Hepatitis Primary Care: Clinics in Office Practice Luis S. Marsano, MD  Primary Care: Clinics in Office Practice  Volume 30, Issue 1, Pages 81-107 (March 2003) DOI: 10.1016/S0095-4543(02)00061-1

Fig. 1 The diagnosis of acute HAV infection is confirmed during the acute or early convalescent phase of infection by the presence of IgM antibodies to HAV (IgM anti-HAV). IgM anti-HAV is generally present 5–10 days into the incubation period and remains detectable for up to 6 months after onset of illness. IgG anti-HAV, which also appears early in the course of infection, remains detectable for the lifetime of the individual and confers lifelong protection against disease. The concentration of HAV in the stool of infected persons is highest during the 2-week period before onset of jaundice. Fecal HAV excretion generally persists for <1 week after onset of jaundice in adults; however, virus has been detected during disease relapse up to 2 months after illness onset. Children and infants may shed HAV for longer periods than observed in adults, possibly for several weeks after onset of clinical illness. In infants born prematurely, viral RNA has been detected intermittently by PCR in stool specimens for up to 6 months after infection. Chronic shedding of HAV in feces has not been demonstrated (From slide sets that are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm). Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)

Fig. 2 The typical serologic course following HEV infection has been characterized using experimental models of infection in nonhuman primates and human volunteer studies. In two human volunteer studies, liver enzyme elevations occurred 4–5 weeks after oral ingestion and persisted for 20–90 days. Virus excretion in stools occurred approximately 4 weeks after oral ingestion and persisted for about 2 weeks. Both IgM and IgG antibody to HEV (anti-HEV) are elicited following HEV infection. The titer of IgM anti-HEV declines rapidly during early convalescence; IgG anti-HEV persists and appears to provide at least short-term protection against disease. No serologic tests to diagnose HEV infection are commercially available in the United States. Several diagnostic tests are available, however, in research laboratories, including enzyme immunoassays and Western blot assays to detect IgM and IgG anti-HEV in serum, PCR tests to detect HEV RNA in serum and stool, and immunofluorescent antibody blocking assays to detect antibody to HEV antigen in serum and liver (From slide sets that are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm). Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)

Fig. 3 Serologic markers of HBV infection vary depending on whether the infection is acute or chronic. The first serologic marker to appear following acute infection is HBsAg, which can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks (mode, 30–60 days) after exposure to HBV. In persons who recover, HBsAg is no longer detectable in serum after an average period of about 3 months. HBeAg is generally detectable in patients with acute infection; the presence of HBeAg in serum correlates with higher titers of HBV and greater infectivity. A diagnosis of acute HBV infection can be made on the basis of the detection of IgM class antibody to hepatitis B core antigen (IgM anti-HBc) in serum; IgM anti-HBc is generally detectable at the time of clinical onset and declines to subdetectable levels within 6 months. IgG anti-HBc persists indefinitely as a marker of past infection. Anti-HBs becomes detectable during convalescence after the disappearance of HBsAg in patients who do not progress to chronic infection. The presence of anti-HBs following acute infection generally indicates recovery and immunity from re-infection (From slide sets which are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm). Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)

Fig. 4 In patients with chronic HBV infection, both HBsAg and IgG anti-HBc remain persistently detectable, generally for life. HBeAg is variably present in these patients. The presence of HBsAg for 6 months or more is generally indicative of chronic infection. In addition, a negative test for IgM anti-HBc together with a positive test for HBsAg in a single serum specimen usually indicates that an individual has chronic HBV infection (From slide sets which are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm). Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)

Fig. 5 The serologic course of HDV infection varies depending on whether the virus is acquired as a coinfection with HBV or as a superinfection of a person with chronic HBV infection. In most persons with HBV-HDV coinfection, both IgM antibody to HDV (anti-HDV) and IgG anti-HDV are detectable during the course of infection. In about 15% of patients, however, the only evidence of HDV infection may be the detection of either IgM anti-HDV alone during the early acute period of illness or IgG anti-HDV alone during convalescence. Anti-HDV generally declines to subdetectable levels after the infection resolves, and there is no serologic marker that persists to indicate that the patient was ever infected with HDV. Hepatitis delta antigen (HDAg) can be detected in serum in only about 25% of patients with HBV-HDV coinfection. When HDAg is detectable, it generally disappears as HBsAg disappears, and most patients do not develop chronic infection. Tests for IgG anti-HDV are commercially available in the United States. Tests for IgM anti-HDV, HDAg, and HDV RNA by PCR are only available in research laboratories (From slide sets which are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm). Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)

Fig. 6 In patients with chronic HBV infection who are superinfected with HDV, several characteristic serologic features generally occur, including: (1) the titer of HBsAg declines at the time HDAg appears in the serum, (2) HDAg and HDV RNA remain detectable in the serum because chronic HDV infection generally occurs in most patients with HDV superinfection, unlike the case with coinfection, and (3) high titers of both IgM and IgG anti-HDV are detectable, which persist indefinitely (From slide sets which are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm). Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)

Fig. 7 Serologic pattern of acute HCV infection with recovery. (From slide sets which are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm). Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)

Fig. 8 Serologic pattern of acute HCV infection with progression to chronic infection. (From slide sets which are available to the public on the National Center for Infectious Diseases, Centers for Disease Control website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/index.htm) Primary Care: Clinics in Office Practice 2003 30, 81-107DOI: (10.1016/S0095-4543(02)00061-1)