Acute hepatitis B infection often features gastrointestinal symptoms and jaundice, as well as elevated transaminase levels and the presence of hepatitis B surface antigen and immunoglobulin M antibodies to hepatitis B core antigen. More than 95% of adults clear an acute infection spontaneously. Chronic hepatitis B infection is diagnosed when hepatitis B surface antigen is present for at least 6 months. Evaluation of chronic cases includes a family history of hepatocellular carcinoma, assessment of liver function and fibrosis risk, and serologies for viral coinfections and immunity. The goal of therapy is to reduce the risk of cirrhosis, hepatocellular carcinoma, and liver-related mortality. Oral nucleoside/nucleotide analogues are well tolerated and have a high barrier to resistance, which enables long-term use. With current therapies, functional cure (loss of hepatitis B surface antigen) is uncommon. Nucleoside/nucleotide analogue therapy is warranted when a patient has an elevated alanine transaminase level and a hepatitis B DNA measurement more than 2,000 IU/mL, or cirrhosis with detectable virus. Prophylactic viral suppression with oral nucleoside/nucleotide analogues is recommended during immunosuppression. Patients with cirrhosis or increased risk of cirrhosis should receive surveillance for hepatocellular carcinoma with right upper quadrant ultrasonography and serum alpha-fetoprotein testing every 6 months.
Although hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) and liver-related mortality worldwide, less than 2% of people with chronic HBV infection receive treatment each year.1 A large, cross-sectional study found that in 2016, only 19% of patients with chronic HBV infection in the United States had been diagnosed and about 30% of those received antiviral therapy.2 Low rates of diagnosis and treatment are at least partly due to complex and heterogeneous HBV guidelines. Many patients with HBV do not receive regular monitoring or HCC surveillance. Simplification of HBV treatment algorithms should facilitate higher rates of HBV management in primary care settings. Part II of this article discusses updated guidelines for diagnosis and management of HBV, including surveillance for liver cancer. Part I of this article, which appears in this issue of American Family Physician, summarizes new recommendations regarding screening and prevention of HBV.
WHAT'S NEW ON THIS TOPIC
| In 2016, only 19% of patients with chronic HBV in the United States had been diagnosed; of those, about 30% had received antiviral therapy. |
| The 2024 World Health Organization guidelines streamlined diagnosis and treatment algorithms for chronic HBV. |
| The 2025 American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines expanded HBV treatment eligibility and clarified the hepatocellular carcinoma surveillance recommendations. |
HBV = hepatitis B virus.
SORT: KEY RECOMMENDATIONS FOR PRACTICE
| Clinical recommendation | Evidence rating | Comments |
|---|---|---|
| Noninvasive testing (Fibrosis-4 score, aspartate transaminase to platelet ratio index, transient elastography) can be used in lieu of liver biopsy in most patients with chronic hepatitis B to effectively assess degree of liver fibrosis.11–14 | B | Findings from cohort studies showing good correlation with liver biopsy and noninvasive tests for significant fibrosis or cirrhosis |
| Patients without cirrhosis who meet clinical criteria for active hepatitis B should be treated with antiviral therapy.7,9,18–20,30,31,33 | A | Data from multiple RCTs and meta-analysis of observational cohort studies; HBV treatment consistently achieves serologic end points that correlate with clinical outcomes, including decreased risk of cirrhosis, HCC, and mortality |
| All patients with cirrhosis and any detectable HBV DNA should be started on oral nucleoside/nucleotide analogue therapy.7,9,18,21,22 | A | Results from multiple RCTs and meta-analysis of large, cohort studies; HBV treatment in patients with cirrhosis decreases liver decompensation, HCC, and mortality |
| Surveillance for HCC with liver ultrasonography and measurement of serum alpha-fetoprotein should be performed every 6 months in patients with chronic hepatitis B who are at increased risk of HCC.7,9,38–41 | B | Data from one RCT and meta-analysis of multiple cohort studies showing that surveillance improves early detection and curative treatments and reduces HCC-related mortality |
HBV = hepatitis B virus; HCC = hepatocellular carcinoma; RCT = randomized controlled trial.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.
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