Chronic Hepatitis B Infection: A Review

JAMA. 2018 May 1;319(17):1802-1813. doi: 10.1001/jama.2018.3795.


Importance: More than 240 million individuals worldwide are infected with chronic hepatitis B virus (HBV). Among individuals with chronic HBV infection who are untreated, 15% to 40% progress to cirrhosis, which may lead to liver failure and liver cancer.

Observations: Pegylated interferon and nucleos(t)ide analogues (lamivudine, adefovir, entecavir, tenofovir disoproxil, and tenofovir alafenamide) suppress HBV DNA replication and improve liver inflammation and fibrosis. Long-term viral suppression is associated with regression of liver fibrosis and reduced risk of hepatocellular carcinoma in cohort studies. The cure (defined as hepatitis B surface antigen loss with undetectable HBV DNA) rates after treatment remain low (3%-7% with pegylated interferon and 1%-12% with nucleos[t]ide analogue therapy). Pegylated interferon therapy can be completed in 48 weeks and is not associated with the development of resistance; however, its use is limited by poor tolerability and adverse effects such as bone marrow suppression and exacerbation of existing neuropsychiatric symptoms such as depression. Newer agents (entecavir, tenofovir disoproxil, and tenofovir alafenamide) may be associated with a significantly reduced risk of drug resistance compared with older agents (lamivudine and adefovir) and should be considered as the first-line treatment.

Conclusions and relevance: Antiviral treatment with either pegylated interferon or a nucleos(t)ide analogue (lamivudine, adefovir, entecavir, tenofovir disoproxil, or tenofovir alafenamide) should be offered to patients with chronic HBV infection and liver inflammation in an effort to reduce progression of liver disease. Nucleos(t)ide analogues should be considered as first-line therapy. Because cure rates are low, most patients will require therapy indefinitely.

Publication types

  • Review

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Disease Progression
  • Female
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / epidemiology
  • Humans
  • Interferon-alpha / therapeutic use
  • Liver Cirrhosis / drug therapy
  • Liver Neoplasms / prevention & control
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Risk Factors
  • United States / epidemiology


  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2a