Laboratory Features of hepatitis virus infections in humans
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p518-522
2025-12-03
12
Liver biopsy permits a tissue diagnosis of hepatitis. Tests for abnormal liver function, such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin, supplement the clinical, pathologic, and epidemiologic findings.
A. Hepatitis A
The clinical, virologic, and serologic events after exposure to HAV are shown in Figure 1. Virus particles have been detected by immune electron microscopy in fecal extracts of hepatitis A patients. Virus appears early in the disease and disappears within 2 weeks after the onset of jaundice.
Fig1. Immunologic and biologic events associated with human infection with hepatitis A virus. IgG, immunoglobulin G; IgM, immunoglobulin M. (Reproduced from Hollinger FB, Ticehurst JR: Hepatitis A virus. In Fields BN, Knipe DM, Howley PM [editors in-chief]. Fields Virology, 3rd ed. Lippincott-Raven, 1996. Modified with permission from Hollinger FB, Dienstag JL: Hepatitis viruses. In Lennette EH [editor]. Manual of Clinical Microbiology, 4th ed. American Society for Microbiology, 1985.)
HAV can be detected in the liver, stool, bile, and blood of naturally infected humans and experimentally infected non-human primates by immunoassays, nucleic acid hybridization assays, or PCR. HAV is detected in the stool from about 2 weeks before the onset of jaundice up to 2 weeks after.
Anti-HAV appears in the immunoglobulin M (IgM) fraction during the acute phase, peaking about 2 weeks after elevation of liver enzymes (Table 1). Anti-HAV IgM usually declines to nondetectable levels within 3–6 months. Anti HAV IgG appears soon after the onset of disease and persists for decades. Thus, detection of IgM-specific anti-HAV in the blood of an acutely infected patient confirms the diagnosis of hepatitis A. Enzyme-linked immunosorbent assay is the method of choice for measuring HAV antibodies.
Table1. Interpretation of Hepatitis A, C, and D Virus Serologic Markers in Patients with Hepatitis
B. Hepatitis B
Clinical and serologic events after exposure to HBV are depicted in Figure 2 and summarized in Table 2. DNA polymerase activity, HBV DNA, and HBeAg, which are representative of the viremic stage of hepatitis B, occur early in the incubation period, concurrently or shortly after the first appearance of HBsAg. High concentrations of HBV particles may be present in the blood (up to 1010 particles/mL) during the initial phase of infection; communicability is highest at this time. HBsAg is usually detectable 2–6 weeks in advance of clinical and biochemical evidence of hepatitis and persists throughout the active course of the disease. Disappearance of HBsAg is thought to be associated with recovery from infection, but some patients continue to have occult HBV infection with detectable HBV DNA and can still transmit virus.
Table2. Interpretation of Hepatitis B Virus Serologic Markers in Patients with Hepatitis a
Fig2. Clinical and serologic events occurring in a patient with acute hepatitis B virus infection. The common diagnostic tests and their interpretation are presented in Table 35-8. ALT, alanine aminotransferase; anti-HBc, antibody to hepatitis B core antigen; anti-HBe, antibody to hepatitis B e antigen; anti-HBs, antibody to hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IgG, immunoglobulin G; IgM, immunoglobulin M. (Reproduced with permission from Hollinger FB, Dienstag JL: Hepatitis B and D viruses. In Murray PR [editor]. Manual of Clinical Microbiology, 7th ed. Washington DC: ASM Press, 1999. ©1999 American Society for Microbiology. No further reproduction or distribution is permitted without the prior written permission of American Society for Microbiology.)
High levels of IgM-specific anti-HBc are frequently detected at the onset of clinical illness. Because this antibody is directed against the 27-nm internal core component of HBV, its appearance in the serum is indicative of viral replication. Antibody to HBsAg is first detected at a variable period after the disappearance of HBsAg. It is present in low concentrations. Before HBsAg disappears, HBeAg is replaced by anti-HBe, signaling the start of resolution of the disease. However, some patients can develop HBeAg negative chronic hepatitis with pre-core HBV mutants, usually associated with a stop codon mutation at nucleotide 1896 that results in absent HBeAg production but with continued viral progression.
By definition, HBV chronic carriers are those in whom HBsAg persists for more than 6 months in the presence of HBeAg or anti-HBe. HBsAg may persist for years after loss of HBeAg. In contrast to the high titers of IgM-specific anti HBc observed in acute disease, low titers of IgM anti-HBc are found in the sera of most chronic HBsAg carriers. Small amounts of HBV DNA are usually detectable in the serum as long as HBsAg is present.
The most useful detection methods are enzyme-linked immunosorbent assay for HBV antigens and antibodies and PCR for viral DNA.
C. Hepatitis C
Clinical and serologic events associated with HCV infections are shown in Figure 3. Most primary infections are asymptomatic or clinically mild (20–30% have jaundice; 10–20% have only nonspecific symptoms such as anorexia, malaise, and abdominal pain). Serologic assays are available for diagnosis of HCV infection. Enzyme immunoassays detect antibodies to HCV but do not distinguish among acute, chronic, or resolved infection (see Table 1). Anti HCV antibodies can be detected in 50–70% of patients at the onset of symptoms, but in others, antibody appearance is delayed 3–6 weeks. Antibodies are directed against core, envelope, and NS3 and NS4 proteins and tend to be relatively low in titer. Nucleic acid-based assays (eg, reverse transcription PCR) detect the presence of circulating HCV RNA and are useful for diagnosis of acute infection soon after exposure and for monitoring patients on antiviral therapy. Nucleic acid assays also are used to genotype HCV isolates.
Fig3. Clinical and serologic events associated with hepatitis C virus (HCV) infection. ALT, alanine aminotransferase; anti-HCV, antibody to HCV; HCC, hepatocellular carcinoma. (Reproduced with permission from Garnier L, Inchauspé G, Trépo C: Hepatitis C virus. In Richman DD, Whitley RJ, Hayden FG [editors]. Clinical Virology, 2nd ed. ASM Press, 2002. Washington, DC. ©2002 American Society for Microbiology. No further reproduction or distribution is permitted without the prior written permission of American Society for Microbiology.)
D. Hepatitis D
Serologic patterns after HDV infection are shown in Figure 4 and listed in Table 1. Because HDV depends on a coexistent HBV infection, acute type D infection occurs either as a simultaneous infection (coinfection) with HBV or as a superinfection of a person chronically infected with HBV. In the coinfection pattern, antibody to HDAg develops late in the acute phase of infection and may be of low titer. Assays for HDAg or HDV RNA in the serum or for IgM-specific anti HDV are preferable. All markers of HDV replication disappear during convalescence; even the HDV antibodies may disappear within months to years. However, superinfection by HDV usually results in persistent HDV infection (>70% of cases). High levels of both IgM and IgG anti-HD persist, as do levels of HDV RNA and HDAg. HDV superinfections may be associated with fulminant hepatitis.
Fig4. Serologic patterns of type D hepatitis after coinfection or superinfection of a person with hepatitis B virus (HBV) infection. Top: Coexistent acute hepatitis B and hepatitis D. Middle: Acute hepatitis D superimposed on a chronic HBV infection. Bottom: Acute hepatitis D progressing to chronic hepatitis, superimposed on a chronic HBV infection. ALT, alanine aminotransferase; anti-HBc, antibody to hepatitis B core antigen; anti-HD, antibody to delta antigen; HBsAg, hepatitis B surface antigen; HDAg, delta antigen; HDV, hepatitis D virus; IgG, immunoglobulin G; IgM, immunoglobulin M. (Reproduced with permission from Purcell RH et al: Hepatitis. In Schmidt NJ, Emmons RW [editors]. Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections, 6th ed. American Public Health Association, 1989.)
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