The clinical picture of viral hepatitis is extremely variable, ranging from asymptomatic infection without jaundice to acute liver failure and death in a few days to weeks. Figure 16–2 shows the typical course of acute HBV infection. The onset may be abrupt or insidious, and the clinical features are similar to those for acute hepatitis A (see earlier). Serum sickness may be seen early in acute hepatitis B. Fever is generally present and is low-grade. Defervescence and a fall in pulse rate often coincide with the onset of jaundice. Infection caused by HBV may be associated with glomerulonephritis and polyarteritis nodosa.
The typical course of acute type B hepatitis. (anti-HBs, antibody to HBsAg; HBeAg, hepatitis Be antigen; HBsAg, hepatitis B surface antigen; anti-HBe, antibody to HBeAg; anti-HBc, antibody to hepatitis B core antigen; ALT, alanine aminotransferase.) (Reprinted, with permission, from Koff RS. Acute viral hepatitis. In: Friedman LS, Keeffe EB [editors]. Handbook of Liver Disease, 3rd ed. Philadelphia: Saunders Elsevier, 2012. Copyright © Elsevier.)
The acute illness usually subsides over 2–3 weeks with complete clinical and laboratory recovery by 16 weeks. In 5–10% of cases, the course may be more protracted, but less than 1% will develop acute liver failure. Hepatitis B may become chronic.
The laboratory features are similar to those for acute hepatitis A, although serum aminotransferase levels are higher on average in acute hepatitis B, and marked cholestasis is not a feature. Marked prolongation of the prothrombin time in severe hepatitis correlates with increased mortality.
There are several antigens and antibodies as well as HBV DNA that relate to HBV infection and that are useful in diagnosis. Interpretation of common serologic patterns is shown in Table 16–5.
Table 16–5.Common serologic patterns in hepatitis B virus (HBV) infection and their interpretation. ||Download (.pdf) Table 16–5. Common serologic patterns in hepatitis B virus (HBV) infection and their interpretation.
|HBsAg ||Anti-HBs ||Anti-HBc ||HBeAg ||Anti-HBe ||Interpretation |
|+ ||– ||IgM ||+ ||– ||Acute hepatitis B |
|+ ||– ||IgG1 ||+ ||– ||Chronic hepatitis B with active viral replication |
|+ ||– ||IgG ||– ||+ ||Inactive HBV carrier state (low HBV DNA level) or HBeAg-negative chronic hepatitis B with active viral replication (high HBV DNA level) |
|+ ||+ ||IgG ||+ or – ||+ or – ||Chronic hepatitis B with heterotypic anti-HBs (about 10% of cases) |
|– ||– ||IgM ||+ or – ||– ||Acute hepatitis B |
|– ||+ ||IgG ||– ||+ or – ||Recovery from hepatitis B (immunity) |
|– ||+ ||– ||– ||– ||Vaccination (immunity) |
|– ||– ||IgG ||– ||– ||False-positive; less commonly, infection in remote past |
The appearance of HBsAg in serum is the first evidence of infection, appearing before biochemical evidence of liver disease, and persisting throughout the clinical illness. Persistence of HBsAg more than 6 months after the acute illness signifies chronic hepatitis B.
Specific antibody to HBsAg (anti-HBs) appears in most individuals after clearance of HBsAg and after successful vaccination against hepatitis B. Disappearance of HBsAg and the appearance of anti-HBs signal recovery from HBV infection, noninfectivity, and immunity.
IgM anti-HBc appears shortly after HBsAg is detected. (HBcAg alone does not appear in serum, although a hepatitis B core-related antigen [HBcrAg] has been identified, and its presence in serum correlates with the presence of covalently closed circular DNA [cccDNA] in the nuclei of infected hepatocytes.) In the setting of acute hepatitis, IgM anti-HBc indicates a diagnosis of acute hepatitis B, and it fills the serologic gap in rare patients who have cleared HBsAg but do not yet have detectable anti-HBs. IgM anti-HBc can persist for 3–6 months, and sometimes longer. IgM anti-HBc may also reappear during flares of previously inactive chronic hepatitis B (see later). IgG anti-HBc also appears during acute hepatitis B but persists indefinitely, whether the patient recovers (with the appearance of anti-HBs in serum) or chronic hepatitis B develops (with persistence of HBsAg). In asymptomatic blood donors, an isolated anti-HBc with no other positive HBV serologic results may represent a falsely positive result or latent infection in which HBV DNA is detectable in serum only by polymerase chain reaction (PCR) testing.
HBeAg is a secretory form of HBcAg that appears in serum during the incubation period shortly after the detection of HBsAg. HBeAg indicates viral replication and infectivity. Persistence of HBeAg beyond 3 months indicates an increased likelihood of chronic hepatitis B. Its disappearance is often followed by the appearance of anti-HBe, generally signifying diminished viral replication and decreased infectivity.
The presence of HBV DNA in serum generally parallels the presence of HBeAg, although HBV DNA is a more sensitive and precise marker of viral replication and infectivity. Very low levels of HBV DNA, detectable only by PCR testing, may persist in serum and liver long after a patient has recovered from acute hepatitis B, but the HBV DNA in serum is bound to IgG and is rarely infectious. Occasional persons have “occult” HBV infection with detectable HBV DNA in the liver in the absence of conventional serologic markers. In some patients with chronic hepatitis B, HBV DNA is present at high levels without HBeAg in serum because of development of a mutation in the core promoter or precore region of the gene that codes HBcAg; these mutations prevent synthesis of HBeAg in infected hepatocytes. When additional mutations in the core gene are also present, the severity of HBV infection is enhanced and the risk of cirrhosis is increased (see later).