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Clinical manifestations and natural history of hepatitis B virus infection

Anna SF Lok, MD
Section Editor
Rafael Esteban, MD
Deputy Editor
Jennifer Mitty, MD, MPH


The spectrum of clinical manifestations of hepatitis B virus (HBV) infection varies in both acute and chronic disease. During the acute phase, manifestations range from subclinical or anicteric hepatitis to icteric hepatitis and, in some cases, fulminant hepatitis; during the chronic phase, manifestations range from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Extrahepatic manifestations can also occur with both acute and chronic infection.

The clinical manifestations and natural history of HBV infection will be reviewed here. Issues related to epidemiology, transmission, and treatment are discussed separately. (See appropriate topic reviews). Terms used to define different clinical states are summarized in the table (table 1). These terms will be used throughout the discussion.


Approximately 70 percent of patients with acute hepatitis B have subclinical or anicteric hepatitis, while 30 percent develop icteric hepatitis. The disease may be more severe in patients coinfected with other hepatitis viruses or with underlying liver disease [1].

Fulminant hepatic failure is unusual, occurring in approximately 0.1 to 0.5 percent of patients. Fulminant hepatitis B is believed to be due to massive immune-mediated lysis of infected hepatocytes. This explains why many patients with fulminant hepatitis B have no evidence of HBV replication at presentation [2].

The reasons that HBV has a fulminant course in some patients are not well-understood. A case-control study evaluated risk factors for a fulminant course in an outbreak among injection drug users [3]. Compared with control patients, case patients were more likely to have used acetaminophen during their illness (p = 0.08), used more alcohol and methamphetamine, and lost more weight in the six months before illness. Furthermore, all nine isolates were genotype D. Whether viral or environmental factors led to the fulminant course in this outbreak is unclear [4]. (See "Clinical significance of hepatitis B virus genotypes".)


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