Hepatitis B: A High-Yield USMLE Review

Hepatitis B is a bloodborne, sexually, and perinatally transmitted viral infection that can cause both acute and chronic liver disease. It is a cornerstone USMLE topic because of its serologic panel interpretation and its progression pathway: chronic HBV can lead to cirrhosis and hepatocellular carcinoma. The likelihood of chronicity depends heavily on the age at acquisition.

Presentation

• Acute infection may present with hepatitis symptoms and jaundice, or may be entirely asymptomatic.
• Many patients from endemic areas acquire HBV perinatally and remain chronically infected since birth, often asymptomatic despite high viral loads.
• Chronic HBV can progress to cirrhosis and hepatocellular carcinoma.
• In the acute "window period," patients may present with hepatitis symptoms while HBsAg has cleared and anti-HBs has not yet appeared.

Diagnosis

• Serologic HBV panel: HBsAg positive indicates active infection; anti-HBs negative indicates no immunity; anti-HBc IgM positive confirms acute infection; anti-HBc IgG indicates current or past infection.
• HBeAg and HBV DNA measure viral replication — HBeAg positivity and very high HBV DNA confirm high-level active replication (HBeAg-positive chronic HBV infection).
• ALT to assess disease activity — elevated ALT combined with significant HBV DNA marks the immune-active phase.
• Fibrosis assessment with FibroScan or liver biopsy to stage disease; presence of cirrhosis is itself an indication to treat.

Management

• Chronic HBV treatment aims to suppress viral replication and prevent progression, using nucleos(t)ide analogues (entecavir, tenofovir) or pegylated interferon.
• Treatment is indicated for immune-active chronic HBV — elevated ALT plus HBV DNA above threshold (>2,000 IU/mL if HBeAg-negative, >20,000 IU/mL if HBeAg-positive) — regardless of fibrosis stage.
• All patients with cirrhosis and any detectable HBV DNA should be treated, even with normal ALT; significant fibrosis is a modifier that lowers the threshold to treat but is not a required criterion.
• Screen family members, vaccinate susceptible contacts, and perform hepatocellular carcinoma surveillance.
• Prevention with hepatitis B vaccination — now universally recommended for adults 19-59.

High-yield

• Transmission is "the bloody and the bodily" — blood, sexual, and perinatal.
• Chronicity is age-dependent: perinatal ~90%, childhood 30-50%, adult ~5%.
• Window period: HBsAg has cleared and anti-HBs has not yet appeared, so anti-HBc IgM is the only positive marker confirming acute infection.
• Chronic HBV → cirrhosis → hepatocellular carcinoma.
• Treat immune-active disease (elevated ALT + HBV DNA >2,000 IU/mL HBeAg-negative or >20,000 IU/mL HBeAg-positive) and all cirrhotics with detectable HBV DNA.
• Nucleos(t)ide analogues (entecavir, tenofovir) or pegylated interferon are the treatment options for chronic HBV.

Pitfalls

• Missing acute HBV in the window period by only checking HBsAg or anti-HBs — anti-HBc IgM is the key marker and must not be overlooked.
• Assuming asymptomatic patients from endemic areas are not infected — many are chronically infected perinatally and remain asymptomatic despite very high viral loads.
• Requiring fibrosis before treating — immune-active disease warrants therapy regardless of fibrosis, and cirrhotics with any detectable HBV DNA are treated even when ALT is normal.
• Confusing acute with chronic infection: anti-HBc IgM indicates acute, while anti-HBc IgG with positive HBsAg indicates current chronic infection.