We focused on advances in the management of hepatitis B in the past 5 years. We searched the Cochrane Library, PubMed, and Embase with the terms “hepatitis B”, “chronic hepatitis B”, and “hepatitis B virus”, together with “epidemiology”, “burden of disease”, “immunopathogenesis”, “prevention”, “vaccination”, “natural history”, “treatment”, “antiviral therapy”, and “hepatocellular carcinoma” for articles published in English between Jan 1, 2008, and Dec 31, 2013. Landmark studies published
SeminarHepatitis B virus infection
Introduction
Hepatitis B virus (HBV) infection is the most common chronic viral infection in the world. An estimated 2 billion people have been infected, and more than 350 million are chronic carriers of the virus.1 In the 2010 Global Burden of Disease study,2 HBV infection ranked in the top health priorities in the world, and was the tenth leading cause of death (786 000 deaths per year). These data have led WHO to include viral hepatitis in its major public health priorities.
Safe and effective prophylactic vaccines and effective antiviral drugs are available to prevent and treat HBV infection, but the global burden will remain high without concerted efforts from governments, health-care providers, and communities to raise awareness and improve access to care.
Section snippets
Epidemiology
Roughly 30% of the world's population shows serological evidence of current or past HBV infection.3, 4 About half the total liver cancer mortality in 2010 was attributed to HBV infection, and from 1990 to 2010, the worldwide mortality associated with liver cancer increased by 62% and that associated with cirrhosis increased by 29%.2
HBV is transmitted through contact with infected blood or semen. Three major modes of transmission prevail. In areas of high endemicity, HBV is transmitted mostly
Prevention
HBV infection can be prevented by avoiding transmission from infected people and by inducing immunity in unexposed people. Screening of blood donors for HBsAg and implementation of universal precautions resulted in a substantial reduction in transmission in health-care settings. The addition of HBV DNA testing to screening processes further decreases the incidence of transfusion-associated disease, but implementation is hampered by incremental cost.10 Counselling infected people to prevent
Diagnosis
Serological markers for HBV infection include HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc IgM and IgG (figure 2; table 1). HBsAg is the hallmark of infection. During acute infection, anti-HBc (initially both IgM and IgG) appears 1–2 weeks after the appearance of HBsAg at the same time as raised aminotransferase concentrations and symptoms, while IgG persists during chronic infection. IgM anti-HBc can be present in some patients with severe exacerbations of chronic HBV infection but the titre
Immunopathogenesis
HBV is not cytopathic: both liver damage and viral control are immunomediated. The clinical outcome of infection is dependent on the complex interplay between HBV replication and host immune response.29, 30, 31 HBV is a weak inducer of the innate immune response.32 Resolution of acute infection is mainly mediated through the adaptive immune response. People with serological recovery from acute HBV infection have strong T-cell responses to several epitopes in different regions of the HBV genome.
Virology
HBV belongs to the Hepadnaviridae family. It is a partly doublestranded DNA virus with approximately 3200 base pairs. The transcriptional template of HBV is the cccDNA, which resides inside the hepatocyte nucleus as a mini-chromosome.42 The maintenance of cccDNA is essential for the persistence of the virus. The replication of HBV implicates reverse transcription of the pregenomic RNA intermediate into HBV DNA. Reverse transcriptase is error prone and the mutation rate is high (appendix). The
Natural history
The occurrence of symptoms during acute HBV infection and the outcome depend on age at infection. Infants and children are mostly asymptomatic, whereas roughly 70% of adults have subclinical or anicteric hepatitis and 30% have icteric hepatitis. Less than 1% of acute HBV infection in adults progresses to fulminant hepatitis, which has a mortality of around 80% without liver transplantation.
HBsAg appears in the serum 2–10 weeks after exposure to HBV, before onset of symptoms and increases in
General
Acute HBV infection is self-limiting in more than 95% of immunocompetent adults. Therefore management is supportive, and so far antiviral therapy is indicated only for patients with protracted or severe acute disease. Management of chronic infection should include assessment of HBV replication status; screening for HIV, hepatitis C virus, and hepatitis D virus co-infection; and assessment of severity of liver disease. Clinical assessment, blood counts, analysis of liver enzymes, and liver
Search strategy and selection criteria
References (101)
- et al.
Hepatitis B virus infection
Lancet
(2009) - et al.
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010
Lancet
(2012) Rocks along the road to the control of HBV and HCC
Ann Epidemiol
(2009)- et al.
Epidemiology of hepatitis B and C viruses: a global overview
Clin Liver Dis
(2010) Should HBV DNA NAT replace HBsAg and/or anti-HBc screening of blood donors?
Transfus Clin Biol
(2004)- et al.
Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention
J Hepatol
(2013) - et al.
Hepatitis B vaccination: a completed schedule enough to control HBV lifelong? Milan, Italy, 17–18 November 2011
Vaccine
(2013) - et al.
Minimization of hepatitis B infection by a 25-year universal vaccination program
J Hepatol
(2012) - et al.
Occult hepatitis B virus infection
J Hepatol
(2007) - et al.
Hepatitis B surface antigen quantification: why and how to use it in 2011—a core group report
J Hepatol
(2011)
Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naive, e antigen-positive patients
J Hepatol
Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: perspectives and challenges
J Hepatol
Targeting innate immunity: a new step in the development of combination therapy for chronic hepatitis B
Gastroenterology
Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis
Gastroenterology
Acute exacerbations in Chinese patients with chronic hepatitis B virus (HBV) infection. Incidence, predisposing factors and etiology
J Hepatol
Serology of acute exacerbation in chronic hepatitis B virus infection
Gastroenterology
Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection
Gastroenterology
Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F
Gastroenterology
A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection
J Hepatol
HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma
Gastroenterology
Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection
Gastroenterology
Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B
Gastroenterology
Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan
Lancet
Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors
J Hepatol
Predicting cirrhosis risk based on the level of circulating hepatitis B viral load
Gastroenterology
Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study)
J Hepatol
Management of hepatitis B: our practice and how it relates to the guidelines
Clin Gastroenterol Hepatol
Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial
Lancet
Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b
Gastroenterology
Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa
Gastroenterology
Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study
Lancet
2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B
Gastroenterology
Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B
Hepatology
Histological outcome during long-term lamivudine therapy
Gastroenterology
The clinical significance of persistently normal ALT in chronic hepatitis B infection
J Hepatol
Hepatitis B. Fact Sheet N°204
The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference
J Viral Hepat
Global immunization data
Seroprevalence of chronic hepatitis B virus infection and prior immunity in immigrants and refugees: a systematic review and meta-analysis
PLoS One
The increasing burden of imported chronic hepatitis B—United States, 1974–2008
PLoS One
Vertical transmission of hepatitis B antigen in Taiwan
N Engl J Med
Antiviral therapy for chronic hepatitis B in pregnancy
Semin Liver Dis
Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose
J Infect Dis
Observational study of vaccine efficacy 24 years after the start of hepatitis B vaccination in two Gambian villages: no need for a booster dose
PLoS One
Chronic hepatitis B infection in adolescents who received primary infantile vaccination
Hepatology
Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study
J Natl Cancer Inst
Surveillance for acute viral hepatitis–United States, 2006
MMWR Surveill Summ
The prevalence of hepatitis B virus infection in the United States in the era of vaccination
J Infect Dis
Prevalence of hepatitis B virus infection in The Netherlands in 1996 and 2007
Epidemiol Infect
Should Europe have a universal hepatitis B vaccination programme?
BMJ
Cited by (1246)
Impact of DNA on interactions between core proteins of Hepatitis B virus-like particles comprising different C-terminals
2024, International Journal of Biological MacromoleculesIdentification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents
2024, European Journal of Medicinal ChemistrySeroprevalence of hepatitis B virus infection (HBsAg) and associated factors among antenatal clinic attendees in a secondary-level facility in southern Ghana
2024, Clinical Epidemiology and Global HealthLiver organoids and their application in liver cancer research
2024, Regenerative TherapyEffects of co-infection with Clonorchis sinensis on T cell exhaustion levels in patients with chronic hepatitis B
2024, Journal of Helminthology