EASL Clinical Practice Guidelines: management of chronic hepatitis B.

Our understanding of the natural history of hepatitis B virus (HBV) infection and the potential for therapy of the resultant disease has improved. Several new and effective antiviral agents have been evaluated and licensed since the EASL International Consensus Conference on hepatitis B held in 2002 [1]. The objective of these EASL Clinical Practice Guidelines (CPGs) is to update recommendations for the optimal management of chronic hepatitis B (CHB). The CPGs do not focus on prevention and vaccination. Several difficulties remain in formulating treatments for CHB; thus areas of uncertainty exist. At the present time clinicians, patients and public health authorities must continue to make choices on the basis of evidence that is not fully matured.

[1]  A. Heath,et al.  An international collaborative study to establish a World Health Organization international standard for hepatitis B virus DNA nucleic acid amplification techniques , 2001, Vox sanguinis.

[2]  B. McMahon,et al.  Chronic hepatitis B , 2001, Hepatology.

[3]  E. Schiff,et al.  A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group. , 1990, The New England journal of medicine.

[4]  G. Mantzaris,et al.  Lamivudine treatment for acute severe hepatitis B: report of a case and review of the literature. , 2008, Acta gastro-enterologica Belgica.

[5]  P. Marcellin,et al.  HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa‐2a for HBeAg‐positive chronic hepatitis B , 2008, Hepatology.

[6]  J. Hoofnagle,et al.  Management of hepatitis B: Summary of a clinical research workshop , 2007, Hepatology.

[7]  P. Marcellin,et al.  Efficacy of peginterferon alpha‐2b in chronic hepatitis delta: Relevance of quantitative RT‐PCR for follow‐up , 2006, Hepatology.

[8]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .

[9]  M. Manns,et al.  Tenofovir disoproxil fumarate (TDF) for the treatment of HBeAg-negative chronic Hepatitis B: Week 72 TDF data and week 24 Adefovir dipivoxil switch data (Study 102) , 2008 .

[10]  G. Fattovich,et al.  Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years , 2007, Gut.

[11]  Y. Liaw.  Prevention and surveillance of hepatitis B virus-related hepatocellular carcinoma. , 2005, Seminars in liver disease.

[12]  G. Guyatt,et al.  GRADE: an emerging consensus on rating quality of evidence and strength of recommendations , 2008, BMJ : British Medical Journal.

[13]  J. Sch.  GRADE: grading quality of evidence and strength of recommendations for diagnostic tests and strategies , 2008, BMJ : British Medical Journal.

[14]  P. Marcellin,et al.  Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. , 2004, The New England journal of medicine.

[15]  C. Chu,et al.  Hepatitis B virus-related cirrhosis: natural history and treatment. , 2006, Seminars in liver disease.

[16]  J. Stockman,et al.  Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B , 2007 .

[17]  M. Buti,et al.  Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group. , 1999, Hepatology.

[18]  H. Kumada,et al.  [Chronic hepatitis B]. , 2001, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology.

[19]  Oliver N Keene,et al.  Lamivudine for patients with chronic hepatitis B and advanced liver disease. , 2004, The New England journal of medicine.

[20]  M. Manns,et al.  The HEP-NET B/C co-infection trial: A prospective multicenter study to investigate the efficacy of pegylated interferon-alpha2b and ribavirin in patients with HBV/HCV co-infection. , 2008, Journal of hepatology.

[21]  George Kitis,et al.  Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. , 2006, Gastroenterology.

[22]  G. Lau.  Hepatitis B reactivation after chemotherapy: two decades of clinical research , 2008, Hepatology international.

[23]  V. Paradis,et al.  Sampling variability of liver fibrosis in chronic hepatitis C , 2003, Hepatology.

[24]  E. Schiff,et al.  A Randomized, Controlled Trial of Interferon Alfa-2b Alone and after Prednisone Withdrawal for the Treatment of Chronic Hepatitis B , 1990 .

[25]  H. Senturk,et al.  Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers. , 2008, The Netherlands journal of medicine.

[26]  G. Guyatt,et al.  Grades of recommendation for antithrombotic agents. , 1998, Chest.

[27]  Jean-Michel Pawlotsky,et al.  Performance of the Cobas AmpliPrep/Cobas TaqMan Real-Time PCR Assay for Hepatitis B Virus DNA Quantification , 2008, Journal of Clinical Microbiology.

[28]  J. Stockman,et al.  A Comparison of Entecavir and Lamivudine for HBeAg-Positive Chronic Hepatitis B , 2007 .

[29]  Thomas Berg,et al.  Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. , 2005, The New England journal of medicine.

[30]  Ching-Lung Lai,et al.  Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. , 2006, The New England journal of medicine.

[31]  Angeline Bartholomeusz,et al.  Antiviral drug‐resistant HBV: Standardization of nomenclature and assays and recommendations for management , 2007, Hepatology.

[32]  G. Fattovich.  Natural History and Prognosis of Hepatitis B , 2003, Seminars in liver disease.

[33]  G. Dore,et al.  Hepatitis B and C virus coinfection in The TREAT Asia HIV Observational Database , 2007, Journal of gastroenterology and hepatology.

[34]  G. Gerken,et al.  Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial , 2005, The Lancet.

[35]  H. Janssen,et al.  Treatment with Peg-Interferon α-2b for HBeAg-Positive Chronic Hepatitis B: HBsAg Loss Is Associated with HBV Genotype , 2006, The American Journal of Gastroenterology.

[36]  L. Rostaing,et al.  Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation. , 1997, Transplantation.

[37]  M. Loriot,et al.  Redevelopment of hepatitis B surface antigen after renal transplantation. , 1991, Gastroenterology.

[38]  M. Buendia,et al.  Statements from the Taormina expert meeting on occult hepatitis B virus infection. , 2008, Journal of hepatology.

[39]  Giorgio Palù,et al.  Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. , 2005, Journal of hepatology.

[40]  Gordon H Guyatt,et al.  GrADe : what is “ quality of evidence ” and why is it important to clinicians ? rATING quALITY of evIDeNCe AND STreNGTH of reCommeNDATIoNS , 2022 .

[41]  P. Farci.  Treatment of chronic hepatitis D: New advances, old challenges , 2006, Hepatology.

[42]  D. Samuel.  Management of hepatitis B in liver transplantation patients. , 2004, Seminars in liver disease.

[43]  P. van Eyken,et al.  Treatment of chronic hepatitis D with interferon alfa-2a. , 1994, The New England journal of medicine.

[44]  M. Manns,et al.  Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience , 2006, Journal of viral hepatitis.

[45]  M. Rizzetto.  Viral hepatitis in the third millennium. , 1998, Research in virology.

[46]  Ding‐Shinn Chen,et al.  Kinetics of hepatitis B virus reactivation after chemotherapy: more questions than answers. , 2006, Gastroenterology.

[47]  E. Schiff,et al.  Adefovir dipivoxil for wait‐listed and post–liver transplantation patients with lamivudine‐resistant hepatitis B: Final long‐term results , 2007, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[48]  Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group. , 1999 .

[49]  A. Dhawan,et al.  The Pharmacokinetics and Safety of Adefovir Dipivoxil in Children and Adolescents With Chronic Hepatitis B Virus Infection , 2008, Journal of clinical pharmacology.

[50]  M. Jonas,et al.  Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B , 2008, Hepatology.

[51]  R. Figueroa Barrios.  [Chronic hepatitis]. , 1995, Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru.

[52]  William M. Lee,et al.  Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. , 2004, Gastroenterology.

[53]  P. Marcellin,et al.  Predicting response to peginterferon α-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B , 2006, Gut.

[54]  Yao Guang.  Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B in China , 2005 .

[55]  R. Bruno,et al.  Natural history of chronic hepatitis B in co-infected patients. , 2006, Journal of hepatology.

[56]  C. Yurdaydın,et al.  A pilot study of 2 years of interferon treatment in patients with chronic delta hepatitis , 2007, Journal of viral hepatitis.

[57]  J. Rockstroh.  Influence of viral hepatitis on HIV infection. , 2006, Journal of hepatology.

[58]  G. Guyatt,et al.  Going from evidence to recommendations , 2008, BMJ : British Medical Journal.

[59]  E. Schiff,et al.  Hepatitis B virus reactivation after cytotoxic chemotherapy: the disease and its prevention. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[60]  S. Sarin,et al.  Hepatitis B e‐antigen negative chronic hepatitis B , 2002, Journal of gastroenterology and hepatology.

[61]  A. Lok,et al.  Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e Antigen–negative patients receiving lamivudine therapy , 2000, Hepatology.

[62]  R. Bruno,et al.  European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV‐infected adults , 2008, HIV medicine.

[63]  R. Fontana,et al.  Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy. , 2002, Gastroenterology.

[64]  P. Marcellin,et al.  Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. , 2002, Journal of hepatology.

[65]  P. Marcellin,et al.  Influence of HIV infection on the response to interferon therapy and the long-term outcome of chronic hepatitis B. , 2002, Gastroenterology.

[66]  M. Jonas,et al.  Long‐term lamivudine treatment of children with chronic hepatitis B: durability of therapeutic responses and safety , 2007, Journal of viral hepatitis.

[67]  P. Marcellin,et al.  Characteristics of patients with chronic hepatitis B in France: predominant frequency of HBe antigen negative cases. , 2006, Journal of hepatology.

[68]  Ally,et al.  A ONE-YEAR TRIAL OF LAMIVUDINE FOR CHRONIC HEPATITIS B , 2000 .

[69]  M. Buti,et al.  Peginterferon alpha‐2b is safe and effective in HBeAg‐positive chronic hepatitis B patients with advanced fibrosis , 2007, Hepatology.

[70]  D. Vassilopoulos,et al.  Hepatitis B e antigen–negative chronic hepatitis B , 2001, Hepatology.

[71]  G. Fattovich,et al.  Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. , 2008, Journal of hepatology.

[72]  C. Thio,et al.  Clinical implications of HIV and hepatitis B co-infection in Asia and Africa. , 2007, The Lancet. Infectious diseases.

[73]  M. Wulfsohn,et al.  Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. , 2003, The New England journal of medicine.

[74]  Gordon H Guyatt,et al.  Incorporating considerations of resources use into grading recommendations , 2008, BMJ : British Medical Journal.

[75]  Pierre Bedossa,et al.  Non‐invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B , 2009, Liver international : official journal of the International Association for the Study of the Liver.

[76]  Jean-Michel Pawlotsky,et al.  Virologic monitoring of hepatitis B virus therapy in clinical trials and practice: recommendations for a standardized approach. , 2008, Gastroenterology.

[77]  M. Manns,et al.  [4] 72 WEEK DATA OF THE HIDIT-1 TRIAL: A MULTICENTER RANDOMISED STUDY COMPARING PEGINTERFERON α-2a PLUS ADEFOVIR VS. PEGINTERFERON α-2a PLUS PLACEBO VS. ADEFOVIR IN CHRONIC DELTA HEPATITIS , 2007 .

[78]  N. Terrault,et al.  Treating chronic hepatitis B infection in patients who are pregnant or are undergoing immunosuppressive chemotherapy. , 2007, Seminars in liver disease.

[79]  M. Alter,et al.  Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in health care workers (HCWs): guidelines for prevention of transmission of HBV and HCV from HCW to patients. , 2003, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[80]  F. Zoulim,et al.  Characterization of a New Sensitive PCR Assay for Quantification of Viral DNA Isolated from Patients with Hepatitis B Virus Infections , 2007, Journal of Clinical Microbiology.

[81]  C. Hsiung,et al.  A revisit of prophylactic lamivudine for chemotherapy‐associated hepatitis B reactivation in non‐Hodgkin's lymphoma: A randomized trial , 2008, Hepatology.

[82]  M. Yuen,et al.  Hepatitis B virus DNA levels at week 4 of lamivudine treatment predict the 5‐year ideal response , 2007, Hepatology.

[83]  E. Jury.  EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002: Geneva, Switzerland. Consensus statement (short version). , 2003, Journal of hepatology.

[84]  Y. Jeng,et al.  Ribavirin and interferon is effective for hepatitis C virus clearance in hepatitis B and C dually infected patients , 2003, Hepatology.

[85]  Francesco Donato,et al.  Hepatocellular carcinoma in cirrhosis: incidence and risk factors. , 2004, Gastroenterology.

[86]  C. Katlama,et al.  Anti‐hepatitis B virus efficacy of tenofovir disoproxil fumarate in HIV‐infected patients , 2006, Hepatology.

[87]  P. Marcellin,et al.  57 TENOFOVIR DISOPROXIL FUMARATE (TDF) FOR THE TREATMENT OF HBEAG-NEGATIVE CHRONIC HEPATITIS B: WEEK 72 TDF DATA AND WEEK 24 ADEFOVIR DIPIVOXIL SWITCH DATA (STUDY 102) , 2008 .

[88]  E. Stelzl,et al.  Rapid Quantification of Hepatitis B Virus DNA by Automated Sample Preparation and Real-Time PCR , 2004, Journal of Clinical Microbiology.

[89]  D. Ganem,et al.  Hepatitis B virus infection--natural history and clinical consequences. , 2004, The New England journal of medicine.

[90]  William M. Lee,et al.  Acute liver failure: Summary of a workshop , 2007, Hepatology.

[91]  M. Colombo,et al.  696 ADD ON ADEFOVIR PREVENTS THE EMERGENCE OF ADV RESISTANCE IN LAMIVUDINE-RESISTANT PATIENTS: A 4-YEAR STUDY , 2008 .

[92]  A. Andriulli,et al.  Pegylated interferon alpha‐2b as monotherapy or in combination with ribavirin in chronic hepatitis delta , 2006, Hepatology.

[93]  F. Zoulim,et al.  Antiviral therapy of chronic hepatitis B: prevention of drug resistance. , 2007, Clinics in liver disease.

[94]  V. Soriano,et al.  Care of patients with chronic hepatitis B and HIV co-infection: recommendations from an HIV-HBV International Panel. , 2002, AIDS.

[95]  Shou-Dong Lee,et al.  Hepatitis B virus/hepatitis C virus coinfection: Epidemiology, clinical features, viral interactions and treatment , 2008, Journal of gastroenterology and hepatology.

[96]  J. Hayashi,et al.  Transient elastography for patients with chronic hepatitis B and C virus infection: Non‐invasive, quantitative assessment of liver fibrosis , 2007, Hepatology research : the official journal of the Japan Society of Hepatology.

[97]  A. Detsky,et al.  Effect of Alpha-Interferon Treatment in Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B , 1993, Annals of Internal Medicine.

[98]  D. Shouval,et al.  Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies , 2007, British journal of haematology.

[99]  T. Poynard,et al.  Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B. , 2003, Journal of hepatology.

[100]  H. Janssen,et al.  Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection , 2003, Journal of viral hepatitis.

[101]  H. Tillmann,et al.  Telbivudine versus lamivudine in patients with chronic hepatitis B. , 2008, The New England journal of medicine.

[102]  M. Loss,et al.  Solid-organ transplantation in HBsAg-negative patients with antibodies to HBV core antigen: low risk of HBV reactivation. , 2005, Transplantation.

[103]  S. Hadziyannis,et al.  Efficacy of long‐term lamivudine monotherapy in patients with hepatitis B e antigen–negative chronic hepatitis B , 2000, Hepatology.

[104]  E. Schiff,et al.  Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B , 2002, Hepatology.

[105]  Patrice Cacoub,et al.  Meta-analyses of FibroTest diagnostic value in chronic liver disease , 2007, BMC gastroenterology.

[106]  H. Senturk,et al.  Chronic hepatitis C responds poorly to combination therapy in chronic hepatitis b carriers , 2008 .

[107]  M. Rizzetto,et al.  Chronic HBV-related liver disease. , 2008, Molecular aspects of medicine.

[108]  P. Farci,et al.  Treatment of chronic hepatitis D , 2007, Journal of viral hepatitis.

[109]  A. Burroughs,et al.  Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis , 1996, The Lancet.

[110]  Y. Ngo,et al.  An Accurate Definition of the Status of Inactive Hepatitis B Virus Carrier by a Combination of Biomarkers (FibroTest-ActiTest) and Viral Load , 2008, PloS one.

[111]  R. D. de Man,et al.  Exacerbation of chronic hepatitis B infection after delivery , 2007, Journal of viral hepatitis.

[112]  M. Sulkowski,et al.  Viral hepatitis and HIV coinfection. , 2008, Journal of hepatology.

[113]  F. Zoulim,et al.  Hepatitis B: reflections on the current approach to antiviral therapy. , 2008, Journal of hepatology.

[114]  G. Guyatt,et al.  Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive , 2008, BMJ : British Medical Journal.