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Recompensation of Decompensated Hepatitis B Cirrhosis: Current Status and Challenges. BIOMED RESEARCH INTERNATIONAL 2020; 2020:9609731. [PMID: 33029534 PMCID: PMC7527887 DOI: 10.1155/2020/9609731] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 09/07/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023]
Abstract
Liver-function decompensation or hepatocellular carcinoma (HCC) gradually appears after chronic hepatitis B progresses to cirrhosis. Effective antiviral treatment can significantly improve the long-term prognosis of decompensated patients, and some patients present recompensation of decompensated hepatitis B cirrhosis. At present, there are limited research data on the recompensation of decompensated hepatitis B cirrhosis. There is still controversy regarding the evaluation time, evaluation indicators, influencing factors, and long-term prognosis of recompensation.
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Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
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Saab S, Rheem J, Jimenez MA, Fong TM, Mai MH, Kachadoorian CA, Esmailzadeh NL, Bau SN, Kang S, Ramirez SD, Grotts J, Choi G, Durazo FA, El-Kabany MM, Han SHB, Busuttil RW. Effectiveness of Ledipasvir/Sofosbuvir with/without Ribavarin in Liver Transplant Recipients with Hepatitis C. J Clin Transl Hepatol 2017; 5:101-108. [PMID: 28660147 PMCID: PMC5472930 DOI: 10.14218/jcth.2016.00070] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 03/26/2017] [Accepted: 04/03/2017] [Indexed: 12/16/2022] Open
Abstract
Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months. The mean (± SD) age of the cohort was 63 (±8.6) years old. Most recipients were male (70%). Baseline alanine transaminase, total bilirubin, and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126) mg/dL, 0.8 (±1.3) U/L, and 8,010,421.9 (±12,420,985) IU/mL, respectively. Five of 43 recipients who were treated with ribavirin required drug cessation due to side effects, with 4 of those being anemia complications. No recipient discontinued the ledipasvir/sofosbuvir. Eighty-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy, and all recipients had complete viral suppression at the end of therapy. The sustained viral response at 12 weeks after completion of therapy was 94%. Conclusion : Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after LT. Anemia is not uncommon in LT recipients receiving ribavirin.
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Affiliation(s)
- Sammy Saab
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Justin Rheem
- Department of Medicine at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA
| | - Melissa A. Jimenez
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Tiffany M. Fong
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Michelle H. Mai
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Caterina A. Kachadoorian
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Negin L. Esmailzadeh
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Sherona N. Bau
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Susan Kang
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Samantha D. Ramirez
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Jonathan Grotts
- Department of Biostatistics at the University of California at Los Angeles, Los Angeles, California, USA
| | - Gina Choi
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Francisco A. Durazo
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Mohammed M. El-Kabany
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Steven-Huy B. Han
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Ronald W. Busuttil
- Departments of Medicine at the University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
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EXP CLIN TRANSPLANTExp Clin Transplant 2016; 14. [DOI: 10.6002/ect.2015.0284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Honda K, Seike M, Murakami K. Benefits of nucleos(t)ide analog treatments for hepatitis B virus-related cirrhosis. World J Hepatol 2015; 7:2404-2410. [PMID: 26464756 PMCID: PMC4598611 DOI: 10.4254/wjh.v7.i22.2404] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/02/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs (NUCs) became established as a safe and effective treatment for hepatitis B, it was difficult to suppress the activity of the hepatitis B virus (HBV). Currently, many patients with hepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time, and the effects, benefits, and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis, its natural course and survival, histological improvement after NUC treatments, treatment effects for decompensated cirrhosis, the incidence of hepatocellular carcinoma (HCC) after NUC treatments, and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements, including regression of fibrosis, that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied, and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However, cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments, and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur, it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved.
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Li CZ, Cheng LF, Li QS, Wang ZQ, Yan JH. Antiviral therapy delays esophageal variceal bleeding in hepatitis B virus-related cirrhosis. World J Gastroenterol 2013; 19:6849-6856. [PMID: 24187460 PMCID: PMC3812484 DOI: 10.3748/wjg.v19.i40.6849] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2013] [Revised: 08/13/2013] [Accepted: 09/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of antiviral therapy with nucleoside analogs in hepatitis B virus (HBV)-related cirrhosis and esophageal varices.
METHODS: Eligible patients with HBV-related cirrhosis and esophageal varices who consulted two tertiary hospitals in Beijing, China, the Chinese Second Artillery General Hospital and Chinese PLA General Hospital, were enrolled in the study from January 2005 to December 2009. Of 117 patients, 79 received treatment with different nucleoside analogs and 38 served as controls. Bleeding rate, change in variceal grade and non-bleeding duration were analyzed. Multivariate Cox proportional hazard regression was used to identify factors related to esophageal variceal bleeding.
RESULTS: The bleeding rate was decreased in the antiviral group compared to the control group (29.1% vs 65.8%, P < 0.001). Antiviral therapy was an independent factor related to esophageal bleeding in multivariate analysis (HR = 11.3, P < 0.001). The mean increase in variceal grade per year was lower in the antiviral group (1.0 ± 1.3 vs 1.7 ± 1.2, P = 0.003). Non-bleeding duration in the antiviral group was prolonged in the Kaplan-Meier model. Viral load rebound was observed in 3 cases in the lamivudine group and in 1 case in the adefovir group, all of whom experienced bleeding. Entecavir and adefovir resulted in lower bleeding rates (17.2% and 28.6%, respectively) than the control (P < 0.001 and P = 0.006, respectively), whereas lamivudine (53.3%) did not (P = 0.531).
CONCLUSION: Antiviral therapy delays the progression of esophageal varices and reduces bleeding risk in HBV-related cirrhosis, however, high-resistance agents tend to be ineffective for long-term treatment.
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Srivastava M, Rungta S, Dixit VK, Shukla SK, Singh TB, Jain AK. Predictors of survival in hepatitis B virus related decompensated cirrhosis on tenofovir therapy: an Indian perspective. Antiviral Res 2013; 100:300-5. [PMID: 24012998 DOI: 10.1016/j.antiviral.2013.08.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Revised: 08/21/2013] [Accepted: 08/27/2013] [Indexed: 12/12/2022]
Abstract
Decompensated cirrhosis has low survival rate compared to compensated state. Effective viral suppression due to antiviral therapy (tenofovir) has been shown to slow disease progression and may delay the burden of liver transplantation. We aimed to evaluate the usefulness of various prognostic indicators in predicting the 24-months survival in HBV related decompensated cirrhosis after tenofovir therapy and to evaluate the post-treatment outcome. Ninety-six HBV related decompensated patients on antiviral (tenofovir) therapy were prospectively studied for 24months survival and mortality. Cutoff levels for several prognostic indicators were generated by ROC. Prediction of overall probability of mortality was also calculated. The overall probability of survival observed at 12months was 0.947 whereas at 24months it was found to be 0.833. According to Cox proportional hazards model, the univariate analysis revealed cutoff of >7.4logcopies/ml for HBV DNA, >1.2mg/dl for serum creatinine, >3.7mg/dl for total bilirubin, ⩽0.75 for platelets count, >10 for CTP and >20 for MELD as predictors of poor survival. Multivariate analysis showed MELD score of >20 was the most robust predictor of mortality, with 58 times higher risk (HR: 58.73, p<0.001). Post-treatment response with tenofovir for 24months significantly improved the hepatic functions and reverses decompensation and showed incredible efficacy in improvement of hepatic functional status with reduced viremia in a great majority of decompensated cirrhosis subjects having high MELD and HBV DNA level.
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Affiliation(s)
- Manjita Srivastava
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India
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Roche B, Samuel D. Treatment of patients with HBV-related decompensated cirrhosis and liver transplanted patients. Clin Liver Dis 2013; 17:451-73. [PMID: 23905816 DOI: 10.1016/j.cld.2013.05.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.
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Affiliation(s)
- Bruno Roche
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France
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Huang Y, Wu H, Wu S, Fu D, Ma Y, Shen X. A meta-analysis of nucleos(t)ide analogues in patients with decompensated cirrhosis due to hepatitis B. Dig Dis Sci 2013; 58:815-23. [PMID: 23053891 DOI: 10.1007/s10620-012-2414-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2012] [Accepted: 09/12/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND The effect of nucleos(t)ide analogues therapy in patients with decompensated cirrhosis remains unclear. AIM The purpose of this study was to evaluate the effect of nucleos(t)ide analogues on decompensated cirrhotic patients. METHODS An online search within PubMed, Web of Science, Embase, Cochrane Central of Register of Controlled Trials and China Biology Medicine disc from 1998-01-01 to 2011-09-05 was conducted. A meta-analysis was performed. Relative risks of mortality rate, Child-Pugh-Turcotte score and hepatitis B e-antigen (HBeAg) seroconversion of the decompensated patients were studied. RESULTS Eight studies involving 511 patients were included. Data showed that lamivudine and telbivudine significantly decreased the mortality rate (relative risk 0.36, 95 % confidence interval 0.25-0.54), improved the Child-Pugh-Turcotte scores (mean difference -3.23, 95 % confidence interval -3.98 to -2.48) and promoted HBeAg seroconversion (relative risk 7.48, 95 % confidence interval 2.31-24.20). CONCLUSION For patients with decompensated cirrhosis, lamivudine and telbivudine significantly decrease the mortality rate and disease severity. Also, they promote their HBeAg seroconversion.
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Affiliation(s)
- Yingnan Huang
- Department of Gastroenterology , Zhongshan Hospital of Fudan University, Shanghai, 200032, People's Republic of China
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The effect of pretransplantation lamivudine resistance on the prognosis of liver transplant recipients. Transplant Proc 2013; 45:231-5. [PMID: 23375306 DOI: 10.1016/j.transproceed.2012.06.078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2012] [Accepted: 06/19/2012] [Indexed: 11/23/2022]
Abstract
BACKGROUND Since the introduction of lamivudine to treat chronic hepatitis B (CHB), the prevalence of lamivudine resistance is increasing among orthotopic liver transplant (OLT) candidates in Korea. OBJECTIVE The purpose of this study was to evaluate the effect of pre-OLT lamivudine-resistance on the post-OLT prognosis of recipients. MATERIAL AND METHODS Consecutive OLT recipient at a single tertiary care center (n = 8) between September 1999 and August 2009 were tested preoperatively for genotypic lamivudine resistance. We compared overall survival as well as incidences of graft failure, recurrent hepatitis, and hepatocellular carcinoma (HCC) between patients with (n = 35) versus without (n = 46) lamivudine-resistance. RESULTS Mortality occurred in 2 resistant and 3 nonresistant individuals. The occurrences of graft failure, recurrent hepatitis, and HCC were 1, 2, and 2 cases, respectively, in the resistance group versus 2, 2, and 2 cases, respectively, in the nonresistance cohort. Univariate analysis showed no significant difference in survival, graft failure, HCC occurrence, and recurrent hepatitis. CONCLUSIONS Our results indicated that pre-OLT lamivudine-resistance did not significantly affect the post-OLT prognosis. Thus, lamivudine-resistance may not be a barrier when considering OLT in patients with underlying CHB as a therapeutic modality, if it is treated with appropriate antiviral agents.
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Ma H, Jia J. Why do I treat HBeAg-positive chronic hepatitis B patients with a nucleoside analogue. Liver Int 2013; 33 Suppl 1:133-6. [PMID: 23286857 DOI: 10.1111/liv.12065] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Chronic hepatitis B (CHB) is a worldwide public health problem which represents an enormous economic and social burden. Convincing evidence has shown that persistent active viral replication is an independent predictor of disease progression. Therefore, sustained suppression of HBV replication is the cornerstone for preventing the progression of disease and prolonging survival in patients with CHB. Pivotal clinical trials and real-world studies show that nucleos(t)ide analogues (NAs) are potent suppressors of HBV DNA replication with very good safety profiles. Although 1-year treatment with NAs only results in a modest rate of HBeAg seroconversion, extended treatment could increase this rate. Profound suppression of HBV DNA can result in histological improvement and a clinical benefit with a decrease in disease progression in patients with compensated or decompensated cirrhosis. Treatment must be begun with a highly potent and low resistant regimen to obtain long-term suppression of viral replication. An alternative solution may be a roadmap approach in which an inexpensive antiviral drug is started and another drug is added-on or switched-to if there is a suboptimal on-treatment decrease in HBV DNA. Clinical evidence has shown that once HBV DNA is suppressed and long-term HBeAg seroconversion is achieved, NAs can be stopped. In summary, high antiviral efficacy, excellent tolerance, extensive applicability, clearly proven histological improvement and long-term clinical benefit all make NAs the preferred choice for the management of CHB in most patients.
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Affiliation(s)
- Hong Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Honda K, Seike M, Maehara SI, Tahara K, Anai H, Moriuchi A, Muro T. Lamivudine treatment enabling right hepatectomy for hepatocellular carcinoma in decompensated cirrhosis. World J Gastroenterol 2012; 18:2586-90. [PMID: 22654459 PMCID: PMC3360460 DOI: 10.3748/wjg.v18.i20.2586] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2011] [Revised: 02/15/2012] [Accepted: 03/09/2012] [Indexed: 02/06/2023] Open
Abstract
A 69-year-old man was admitted to our hospital in October 2003, for further examination of two liver tumors. He was diagnosed with hepatocellular carcinoma (HCC) arising from decompensated hepatitis B virus (HBV)-related cirrhosis. Long-term lamivudine administration improved liver function dramatically despite repeated treatment for HCC. His Child-Pugh score was 9 points at start of lamivudine treatment, improving to 5 points after 1 year. His indocyanine green at 15 min after injection test score was 48% before lamivudine treatment, improving to 22% after 2 years and to 5% after 4 years. Radiofrequency ablation controlled the HCC foci and maintained his liver function. In April 2009, abdominal computed tomography revealed a tumor thrombus in the right portal vein. Since his indocyanine green test results had improved to less than 10%, we performed a right hepatectomy, which was successful. To our knowledge, there have been no documented reports of patients undergoing successful right hepatectomy for HCC arising from decompensated cirrhosis. The findings observed in our patient indicate the importance of nucleoside analogs for treating HBV-related HCC.
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Crespo G, Mariño Z, Navasa M, Forns X. Viral hepatitis in liver transplantation. Gastroenterology 2012; 142:1373-1383.e1. [PMID: 22537446 DOI: 10.1053/j.gastro.2012.02.011] [Citation(s) in RCA: 143] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2011] [Revised: 01/30/2012] [Accepted: 02/08/2012] [Indexed: 12/11/2022]
Abstract
Liver transplantation is the only alternative for patients with end-stage liver disease. Viral hepatitis B and C are among the most common causes of cirrhosis and hepatocellular carcinoma and a frequent indication for liver transplantation. Hepatitis B virus immunoglobulin and nucleot(s)ide analogues have facilitated the management of patients with hepatitis B who have received liver transplants and resulted in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Current therapeutic approaches are far from optimal, because sustained virologic responses are only achieved in one-third of treated patients, and adverse effects are common and severe. However, the rapid development of direct-acting antivirals against hepatitis C virus will change the management of this disease and in a few years prevent graft infection with this virus.
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Affiliation(s)
- Gonzalo Crespo
- Liver Unit, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Singal AK, Fontana RJ. Meta-analysis: oral anti-viral agents in adults with decompensated hepatitis B virus cirrhosis. Aliment Pharmacol Ther 2012; 35:674-89. [PMID: 22257108 DOI: 10.1111/j.1365-2036.2011.04990.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2011] [Revised: 08/05/2011] [Accepted: 12/27/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND The optimal oral anti-viral agent to use in patients with decompensated HBV cirrhosis remains unclear. AIM We performed a meta-analysis of the oral nucleos(t)ide analogues in patients with decompensated HBV cirrhosis. METHODS One year efficacy and safety outcomes in 22 studies published in English between '95 and 2010 were analysed. RESULTS Substantial heterogeneity was noted in the inclusion/exclusion criteria, controls, and sensitivity of the HBV DNA assay used. Pooled 1-year data showed benefit favouring lamivudine (LAM) vs. untreated controls for Child-Turcotte-Pugh (CTP) score improvement by ≥2 (OR: 117 (15 921), P ≤ 0.0001) and transplant-free survival (OR: 3.2 (1.2, 9), P = 0.022). Adefovir (ADV) led to undetectable HBV DNA at 1-year in 41% compared to 83% with LAM and 80% with entecavir (ETV). Overall, 1-year transplant-free survival rates varied from 78% with LAM to 95% and 94% with Tenofovir (TDF) and Telbivudine (TBV), respectively. The 1-year incidence of drug resistant HBV was 0% with ADV, ETV and TDF and 11% with LAM although TBV was associated with a 29% incidence at 2 years. Drug-related adverse events were infrequently reported. CONCLUSIONS All the oral anti-viral agents were associated with improved virological, biochemical and clinical parameters at 1-year. However, the efficacy of lamivudine and telbivudine is limited by drug resistance, and adefovir is limited by its potency and slower onset of action. Additional studies of tenofovir and entecavir are needed to determine the optimal agent(s) for treatment naïve patients and in those with drug-resistant decompensated HBV cirrhosis.
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Affiliation(s)
- A K Singal
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
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Kim YS. [Efficacy of entecavir treatment in hepatitis B virus-related decompensated cirrhosis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2012; 59:203-204. [PMID: 22563614 DOI: 10.4166/kjg.2012.59.3.203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
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McCaughan GW. Prevention of post liver transplant HBV recurrence. Hepatol Int 2011; 5:876-81. [PMID: 22020819 DOI: 10.1007/s12072-011-9293-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2011] [Accepted: 06/18/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND Twenty years ago, liver transplantation for hepatitis B had been a relative contraindication to universal HBV recurrence and poor outcomes. Over the ensuing two decades, there has been refinement of prevention strategies in order to minimize HBV recurrence in the allograft. RESULTS Currently, the most efficacious and cost-effective strategies include newer oral antiviral drugs in combination with low doses of hepatitis B immunoglobulin (HBIG). More recently, strategies have been successful in withdrawing HBIG and newer approaches of HBIG avoidance are currently under development. CONCLUSION Thus, 20 years afterward, HBV recurrence is <5% and outcomes following liver transplantation are excellent.
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Affiliation(s)
- Geoffrey W McCaughan
- The AW Morrow Gastroenterology and Liver Centre, The Centenary Research Institute, Royal Prince Alfred Hospital and The University of Sydney, Missenden Road, Camperdown, NSW, 2050, Australia.
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Liaw YF, Raptopoulou-Gigi M, Cheinquer H, Sarin SK, Tanwandee T, Leung N, Peng CY, Myers RP, Brown RS, Jeffers L, Tsai N, Bialkowska J, Tang S, Beebe S, Cooney E. Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized, open-label study. Hepatology 2011; 54:91-100. [PMID: 21503940 DOI: 10.1002/hep.24361] [Citation(s) in RCA: 147] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
A randomized, open-label comparative study of entecavir versus adefovir therapy was performed in subjects with chronic hepatitis B who had hepatic decompensation (Child-Turcotte-Pugh score ≥7). Adult subjects were randomized and treated (n = 191) with entecavir 1.0 mg or adefovir 10 mg daily for up to 96 weeks from the date of last subject randomization. Subjects were positive or negative for hepatitis B e antigen and experienced or naive for treatment with nucleos(t)ide analogues. The primary efficacy endpoint was the mean reduction in serum hepatitis B virus (HBV) DNA, as determined by polymerase chain reaction, at week 24, adjusted for baseline HBV DNA and lamivudine resistance status by linear regression analysis. Entecavir demonstrated superiority to adefovir for this endpoint (treatment difference 1.74 log(10) copies/mL [95% confidence interval -2.30, -1.18]; P < 0.0001). The entecavir group showed a greater change from baseline in HBV DNA at all time points through week 48 and a higher proportion of subjects who achieved HBV DNA < 300 copies/mL at weeks 24 (entecavir 49%; adefovir 16%; P < 0.0001) and 48 (entecavir 57%; adefovir 20%; P < 0.0001). Approximately two-thirds of subjects in both groups showed improvement/stabilization in Child-Turcotte-Pugh status. Model for End-Stage Liver Disease score change at week 48 was -2.6 for entecavir and -1.7 for adefovir. Adverse event rates were comparable between groups. Cumulative hepatocellular carcinoma rates were 12% for entecavir and 20% for adefovir. Cumulative death rates were 23% for entecavir and 33% for adefovir. Week 24 mortality rates were 12% for both groups. conclusion: Entecavir demonstrated superior virologic efficacy to adefovir in a population of patients with chronic hepatitis B who had hepatic decompensation. Biochemical and clinical benefits were also demonstrated. Entecavir was well tolerated, and early mortality rates were consistent with rates observed in similar populations treated with lamivudine.
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Affiliation(s)
- Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
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18
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Abstract
The consequences of chronic hepatitis B virus infection include hepatocellular carcinoma and liver cirrhosis. Effective antiviral therapy in patients with hepatitis B with advanced liver disease with viral suppression and sustained HBeAg seroconversion (where applicable) may abort hepatic decompensation, diminish hepatocellular risk, and reduce the risk of viral recurrence after transplantation. Overt hepatic decompensation is an indication for referral to a transplant center.
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Affiliation(s)
- Hui-Hui Tan
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Republic of Singapore.
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19
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Hsu CY, Lin HC, Huang YH, Su CW, Lee FY, Huo TI, Lee PC, Lee JY, Lee SD. Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa for outcome prediction in patients with acute decompensated hepatitis. Dig Liver Dis 2010; 42:137-42. [PMID: 19595648 DOI: 10.1016/j.dld.2009.06.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2009] [Revised: 05/28/2009] [Accepted: 06/10/2009] [Indexed: 02/09/2023]
Abstract
BACKGROUND AND AIM The model for end-stage liver disease (MELD) is used to predict the outcome of patients with cirrhosis. Incorporation of serum sodium (Na) into MELD may further increase its prognostic ability. Two Na-containing MELD models, MELD-Na and MELDNa, were proposed to enhance the prognostic ability. This study compared the predictive accuracy of these models for acute decompensated hepatitis. METHODS We investigated the outcome of 182 patients with acute decompensated hepatitis. RESULTS Twenty (11%) patients died at 3 months. The MELD-Na and MELDNa both had significantly higher area under the receiver operating characteristic curve (AUC) in comparison to MELD (MELD-Na: 0.908, MELDNa: 0.895, MELD: 0.823, p=0.004 and 0.001, respectively). Among 96 patients without specific antiviral treatment, the MELD-Na and MELDNa consistently had significantly higher AUC than the MELD (MELD-Na: 0.901, MELDNa: 0.882, MELD: 0.810, p=0.008 and 0.004, respectively). Three independent indicators, pre-existing cirrhosis (odds ratio [OR]: 5.67, 95% confidence interval [CI]: 1.72-18.7), serum albumin<3.7 g/dL (OR: 5.68, 95% CI: 1.18-27.03) and serum sodium (Na)<138 mequiv./L (OR: 10.0, 95% CI: 2.08-47.62), were associated with 3-month mortality. CONCLUSION MELD-Na and MELDNa provide better prognostic accuracy than the MELD for patients with acute decompensated hepatitis. The adequacy of liver reserve determines the outcome of these patients.
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Affiliation(s)
- C-Y Hsu
- Department of Medicine, Taipei Veterans General Hospital, and Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
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20
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Saab S, Ham MY, Stone MA, Holt C, Tong M. Decision analysis model for hepatitis B prophylaxis one year after liver transplantation. Liver Transpl 2009; 15:413-20. [PMID: 19326401 DOI: 10.1002/lt.21712] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In patients receiving orthotopic liver transplantation, hepatitis B recurrence rates have decreased significantly with the use of various methods for prophylaxis. At present, a combination of hepatitis B immunoglobulin (HBIG) and lamivudine is the standard of care, resulting in recurrence rates of 0% to 11%. Recent data suggest that the addition of adefovir to lamivudine is successful in treating patients with recurrent hepatitis B infection. A Markov model was used to compare costs and outcomes of 2 strategies for hepatitis B prophylaxis 1 year after transplantation. The first consisted of prophylaxis with lamivudine and adefovir (strategy 1), whereas the second consisted of intramuscular HBIG and lamivudine (strategy 2) with the addition of adefovir in patients who subsequently developed hepatitis B recurrence. Patients who failed with adefovir and lamivudine were then treated with tenofovir and entecavir. 16.8% of liver transplant recipients had hepatitis B recurrence after 10 years of treatment with lamivudine and HBIG. The medical costs for strategy 1 and strategy 2 after 10 years of therapy were $151,819 and $166,246, respectively, and this resulted in cost savings of $14,427. The decision analysis model began 1 year after liver transplantation. A 1-way sensitivity analysis demonstrated that the model was most sensitive to cost changes of adefovir and HBIG injections as well as variations in the hepatitis B virus recurrence rate. The model was robust to costs of lamivudine, laboratory costs, administrative fees, and office visit fees. Our decision analysis model resulted in marked savings in costs with strategy 1 (lamivudine and adefovir), providing pharmacoeconomic support for the use of this strategy as first-line therapy in hepatitis B prophylaxis in liver transplant recipients 1 year after liver transplantation.
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Affiliation(s)
- Sammy Saab
- Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
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21
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Abstract
Since the introduction of the hepatitis B vaccine and other preventive measures, the worldwide prevalence of hepatitis B infection has fallen. However, chronic infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of hepatic decompensation, cirrhosis, and hepatocellular carcinoma. An improved understanding of hepatitis B virology, immunology, and the natural course of chronic infection, has identified hepatitis B virus replication as the key driver of immune-mediated liver injury and disease progression. The approval of potent oral antiviral agents has revolutionised hepatitis B treatment since 1998. Conventional and pegylated interferon alfa and nucleoside and nucleotide analogues are widely authorised treatments, and monotherapy with these drugs greatly suppresses virus replication, reduces hepatitis activity, and halts disease progression. However, hepatitis B virus is rarely eliminated, and drug resistance is a major drawback during long term therapy. The development of new drugs and strategies is needed to improve treatment outcomes.
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Affiliation(s)
- Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
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22
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Zoulim F, Radenne S, Ducerf C. Management of patients with decompensated hepatitis B virus associated [corrected] cirrhosis. Liver Transpl 2008; 14 Suppl 2:S1-7. [PMID: 18825719 DOI: 10.1002/lt.21615] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
1. Hepatitis B virus replication is associated with a severe outcome in patients with decompensated cirrhosis. 2. Viral suppression induced by antivirals results in a clinical improvement that allows liver transplantation to be delayed or avoided. 3. Early treatment intervention is mandatory in patients with decompensated cirrhosis because of the delay in the restoration of liver functions. 4. Lamivudine is no longer the drug of choice because the initial enthusiasm has been tempered by the high rate of resistance development. 5. Early add-on therapy with adefovir allows us to rescue lamivudine resistance, but its use may be limited by nephrotoxicity. 6. Studies are ongoing with the newer generation of antivirals (telbivudine, tenofovir, entecavir, and emtricitabine) in monotherapy or in combination to determine the best strategy for achieving rapid and prolonged suppression of viral replication. These improved strategies should enhance treatment success enough to obtain clinical stabilization, to delay or prevent the need for transplantation, and to reduce the risk of hepatitis B virus recurrence on the graft.AASLD.
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23
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Li Y, Kan ZC, Han T. Lamivudine therapy after transcatheter arterial chemoembolization for patients with Hepatocellular carcinoma complicated by hepatitis B virus: an analysis of 30 cases. Shijie Huaren Xiaohua Zazhi 2008; 16:1700-1703. [DOI: 10.11569/wcjd.v16.i15.1700] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [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 evaluate therapeutic effects and prognosis of lamivudine therapy after transcatheter arterial chcmoemholization (TACE) in patients with hepatocellular carcinoma(HCC) complicated by hepatitis B virus (HBV).
METHODS: Sixty patients with advanced HCC complicated by HBV and cirrhosis were randomly divided into 2 groups: TACE + lamivudine treatment group (n = 30) and TACE control group (n = 30). HBV-DNA, Child-pugh score and 2-year survival rate were measured.
RESULTS: After one or two years' treatment, Rate of HBV-DNA of treatment group was significantly lower than that of the control group (χ2 = 9.788, P = 0.002, χ2 = 3.962, P = 0.047). Child-pugh scores of treatment group were significantly lower than those of the control group (7.13 ± 1.30 vs 8.44 ± 1.79, 7.40 ± 1.35 vs 9.09 ± 1.76 respectively, both P < 0.05). 1-year and 2-year survival rates were 66.67% and 36.67% respectively (P < 0.05).
CONCLUSION: Lamivudine therapy after TACE can inhibit duplication of HBV, protect liver functions and improve survival rate in patients with HCC complicated by HBV.
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24
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Jia JD. Antiviral therapy for various stages of HBV-related diseases: lamivudine and beyond. J Gastroenterol Hepatol 2008; 23:681-2. [PMID: 18410600 DOI: 10.1111/j.1440-1746.2008.05445.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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The long-term effects of lamivudine treatment in patients with HBeAg-negative liver cirrhosis. Adv Ther 2008; 25:190-200. [PMID: 18385953 DOI: 10.1007/s12325-008-0038-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
INTRODUCTION In hepatitis B virus (HBV)-related liver cirrhosis, patients with HBV replication show a higher mortality rate than those without. We aimed to investigate the long-term effects of lamivudine on HBV DNA suppression, Child-Pugh score, and survival in patients with hepatitis Be antigen (HBeAg)-negative liver cirrhosis. METHODS Sixty-eight patients (51 male, 17 female) diagnosed with HBV-positive liver cirrhosis, who were monitored by the hepatology and liver transplantation outpatient clinics of our hospital between June 1999 and May 2007, were included in the study. Lamivudine (100 mg/day) was administered orally. Follow-up visits were scheduled monthly during the first 3 months, and every 3 months thereafter. Complete blood count, haemostasis, biochemistry (aspartate aminotransferase [AST], alanine aminotransferase [ALT], amylase, urea, creatinine, total bilirubin, direct bilirubin, total protein, albumin), and alpha-foetoprotein were recorded every 3 months. HBV DNA levels, abdominal ultrasound and the Child-Pugh score were evaluated every 6 months. RESULTS Sixty-eight patients (mean age, 52.05+/-12.6 years) were monitored for 49.51+/-18.51 months. Basal ALT, HBV DNA levels and Child-Pugh scores were 103.9+/-73.9 IU/ml, 4133+/-121,94 IU/ml, and 7.6+/-2.4, respectively. The ALT normalisation was 59.7% during the first year, 68.2% during the second year and 44.4% during the fifth year. There was a significant decrease in Child-Pugh scores in the first 3 follow-up years when compared with the baseline score (P<0.05). During the treatment, HBV DNA positivity and YMDD mutations were determined in 20 of 68 (29.4%) patients at 46+/-17.9 months. Nine patients (13.2%) developed hepatocellular carcinoma at 44.8+/-21.5 months. Thirteen patients (19.1%) died during the treatment due to liver failure or variceal bleeding. CONCLUSION Lamivudine is beneficial in patients with HBeAg-negative liver cirrhosis in terms of improvement in liver function and enhancement of survival and quality of life. An HBV DNA suppressive effect and improvement in Child-Pugh score were seen especially in the first years. It is important to be aware of YMDD mutation early, as addition of new antivirals is necessary to overcome unwanted results of the mutation.
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Yuan Y, Iloeje U, Li H, Hay J, Yao GB. Economic implications of entecavir treatment in suppressing viral replication in chronic hepatitis B (CHB) patients in China from a perspective of the Chinese Social Security program. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2008; 11 Suppl 1:S11-22. [PMID: 18387054 DOI: 10.1111/j.1524-4733.2008.00362.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
OBJECTIVES Of estimated 112 million persons infected with chronic hepatitis B (CHB) in China, 15% to 40% will eventually develop liver complications. Most patients do not actively seek antiviral agents for treatment due in part to lack of good understanding of the disease. Entecavir is a new therapeutic option for CHB patients and the purpose of this study was to evaluate the cost-effectiveness of entecavir treatment in China, based on projected clinical benefits from its superior viral suppression efficacy. METHODS The analysis was based on the perspective of the Chinese Social Security program. Adjusted relative risks on the association between viral load (VL) and clinical end points (liver cirrhosis/hepatocellular carcinoma) were derived from a publication of a Taiwan CHB prospective cohort with 42,115 person-years of follow-up, and applied to patients enrolled in a randomized phase III trial in China. In this trial, hepatitis B virus (HBV) DNA (by polymerase chain reaction assay) was the key efficacy end point after 48 weeks of treatment with either entecavir or lamivudine monotherapy. Entecavir and lamivudine daily prices were assumed to be Renminbi Yuan (RMB) 40 and 16.71, respectively. Life expectancy tables were based on China vital statistics. Direct medical cost and utility scores for different phases of CHB were estimated from published China specific data, and costs were adjusted to 2006 values using the Chinese Consumer Price Index. Probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty on event distribution and treatment failure rates beyond the trial period. RESULTS A total of 519 subjects were enrolled in the study, comprising of 82% males, 87% HBeAg+, and a mean age of 30 years. Based on the efficacy measurement of the percentage of patients achieving HBV DNA <300 copies/ml at week 48, entecavir was superior to lamivudine (78.7% vs. 46.7%, respectively [P < 0.05]). In the base case, compared with lamivudine, 1 year of entecavir therapy gained 0.305 quality-adjusted life year (QALY) at an incremental cost of 5368 RMB, with a 3% annual discount. Compared with lamivudine, using entecavir cost an incremental 17,590 RMB per QALY gained (95% CI 6333-56,407). CONCLUSIONS Based on the results of this study, entecavir is likely to be cost-effective in treating hepatitis B patients in China based on the World Health Organization's recommended maximum willingness to pay threshold.
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Affiliation(s)
- Yong Yuan
- Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA.
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27
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Osborn MK, Han SH, Regev A, Bzowej NH, Ishitani MB, Tran TT, Lok AS, Group TNIHHBVOLTS. Outcomes of patients with hepatitis B who developed antiviral resistance while on the liver transplant waiting list. Clin Gastroenterol Hepatol 2007; 5:1454-61. [PMID: 17977800 PMCID: PMC2645788 DOI: 10.1016/j.cgh.2007.08.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Lamivudine has been shown to improve liver disease and survival of hepatitis B virus patients on the orthotopic liver transplantation (OLT) waiting list, but liver failure might worsen in patients with drug resistance. Use of antiviral salvage therapy might decrease this risk. METHODS We analyzed data from patients enrolled in the NIH HBV OLT cohort to study the effects of pretransplant antiviral therapy on transplant-free survival and survival without transplant. We also compared the clinical outcomes of those who did or did not develop antiviral failure (virologic breakthrough or genotypic resistance) while awaiting transplant. RESULTS One hundred twenty-two eligible patients received antiviral therapy before OLT and were followed for a median of 40.5 months (range, 0.4-123.0 months) after initiation of antiviral therapy. Forty-four (36.1%) patients developed antiviral failure; all had lamivudine monotherapy as initial treatment. Forty-two patients started salvage therapy a median of 5 months after lamivudine failure; the median Model for End-Stage Liver Disease (MELD) score was 12. Twenty-one (50%) patients had a full response to salvage therapy. Eleven (26.2%) patients had a suboptimal virologic response but remained clinically compensated. Antiviral failure was not a significant predictor of transplant or death (P = .09) or death without transplant (P = .39). Multivariate predictors of transplant or death were high MELD score, hepatocellular carcinoma, and low albumin. High MELD score and low albumin were predictors of death without transplant. CONCLUSIONS Antiviral failure in patients with HBV on the OLT waiting list did not impair clinical outcome if recognized early and if salvage therapy is promptly initiated.
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Affiliation(s)
| | - Steven H. Han
- University of California – Los Angeles, Los Angeles, CA
| | - Arie Regev
- University of Miami, Leonard M. Miller School of Medicine, Miami, FL
| | | | | | | | - Anna S.F. Lok
- University of Michigan Medical Center, Ann Arbor, MI
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29
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Abstract
Hepatitis B virus (HBV) is the most common cause of chronic hepatitis and end-stage liver disease worldwide. Untreated, chronic hepatitis B acquired early in life results in cirrhosis, liver failure, or hepatocellular carcinoma in up to 40% of individuals. Until recently, the options for a patient who had end-stage hepatitis B cirrhosis were severely limited, but during the past 15 years great strides have been made in prevention and treatment of hepatitis B cirrhosis. This article reviews recent advances in the understanding of the natural history, prevention, and medical management of HBV-related end-stage liver disease.
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Affiliation(s)
- Ilan S Weisberg
- Division of Gastroenterology and Hepatology, New York Weill Cornell Medical Center, 525 E. 68th Street, New York, NY 10021, USA
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30
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Wong VWS, Chim AML, Wong GLH, Sung JJY, Chan HLY. Performance of the new MELD-Na score in predicting 3-month and 1-year mortality in Chinese patients with chronic hepatitis B. Liver Transpl 2007; 13:1228-35. [PMID: 17763399 DOI: 10.1002/lt.21222] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The new Model for End-Stage Liver Disease (MELD)-Na score has been validated in a population predominantly affected by chronic hepatitis C and alcoholic liver disease. We aimed to validate the score in Chinese patients with chronic hepatitis B-related complications admitted to the hospital from 1996 to 2003. MELD and the new MELD-Na scores (MELD-Na = MELD + 1.59 [135 - Na] with maximum and minimum Na of 135 and 120 mmol/L, respectively) on initial admissions were calculated. Cox proportional hazard model was used to assess factors associated with mortality. The area under the receiver operator characteristic curve (AUC) was used to compare the predictive abilities of MELD and MELD-Na scores for 3-month and 1-yr mortalities. Patients with hepatocellular carcinoma were excluded. A total of 2,073 patients with liver disease were admitted during the study period and 363 patients had chronic hepatitis B-related complications other than hepatocellular carcinoma. At a median follow-up of 106 weeks, 134 patients died and 14 received liver transplantation. Patients with MELD-Na scores 11-20, 21-30, and >30 had mortality increased by 2.0-fold, 4.7-fold, and 7.6-fold, respectively, compared to patients with scores < or =10. At 3 months and 1 yr, the AUC of the MELD-Na score (0.75 and 0.79, respectively) was superior to those of the MELD score (0.72 and 0.75, respectively) (P = 0.004) in predicting mortality. In conclusion, the new MELD-Na score is a valid model to predict mortality in patients with complications of chronic hepatitis B.
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Affiliation(s)
- Vincent Wai-Sun Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Republic of China
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31
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Chae HB, Hann HW. Baseline HBV DNA level is the most important factor associated with virologic breakthrough in chronic hepatitis B treated with lamivudine. World J Gastroenterol 2007; 13:4085-4090. [PMID: 17696226 PMCID: PMC4205309 DOI: 10.3748/wjg.v13.i30.4085] [Citation(s) in RCA: 18] [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: 05/16/2007] [Revised: 05/23/2007] [Accepted: 06/04/2007] [Indexed: 02/06/2023] Open
Abstract
AIM To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-positive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.
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Affiliation(s)
- Hee Bok Chae
- Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Department of Medicine, Jefferson Medical College and Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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32
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Haché C, Villeneuve JP. Lamivudine treatment in patients with chronic hepatitis B and cirrhosis. Expert Opin Pharmacother 2007; 7:1835-43. [PMID: 16925509 DOI: 10.1517/14656566.7.13.1835] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Chronic hepatitis B is a common disease and approximately 20% of infected patients with compensated cirrhosis will decompensate over 5 years. If untreated, the survival of decompensated cirrhosis is poor (15% at 5 years). The extent of hepatitis B virus (HBV) replication, as assessed by serum HBV-DNA level, is a strong predictor of the risk of disease progression and hepatocellular carcinoma. This provides a rationale for antiviral therapy to arrest progression of liver disease. Lamivudine is a pyrimidine analogue that inhibits HBV-DNA reverse transcriptase. It decreases HBV replication, normalises alanine aminotransferase levels and reduces hepatic inflammation and fibrosis in patients with chronic hepatitis B. This article will focus on the use of lamivudine in patients with HBV-cirrhosis. In patients with compensated HBV-cirrhosis, a randomised, placebo-controlled trial has shown that lamivudine significantly reduced the rate of disease progression and hepatocellular carcinoma development over a 3-year period. In patients with decompensated cirrhosis, treatment with lamivudine can produce spectacular improvements of liver function, but the improvement is slow and a clinical benefit is usually not observed until after at least 3-6 months of treatment. A major drawback of lamivudine treatment is the development of resistance, observed in 15-20% of patients after 1 year and up to 70% after 5 years of continued treatment. Thus, patients with HBV-cirrhosis treated with lamivudine should have regular monitoring of serum HBV-DNA levels and prompt institution of additional antiviral therapy if viral breakthrough is observed. Adefovir, tenofovir and entecavir have demonstrated efficacy in patients with lamivudine resistance. In patients with decompensated cirrhosis, in whom the development of resistance can be fatal, combination therapy (such as lamivudine plus adefovir) may prove more effective than monotherapy and this issue needs further study.
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Affiliation(s)
- Chantal Haché
- Division of Hepatology, Hôpital Saint-Lucdu Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada
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Abstract
Infections in patients with end-stage liver disease (ESLD) are an important cause of morbidity and mortality in these patients. Abnormalities in their natural defense mechanisms, alterations in the enteric flora and the growing utilization of invasive procedures increase the risk of infections in these patients. Common bacterial infections in ESLD patients include spontaneous bacterial peritonitis, urinary tract infections, community-acquired pneumonia, dermatologic infections, and bacteremia. Viral infections such as influenza can have a devastating course in ESLD patients. Hepatitis B and C are now among the most common causes of ESLD. They also present an important therapeutic challenge. As patients with human immunodeficiency virus are surviving longer, ESLD due to hepatitis C is now emerging as a leading cause of morbidity in these patients. Prompt detection of infections, use of appropriate antibiotics for treatment and prophylactic measures such as vaccinations can help improve survival in these patients.
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Affiliation(s)
- Rekha Cheruvattath
- Division of Transplant Medicine, Mayo Clinic Hospital, 5777 E Mayo Boulevard, 5th Floor, Phoenix, AR 85054, USA
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34
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Hann HWL, Hann RS, Maddrey WC. Hepatitis B virus infection in 6,130 unvaccinated Korean-Americans surveyed between 1988 and 1990. Am J Gastroenterol 2007; 102:767-772. [PMID: 17397407 DOI: 10.1111/j.1572-0241.2007.01060.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES During the past decades, the influx of immigrants from hepatitis B virus (HBV) endemic regions has brought significant changes in the prevalence of HBV-associated liver diseases and hepatocellular carcinoma (HCC) in the United States. Our program, which was intended to identify those in need of hepatitis B vaccination, helped us to learn of the natural history of HBV infection in Korean Americans. METHODS Between November of 1988 and May 1990, we screened 6,130 Korean Americans in the eastern United States for HBV infection. RESULTS The overall hepatitis B surface antigen (HBsAg) (+) rate was 6.1%, with 8.0% for males and 4.4% for females. The carrier rate peaked in subjects between the ages of 21 and 40 yr. The HBsAg (+) rate for 452 U.S.-born children was lower (2.7%) than that of 623 Korean-born (5.5%). None received hepatitis B immune-globulin or HBV vaccination. The vertical transmission rate was 30.3% in children born to HBsAg (+) mothers and 100% in those born to hepatitis B e antigen (HBeAg) positive mothers. In contrast, the paternal transmission rate was low; 10.3% in children with HBsAg (+) fathers and 19.2% in those with HBeAg (+) fathers. Another significant observation was the unexpected finding of ongoing liver diseases in incidentally identified carriers. Evaluation of 139 asymptomatic adult carriers revealed that 42% had elevated liver enzymes and 11% had already developed liver cirrhosis. CONCLUSION These findings strongly suggest the need for active HBV screening of immigrants from endemic regions and, most importantly, the need for careful monitoring of the carriers.
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Affiliation(s)
- Hie-Won L Hann
- Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, USA
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35
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Suzuki Y, Yotsuyanagi H, Okuse C, Nagase Y, Takahashi H, Moriya K, Suzuki M, Koike K, Iino S, Itoh F. Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report. World J Gastroenterol 2007; 13:964-9. [PMID: 17352033 PMCID: PMC4065939 DOI: 10.3748/wjg.v13.i6.964] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of α-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.
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Affiliation(s)
- Yuka Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
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36
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Abstract
Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.
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Affiliation(s)
- Steven-Huy B Han
- David Geffen School of Medicine at UCLA, Los Angeles, California 90095-7302, USA.
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37
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Kim KM, Choi WB, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Adefovir dipivoxil alone or in combination with ongoing lamivudine in patients with decompensated liver disease and lamivudine-resistant hepatitis B virus. J Korean Med Sci 2005; 20:821-8. [PMID: 16224157 PMCID: PMC2779280 DOI: 10.3346/jkms.2005.20.5.821] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The purpose of this prospective study was to evaluate the efficacy and safety of adefovir dipivoxil with or without ongoing lamivudine in decompensated lamivudine-resistant chronic hepatitis B patients. Forty-six hepatitis B e antigen (HBeAg)-positive patients with decompensated liver function and lamivudine-resistant hepatitis B virus (HBV) were assigned to adefovir dipivoxil monotherapy (n=18) or combination therapy with ongoing lamivudine (n=28) according to their own preference. After 24 weeks of treatment, 83% of monotherapy and 86% of combination therapy showed serum HBV DNA below detection limit (<0.5 pg/mL). Alanine aminotransferase (ALT) normalized in 78% and 82% respectively. Median Child-Pugh-Turcotte (CPT) score or Model for End-Stage Liver Disease (MELD) score reduced significantly by 3 or 5 point in monotherapy and 2 or 2 point in combination therapy respectively. There were no significant differences in rate of undetectable serum HBV DNA, median change of ALT and median reduction of CPT or MELD scores between the two groups. In conclusion, both adefovir dipivoxil monotherapy and combination therapy with ongoing lamivudine result in comparable virologic, biochemical, and clinical improvements in HBeAg-positive patients with decompensated liver function and lamivudine-resistant HBV. Combination with lamivudine showed no additional benefit over monotherapy during 24 weeks of treatment in these patients.
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Affiliation(s)
- Kang Mo Kim
- Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea
| | - Won-Beom Choi
- Department of Internal Medicine, Dongguk University International Hospital, University of Dongguk College of Medicine, Goyang, Korea
| | - Young-Suk Lim
- Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea
| | - Han-Chu Lee
- Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Hwa Chung
- Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Sang Lee
- Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Jin Suh
- Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea
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38
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Ryu KW, Lee JH, Kim YW, Park JW, Bae JM. Management of ascites after radical surgery in gastric cancer patients with liver cirrhosis and minimal hepatic dysfunction. World J Surg 2005; 29:653-6. [PMID: 15827849 DOI: 10.1007/s00268-005-7715-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
A radical lymph node dissection is important for the cure of gastric cancer. However, such a procedure in patients with liver cirrhosis (LC) could develop serious complications such as massive ascites. To determine the management of postoperative ascites, 26 gastric cancer patients with LC were reviewed retrospectively. Child-Pugh status was grade A in all 26 patients. Thirteen (50%) patients had advanced gastric cancer, and a D2 lymph nodes dissection was performed in 25 (96.2%) patients. The mean number of dissected lymph nodes was 33 +/- 11 (range: 11-54). An abdominal closed suction drain was placed in 12 (46.2%) patients, and the average amount of fluid drainage was 463 ml/day. The drainage tube was removed on about the eleventh postoperative day (range: day 6 to day 13), and diuretics were used in 8 (30.8%) patients. A paracentesis was needed in one patient but no postoperative surgical morbidity or mortality was observed. Therefore, an extended lymph node dissection is safe in gastric cancer patients with mild hepatic dysfunction. Liver cirrhosis and postoperative ascites can be managed conservatively without any complications.
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Affiliation(s)
- Keun Won Ryu
- Research Institute and Hospital, National Cancer Center, 809 Madu-dong, Ilsan-gu, 411-764, Goyang, Gyeonggi, Korea.
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Tseng PL, Lu SN, Tung HD, Wang JH, Changchien CS, Lee CM. Determinants of early mortality and benefits of lamivudine therapy in patients with hepatitis B virus-related decompensated liver cirrhosis. J Viral Hepat 2005; 12:386-92. [PMID: 15985009 DOI: 10.1111/j.1365-2893.2005.00608.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis B infection (HBV) is a major health problem worldwide. The prognosis is grave for patients with HBV-related decompensated liver cirrhosis (LC). We evaluated the effectiveness and the determinants of early mortality of lamivudine treatment in patients with HBV-related decompensated LC. Thirty patients with HBV-related decompensated LC and active viral replication were treated with lamivudine 100 mg daily for a median duration of 9 months. Among these patients, five patients died within 3 months. Two patients were lost to follow-up at week 8 and 9. One patient was treated for <6 months. Twenty-two patients were treated over 6 months. Univariate analysis revealed that the total bilirubin (P = 0.008), prothrombin time (P = 0.004), Child-Turcotte-Pugh score (P = 0.005), the model of efd-stage liver disease score (P = 0.004) and stage III hepatic encephalopathy (P = 0.001) were predictive factors of early mortality. Multivariate analysis revealed that the independent factor associated with early mortality was stage III encephalopathy. Among 22 patients, liver function improved markedly after lamivudine therapy. Of the nine hepatitis B e antigen (HBeAg)-positive patients, three had HBeAg seroconversion. Two patients had YMDD mutant and virological breakthrough at 41 and 46 weeks. One of the two had hepatocellular carcinoma and died of hepatic failure at week 125; the other received adefovir and is doing well. Lamivudine appeared to have benefits in viral suppression and significant improvement in liver function in patients with HBV-related decompensated LC. As noted in prior studies, poor baseline liver function is associated with a poor prognosis in Asian patients with decompensated HBV cirrhosis treated with lamivudine.
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Affiliation(s)
- Po-Lin Tseng
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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40
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Liaw YF, Leung N, Guan R, Lau GKK, Merican I, McCaughan G, Gane E, Kao JH, Omata M. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int 2005; 25:472-89. [PMID: 15910483 DOI: 10.1111/j.1478-3231.2005.01134.x] [Citation(s) in RCA: 265] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND/AIMS A large amount of new data on the treatment of chronic hepatitis B has become available such that the 2003 consensus statement requires revision and update. METHODS New data were presented, discussed and debated in an expert pre-meeting to draft a revision. The revised contents were finalized after discussion in a general meeting of APASL. RESULTS Conceptual background, including the efficacy and safety profile of currently available and emerging drugs, was reviewed. Nineteen recommendations were formed and unresolved issues and areas for further study were suggested. CONCLUSION The current therapy of chronic hepatitis B is modestly effective but not satisfactory. The development of new drugs and new strategies is required to further improve the outcomes of treatment.
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Affiliation(s)
- Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan.
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41
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Pei F, Ning JY, You JF, Yang JP, Zheng J. YMDD variants of HBV DNA polymerase gene: Rapid detection and clinicopathological analysis with long-term lamivudine therapy after liver transplantation. World J Gastroenterol 2005; 11:2714-9. [PMID: 15884109 PMCID: PMC4305903 DOI: 10.3748/wjg.v11.i18.2714] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To look for a rapid low-cost technique for the detection of HBV variants.
METHODS: Two patients who underwent orthotopic liver transplantation (OLT) for HBV infection were treated with lamivudine (100 mg daily) and HBV infection recurred in the grafted livers. The patients were monitored intensively for liver enzymes, hepatitis B surface antigen (HBsAg) and HBV DNA in serum. Liver biopsy was performed regularly. HBV DNA in a conserved polymerase domain (the YMDD locus) was amplified from serum of each patient by PCR and sequenced. HBV genotypes were analyzed by restriction fragment length polymorphism (RFLP) of the PCR products generated from a fragment of the polymerase gene.
RESULTS: YMDD wild-type HBV was detected in one patient by PCR-RFLP and DNA sequencing 19 mo after OLT, and YIDD mutant-type HBV in the other patient, 16 mo after OLT.
CONCLUSION: PCR-RFLP assay is an accurate and simple method for genotyping lamivudine-resistant HBV variants.
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Affiliation(s)
- Fei Pei
- Department of Pathology, Health Science Center, Peking University, Beijing 100083, China
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42
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Hann HWL, Jonsson Funk ML, Rosenberg DM, Davis R. Factors associated with response to lamivudine: Retrospective study in a tertiary care clinic serving patients with chronic hepatitis B. J Gastroenterol Hepatol 2005; 20:433-440. [PMID: 15740489 DOI: 10.1111/j.1440-1746.2005.03577.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS Chronic hepatitis B (CHB) is an important cause of end stage liver disease and hepatocellular carcinoma. Controlled clinical trials indicate treatment with lamivudine results in positive clinical responses. The study goal was to determine if the response to lamivudine treatment (HBeAg loss, HBV DNA loss and alanine aminotransferase [ALT] reduction) differs according to pretherapy (pre-tx) ALT levels. METHODS This was a retrospective review of medical record data. All CHB patients at all stages of disease (including cirrhotic) with more than two visits to the clinic were included in the study (n = 719). Kaplan-Meier survival and Cox proportional hazards were estimated. RESULTS Of the total 719 HBsAg (+) patients, 317 were treated with lamivudine 150 mg or 100 mg daily. Among HBeAg positive patients, at 3 years, Kaplan-Meier estimates of the loss of HBeAg were 40%, 57% and 61% for pre-tx ALT < upper limit of normal (ULN), 1-2 x ULN and >2 x ULN, respectively. Similar results of HBV-DNA loss were seen in HBeAg negative patients. CONCLUSIONS In this setting, we observed that pre-tx ALT levels were not associated with response to lamivudine, but that lower platelet count and female sex in HBeAg (+) patients were important predictive factors of a favorable response to lamivudine therapy.
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Affiliation(s)
- Hie-Won L Hann
- Liver Disease Prevention Center Clinic, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
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Di Marco V, Marzano A, Lampertico P, Andreone P, Santantonio T, Almasio PL, Rizzetto M, Craxì A. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology 2004; 40:883-91. [PMID: 15382125 DOI: 10.1002/hep.20381] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The effect of lamivudine treatment on the outcome of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis is unclear. In a retrospective multicenter study, we have analyzed the virological events observed during lamivudine therapy in patients with HBeAg-negative chronic hepatitis and evaluated the correlation between virological response and clinical outcomes. Among 656 patients (mean age 49.1 years) included in the database, 54% had chronic hepatitis, 30% had Child-Turcotte-Pugh (CTP) A cirrhosis, and 16% had CTP B/C cirrhosis. On therapy (median 22 months, range 1-66), a virological response was obtained in 616 patients (93.9%). The rate of maintained virological response was 39% after 4 years. During follow-up, 47 (7.2%) patients underwent liver transplantation, liver disease worsened in 31 (4.7%), hepatocellular carcinoma (HCC) developed in 31 (4.7%), and 24 patients (3.6%) died of liver-related causes. Patients who had cirrhosis and who maintained virological response were less likely than those with viral breakthrough to develop HCC (P <.001) and disease worsening (P <.001). Survival was better in CTP A patients with cirrhosis and maintained virological response (P =.01 by rank test). Multivariate analysis revealed that presence of cirrhosis and viral breakthrough were independently related to mortality and development of HCC. In conclusion, lamivudine is highly effective in reducing viral load in HBeAg-negative patients. After 4 years of therapy, 39% of patients maintain a virological and biochemical response. Loss of virological response may lead to clinical deterioration in patients with cirrhosis.
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Affiliation(s)
- Vito Di Marco
- Cattedra e U.O.C. di Gastroenterologia, Clinica Medica, Università di Palermo, Palermo, Italy.
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Di Marco V, Marzano A, Lampertico P, Andreone P, Santantonio T, Almasio PL, Rizzetto M, Craxì A. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology 2004; 40:883-891. [PMID: 15382125 DOI: 10.1002/hep.1840400418] [Citation(s) in RCA: 154] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The effect of lamivudine treatment on the outcome of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis is unclear. In a retrospective multicenter study, we have analyzed the virological events observed during lamivudine therapy in patients with HBeAg-negative chronic hepatitis and evaluated the correlation between virological response and clinical outcomes. Among 656 patients (mean age 49.1 years) included in the database, 54% had chronic hepatitis, 30% had Child-Turcotte-Pugh (CTP) A cirrhosis, and 16% had CTP B/C cirrhosis. On therapy (median 22 months, range 1-66), a virological response was obtained in 616 patients (93.9%). The rate of maintained virological response was 39% after 4 years. During follow-up, 47 (7.2%) patients underwent liver transplantation, liver disease worsened in 31 (4.7%), hepatocellular carcinoma (HCC) developed in 31 (4.7%), and 24 patients (3.6%) died of liver-related causes. Patients who had cirrhosis and who maintained virological response were less likely than those with viral breakthrough to develop HCC (P <.001) and disease worsening (P <.001). Survival was better in CTP A patients with cirrhosis and maintained virological response (P =.01 by rank test). Multivariate analysis revealed that presence of cirrhosis and viral breakthrough were independently related to mortality and development of HCC. In conclusion, lamivudine is highly effective in reducing viral load in HBeAg-negative patients. After 4 years of therapy, 39% of patients maintain a virological and biochemical response. Loss of virological response may lead to clinical deterioration in patients with cirrhosis.
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Affiliation(s)
- Vito Di Marco
- Cattedra e U.O.C. di Gastroenterologia, Clinica Medica, Università di Palermo, Palermo, Italy.
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Abstract
The virological profile of infection with the hepatitis B virus (HBV) is changing in many parts of the world from the classical hepatitis B e antigen (HBeAg)-positive serological pattern to a HBeAg-negative pattern, linked to the replacement of wild-type HBV by HBV variants with mutations in the core-promoter and in the precore region that prevent the secretion of HBeAg. The wild-type HBV disease is characterised by steady levels of alanine aminotransferase (ALT) and high HBV-DNA levels, responding relatively well to IFN treatment (3 - 5 MU/day or 10 MU every other day for 16 weeks), which induces anti-HBe seroconversion and normalises ALT levels in approximately 30% of the adults, with a minimal risk of relapse. Pegylated-IFN appears to have superior efficacy over conventional IFN-alpha. Mutant-type disease (anti-HBe-positive/HBeAg-negative) is less responsive to IFN given for 6 - 12 months. This has led to the use of novel nucleoside analogues, of which the prototype is lamivudine. The response to lamivudine therapy shares with IFN a rapid decline in ALT accompanied by an improvement in histology; at variance with IFN, in HBeAg-positive chronic hepatitis B (CHB) there is delayed seroconversion to anti-HBe which accumulates over time, the switch to anti-HBs is more rare and in the long-term, the activity of the drug is abolished by the emergence of viral mutations (YMDD-motif mutants) that may rekindle the disease. The combination of IFN plus lamivudine may be more efficacious than IFN or lamivudine monotherapy. Lamivudine therapy needs to be prolonged in HBeAg-negative CHB. Short-term lamivudine-therapy is highly efficacious in preventing HBV reinfection in liver transplants. Recent data suggest that long-term IFN therapy (24 months) may achieve a response in 30% of HBeAg-negative patients. The advent of adefovir, an analogue of adenosine monophosphate, may provide a safer alternative to lamivudine in the control of HBV disease; the drug is well-tolerated and treatment raises drug-resistant mutants in < 2% of the patients over 2 years of therapy. Adefovir provides rescue therapy against YMDD mutants raised by lamivudine therapy.
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Affiliation(s)
- M Lagget
- Division of Gastroenterology, Ospedale Molinatte, Torino, Italy
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