Laboratory Diagnosis

Routine biochemical tests of liver function distinguish viral hepatitis from the many nonviral, for example, obstructive or toxic, causes of jaundice. Characteristically, levels of serum transaminases (aminotransferases) are elevated markedly (5- to 100-fold) in acute symptomatic viral hepatitis, whether due to hepatitis A, B, C, D, or E. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rise together late in the incubation period to peak about the time jaundice appears; they gradually revert to normal over the ensuing 2 months in an uncomplicated case. Serum bilirubin may rise anything up to 25-fold, depending on the severity of the case, and may of course be close to normal in anicteric viral hepatitis.

To date, HBV has been reproducibly isolated in chimpanzees and certain other simian species, and irreproducibly in organ cultures or primary cultures of human hepatocytes, which are impracticable for routine diagnostic use. Serology forms the basis of the diagnosis of hepatitis B and of the differentiation of the various clinical forms of hepatitis B from one another. Although many types of immunoassays have been successfully applied to HBV, the most widely used and most sensitive have been radioimmunoassay (RIA) and enzyme immunoassay (EIA). Six markers, all found in serum, are of particular diagnostic importance: HBsAg, HBV DNA, HBeAg, antibody to HBsAg (anti-HBs), anti-FfBe, and anti-HBc.

Acute infection with hepatitis B virus (Fig. 22-6A) is characterized by the appearance of HBsAg in the blood a month or two after infection, rising to a peak shortly before symptoms develop, then gradually disappearing coinci-

Months after exposure

Months Years

Time after exposure

Fig. 22-6 Serological events associated with the typical course of acute type B hepatitis (A) arid the development of the chronic hepatitis B virus carrier state (B) HBsAg, hepatitis B surface antigen, HBeAg, hepatitis B e antigen, ALT, alanine aminotransferase, anti-HBs, antibody to HBsAg, anti-HBc, antibody to hepatitis B core antigen; anti-HBe, antibody to HBeAg. [Modified from J. H. Hoofnagle, Amu. Rev Med. 32, 1 (1981) Copyright 1981 by Annual Reviews Inc.]

Months Years

Time after exposure

Fig. 22-6 Serological events associated with the typical course of acute type B hepatitis (A) arid the development of the chronic hepatitis B virus carrier state (B) HBsAg, hepatitis B surface antigen, HBeAg, hepatitis B e antigen, ALT, alanine aminotransferase, anti-HBs, antibody to HBsAg, anti-HBc, antibody to hepatitis B core antigen; anti-HBe, antibody to HBeAg. [Modified from J. H. Hoofnagle, Amu. Rev Med. 32, 1 (1981) Copyright 1981 by Annual Reviews Inc.]

dentally with the fall in transaminase levels over the next few months. Viral DNA and HBeAg appear at about the same time as HBsAg but disappear more abruptly when symptoms and enzyme levels peak. The first antibody detected is anti-HBc; it usually appears before symptoms develop, rises rapidly to high titer, and persists indefinitely. Anti-HBs, on the other hand, does not become detectable until HBsAg has been cleared and recovery is complete {usually within a year); indeed, there is sometimes a window in time during which neither HBsAg nor anti-HBs is demonstrable, and anti-HBc is the only positive marker of infection.

Chronic hepatitis B infection (Fig. 22-6B) is characterized by the persistence of HBsAg for at least 6 months, but often for years or even for life. As long as HBs antigenemia persists anti-HBs antibody is usually not found free, but in about 10% of carriers it is complexed in low amounts with HBsAg. Anti-HBc rises to very high titer and persists for life in the normal way. This is the picture with the HBsAg carrier state.

Chronic active hepatitis is distinguished from the asymptomatic carrier state by progression of liver damage, as indicated by continuing elevation of serum transaminase levels and histologic evidence on liver biopsy. Persistence of HBV DNA, viral polymerase, HBeAg, and virions implies active viral multiplication, high infectivity, and progressive liver damage, the hallmarks of the high replicative phase, in contrast, anti-HBe, which develops only after HBeAg disappears and enzyme levels have declined, indicates a longer standing carrier state characteristic of the low replicative phase.

Table 22-2 summarizes the patterns of serological markers that characterize the various outcomes of hepatitis B infection. Note that the key markers are HBsAg, anti-HBs, anti-HBc, and HBV DNA; the pattern of these can distinguish most of the important situations. Note also that (1) the single most reliable marker of past or present HBV infection is anti-HBc; (2) persistence of HBV DNA in chronic active hepatitis portends an unfavorable outcome in the long run; and (3) anti-HBs, which is the neutralizing antibody, appears only after HBsAg has vanished, hence is a reliable indicator of recovery and of immunity to reinfection.

Table 22-2

Serological Markers of Hepatitis B Infection

Table 22-2

Serological Markers of Hepatitis B Infection

Clinical condition

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