Hepatitis B virus infection: Understanding its epidemiology, course, and diagnosis
ABSTRACTAlthough hepatitis B virus (HBV) infection is not as common in the United States as in some countries, 5,000 Americans die from it every year. This number can be significantly decreased with proper screening and by vaccinating people at risk. Internists should be aware of the natural history of HBV infection, a vital prerequisite to correctly assessing disease severity and subsequently determining the need for antiviral therapy.
KEY POINTS
- HBV infection is much more likely to persist and become chronic if it is acquired at birth or in early childhood rather than during adulthood.
- Chronic HBV infection is defined as persistence of HBV surface antigen in the serum for more than 6 months.
- Although many cases of chronic HBV infection resolve spontaneously, some progress to cirrhosis, hepatocellular carcinoma, and death.
CLINICAL MANIFESTATIONS VARY
HBV infection, acute or chronic, has variable manifestations. During the acute stage, HBV infection can manifest as anicteric (subclinical) hepatitis, icteric hepatitis, or, rarely, acute fulminant hepatitis. Chronic HBV infection can be asymptomatic (the HBV surface antigen carrier state), or it can be manifested by symptoms and signs of cirrhosis or hepatocellular carcinoma or both. Extrahepatic manifestations, including serum sickness, polyarteritis nodosa, essential mixed cryoglobulinemia, membranous glomerulonephritis, and aplastic anemia, have been reported in patients with HBV infection.26
Acute hepatitis B
The incubation period of HBV ranges from 2 weeks to 4 months. Initially, patients complain of fatigue, malaise, anorexia, right upper quad-rant discomfort, or flu-like symptoms (coryza, photophobia, headache, and myalgia); then jaundice becomes apparent, usually within 10 days of the onset of symptoms. Low-grade fever, jaundice, and mildly tender hepatomegaly are the most common signs. Generalized lymphadenopathy is not a feature of acute HBV infection. If the patient also has hepatitis D virus infection or underlying liver disease (eg, alcoholic liver disease), then acute HBV infection may be more severe.
In the acute phase, ALT and AST levels rise, sometimes to values above 1,000 IU/L. In icteric hepatitis, bilirubin levels also rise, usually after the ALT level does. Although the peak ALT level reflects the hepatocellular injury, it has no prognostic value. With recovery, ALT levels normalize in 1 to 4 months.
Acute fulminant hepatitis B occurs in 0.1% to 0.5% of patients, and causes about 10% of cases of acute liver failure in the United States.27 Patients typically present with rapidly progressive acute hepatitis characterized by signs of liver failure, such as coagulopathy, encephalopathy, and cerebral edema.
In the so-called window phase, laboratory testing may not reveal HBV surface antigen because of early clearance but shows IgM antibody against the HBV core antigen. HBV DNA may be low or undetected.
Chronic hepatitis B
Chronic hepatitis B is usually diagnosed as a result of a workup for abnormal liver function tests or as a result of screening patients at risk for HBV infection. Many patients with chronic hepatitis B have no symptoms or have nonspecific symptoms such as fatigue or right upper quadrant discomfort.
Acute exacerbations due to HBV e antigen seroreversion (ie, in which e antigen reappears) occasionally occur in patients with chronic hepatitis B. Most of these exacerbations are asymptomatic, but occasionally an acute hepatitis-like clinical picture with detectable IgM antibody against the core antigen occurs, leading to misdiagnosis of acute HBV infection in patients not previously known to have chronic HBV infection.28
In late cases, signs of cirrhosis such as jaundice, ascites, splenomegaly, pedal edema, encephalopathy, or variceal bleeding can be present.
Hepatocellular carcinoma should be suspected in cirrhotic patients with new-onset right upper quadrant pain, rapidly developing ascites, a palpable liver mass, or hepatic encephalopathy. Other nonspecific features of hepatocellular carcinoma include watery diarrhea, hypoglycemia, and certain cutaneous manifestations such as acanthosis nigricans and the Leser-Trelat sign (multiple pruritic seborrheic keratoses of sudden onset).
In chronic hepatitis B, liver enzyme levels can be normal, even in patients with wellcompensated cirrhosis. ALT levels may range from normal to five times higher than normal. Thrombocytopenia, hypoalbuminemia, direct hyperbilirubinemia, and prolonged prothrombin time suggest cirrhosis.
Findings of chronic hepatitis B on liver biopsy range from minimal inflammation to cirrhosis. The most characteristic histologic feature of chronic HBV infection is the “ground-glass hepatocyte,” which is due to intracellular accumulation of HBV surface antigen. 29
FEW ADULTS (BUT MANY CHILDREN) REMAIN CHRONICALLY INFECTED
HBV surface antigen can be detected in the blood approximately 2 to 4 weeks after inoculation. Simultaneously, HBV DNA, usually in very high levels, is also detectable in the blood. However, in the rare cases of acute fulminant hepatitis, HBV DNA levels can be low or undetectable at the time of presentation because the immune system mounts a robust response with extensive damage to HBVinfected hepatocytes.
The rate of spontaneous recovery from acute HBV infection varies, depending on the patient’s age at the time of HBV acquisition and the patient’s immune status. Fewer than 5% of immunocompetent adults infected with HBV remain chronically infected, defined as being positive for HBV surface antigen for more than 6 months. On the other hand, 80% to 90% of infected infants and about 20% to 50% of children 1 to 5 years old at the time of acute infection remain chronically infected.21
