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Management of Hepatitis B Infection

Stefan Zeuzem, MD
Program Director
Harry L. A. Janssen, MD, PhD
Milan J. Sonneveld, MD, PhD, MSc
Released: June 17, 2019

Management of Acute HBV Infection

The symptoms and course of acute HBV infection depends strongly on the age at the time of infection.[5] Acute hepatitis B is usually subclinical in neonates, whereas up to one third of adults may experience symptoms.[6] Early symptoms include influenzalike symptoms, gastrointestinal symptoms, and fatigue. When these symptoms subside, darkening of urine, pale stool, and jaundice may be observed. Physical examination findings are nonspecific, and may include mild enlargement and slight tenderness of the liver, and mild splenomegaly.

The diagnosis of acute HBV infection is based on the presence of hepatitis B surface antigen (HBsAg) and IgM antibodies to hepatitis B core antigen (IgM anti-HBc) in serum.[3] During the initial phase, patients may also be positive for hepatitis B e antigen (HBeAg), and high levels of HBV DNA may be detected. In patients with self-limiting disease, antibodies to HBsAg (anti-HBs) develop, but there may be a window period where both anti-HBs and HBsAg are negative, leaving anti-HBc the only detectable marker. If HBsAg is not cleared from serum, chronic HBV infection is diagnosed after documented positivity for 6-12 months.[3]

Treatment is generally not indicated for acute HBV infection because most patients (> 95%) recover spontaneously.[5] Therefore, management of acute hepatitis B infection is typically supportive, and close monitoring may help early identification of fulminant hepatitis with liver failure. However, treatment is indicated for patients with acute hepatitis B and acute liver failure or with a protracted, severe course (ie, total bilirubin > 3 mg/dL or direct bilirubin > 1.5 mg/dL, international normalized ratio > 1.5, encephalopathy, or ascites) according to the AASLD.[3] Likewise, the EASL recommends treatment for patients with severe acute hepatitis B, characterized by coagulopathy or protracted course.[4] For such patients, the EASL guidelines state that tenofovir DF, entecavir, or lamivudine may be used and that tenofovir alafenamide (AF) should work, although no supporting data are yet available for tenofovir AF in this patient population.[4] The AASLD guidelines recommend use of entecavir, tenofovir DF, or tenofovir AF.[3]

Studies show that, although lamivudine therapy does not appear to increase the probability of HBsAg clearance,[7,8] treatment reduces mortality in patients with severe acute hepatitis B.[7] Indeed, in one study of 80 patients with acute HBV infection receiving either lamivudine or no therapy, mortality was significantly higher in the control group at 25.0% vs the lamivudine group at 7.5% (P = .034).[7] Interferon therapy is contraindicated in patients with acute HBV infection because of the high rate of adverse effects and the risk of worsening hepatitis.[3] Treatment of acute HBV infection should be continued until HBsAg clearance or indefinitely in patients who undergo liver transplantation.[3]

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