the lungs. The IgG titers were measured in the serum for 24 weeks after the initial immunization; IgA titers were measured in the bronchio-alveolar lavage fluid. While the highest titer of serum IgG antibody was observed in guinea pigs immunized with AlumAg administered by the IM route, animals immunized with powder formulations via the pulmonary route exhibited high IgA titers. In addition, guinea pigs immunized with AgNA(SD) via the pulmonary route exhibited IgG titers above 1,000 mIU/ml in the serum (IgG titers above 10 mIU/ml is considered protective). Thus, the disadvantages observed with the existing hepatitis B vaccine administered by the parenteral route may be overcome by administering them as novel dry powders to the lungs. In addition, these powders have the advantage of eliciting a high mucosal immune response in the lungs without traditional adjuvants.
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Affiliation(s)
- Pavan Muttil
- Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7571, USA
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16
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Wang HS, Tran TT. Acute Liver Failure and HBV: Is there a Role for HBV Therapy? CLINICAL DILEMMAS IN VIRAL LIVER DISEASE 2010:159-162. [DOI: 10.1002/9781444319590.ch34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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17
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Fontana RJ. Entecavir in decompensated HBV cirrhosis: the future is looking brighter. J Hepatol 2010; 52:147-9. [PMID: 20006400 DOI: 10.1016/j.jhep.2009.10.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2009] [Accepted: 10/26/2009] [Indexed: 12/19/2022]
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18
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Abstract
The aim of this review is to summarize the safety profile of the five approved oral nucleoside analogs used to treat chronic hepatitis B virus (HBV) infection, focusing on both the class adverse effects and those that have been reported with individual agents, as well as their safety in pregnancy. All nucleoside analogs have a "Black Box" warning because of their potential for inhibition of human DNA polymerase gamma involved in mitochondrial DNA replication. A reduction in intracellular mitochondrial DNA levels can lead to varying clinical manifestations of mitochondrial toxicity (i.e., neuropathy, myopathy, lactic acidosis), but these side effects are rarely reported with the oral antiviral agents active against HBV. Adefovir and tenofovir are associated with a dose-dependent but usually reversible proximal renal tubular toxicity. For these reasons, patients receiving these agents should be monitored for renal toxicity and the dose modified for renal insufficiency. Prolonged use of tenofovir has also been reported to lead to reduced bone mineral density in patients with human immunodeficiency virus infection, but prospective studies in patients with HBV infection are lacking. Telbivudine treatment is associated with moderate serum creatine phosphokinase elevations in up to 12% of patients. There have been few prospective studies on the safety of nucleoside analogs during pregnancy. According to the Antiretroviral Pregnancy Registry, the incidence of birth defects associated with lamivudine and tenofovir use during pregnancy is not increased. Studies on the safety of long-term therapy with the nucleoside analogs, alone and in combination, are needed as are further studies of children, the elderly, pregnant women, and patients with renal insufficiency.
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Affiliation(s)
- Robert J Fontana
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0362, USA.
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19
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Micco L, Fiorino S, Loggi E, Lorenzini S, Vitale G, Cursaro C, Riili A, Bernardi M, Andreone P. Polymorphism rtQ215H in primary resistance to adefovir dipivoxil in hepatitis B virus infection: a case report. BMJ Case Rep 2009; 2009:bcr06.2008.0287. [PMID: 21686872 PMCID: PMC3030117 DOI: 10.1136/bcr.06.2008.0287] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The benefit of lamivudine (LAM) in hepatitis B virus (HBV) infection is compromised by the progressively increasing emergence of drug-resistant mutant strains. Although the addition of adefovir dipivoxil (ADV) usually induces complete suppression of viral replication, primary non-response to ADV in LAM resistant patients has been reported in a variable percentage of cases. Here we report a case of a patient with HBV infection and hepatocellular carcinoma who started LAM therapy and subsequently developed virological breakthrough. The patient was given ADV, but HBV-DNA negativisation was not reached. However, HBV clearance was obtained when the patient was switched from ADV to tenofovir. Virological evaluations showed two well-known LAM-related mutations (rtL180M and rtM204I) in addition to reverse-transcriptase rtQ215H. This is the first case suggesting that this mutation may have an impact on viral replication. Finally, we also report that rtQ215H is responsive to tenofovir.
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Affiliation(s)
- Lorenzo Micco
- University of Bologna, Clinical Medicine, via Massarenti 9, Bologna 40138, Italy
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20
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Tong MJ, Hsien C, Hsu L, Sun HE, Blatt LM. Treatment recommendations for chronic hepatitis B: an evaluation of current guidelines based on a natural history study in the United States. Hepatology 2008; 48:1070-8. [PMID: 18688879 DOI: 10.1002/hep.22476] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
UNLABELLED Current guidelines for treatment of chronic hepatitis B include hepatitis B e antigen (HBeAg) status, levels of hepatitis B virus (HBV) DNA, and serum alanine aminotransferase (ALT) values in the setting of either chronic hepatitis or cirrhosis. Based on findings from a prospective study of hepatitis B surface antigen (HBsAg)-positive patients, we determined whether these guidelines included patients who developed hepatocellular carcinoma (HCC) and who died of non-HCC liver-related complications. The criteria for treatment from four published guidelines were matched to a cohort of 369 HBsAg-positive patients enrolled in the study. During a mean follow-up of 84 months, 30 patients developed HCC and 37 died of non-HCC liver-related deaths. Using criteria for antiviral therapy as stated by the four guidelines, only 20%-60% of the patients who developed HCC, and 27%-70% of patients who died of non-HCC liver-related deaths would have been identified for antiviral therapy according to current treatment recommendations. If baseline serum albumin levels of 3.5 mg/dL or less or platelet counts of 130,000 mm(3) or less were added to criteria from the four treatment guidelines, then 89%-100% of patients who died of non-HCC liver-related complications, and 96%-100% of patients who developed HCC would have been identified for antiviral therapy. In addition, if basal core promoter T1762/A1764 mutants and precore A1896 mutants also were included, then 100% of patients who developed HCC would have been identified for treatment. CONCLUSION This retrospective analysis showed that the current treatment guidelines for chronic hepatitis B excluded patients who developed serious liver-related complications.
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Affiliation(s)
- Myron John Tong
- The Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine at the University of California in Los Angeles, CA, USA.
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21
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Leung N. Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues. Hepatol Int 2008; 2:163-78. [PMID: 19669301 PMCID: PMC2716844 DOI: 10.1007/s12072-008-9061-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2007] [Accepted: 01/25/2008] [Indexed: 12/13/2022]
Abstract
Forty years ago in 1967, Professor Blumberg discovered the Australian Antigen, later known as the hepatitis B surface antigen, and was awarded the Nobel Prize. This discovery enables the diagnosis of hepatitis B virus (HBV) infection and defines its epidemiology. Viral hepatitis B infection affects global health situation, and chronic hepatitis B (CHB) is particularly serious in the Asia-Pacific region. HBV vaccines created the first breakthrough in HBV prevention. Through universal HBV vaccination program for the newborns, promoted since the mid-1980s, the main route that perpetuates chronic infection from mother to child is curbed. Most children and young adults now have immunity against HBV infection. The next breakthrough comes with therapy for CHB. This prevents progression to cirrhosis and hepatocellular carcinoma. Standard interferon therapy with modest efficacy has been largely replaced by therapy with nuclos(t)ide analogues or pegylated interferons alfa-2a and -2b. Lamivudine was approved by the FDA USA in 1998, followed by adefovir dipivoxil in 2002, entecavir in 2005, and telbivudine in 2006. Clevudine, tenofovir, and many promising candidates are in different stages of development and clinical trial. This paper critically reviews recent data published or presented since the APASL Consensus and Guideline Update of 2005. Clinical efficacy mostly in patients with raised serum alanine aminotransferase will be analyzed.
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Affiliation(s)
- Nancy Leung
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Room 65, J6, 11 Chuen On Road, Taipo, NT, Hong Kong,
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22
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Ferreira MS, Borges AS. [Advances in the treatment of hepatitis B]. Rev Soc Bras Med Trop 2008; 40:451-62. [PMID: 17876470 DOI: 10.1590/s0037-86822007000400016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2006] [Accepted: 07/18/2007] [Indexed: 12/14/2022] Open
Abstract
Over the last years there has been considerable progress in the treatment of chronic hepatitis B. Five drugs are now approved for the treatment of this virosis: interferon alpha, lamivudine, adefovir, entecavir and telbivudine. Interferons (conventional or PEG) were the first medicine used in the treatment of hepatitis being able to lead the persistent response (loss of DNA-HBV and of AgHbe) to up to one third of treated cases. A large number of nucleoside/nucleotide analogues are, at present, available to treat hepatitis B. The efficacy of lamivudine, the first nucleoside analogue used, is limited by the high rate of resistance. Adefovir has efficacy comparable to that of lamivudine, but with low resistance rate. Entecavir and tenofovir have also been particularly active in the control of hepatitis B virus replication and are associated with minimal resistance development, even during long treatment regimens. Other drugs, such as telbivudine, emtricitabine and clevudine, will become new treatment options in the near future. Individuals co-infected with HIV/HBV are particularly difficult to manage and are nowadays able to benefit from combinations of drugs of the HAART therapy, which should be effective towards both viruses. The development of more potent antiviral drugs as well as new drug combinations, together with a better understanding of hepatitis B virus resistance mechanisms are important milestones to improve treatment efficacy and to diminish, in the future, the global burden of hepatitis B virus.
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Affiliation(s)
- Marcelo Simão Ferreira
- Serviço de Infectologia, Hospital de Clínicas, Universidade Federal de Uberlândia, Uberlandia, MG.
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23
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Abstract
Recurrence of the original liver disease following liver transplantation is a typical complication in viral hepatitis. Recent advances, particularly the development of strategies to prevent or effectively treat hepatitis B, have led to substantial improvements in the post-transplantation outcome of hepatitis B candidates. While the efficacy of antivirals to treatrecurrent hepatitis C has improved in recent years, there is as yet no therapy to universally prevent recurrent infection, and tolerability of antivirals remains a matter of concern.
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Affiliation(s)
- Marina Berenguer
- Ciberehd and Department of Medicine, Medical University in Valencia, Spain
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24
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Kim YK, Kim CS, Chung GH, Han YM, Lee SY, Jin GY, Lee JM. Radiofrequency ablation of hepatocellular carcinoma in patients with decompensated cirrhosis: evaluation of therapeutic efficacy and safety. AJR Am J Roentgenol 2007; 186:S261-8. [PMID: 16632686 DOI: 10.2214/ajr.04.1266] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
OBJECTIVE Our objective was to determine the therapeutic efficacy and safety of radiofrequency ablation in the treatment of hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis. SUBJECTS AND METHODS Nineteen patients with 26 HCC nodules (range, 0.8-5 cm; mean, 1.96 cm) and decompensated liver cirrhosis (mean Child score, 10.7) were treated with radiofrequency ablation using cooled-tip electrodes and a 200-W generator. Radiofrequency ablation was performed under the guidance of sonography or CT. Procedure-related complications, therapeutic efficacy, each patient's survival, changes in blood test results--that is, serum aminotransferase and bilirubin--and changes in the Child score before and after ablation therapy were analyzed. To assess the therapeutic response of the tumor to radiofrequency ablation, we performed contrast-enhanced CT after the procedure and during follow-up. RESULTS Complete necrosis without marginal recurrence at the 6-month follow-up was attained in 23 lesions (88.5%). During follow-up (mean, 13.3 months), one patient experienced a remote tumor recurrence in the liver. The median survival time was 12.0 +/- 1.7 months. Two patients died of liver failure--one at 2 months and one at 4 months after treatment. The other patients were followed for at least 6 months (range, 6-28 months; mean, 12 months). The first and second weeks after therapy, the serum aminotransferase and bilirubin levels were significantly higher than were pretreatment levels (p < 0.05). However, 3 weeks after therapy, those figures were nearly restored to the pretreatment levels. The mean Child scores 3 weeks after radiofrequency ablation (10.8) were similar to those before treatment (10.7). CONCLUSION Radiofrequency ablation can be used selectively for treatment of HCC in patients with decompensated cirrhosis but has the potential to aggravate the preexisting hepatic dysfunction.
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Affiliation(s)
- Young Kon Kim
- Department of Diagnostic Radiology, Chonbuk National University Hospital and Medical School, Jeonju, South Korea
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25
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Prevention and treatment of hepatitis B virus recurrence after liver transplantation. Curr Opin Organ Transplant 2006. [DOI: 10.1097/mot.0b013e3280102b22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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26
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Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ. Entecavir resistance is rare in nucleoside naïve patients with hepatitis B. Hepatology 2006; 44:1656-65. [PMID: 17133475 DOI: 10.1002/hep.21422] [Citation(s) in RCA: 261] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Comprehensive monitoring of genotypic and phenotypic antiviral resistance was performed on 673 entecavir (ETV)-treated nucleoside naïve hepatitis B virus (HBV) patients. ETV reduced HBV DNA levels to undetectable by PCR (<300 copies/mL, <57 IU/mL) in 91% of hepatitis B e antigen (HBeAg)-positive and -negative patients by Week 96. Thirteen percent (n = 88) of the comparator lamivudine (LVD)-treated patients experienced a virologic rebound (> or =1 log increase from nadir by PCR) in the first year, with 74% of these having LVD resistance (LVDr) substitutions evident. In contrast, only 3% (n = 22) of ETV-treated patients exhibited virologic rebound by Week 96. Three ETV rebounds were attributable to LVDr virus present at baseline, with one having a S202G ETV resistance (ETVr) substitution emerge at Week 48. None of the other rebounding patients had emerging genotypic resistance or loss of ETV susceptibility. Genotyping all additional ETV patients with PCR-detectable HBV DNA at Weeks 48, 96, or end of dosing identified seven additional patients with LVDr substitutions, including one with simultaneous emergence of LVDr/ETVr. Generally, ETV patients with LVDr were detectable at baseline (8/10) and most subsequently achieved undetectable HBV DNA levels on ETV therapy (7/10). No other emerging substitutions identified decreased ETV susceptibility. In conclusion, ETVr emergence in ETV-treated nucleoside naïve patients over a 2-year period is rare, occurring in two patients with LVDr variants. These findings suggest that the rapid, sustained suppression of HBV replication, combined with a requirement for multiple substitutions, creates a high genetic barrier to ETVr in nucleoside naïve patients.
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Affiliation(s)
- Richard J Colonno
- Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA.
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27
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Transplantation and viral hepatitis: major progress. Curr Opin Organ Transplant 2006. [DOI: 10.1097/mot.0b013e3280105a65] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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28
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Zarski JP. Prise en charge de la résistance aux analogues antiviraux chez un patient atteint de cirrhose décompensée. ACTA ACUST UNITED AC 2006. [DOI: 10.1016/s0399-8320(06)73526-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Bourlière M. [Future perspectives and strategies in managing resistance to analogue antiviral drugs in the treatment of chronic hepatitis B]. GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE 2006; 30:3S34-3S36. [PMID: 17075495 DOI: 10.1016/s0399-8320(06)73530-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Affiliation(s)
- Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph, 26 bd de Louvain, 13008 Marseille, France.
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30
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Abstract
Lamivudine, adefovir, and entecavir are safe and effective orally administered inhibitors of hepatitis B virus (HBV) replication, but drug-resistant strains of HBV with point mutations in the HBV polymerase gene are being reported with prolonged treatment that can lead to viral rebound and serum alanine aminotransferase flares. Salvage treatment with antiviral agents including investigational nucleoside/nucleotide analogues is available but highlights the limitations and hazards of sequential antiviral monotherapy for chronic HBV. Studies of pegylated interferon combined with an antiviral agent or dual nucleoside/nucleotide combination therapy are awaited to minimize the incidence of drug-resistant HBV and improve long-term outcomes.
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Affiliation(s)
- Scott K Fung
- Division of Gastroenterology, University of Michigan Medical School, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
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31
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Tillmann HL, Hadem J, Leifeld L, Zachou K, Canbay A, Eisenbach C, Graziadei I, Encke J, Schmidt H, Vogel W, Schneider A, Spengler U, Gerken G, Dalekos GN, Wedemeyer H, Manns MP. Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience. J Viral Hepat 2006; 13:256-63. [PMID: 16611192 DOI: 10.1111/j.1365-2893.2005.00695.x] [Citation(s) in RCA: 131] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.
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Affiliation(s)
- H L Tillmann
- Medical Clinic and Policlinic II, University Leipzig, Germany.
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32
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Eckert V, Struff WG. Hepatitis B: Where Are We Today? Transfus Med Hemother 2006. [DOI: 10.1159/000093298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Taltavull TC, Chahri N, Verdura B, Gornals J, Lopez C, Casanova A, Cañas C, Figueras J, Casais LA. Successful treatment with tenofovir in a child C cirrhotic patient with lamivudine-resistant hepatitis B virus awaiting liver transplantation. Post-transplant results. Transpl Int 2005; 18:879-83. [PMID: 15948869 DOI: 10.1111/j.1432-2277.2005.00125.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Antiviral treatment can be complex in decompensated hepatitis B virus (HBV) cirrhosis because of potential emergence of lamivudine-resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-DNA status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54-year-old HBV+ liver transplantation candidate who, after testing negative for HBV-DNA, developed YMDD lamivudine-resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV-DNA was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21-month postoperative follow-up, the patient's outcome was excellent. Post-transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.
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Affiliation(s)
- Teresa C Taltavull
- Liver Transplant Unit, Hospital Universitari de Bellvitge, Barcelona, Spain.
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Pineda JA, Romero-Gómez M, Díaz-García F, Girón-González JA, Montero JL, Torre-Cisneros J, Andrade RJ, González-Serrano M, Aguilar J, Aguilar-Guisado M, Navarro JM, Salmerón J, Caballero-Granado FJ, García-García JA. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology 2005; 41:779-89. [PMID: 15800956 DOI: 10.1002/hep.20626] [Citation(s) in RCA: 228] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.
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Affiliation(s)
- Juan A Pineda
- Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario de Valme, 41014 Sevilla, Spain.
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Mahmood S, Niiyama G, Kamei A, Izumi A, Nakata K, Ikeda H, Suehiro M, Kawanaka M, Togawa K, Yamada G. Influence of viral load and genotype in the progression of Hepatitis B-associated liver cirrhosis to hepatocellular carcinoma. Liver Int 2005; 25:220-5. [PMID: 15780042 DOI: 10.1111/j.1478-3231.2005.01077.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
AIM/BACKGROUND Hepatitis B virus (HBV) is an important factor in the development of hepatocellular carcinoma (HCC). We studied the influence of HBV viral load on HCC occurrence in HBV related liver cirrhosis (LC). PATIENTS AND METHODS Ninety-one LC patients were followed up over a period of 7 years. Twenty three patients received Interferon (IFN) therapy. RESULTS In 7 years, 23 patients developed HCC. Of them twenty-two (95.6%) were of genotype C. HBV DNA was found to be the only significant variable associated with HCC occurrence on both univariate (P = 0.029) and multivariate analysis (odds ratio 2.33; P < 0.033). The cumulative survival at 5 years was 83% and the annual rate of hepatitis B surface antigen clearance was 0.9 %. All of 17 HCC patients observed over a period of 5 years or more belonged to the continuously high HBV DNA group (annual average >3.7 log copies/ml) and all but one belonged to the continuously high alanine aminotransferase group (annual average >40 IU/l). CONCLUSION Patients with genotype C and a continuously high HBV DNA for 5 years or more are at a high-risk group for HCC development. Maintaining continuously low HBV DNA for 3 years or more with anti-viral therapy, may be useful in preventing or delaying HCC occurrence.
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MESH Headings
- Adult
- Age Distribution
- Aged
- Aged, 80 and over
- Analysis of Variance
- Biopsy, Needle
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/virology
- Case-Control Studies
- Cohort Studies
- DNA, Viral/analysis
- Disease Progression
- Female
- Genotype
- Hepatitis B, Chronic/epidemiology
- Hepatitis B, Chronic/genetics
- Hepatitis B, Chronic/pathology
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/genetics
- Hepatitis C, Chronic/pathology
- Humans
- Liver Cirrhosis/epidemiology
- Liver Cirrhosis/pathology
- Liver Cirrhosis/virology
- Liver Neoplasms/epidemiology
- Liver Neoplasms/pathology
- Liver Neoplasms/virology
- Male
- Middle Aged
- Multivariate Analysis
- Prevalence
- Probability
- Prognosis
- Risk Assessment
- Severity of Illness Index
- Sex Distribution
- Survival Rate
- Viral Load
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Affiliation(s)
- Sabina Mahmood
- Department of Internal Medicine, Center for Liver Diseases, Kawasaki Hospital, Kawasaki Medical School, Okayama City 2-1-80, Okayama 700-0986, Japan.
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KODAMA M, KITAMOTO M, NAKAHARA H, FUKUDA Y, OHISHI W, MORI N, MATSUMOTO A, ONITAKE T, IMAGAWA M, CHAYAMA K. A case of decompensated hepatitis B virus-related cirrhosis successfully treated with lamivudine and adefovir allowing repeated treatments for hepatocellular carcinomas. KANZO 2005; 46:262-269. [DOI: 10.2957/kanzo.46.262] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Cirrhosis, Fulminant Hepatic Failure, and Liver Transplantation. Crit Care 2005. [DOI: 10.1016/b978-0-323-02262-0.50031-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Liaw YF, Sung JJY, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521-31. [PMID: 15470215 DOI: 10.1056/nejmoa033364] [Citation(s) in RCA: 1737] [Impact Index Per Article: 82.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown. METHODS Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease. An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data. RESULTS We randomly assigned 651 patients (98 percent Asian and 85 percent male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0 to 42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo (hazard ratio for disease progression, 0.45; P=0.001). The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo (hazard ratio, 0.45; P=0.02), whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine, and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 percent vs. <1 percent). Overall, 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events. CONCLUSIONS Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.
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Affiliation(s)
- Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital and University, Taipei, Taiwan.
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Ristig M, Drechsler H, Crippin J, Lisker-Melman M, Tebas P. Management of chronic hepatitis B in an HIV-positive patient with 3TC-resistant hepatitis B virus. AIDS Patient Care STDS 2003; 17:439-42. [PMID: 14588080 DOI: 10.1089/108729103322395456] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Chronic viral hepatitis has emerged as one of the leading causes of morbidity and mortality among HIV-positive patients. These individuals are at risk for aggressive chronic active hepatitis, cirrhosis, and hepatocellular carcinoma, and eventually, death. Currently available therapies for hepatitis B are limited and include interferon-alpha, lamivudine (3TC), and adefovir. Tenofovir (TDF), a recently approved drug for the treatment of HIV, is also active against hepatitis B. We report the case of a HIV-positive patient with liver cirrhosis secondary to chronic hepatitis B virus (HBV) with evidence of resistance to 3TC. The patient was initially accepted as a liver transplant candidate. However, when TDF was added to his treatment, a remarkable virologic and histopathologic improvement was achieved. The patient was subsequently removed from the liver transplant program and has not suffered from any further hepatic complications.
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Affiliation(s)
- Maria Ristig
- Division of Infectious Diseases, Hepatology Program, Washington University School of Medicine, St. Louis, Missouri, USA
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