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Kumar K, Dixit I. Letter to the Editor: Retreatment Decision for Hepatitis B Flare in HBeAg-Negative Chronic Hepatitis B. Hepatology 2021; 73:2081-2082. [PMID: 33030272 DOI: 10.1002/hep.31589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Karan Kumar
- BGS Gleneagles Hospital, Kengeri, Bengaluru, India
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Manolakopoulos S, Kranidioti H, Kourikou A, Deutsch MM, Triantos C, Tsolias C, Manesis EK, Mathou N, Alexopoulou A, Hadziyannis E, Papatheodoridis G. Long-term clinical outcome of HBeAg-negative chronic hepatitis B patients who discontinued nucleos(t)ide analogues. Liver Int 2021; 41:48-57. [PMID: 33373114 DOI: 10.1111/liv.14654] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 08/11/2020] [Accepted: 08/24/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Discontinuation of nucleos(t)ide analogues (NA) remains a debatable issue in HBeAg-negative chronic hepatitis B (CHB). This study aimed to address the outcome of HBeAg-negative CHB patients who discontinued NA therapy. METHODS This prospective study included 57 non-cirrhotic HBeAg-negative Caucasian CHB patients who discontinued NA therapy after median virological remission of 6 years. All patients had regular blood tests. Virological relapse was defined as HBV DNA > 2000 IU/mL or >20 000 IU/mL and biochemical relapse as ALT > ULN (40 IU/mL) or >2xULN. All patients with retreatment predefined criteria restarted entecavir or tenofovir. RESULTS Of the 57 patients, 29 remained without retreatment after median follow-up of 65 months (range: 36-87) following treatment discontinuation. At 3, 6, 12, 24, 36 and 48 months, cumulative rates of retreatment were 16%, 20%, 32%, 35%, 46% and 50%, while the proportion of patients with HBV DNA < 2000 IU/mL and ALT < ULN were 73%, 60%, 52%, 52%, 47% and 37% respectively. All patients had virological and biochemical response after retreatment. No patient developed liver failure, hepatocellular carcinoma or death. Cumulative rates of HBsAg loss were 2%, 4%, 7%, 10% and 20% at 3, 6, 12, 24 and 36 months. HBsAg levels < 100 IU/mL at the end of NA treatment could predict HBsAg loss (P = .001). CONCLUSIONS Our study supports that NA therapy can be safely stopped in non-cirrhotic patients with HBeAg-negative CHB. Over a median follow-up of more than 5 years, half of the patients remained without retreatment with a substantial proportion of them achieving functional cure.
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Affiliation(s)
- Spilios Manolakopoulos
- Liver-GI Unit, 2nd Academic Department of Internal Medicine, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Academic Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Hariklia Kranidioti
- Liver-GI Unit, 2nd Academic Department of Internal Medicine, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Kourikou
- Liver-GI Unit, 2nd Academic Department of Internal Medicine, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Melanie-Maria Deutsch
- Liver-GI Unit, 2nd Academic Department of Internal Medicine, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Athens, Greece
| | - Chrysostomos Tsolias
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Athens, Greece
| | | | - Nicoletta Mathou
- Department of Gastroenterology, "Konstantopoulio-Patission" General Hospital, Nea Ionia, Athens, Greece
| | - Alexandra Alexopoulou
- Liver-GI Unit, 2nd Academic Department of Internal Medicine, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Emilia Hadziyannis
- Liver-GI Unit, 2nd Academic Department of Internal Medicine, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - George Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Persistence and adherence to nucleos(t)ide analogues in chronic hepatitis B: a multicenter cohort study. Eur J Gastroenterol Hepatol 2020; 32:635-641. [PMID: 31688309 DOI: 10.1097/meg.0000000000001558] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Adherence and persistence to long-term therapy with nucleos(t)ides analogues are crucial to the outcome of treatment in chronic hepatitis B. Our aim was to determine the persistence and adherence rates to nucleos(t)ides analogues in chronic hepatitis B patients under maintenance therapy and to identify relative to prediction of adherence factors. METHODS We retrospectively analyzed electronic prescription data of patients (2011-2016; n = 400) with chronic hepatitis B treated with nucleos(t)ides analogues at 4 tertiary liver centers in Greece. RESULTS Two hundred ninety-six of 400 patients were under or initiated treatment in 2011-2012 (existing patients), while the remainder initiated or switched medication from January 2013 and onward (new patients). The median adherence rate was 99%, with 89.7% achieving adherence >80% during a mean follow-up of 28 ± 14 months. The overall 12-month persistence rate was 57%, with no difference between patients receiving tenofovir, entecavir or double therapy (57.8%, 52.8% and 68.4%, respectively, P = 0.399). The decline in persistence was more pronounced during the first 3 months of follow-up and in existing patients (P = 0.057). Overall, 80% and 55.1% of nonpersistent patients succeeded adherence to nucleos(t)ides analogues >80% and >90%, respectively. Multivariate analyses showed that existing (vs. new) patients were less likely to have >80% adherence (odds ratio: 0.324, P = 0.44) and persistence (odds ratio: 0.562, P = 0.057) to nucleos(t)ides analogues therapy. CONCLUSION In this real-world cohort of chronic hepatitis B patients, high adherence to nucleos(t)ides analogues was coupled with suboptimal persistence with prescribing the medication. Our data indicate that persistence and adherence are distinct measures that should be approached separately in educational programs targeting to improve medication-taking behavior in chronic hepatitis B.
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Kranidioti H, Manolakopoulos S, Kontos G, Breen MS, Kourikou A, Deutsch M, Quesada-Del-Bosque ME, Martinez-Nunez RT, Naiyer MM, Woelk CH, Sanchez-Elsner T, Hadziyannis E, Papatheodoridis G, Khakoo SI. Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HBeAg-negative chronic hepatitis B. J Viral Hepat 2019; 26:697-709. [PMID: 30702196 DOI: 10.1111/jvh.13068] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 01/09/2019] [Indexed: 02/07/2023]
Abstract
The optimal duration of treatment with nucleos(t)ide analogues (NAs) for patients with HBeAg-negative chronic hepatitis B (CHB) is unknown. The aim of this study was to identify an immune signature associated with off-treatment remission to NA therapy. We performed microarray analysis of peripheral blood mononuclear cell (PBMCs) from six patients with chronic hepatitis B who stopped NA therapy (three with off-treatment remission, three with relapse) and five patients with chronic HBV infection (previously termed 'inactive carriers') served as controls. Results were validated using qRT-PCR on a second group of 21 individuals (17 patients who stopped treatment and four controls). PBMCs from 38 patients on long-term NA treatment were analysed for potential to stop treatment. Microarray analysis indicated that patients with off-treatment remission segregated as a distinct out-group. Twenty-one genes were selected for subsequent validation. Ten of these were expressed at significantly lower levels in the patients with off-treatment remission compared to the patients with relapse and predicted remission with AUC of 0.78-0.92. IFNγ, IL-8, FASLG and CCL4 were the most significant by logistic regression. Twelve (31.6%) of 38 patients on long-term NA therapy had expression levels of all these four genes below cut-off values and hence were candidates for stopping treatment. Our data suggest that patients with HBeAg-negative CHB who remain in off-treatment remission 3 years after NA cessation have a distinct immune signature and that PBMC RNA levels of IFNγ, IL-8, FASLG and CCL4 may serve as potential biomarkers for stopping NA therapy.
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Affiliation(s)
- Hariklia Kranidioti
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece
| | - Spilios Manolakopoulos
- 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece.,Academic Department of Gastroenterology, Laiko General Hospital of Athens, Athens, Greece
| | - George Kontos
- 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece
| | - Michael S Breen
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Anastasia Kourikou
- 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece
| | - Melanie Deutsch
- 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece
| | | | - Rocio T Martinez-Nunez
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Mohammed M Naiyer
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Christopher H Woelk
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Tilman Sanchez-Elsner
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Emilia Hadziyannis
- Academic Department of Gastroenterology, Laiko General Hospital of Athens, Athens, Greece
| | - George Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital of Athens, Athens, Greece
| | - Salim I Khakoo
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Okada M, Enomoto M, Kawada N, Nguyen MH. Effects of antiviral therapy in patients with chronic hepatitis B and cirrhosis. Expert Rev Gastroenterol Hepatol 2017; 11:1095-1104. [PMID: 28752768 DOI: 10.1080/17474124.2017.1361822] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hepatitis B virus (HBV) infection is the major cause of cirrhosis worldwide. The ultimate goal of current antiviral treatments for chronic hepatitis B (nucleos(t)ide analogs and interferon-α) is to prevent the development of end-stage liver diseases. Areas covered: We present a review of the current literature on antiviral therapy in patients with chronic hepatitis B and cirrhosis. Medline search was performed to identify relevant literature from 1993 through January of 2017. Expert commentary: One randomized controlled trial and a number of observational studies have shown that nucleos(t)ide analogs can decrease the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis. Data from clinical trials of entecavir and tenofovir have shown that histological improvement and regression of fibrosis can be achieved in the majority of patients with chronic hepatitis B by successful viral suppression. Entecavir and tenofovir are the preferred antiviral agents for treatment of chronic hepatitis B in patients with cirrhosis due to their high antiviral potency and high genetic barrier to resistance. Pegylated interferon-α is another therapeutic option for chronic hepatitis B patients with well-compensated cirrhosis. However, interferon therapy is contraindicated in patients with decompensated cirrhosis, and evidence for reduced HCC is currently insufficient.
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Affiliation(s)
- Masako Okada
- a Department of Hepatology , Osaka City University Graduate School of Medicine , Osaka , Japan
| | - Masaru Enomoto
- a Department of Hepatology , Osaka City University Graduate School of Medicine , Osaka , Japan
| | - Norifumi Kawada
- a Department of Hepatology , Osaka City University Graduate School of Medicine , Osaka , Japan
| | - Mindie H Nguyen
- b Division of Gastroenterology and Hepatology , Stanford University Medical Center , Palo Alto , CA , USA
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Striki A, Manolakopoulos S, Deutsch M, Kourikou A, Kontos G, Kranidioti H, Hadziyannis E, Papatheodoridis G. Hepatitis B s antigen kinetics during treatment with nucleos(t)ides analogues in patients with hepatitis B e antigen-negative chronic hepatitis B. Liver Int 2017; 37:1642-1650. [PMID: 28345181 DOI: 10.1111/liv.13432] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 03/17/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Serum hepatitis B s antigen (HBsAg) levels might be used as a predictor of virological breakthrough or of sustained off-treatment virological response in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. We evaluated the changes of HBsAg in those patients under nucleos(t)ide analogue(s) [NA(s)] therapy for ≥12 months. METHODS We included 99 HBeAg-negative CHB patients treated with low-genetic barrier NA(s) for a mean of 66 months (lamivudine: 66, adefovir: 6, lamivudine plus adefovir: 11 and telbivudine: 16) and 86 HBeAg-negative CHB patients treated under entecavir or tenofovir for a mean of 30 months as the comparison group. RESULTS Compared to baseline, HBsAg levels decreased by a median of 162, 1525, 943, 1545, 2163 and 3859 IU/mL at 6, 12, 24, 36, 48 and 60 months of therapy with low-genetic barrier NA(s) respectively. The 6-, 12-, 24-, 36-, 48- and 60-month cumulative rates of HBsAg<100 IU/mL were 2%, 3%, 3%, 5%, 5% and 5%, and <1000 IU/mL 6%, 9%, 15%, 19%, 24% and 61% respectively. Baseline HBsAg levels were the only significant variable associated with the time to HBsAg drop <1000 IU/mL. HBsAg loss occurred in 3.0% of patients. The high-genetic barrier NAs were not found to offer a greater or faster HBsAg decline. CONCLUSIONS In HBeAg-negative CHB patients, long-term therapy with low-genetic barrier NA(s) decreases serum HBsAg levels, but the rate of decline is slow. Lower baseline HBsAg levels are significantly associated with on-therapy HBsAg drop <1000 IU/mL. Serum HBsAg decline is similar during therapy with low- or high-genetic barrier NAs.
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Affiliation(s)
- Athanasia Striki
- 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - Spilios Manolakopoulos
- 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - Melanie Deutsch
- 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Kourikou
- 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - George Kontos
- 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - Hariklia Kranidioti
- 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - George Papatheodoridis
- Department of Gastroenterology, Laiko General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
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7
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Yu Y, Ai J, Zhang W. Current clinical evidence for nucleos(t)ide analogues in patients with HBV-related hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2017; 11:925-937. [PMID: 28661190 DOI: 10.1080/17474124.2017.1343665] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of death globally and is frequently seen following Hepatitis B virus (HBV) or Hepatitis C virus infection. Areas with high HBV infection rates, such as Asia and sub-Saharan Africa, are therefore also high-risk areas for HCC. Areas covered: This review identifies and discusses the current evidence from robust clinical trials which have investigated the benefits of Nucleos(t)ide analogue (NA) antiviral therapy in HBV-related HCC patients, including HCC patients that underwent liver transplantation and HCC patients with or without curative treatment. In addition, we assess how this evidence has influenced current clinical practice, with a particular focus on those areas of high HBV infection rates. Expert commentary: A number of studies have assessed whether NA antiviral treatment can improve the prognosis of HBV-related HCC patients. In this review we evaluate the current evidence, including that from trials in Asia, for antiviral NA treatments in HBV-related HCC patients. We also focus on those NAs with a high genetic barrier to resistance (i.e. ETV or TDF), on different therapeutic approaches, and on the future evidence that is required in this field.
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Affiliation(s)
- Yiqi Yu
- a Department of Infectious Diseases , Huashan Hospital, Fudan University , Shanghai , China
| | - Jingwen Ai
- a Department of Infectious Diseases , Huashan Hospital, Fudan University , Shanghai , China
| | - Wenhong Zhang
- a Department of Infectious Diseases , Huashan Hospital, Fudan University , Shanghai , China
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8
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Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016; 63:261-83. [PMID: 26566064 PMCID: PMC5987259 DOI: 10.1002/hep.28156] [Citation(s) in RCA: 1571] [Impact Index Per Article: 174.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 08/25/2015] [Indexed: 12/11/2022]
Affiliation(s)
| | | | - Kyong-Mi Chang
- Corporal Michael J. Crescenz VA Medical Center & University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Jessica P Hwang
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maureen M Jonas
- Boston Children's Hospital, Harvard Medical School, Boston, MA
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Lok ASF, McMahon BJ, Brown RS, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology 2016; 63:284-306. [PMID: 26566246 DOI: 10.1002/hep.28280] [Citation(s) in RCA: 420] [Impact Index Per Article: 46.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 09/23/2015] [Indexed: 01/10/2023]
Abstract
UNLABELLED Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence-based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate-quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate-quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low-quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen-positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen-negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low-level viremia. CONCLUSION Most of the current literature focuses on the immune active phases of chronic HBV infection; decision-making in other commonly encountered and challenging clinical settings depends on indirect evidence.
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Affiliation(s)
- Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Boston, MA
| | - Ahmed T Ahmed
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Wigdan Farah
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Jehad Almasri
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Fares Alahdab
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Khalid Benkhadra
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | | | - Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Essa A Mohamed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | | | - Zhen Wang
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Mohammad Hassan Murad
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
| | - Khaled Mohammed
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
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Song ZL, Cui YJ, Zheng WP, Teng DH, Zheng H. Application of nucleoside analogues to liver transplant recipients with hepatitis B. World J Gastroenterol 2015; 21:12091-12100. [PMID: 26576094 PMCID: PMC4641127 DOI: 10.3748/wjg.v21.i42.12091] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/22/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus (HBV) core antibody (HBcAb) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues (NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBcAb-positive liver grafts.
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11
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Thiele M, Gluud LL, Fialla AD, Dahl EK, Krag A. Large variations in risk of hepatocellular carcinoma and mortality in treatment naïve hepatitis B patients: systematic review with meta-analyses. PLoS One 2014; 9:e107177. [PMID: 25225801 PMCID: PMC4167336 DOI: 10.1371/journal.pone.0107177] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 08/14/2014] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The complications to chronic hepatitis B (HBV) include incidence of hepatocellular carcinoma (HCC) and mortality. The risk of these complications may vary in different patient groups. AIM To estimate the incidence and predictors of HCC and in untreated HBV patients. METHODS Systematic review with random effects meta-analyses of randomized controlled trials and observational studies. Results are expressed as annual incidence (events per 100 person-years) with 95% confidence intervals. Subgroup and sensitivity analyses of patient and study characteristics were performed to identify common risk factors. RESULTS We included 68 trials and studies with a total of 27,584 patients (264,919 person-years). In total, 1,285 of 26,687 (5%) patients developed HCC and 730 of 12,511 (6%) patients died. The annual incidence was 0.88 (95% CI, 0.76-0.99) for HCC and 1.26 (95% CI, 1.01-1.51) for mortality. Patients with cirrhosis had a higher risk of HCC (incidence 3.16; 95% CI, 2.58-3.74) than patients without cirrhosis (0.10; 95% CI, 0.02-0.18). The risk of dying was also higher for patients with than patients without cirrhosis (4.89; 95% CI, 3.16-6.63; and 0.11; 95% CI, 0.09-0.14). The risk of developing HCC increased with HCV coinfection, older age and inflammatory activity. The country of origin did not clearly predict HCC or mortality estimates. CONCLUSIONS Cirrhosis was the strongest predictor of HCC incidence and mortality. Patients with HBV cirrhosis have a 31-fold increased risk of HCC and a 44-fold increased mortality compared to non-cirrhotic patients. The low incidence rates should be taken into account when considering HCC screening in non-cirrhotic patients. TRIAL REGISTRATION Prospero CRD42013004764.
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Affiliation(s)
- Maja Thiele
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Lise Lotte Gluud
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark
| | - Annette Dam Fialla
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Emilie Kirstine Dahl
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
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12
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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Cholongitas E, Papatheodoridis GV. Review of the pharmacological management of hepatitis B viral infection before and after liver transplantation. World J Gastroenterol 2013; 19:9189-9197. [PMID: 24409047 PMCID: PMC3882393 DOI: 10.3748/wjg.v19.i48.9189] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2013] [Revised: 10/29/2013] [Accepted: 11/19/2013] [Indexed: 02/06/2023] Open
Abstract
The progress in treatment against hepatitis B virus (HBV) with the development of effective and well tolerated nucleotide analogues (NAs) has improved the outcome of patients with HBV decompensated cirrhosis and has prevented post-transplant HBV recurrence. This review summarizes updated issues related to the management of patients with HBV infection before and after liver transplantation (LT). A literature search using the PubMed/Medline databases and consensus documents was performed. Pre-transplant therapy has been initially based on lamivudine, but entecavir and tenofovir represent the currently recommended first-line NAs for the treatment of patients with HBV decompensated cirrhosis. After LT, the combination of HBV immunoglobulin (HBIG) and NA is considered as the standard of care for prophylaxis against HBV recurrence. The combination of HBIG and lamivudine is related to higher rates of HBV recurrence, compared to the HBIG and entecavir or tenofovir combination. In HBIG-free prophylactic regimens, entecavir and tenofovir should be the first-line options. The choice of treatment for HBV recurrence depends on prior prophylactic therapy, but entecavir and tenofovir seem to be the most attractive options. Finally, liver grafts from hepatitis B core antibody (anti-HBc) positive donors can be safely used in hepatitis B surface antigen negative, preferentially anti-HBc/anti-hepatitis B surface antibody positive recipients.
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Thiele M, Gluud LL, Dahl EK, Krag A. Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B: systematic review and meta-analysis. BMJ Open 2013; 3:bmjopen-2013-003265. [PMID: 23945731 PMCID: PMC3752055 DOI: 10.1136/bmjopen-2013-003265] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV. DESIGN Random-effects pairwise meta-analysis of randomised trials and observational studies. SETTING Electronic and manual searches were combined. Randomised controlled trials (RCTs) were included in the primary analyses. Observational studies were included in sensitivity analyses. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome measures were HCC incidence and mortality. The secondary outcome measure was HCC mortality. RESULTS We included 8 RCTs, 8 prospective cohort studies and 19 case-control studies with a total of 3433 patients allocated to antiviral therapy and 4625 controls. The maximum duration of follow-up was 23 years. Randomised trials found no effect of antiviral therapy on HCC or mortality. Cohort studies found that antiviral therapy increased the risk of HCC (risk ratio 1.43; 95% CI 1.06 to 1.95), whereas case-control studies found a decreased risk of HCC in the intervention group (risk ratio 0.69; 95% CI 0.54 to 0.88). There was a clear difference between the results of RCTs and observational studies (test for subgroup differences, p<0.001). Antiviral therapy did not affect mortality in cohort studies, but reduced mortality in case-control studies (relative risk 0.71; 95% CI 0.54 to 0.93; test for subgroup differences, p=0.406). CONCLUSIONS The effect of antiviral therapy on clinical outcomes in HBV remains to be established. Although there was a positive effect in the sensitivity analyses, the strength of the evidence does not allow for extrapolation to clinical practice as research design plays an essential role in the overall assessment. TRIAL REGISTRATION NUMBER Prospero number CRD42013003881.
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Affiliation(s)
- Maja Thiele
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Lise L Gluud
- Department of Medicine, Copenhagen University Hospital of Gentofte, Hellerup, Denmark
| | - Emilie K Dahl
- Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
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15
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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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16
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Yim HJ, Seo YS, Yoon EL, Kim CW, Lee CD, Park SH, Lee MS, Park CK, Chae HB, Kim MY, Baik SK, Kim YS, Kim JH, Lee JI, Lee JW, Hong SP, Um SH. Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial. Liver Int 2013; 33:244-54. [PMID: 23295056 DOI: 10.1111/liv.12036] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2012] [Accepted: 10/15/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Management of lamivudine-resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported. AIMS This multicentre prospective randomized study was designed to compare the efficacy of these two strategies. METHODS Two hundred and nineteen lamivudine-resistant CHB patients were randomized to either adefovir-lamivudine combination group or entecavir monotherapy group (n = 110 vs. 109), and followed up for 24 months. RESULTS One hundred and eighty patients completed this study. At month 24, virological response rate [hepatitis B virus (HBV) DNA <60 IU/ml] was higher in the adefovir-lamivudine combination group compared with entecavir group (56.7% vs. 40%, P = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, P = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, P < 0.001) were more frequent in the entecavir group. However, by subgroup analysis, virological response rates were not significantly different between the two therapies in HBeAg-positive patients (44.9% vs. 35.7%, P = 0.268) or in patients with high baseline HBV DNA (≥7 log IU/ml) (40.7% vs. 31.3%, P = 0.320) at month 24. CONCLUSION This study showed that adefovir-lamivudine combination provides significantly higher antiviral efficacy and the lower resistance rate compared with the entecavir monotherapy in the management of lamivudine-resistant CHB. However, it had limited efficacy in HBeAg-positive patients or in patients with high baseline HBV DNA.
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Affiliation(s)
- Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
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Kwon JH, Jang JW, Choi JY, Park CH, Yoo SH, Bae SH, Yoon SK. Should lamivudine monotherapy be stopped or continued in patients infected with hepatitis B with favorable responses after more than 5 years of treatment? J Med Virol 2013; 85:34-42. [PMID: 23154874 DOI: 10.1002/jmv.23421] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Regarding the limited evidence for determining the optimal duration of antiviral treatment for hepatitis B, the long-term outcome of patients with favorable responses to over 5 years of lamivudine monotherapy was investigated. Two hundred seventy-one patients who had received lamivudine for at least 5 years were enrolled. Ultimately, 72 patients without YMDD mutations and showing hepatitis B virus (HBV) DNA levels <2.5 pg/ml after 5 years of treatment were analyzed. Mean treatment duration with lamivudine was 9.1 ± 2.6 years. During the treatment, HBeAg and HBsAg loss/seroconversion rates were 95 and 6.9%, respectively. Decompensation and hepatocellular carcinoma (HCC) developed in 2.8 and 6.9% of patients, respectively. Old age and cirrhosis were risk factors for HCC development. Finally, 11.1% of patients developed YMDD mutations after 8.3 ± 2.4 years of treatment. There was no hepatic decompensation among the patients who developed delayed YMDD mutations. Sixteen patients who achieved a complete response stopped lamivudine and four patients showed relapses 10.3 ± 8.5 months after stopping lamivudine. Relapsed patients had more cirrhotic livers and higher rates of HBeAg positivity at 5 years than patients who maintained complete response. The present study suggests that patients who do not develop YMDD mutations over 5 years of treatment with lamivudine may continue lamivudine monotherapy until the loss of HBsAg. However, even for the patients showing favorable response over 5 years of treatment, those in older ages, with cirrhosis or who show poor HBeAg responses should be on careful monitoring to detect the development of viral mutations, relapse and even HCC.
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Affiliation(s)
- Jung Hyun Kwon
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
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Köklü S, Tuna Y, Gülşen MT, Demir M, Köksal AŞ, Koçkar MC, Aygün C, Coban S, Ozdil K, Ataseven H, Akin E, Pürnak T, Yüksel I, Ataseven H, Ibiş M, Yildirim B, Nadir I, Küçükazman M, Akbal E, Yüksel O, Başar O, Alkan E, Baykal O. Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis. Clin Gastroenterol Hepatol 2013; 11:88-94. [PMID: 23063679 DOI: 10.1016/j.cgh.2012.10.003] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2012] [Revised: 09/26/2012] [Accepted: 10/02/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 ± 9.7 mo), 77 patients received entecavir (followed up for 24.0 ± 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 ± 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.
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Affiliation(s)
- Seyfettin Köklü
- Department of Gastroenterology, Hacettepe University School of Medicine, Ankara, Turkey.
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19
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Peng CY, Chien RN, Liaw YF. Hepatitis B virus-related decompensated liver cirrhosis: benefits of antiviral therapy. J Hepatol 2012; 57:442-50. [PMID: 22504333 DOI: 10.1016/j.jhep.2012.02.033] [Citation(s) in RCA: 167] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Revised: 02/09/2012] [Accepted: 02/13/2012] [Indexed: 02/08/2023]
Abstract
Following development of liver cirrhosis in patients with chronic hepatitis B, liver disease may continue to progress and decompensation or hepatocellular carcinoma (HCC) may occur, especially in those with active viral replication. Decompensation may manifest with jaundice, ascites, variceal bleeding or hepatic encephalopathy. Earlier studies have shown that the prognosis of decompensated cirrhosis is usually poor with a 5-year survival rate at 14-35% under conventional standard of care. The approval of oral antiviral agents has greatly improved the prognosis, as demonstrated in several cohort studies and randomized clinical trials involving therapy with lamivudine, adefovir dipivoxil, entecavir, telbivudine, or tenofovir disoproxil fumarate. Oral antiviral agents are effective in restoring liver function and improving survival in patients with decompensated cirrhosis especially if therapy is initiated early enough. These agents are generally well tolerated without significant side effects. However, their preventive effect in HCC development has yet to be convincingly demonstrated. Given their known resistance profiles, entecavir and tenofovir should be considered as the first-line therapy for patients with HBV-related decompensated cirrhosis.
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Affiliation(s)
- Cheng-Yuan Peng
- School of Medicine, China Medical University, Taichung, Taiwan
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20
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Hyun JJ, Seo YS, Yoon E, Kim TH, Kim DJ, Kang HS, Jung ES, Kim JH, An H, Kim JH, Yim HJ, Yeon JE, Lee HS, Byun KS, Um SH, Kim CD, Ryu HS. Comparison of the efficacies of lamivudine versus entecavir in patients with hepatitis B virus-related decompensated cirrhosis. Liver Int 2012; 32:656-664. [PMID: 22099071 DOI: 10.1111/j.1478-3231.2011.02676.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2011] [Accepted: 10/10/2011] [Indexed: 02/13/2023]
Abstract
BACKGROUND Suppression of hepatitis B virus (HBV) DNA is more potent, and occurrence of resistant strain is rare with entecavir than lamivudine, but whether these merits result in a more favourable outcome in HBV-related decompensated cirrhosis patients is unclear. AIMS To compare virologic response, changes in liver function, clinical course and predictive factors for early mortality after treatment between patients treated with lamivudine and those with entecavir in HBV-related decompensated cirrhosis patients. METHODS HBV-related decompensated cirrhosis patients [Child-Turcotte-Pugh (CTP) score ≥ 7] treated with either lamivudine or entecavir were enrolled. Serum HBV DNA levels, CTP score and Model for End-stage Liver Disease (MELD) score were monitored every 3 months. RESULTS Eighty-six patients were enrolled; mean age was 54 ± 11 years, and 63 (73.3%) patients were men; 41 (47.7%) and 45 (52.3%) patients were assigned to the lamivudine group and entecavir group respectively. Although suppression of serum HBV DNA level was more potent in the entecavir group, CTP or MELD scores during the course of treatment did not differ between the two groups. Similarly, 6-month survival rates did not differ between the two groups (95.1 vs 93.2%, P = 0.684). Baseline CTP score and MELD score at 3 months of treatment were significantly associated with 6-month mortality. The 6- and 12-month mortality rates for patients with baseline CTP score ≥ 11 and MELD score ≥ 17.5 after 3 months of treatment were 42.9 and 61.9% respectively. CONCLUSIONS Although HBV DNA suppression was more potent in the entecavir group than the lamivudine group, early mortality rates did not differ between the two groups. The baseline CTP score and MELD score 3 months after initiating antiviral treatment were significant predictors of early mortality.
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Affiliation(s)
- Jong Jin Hyun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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21
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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: 62] [Impact Index Per Article: 4.8] [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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22
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Manolakopoulos S, Striki A, Deutsch M, Mela M, Ketikoglou I, Tzourmakliotis D, Manesis EK, Papatheodoridis GV. Long-term adefovir plus lamivudine therapy does not decrease creatinine clearance in HBeAg-negative chronic hepatitis B patients. Liver Int 2011; 31:1525-1532. [PMID: 22093327 DOI: 10.1111/j.1478-3231.2011.02616.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Accepted: 07/08/2011] [Indexed: 12/22/2022]
Abstract
BACKGROUND/AIMS As there are concerns about potential nephrotoxicity of nucleotide analogues, we evaluated renal function parameters during long-term adefovir and lamivudine combination therapy. METHODS Forty-six HBeAg-negative patients with lamivudine-resistance treated with adefovir and lamivudine for up to 90 months were included. Renal function was assessed by estimated creatinine clearance (eC(CR) ) and compared with a matched control group of untreated inactive hepatitis B virus carriers. RESULTS Serum HBV DNA became undetectable in 39 (85%) patients after a mean of 37 ± 21 months. Three (6.5%) patients developed virological breakthrough. Adefovir resistance was detected in two patients. At the end of follow up, there was a significant decrease in mean eC(CR) (95 ± 31-83 ± 30 ml/min, P = 0.003) in the treated patients with 16% presenting aeC(CR) decrease >30%. Similar changes in eC(CR) were observed in the control group (108 ± 28-96 ± 26 ml/min, P = 0.003). In multiple regression analysis, age and baseline eC(CR) were independent predictors of eC(CR) reduction. CONCLUSIONS Adefovir and lamivudine combination therapy is not an independent factor for significant renal dysfunction in HBeAg-negative patients with lamivudine-resistance. Baseline age and creatinine clearance are the only independent predictors of worsening renal function.
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Affiliation(s)
- Spilios Manolakopoulos
- 2nd Academic Department of Internal Medicine, Hippokration Hospital of Athens, Athens, Greece.
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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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24
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Zhang FK, Liu DG, Jia JD. Antiviral therapy for hepatitis B in special populations. Antivir Ther 2010; 15:1067-75. [PMID: 21149913 DOI: 10.3851/imp1663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
There has been much progress in antiviral therapy for chronic hepatitis B; however, antiviral therapy for hepatitis B in special populations is still very challenging. Here, we review antiviral therapy for hepatitis B in special populations, including children and pregnant patients, patients with hepatitis-B-related cirrhosis, patients with acute hepatitis B and chronic hepatitis B surface antigen carriers who receive immunosuppressive or cytotoxic therapy. Major advances have been made in antiviral therapy for hepatitis B in these special populations because of recent increasing availability of oral nucleoside/nucleotide analogues that are well-tolerated and highly effective; however, the findings are mostly based on small uncontrolled short-term studies. More well-designed clinical studies on antiviral therapy for hepatitis B in these special populations are urgently needed to obtain more evidence-based high-quality data.
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Affiliation(s)
- Fu-Kui Zhang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
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25
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Paik YH, Kim JK, Kim DY, Park JY, Ahn SH, Han KH, Chon CY, Lee KS. Clinical efficacy of a 24-months course of lamivudine therapy in patients with HBeAg negative chronic hepatitis B: a long-term prospective study. J Korean Med Sci 2010; 25:882-7. [PMID: 20514309 PMCID: PMC2877218 DOI: 10.3346/jkms.2010.25.6.882] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2009] [Accepted: 12/11/2009] [Indexed: 12/17/2022] Open
Abstract
The optimal duration of oral nucleos(t)ide analogue therapy for HBeAg negative chronic hepatitis B (CHB) has not been defined. The aim of this study was to investigate the clinical efficacy of 24-months course of lamivudine therapy in patients with HBeAg negative CHB in Korea. A total of 50 Korean patients with HBeAg negative CHB were prospectively enrolled. The patients received 100 mg/day of lamivudine orally for 24 months. Patients who showed complete response at 24 months to lamivudine therapy stopped treatment, and regular follow-up was done thereafter. The mean follow-up duration after cessation of therapy was 40.8+/-22.7 (range 12-96) months. The complete response rate at months 12 and 24 were 86.0% (43/50) and 86.0% (43/50), respectively, and the clinical breakthrough at months 12 and 24 were 4.0% (2/50) and 14.0% (7/50), respectively. The expected durability of responses at months 12, 24, and 36 after cessation of lamivudine therapy in 43 complete responders was 79.1%, 64.0%, and 56.9%, respectively. In conclusion, a 24-months course of lamivudine therapy shows high end-treatment response rate and substantial durability of initial response after cessation of therapy in HBeAg negative CHB patients in Korea.
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Affiliation(s)
- Yong Han Paik
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Chae Yoon Chon
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Kwan Sik Lee
- Department of Internal Medicine, Institute of Gastroenterology, Liver Cirrhosis Clinical Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
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Chen EQ, Wang LC, Lei J, Xu L, Tang H. Meta-analysis: adefovir dipivoxil in combination with lamivudine in patients with lamivudine-resistant hepatitis B virus. Virol J 2009; 6:163. [PMID: 19818142 PMCID: PMC2764700 DOI: 10.1186/1743-422x-6-163] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2009] [Accepted: 10/09/2009] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Currently, there are no conclusive results on the efficacy of adefovir dipivoxil (ADV) plus lamivudine (LAM) in LAM-resistant patients with chronic hepatitis B (CHB). The aim of study was to evaluate the efficacy of rescue therapy with ADV plus LAM compared to ADV monotherapy in LAM-resistant CHB patients. RESULTS We searched PUBMED, EMBASE, Web of Science, CNKI (National Knowledge Infrastructure), VIP database, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Six eligible trials (442 patients in total) were included and evaluated for methodologic quality and heterogeneity. Greater virological response and lower emergence rate of ADV-associated mutants was observed in ADV plus LAM compared to ADV monotherapy (both P < 0.05). On the contrary, the rate of ALT normalization, HBeAg clearance and seroconversion were all similar between ADV plus LAM and ADV (all P > 0.05). Additionally, adding-on or switch-to ADV was both well tolerated. CONCLUSION The combination of ADV with LAM was superior in inhibiting HBV replication and preventing drug resistance as compared to ADV alone for LAM-resistant CHB patients.
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Affiliation(s)
- En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Li-Chun Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Jun Lei
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Lu Xu
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, PR China
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Papatheodoridis GV, Cholongitas E, Archimandritis AJ, Burroughs AK. Current management of hepatitis B virus infection before and after liver transplantation. Liver Int 2009; 29:1294-305. [PMID: 19619264 DOI: 10.1111/j.1478-3231.2009.02085.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
The progress in treatment against hepatitis B virus (HBV) has substantially improved the outcome of all HBV-infected patients. We systematically reviewed the existing data in the management of HBV transplant patients in order to assess the optimal regimen in the pretransplant setting, for post-transplant prophylaxis and for therapy of HBV recurrent infection. All data suggest that an effective pretransplant anti-HBV therapy prevents post-transplant HBV recurrence. Pretransplant therapy has been based on lamivudine with addition of adefovir upon lamivudine resistance, but the use of newer, potent high-genetic barrier agents is expected to improve long-term efficacy. Moreover, it may lead to improvement of liver function, which sometimes removes the need for transplantation, although more objective criteria for removal from waiting lists are required. After liver transplantation, the combination of HBV immunoglobulin and one nucleos(t)ide analogue, mostly lamivudine, is currently the best approach, almost eliminating the probability of HBV recurrence. Treatment of post-transplant HBV recurrence has been mainly studied with lamivudine, but it will be most effective with entecavir and tenofovir, which have a low risk of resistance. In conclusion, the newer anti-HBV agents improve the treatment of HBV both pretransplant and post-transplant. HBV immunoglobulin is still used in combination with an anti-HBV agent for post-transplant prophylaxis. Monoprophylaxis with one of the new anti-HBV agents might be possible, particularly in patients preselected as having a low risk of HBV recurrence, but further data are needed and strategies to ensure compliance must be used.
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Affiliation(s)
- George V Papatheodoridis
- 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, 114 Vas. Sophias avenue, Athens, Greece.
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Manolakopoulos S, Triantos C, Theodoropoulos J, Vlachogiannakos J, Kougioumtzan A, Papatheodoridis G, Tzourmakliotis D, Karamanolis D, Burroughs AK, Archimandritis A, Raptis S, Avgerinos A. Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension. J Hepatol 2009; 51:468-74. [PMID: 19616339 DOI: 10.1016/j.jhep.2009.05.031] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2008] [Revised: 03/24/2009] [Accepted: 05/15/2009] [Indexed: 12/16/2022]
Abstract
BACKGROUND/AIMS Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. METHODS We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. RESULTS At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. CONCLUSION In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.
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Almeida AM, Silva DID, Guerra Jr AA, Silva GD, Acurcio FDA. Revisão sistemática da eficácia do interferon alfa (convencional, peguilado) e lamivudina para o tratamento da hepatite crônica B. CAD SAUDE PUBLICA 2009; 25:1667-77. [PMID: 19649408 DOI: 10.1590/s0102-311x2009000800003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
A hepatite crônica B constitui um grave problema de saúde pública e vem demonstrando crescentes gastos com financiamento de medicamentos de dispensação em caráter excepcional e de alto custo no Sistema Único de Saúde (SUS). O objetivo do estudo foi comparar a eficácia do interferon (convencional; peguilado - PEG2a) e lamivudina (LAM) para o tratamento da hepatite crônica B, pelo método de revisão sistemática selecionando ensaios clínicos randomizados e controlados identificados nas bases PubMed e LILACS. As medidas de resultado consideradas foram resposta virológica, soroconversão, resposta bioquímica, resposta histológica e efeitos adversos. Foram selecionados 35 artigos. A presença ou ausência do HBeAg e os níveis de alanina amino transferase (ALT) no pré-tratamento demonstraram papel fundamental na indicação terapêutica inicial. O tratamento com interferons convencionais permite a inativação da doença por longos períodos de tempo, podendo resultar em soroconversão HBsAg. O PEG 2a demonstrou eficácia superior ao interferon e LAM e efeitos colaterais semelhantes ao interferon. A LAM apresenta vantagem de ser sensível para os pacientes HBeAg negativo e apresenta como maior desvantagem o desenvolvimento de resistência.
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Joo MK, Yeon JE, Kim JH, Jung YK, Lee SJ, Kim JH, Yim HJ, Byun KS, Park JJ, Kim JS, Bak YT. Chronic cirrhotic hepatitis B patients with a high incidence of hepatic decompensation after viral breakthrough with lamivudine-resistant mutants and during rescue treatment. Scand J Gastroenterol 2009; 43:1514-21. [PMID: 18663665 DOI: 10.1080/00365520802273033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To compare the rate of biochemical and hepatic decompensation after viral breakthrough (V-BT) caused by lamivudine (LMV)-resistant HBV mutants and during rescue treatment for patients with liver cirrhosis (LC) and chronic hepatitis B (CHB). MATERIAL AND METHODS We reviewed the medical records of 205 CHB patients who developed V-BT with LMV-resistant HBV mutants (134 in the CHB group, 71 in the LC group). RESULTS Sixty-five of the 205 patients had an alanine aminotransferase (ALAT) flare-up (32%) and 21 (10%) had hepatic decompensation. The ALAT flare-up among the CHB and LC groups occurred in 43 (32%) and 22 patients (31%), respectively, and there was no significant difference between the two groups. Hepatic decompensation occurred in 5 (4%) and 16 (23%) patients with CHB and LC, respectively, and these differences were significant (p=0.001). A total of 187 patients were treated by rescue therapy (CHB 121, LC 66) and 13 cases with hepatic decompensation occurred only in LC patients during rescue therapy. Among them, 11 patients had serum ALAT levels two times higher than the upper normal limit (UNL) and the HBV-DNA was more than 10(7) copies/ml at the baseline of rescue therapy. In contrast, the cumulative ALAT normalization and viral response rates were reached significantly earlier in patients with a serum HBV-DNA of < or =10(7) copies/ml compared with those with an HBV-DNA >10(7) copies/ml (p=0.0221 and 0.0002, respectively). CONCLUSION Earlier rescue therapy for cirrhotic patients with genotypic resistance due to LMV-resistant mutants may improve patient outcome.
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Affiliation(s)
- Moon Kyung Joo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Abstract
A 58-year-old Arab-American male with HBeAg-negative chronic hepatitis B (HBV), presented with decompensated cirrhosis and a high HBV DNA level. He responded to entecavir with a significant reduction in serum HBV DNA level after 15 weeks of therapy with entecavir. However, he developed a progressive rise in prothrombin time/international normalized ratio (PT/INR) and bilirubin and underwent liver transplantation after receiving 22 weeks of entecavir therapy. Furthermore, with the continued use of combination entecavir and hepatitis B immunoglobulins (HBIG), he showed improvement in his clinical status with a nondetectable serum HBV DNA level 12 weeks after transplantation. He continued to maintain nondetectable serum HBV DNA 2 years following transplantation. To the best of our knowledge, this is the first reported case of a patient with decompensated chronic HBV who responded to entecavir both before and after transplantation without showing any evidence of recurrent HBV. Larger clinical trials are recommended to compare both short-term and long-term efficacy using entecavir among nucleoside-naïve decompensated chronic HBV patients before and after liver transplantation.
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Papatheodoridis GV, Manolakopoulos S, Archimandritis AJ. Current treatment indications and strategies in chronic hepatitis B virus infection. World J Gastroenterol 2008; 14:6902-10. [PMID: 19058323 PMCID: PMC2773851 DOI: 10.3748/wjg.14.6902] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [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
The optimal approach to the management of several marginal cases with chronic hepatitis B virus (HBV) infection is controversial. Serum HBV DNA and aminotransferase levels, and the degree of necroinflammation and fibrosis determine the therapeutic decisions. All patients with elevated aminotransferase (> twice the upper limit of normal) and serum HBV DNA above 20 000 IU/mL should be treated. Liver biopsy is important for therapeutic decisions in cases with mild aminotransferase elevations and serum HBV DNA below 20 000 IU/mL. Chronic HBV patients who do not receive treatment should be followed for life. There are seven agents licensed for chronic hepatitis B: standard and pegylated interferon-alpha, lamivudine, adefovir, entecavir, telbivudine and tenofovir. One-year courses with pegylated interferon-alpha induce sustained off-therapy remission in 30%-32% of patients with HBeAg-positive chronic hepatitis B and in a smaller proportion of patients with HBeAg-negative chronic hepatitis B. Oral antivirals achieve initial on-therapy responses in the majority of patients, but are intended as long-term therapies. Viral suppression has favourable effects on patients’ outcome and modifies the natural course of the disease. Viral resistance, however, is the major drawback of long-term oral antiviral therapy. Lamivudine monotherapy is associated with the highest and entecavir monotherapy with the lowest resistance rate so far. There has been no resistance to tenofovir, but after only 18 mo of treatment to date. The optimal first-line anti-HBV therapy with the best long-term cost/benefit ratio remains unclear. If oral antiviral agents are used, compliance should always be ascertained and HBV DNA levels should be regularly tested.
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Kuwahara R, Kumashiro R, Ide T, Koga Y, Hino T, Hisamochi A, Tanaka K, Ogata K, Koga H, Takao Y, Sata M. Predictive factors associated with the progression to hepatic failure caused by lamivudine-resistant HBV. Dig Dis Sci 2008; 53:2999-3006. [PMID: 18618250 DOI: 10.1007/s10620-008-0384-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2005] [Accepted: 07/12/2005] [Indexed: 02/07/2023]
Abstract
The aims of this study were to select the patients with a potential for progression to hepatic failure due to lamivudine-resistant HBV and to standardize the treatment for patients with lamivudine-resistant HBV. Patients (n = 47) with reactivated hepatitis due to lamivudine-resistant HBV were classified into two groups, with and without potential for progression to hepatic failure, according to the criteria using the data of serum bilirubin level and prothrombin activity after the reactivated hepatitis. Multivariate analysis showed that prothrombin activity at the initiation of lamivudine therapy was related to the deterioration of the liver function after the emergence of lamivudine-resistant HBV (P = 0.0025, 95%CI 0.8269-0.9601). We assume that earlier additional or substitutive treatment with other antiviral agent, such as adefovir dipivoxil, should be recommended when the lamivudine-resistant HBV is detected in patients with the history of decompensated liver disease before the administration of lamivudine, even when hepatitis has not been reactivated yet.
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Triantos CK, Nikolopoulou V, Burroughs AK. Review article: the therapeutic and prognostic benefit of portal pressure reduction in cirrhosis. Aliment Pharmacol Ther 2008; 28:943-52. [PMID: 18627364 DOI: 10.1111/j.1365-2036.2008.03798.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Hepatic venous pressure gradient (HVPG) measurement is not a routinely used technique, despite its therapeutic and prognostic value. AIM To review the role of HVPG from published literature. METHODS Systematic literature review. RESULTS In acute variceal bleeding, HVPG is prognostic identifying 'difficult to treat' group, which now has defined clinical correlations. In secondary prevention of portal hypertensive bleeding, a reduction to < or = 12 mmHg confers near complete protection against rebleeding. The target of > or = 20% HVPG reduction from baseline needs prospective assessment to test a change of therapy, if no reduction occurs. The acute HVPG response to beta-blockade needs further assessment. In primary prevention, the cost-effectiveness of HVPG measurement is not favourable given the efficacy of medical therapy. In chronic liver disease, wedge hepatic venous pressure (WHVP) is prognostic for survival. Pharmacological reduction in portal pressure decreases complications and improves survival, possibly independent of a concomitant improvement in liver function. This latter requires urgent confirmation as it is clinically very relevant. HVPG monitoring can be used to assess anti-viral therapy particularly in cirrhosis, ergonomically combined with transjugular biopsy. CONCLUSIONS The prognostic and therapeutic value of HVPG is established beyond portal hypertensive bleeding for which there are some clinical surrogates. HVPG measurement should now be part of everyday clinical practice.
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Affiliation(s)
- C K Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital, Patras, Greece
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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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Manolakopoulos S, Bethanis S, Koutsounas S, Goulis J, Vlachogiannakos J, Christias E, Saveriadis A, Pavlidis C, Triantos C, Christidou A, Papatheodoridis G, Karamanolis D, Tzourmakliotis D. Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine. Aliment Pharmacol Ther 2008; 27:266-73. [PMID: 17988233 DOI: 10.1111/j.1365-2036.2007.03567.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation. AIM To assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants. METHODS Fifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy. RESULTS The median follow-up after adefovir's onset was 31 (18-40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA <10(4) copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months. CONCLUSION In HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.
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Affiliation(s)
- S Manolakopoulos
- Department of Gastroenterology, Polyclinic General Hospital, Athens, Greece.
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Dai CY, Yu ML, Hsieh MY, Lee LP, Hou NJ, Huang JF, Chen SC, Lin ZY, Hsieh MY, Wang LY, Tsai JF, Chang WY, Chuang WL. Early response to lamivudine therapy in clinically non-cirrhotic chronic hepatitis B patients with decompensation. Liver Int 2007; 27:1364-1370. [PMID: 17900250 DOI: 10.1111/j.1478-3231.2007.01565.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
This study aimed to elucidate the rate and predictors of early (6 months) therapeutic responses to lamivudine, the rate of early mortality and the use of the model for end-stage liver disease (MELD) and Index in predicting the survival in patients with a clinical diagnosis of non-cirrhotic chronic hepatitis B with decompensation. Ninety-eight patients with lamivudine therapy were enrolled and MELD and Index scores were calculated. Surviving patients were treated with lamivudine for more than 6 months. Four (4.1%) of the 98 patients died after initiation of lamivudine therapy. After a 6-month lamivudine therapy, 80 (85.1%) patients and 71 (75.5%) patients had normal alanine aminotransferase (ALT) values and negative hepatitis B virus (HBV) DNA (<200 copies/mL), respectively, and hepatitis B e antigen (HBeAg)-negative patients had a significantly higher rate of negative HBV DNA than HBeAg-positive patients (P=0.002). The rates of HBeAg seroconversion and negative HBV DNA were 28.8 and 63.5%, respectively, and patients with HBeAg seroconversion had a significantly higher rate of negative HBV DNA (P=0.004). By multivariate analyses, older age, HBV nongenotype B infection, negative HBeAg and higher ALT levels were factors associated with negative HBV DNA, and a higher ALT level was associated with HBeAg seroconversion at month 6 after lamivudine therapy. MELD score and Index score were significantly associated with death and areas under the receiver operating characteristic curve for predicting survival were 0.936 and 0.907 respectively. We concluded that after 6-month lamivudine therapy, the patients who survived achieved favourable biochemical, virological responses and rate of HBeAg seroconversion. Both MELD and Index scoring systems are good models to predict the 6-month survival.
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Affiliation(s)
- Chia-Yen Dai
- Department of Internal Medicine, Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Therapeutic strategies in the management of patients with chronic hepatitis B virus infection. THE LANCET. INFECTIOUS DISEASES 2007; 8:167-78. [PMID: 18053766 DOI: 10.1016/s1473-3099(07)70264-5] [Citation(s) in RCA: 156] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Currently available options for the treatment of chronic hepatitis B virus (HBV) infection include standard and pegylated interferon alfa and four oral antiviral agents (lamivudine, adefovir, entecavir, and telbivudine). These treatment strategies are either therapies of finite duration that aim to achieve sustained off-therapy responses, or long-term treatments that aim to maintain on-therapy remission. Pegylated interferon alfa may offer higher sustained off-therapy responses after 1 year, but most patients do not respond. Oral antivirals are the only candidates for long-term treatment of patients with chronic HBV infection. Viral suppression has favourable effects on patients' outcome and modifies the natural history of the disease. Viral resistance is the main drawback of long-term antiviral therapy. Lamivudine monotherapy is associated with higher resistance (year 1, 10-27%; year 2, 37-48%; year 4, 60-65%) than adefovir (year 1, 0%; year 2, 3%; year 5, 29%) or telbivudine (year 1, 3-4%; year 2, 9-22%). Entecavir resistance is rare in naive individuals (year 4, <1%), but increases over time in lamivudine-resistant patients (year 4, 43%). The best strategy for long-term therapy in chronic HBV infection has yet to be established.
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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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Koga H, Ide T, Oho K, Kuwahara R, Hino T, Ogata K, Hisamochi A, Tanaka K, Kumashiro R, Toyonaga A, Sata M. Lamivudine treatment-related morphological changes of esophageal varices in patients with liver cirrhosis. Hepatol Res 2007; 37:503-9. [PMID: 17539992 DOI: 10.1111/j.1872-034x.2007.00087.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
AIM Many studies have reported the therapeutic effects of lamivudine on cirrhotic patients with hepatitis B; however, no study has investigated the morphological changes of esophageal varices after lamivudine treatment. METHOD The morphological changes of esophageal varices in patients with cirrhosis were retrospectively compared between 12 patients treated with lamivudine and six historical untreated patients. RESULTS In the treated group, the HBV DNA and hyaluronic acid (HA) levels in the serum were significantly lower than those in the untreated group (P = 0.013 and P = 0.009, respectively) at the end of follow-up, with a significant improvement in the Child-Pugh-Turcotte score (P = 0.022). In the treated group, the disappearance or reduction of esophageal varices was observed in six (50%) of the 12 patients. In three (25%) of the 12 patients, esophageal varices worsened. In the remaining three patients (25%), there were no changes in esophageal varices. In the untreated group, all patients showed the worsening of esophageal varices during the follow-up period, with a significant difference between this group and the treated group (P = 0.009). The serum HA level decreased in the nine treated patients without worsening of esophageal varices. However, in the three patients with worsening, the HA level significantly increased. CONCLUSION Lamivudine treatment for patients with cirrhosis improves not only liver function but also esophageal varices.
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Affiliation(s)
- Hiroyuki Koga
- Second Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan
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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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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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Saikia N, Talukdar R, Mazumder S, Khanna S, Tandon R. Management of patients with HBeAg-negative chronic hepatitis B. Postgrad Med J 2007; 83:32-9. [PMID: 17267676 PMCID: PMC2599959 DOI: 10.1136/pgmj.2006.044826] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2006] [Accepted: 04/10/2006] [Indexed: 12/16/2022]
Abstract
Chronic hepatitis B (CHB) is one of the leading causes of morbidity and mortality worldwide. Although various drugs are available for the treatment of CHB, emergence of the hepatitis B e antigen (HBeAg)-negative mutant variant, specifically in Asia, the Middle East and southern Europe, is creating a new challenge as this variant is less responsive to available treatments. HBeAg-negative CHB rapidly progresses to cirrhosis and its related complications. This review discusses the available literature on the approved and under-trial treatment options and their respective efficacies for HBeAg-negative CHB.
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Affiliation(s)
- Nripen Saikia
- Department of Gastroenterology, Pushpawati Singhania Research Institute, New Delhi, India.
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Dai CY, Chuang WL, Hou NJ, Lee LP, Hsieh MY, Lin ZY, Chen SC, Huang JF, Hsieh MY, Wang LY, Tsai JF, Wen-Yu, Yu ML. Early mortality in Taiwanese lamivudine-treated patients with chronic hepatitis B-related decompensation: evaluation of the model for end-stage liver disease and index scoring systems as prognostic predictors. Clin Ther 2006; 28:2081-2092. [PMID: 17296464 DOI: 10.1016/j.clinthera.2006.12.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/23/2006] [Indexed: 12/14/2022]
Abstract
BACKGROUND Both Model for End-stage Liver Disease (MELD) and Index scores have been used to predict mortality in patients with end-stage liver disease and cirrhosis in Western countries. OBJECTIVES This study aimed to determine mortality rates, identify prognostic indicators, and determine the usefulness of these 2 scoring systems in predicting short-term (6-month) survival in Taiwanese patients with chronic hepatitis B (CHB)-related decompensation who were treated with lamivudine. METHODS This study was conducted at the Kaohsiung Medical University Hospital and the Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. Eligible patients were aged 18 to 85 years with CHB with related decompensation (with either serum total bilirubin level, >or=3 mg/dL or prolonged prothrombin time, >or=3 seconds) and were treatment naive. All patients were treated with lamivudine 100 mg PO (tablet) once daily; surviving patients were treated for at least 6 months. The clinical data, including hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B virus (HBV) DNA, were measured before treatment. Pre-treatment MELD and Index scores were calculated for all patients. RESULTS Ninety-six patients were enrolled (79 men, 17 women; mean [SD] age, 44.5 [15.2] years). Thirteen (13.5%) patients died within 6 months. Higher international normalized ratio (INR) for prothrombin time, lower albumin level, and higher HBV DNA level (>or=10(5) copies/mL) were factors significantly associated with death. The areas under the receiver operating characteristic curve for predicting survival by the MELD and Index scores were 0.822 and 0.788, respectively. Albumin level, which was not included in the scoring systems, also was found to be a significant predictor. CONCLUSIONS : We found that with a 13.5% mortality rate, albumin, INR, and HBV DNA levels were good prognostic indicators in Taiwanese patients with CHB-related decompensation treated with lamivudine therapy. The MELD and Index scoring systems were good predictors of 6-month survival in the patients in this study.
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Affiliation(s)
- Chia-Yen Dai
- Faculty of Internal Medicine, College o f Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Wen R, Wang J, Chen M, Yan M. Chinese medicine Jiangganlong combined with anti-virus medicine in long-term treatment of active liver cirrhosis and its effect on prognosis of patients. Shijie Huaren Xiaohua Zazhi 2006; 14:2860-2864. [DOI: 10.11569/wcjd.v14.i29.2860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the efficacy of Chinese medicine Jiangganlong combined with anti-virus medicine in the treatment of active liver cirrhosis (ALC).
METHODS: A total of 114 ALC patients were divided into treatment group and control group, named A and B, respectively. The patients in group A were treated with Jiangganlong and lamivudine (LAM). Jiangganlong decoction or pills were given a dose every three days, or 4.0 g (tid). LAM was administered 0.1 g per day. After the emergence of YMDD variations, adefovir (ADV) was added. LAM was stopped when HBV DNA YMDD variation became negative. The patients in group B received general and symptomatic treatment. The mean treatment therapeutic time was 36 months.
RESULTS: The rates of negative conversion for the serum HBV DNA were 75.4% (43/57) and 3.5% (2/57) in group A and B, respectively, and there was significant difference between them (P < 0.01). The cumulative rate of YMDD variations among patients of group A was 40.4% (23/57). After the emergence of YMDD variations, 20 patients received ADV treatment, 90% (18/20) of which were found YMDD variation-negative; there were 3 patients who did not receive ADV treatment, and they died of liver failure. The negative conversion rates of HBeAg were 44.4% (16/36), 16.7% (5/30) in group A, B, respectively, and there was marked difference between them (P < 0.05). The total bilirubin (TBIL) and alanine aminotransferase (ALT) returned to the normal level, and the albumin level, Child-Pugh score, and decompensation status were improved in group A. The rate of complications was dramatically lower in group A than that in group B [14.0% (8/57) vs 50.8% (29/57), P < 0.01]. The mortality rate was also decreased in group A as compared with that in group B [7.0% (4/57) vs 29.8% (17/57), P < 0.01], while the survival time was notably prolonged (3.3 ± 2.1 year vs 1.1 ± 1.0 year, P < 0.01).
CONCLUSION: Chinese medicine Jiangganlong combined with anti-virus medicine can inhibit the replication of HBV DNA, ameliorate liver function, decrease the rate of complications, reduce the mortality rate, and prolong the survival time as well as improve the prognosis of ALC patients.
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Bolukbas C, Bolukbas FF, Kendir T, Akbayir N, Ince AT, Abut E, Horoz M, Dalay AR, Sokmen MH, Ovunc O. The effectiveness of lamivudine treatment in cirrhotic patients with HBV precore mutations: a prospective, open-label study. Dig Dis Sci 2006; 51:1196-202. [PMID: 16944009 DOI: 10.1007/s10620-006-8032-9] [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] [Received: 03/11/2005] [Accepted: 06/02/2005] [Indexed: 12/31/2022]
Abstract
In this study, the effect of lamivudine therapy on viral suppression, Child-Pugh score, and survival was assessed in patients with decompensated cirrhosis due to precore mutant hepatitis B virus and the results were compared with those for nonreplicative cirrhotic patients. Twenty-three replicative patients who received lamivudine and 15 nonreplicative patients were included and followed up for an average of 23.7+/-13.4 months. At baseline, there were no significant differences between the groups with regard to clinical and biochemical parameters or Child-Pugh scores, except for serum alanine aminotransferase levels (P<0.05) and quantitative hepatitis B virus DNA measurements (P<0.001). Compared to baseline, there was no significant difference in Child-Pugh score in the lamivudine group at the last visit (P=0.202), whereas a marked increase was observed in nonreplicative patients (P=0.002). Mortality rates in the lamivudine and nonreplicative groups were 17.43% and 13.3%, respectively (P=0.556), and there was no difference in survival analysis (P=0.809). Lamivudine therapy stabilizing clinical situation in decompensated cirrhotics with precore mutation makes the natural history of the disease equal with nonreplicative decompensated cirrhotics or even provides some advantages over them.
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Affiliation(s)
- Cengiz Bolukbas
- Department of Internal Medicine, Division of Gastroenterology, Harran University, Sanliurfa, and Gastroenterology Clinic, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
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Manolakopoulos S, Bethanis S, Elefsiniotis J, Karatapanis S, Triantos C, Sourvinos G, Touloumi G, Economou M, Vlachogiannakos J, Spandidos D, Avgerinos A, Tzourmakliotis D. Lamivudine monotherapy in HBeAg-negative chronic hepatitis B: prediction of response-breakthrough and long-term clinical outcome. Aliment Pharmacol Ther 2006; 23:787-95. [PMID: 16556181 DOI: 10.1111/j.1365-2036.2006.02806.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined. AIM To determine pre-treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg-negative chronic hepatitis B receiving long-term lamivudine. METHODS Seventy-nine patients, with chronic HBeAg-negative hepatitis B, who received lamivudine for a median of 31 months were included in the study. RESULTS Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre-treatment serum hepatitis B virus DNA concentrations of more than 10(6) copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated. CONCLUSIONS In HBeAg-negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 10(6) copies/mL is a strong predictor for breakthrough because of drug-resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre-existing cirrhosis.
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Affiliation(s)
- S Manolakopoulos
- Department of Gastroenterology, Polyclinic General Hospital, Athens, Greece.
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Abstract
Chronic hepatitis B infection presents a number of challenges to clinicians. There are additional considerations when defining management strategies for individuals with advanced liver disease, or coinfection, or those at high risk of developing hepatocellular carcinoma (HCC). Treatment of decompensated cirrhosis is particularly important. Evidence suggests that suppression of viral replication through nucleos(t)ide analog therapy leads to longer time to transplantation, improved liver function, and improved survival times. The use of interferon in patients with decompensated hepatitis B is associated with serious complications and is currently contraindicated for these patients by the AASLD Practice Guidelines. Hepatitis B coinfection is often associated with more extensive disease. In patients with HBV/HCV coinfection, one disease is usually dominant and consequently should be the focus of therapy. HIV/HBV coinfection increases the risk of progressive liver disease. Therapeutic agents active against both viruses should be utilized at the correct dose to limit the development of resistance. Agents specific for HBV, e.g., entecavir, enable hepatitis to be treated while avoiding the risk of HIV resistance developing. Dual infection with HBV and HDV is particularly challenging. Nucleos(t)ide analogs are ineffective in treating HDV infection, and there is limited data concerning the efficacy of interferon in this setting. The association between chronic hepatitis B infection and hepatocellular carcinoma (HCC) is well established. In patients at high risk of HCC, screening regimes may be effective. Furthermore, there is an increasing body of evidence indicating that effective suppression of viral replication may be associated with a reduced risk of HCC.
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Affiliation(s)
- Morris Sherman
- University of Toronto and University Health Network, Toronto General Hospital 9N-981, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
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Wright TL, Avunduk C, Dienstag JL, Freston JW, Jacobson IM, Nord HJ, Sherman M. Advancing patient care: integrating new data. Am J Gastroenterol 2006; 101 Suppl 1:S32-9. [PMID: 16448450 DOI: 10.1111/j.1572-0241.2006.00376.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Physicians involved in the management of patients with chronic hepatitis B infection are frequently faced with complex clinical issues concerning the diagnosis, investigation, and treatment of patients. Guidelines exist within the literature that help with decision making; however, in practice individual nuances are often encountered necessitating decisions that go beyond the current guidelines. Following presentation of the available data, a panel of expert hepatologists and gastroenterologists sought to identify and solve challenges that are faced by clinicians in the daily management of patients with chronic hepatitis B infection. The following summary provides an overview of the outcome of these discussions. Because of the complexities of clinical management, the recommendations reflect the opinion of the majority; however, many recommendations were not unanimous. Furthermore, the recommendations that follow are limited to adult patients; the treatment of children was not discussed. A number of issues were identified, and statements concerning possible management strategies that could be applied were developed.
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Affiliation(s)
- Teresa L Wright
- University of California-San Francisco, and VA Medical Center 111B, San Francisco, CA 94121, USA
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