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Pathogen:
Non-opportunistic hepatotrophic viruses including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and non-A, non-B, non-C (NANBNC) hepatitis virus (hepatitis G).
Hepatitis A
Most cases of HAV are subclinical. The virus disappears following acute infection. HAV has no known carrier state and plays no role in the production of chronic active
hepatitis or cirrhosis. Transmission is primarily through oral-fecal contact.
Hepatitis B
More than 84 percent of the HIV-infected population present with HBV blood markers. This high frequency of superinfection is consistent with the similar transmission pathways of HBV and HIV. HBV is transmitted parenterally, typically by contaminated blood or blood products, and through sexual, perinatal, and occupational contact with infected body fluids.
Previous conclusions by Eskild et al. that the presence of hepatitis B antibodies in HIV-infected patients is associated with more rapid clinical progression to AIDS have not been confirmed. Recent studies (Stevenson M et al.; Meier K et al.) have shown that co-infection appears to make no difference in clinical outcome.
Hepatitis C
The incidence of HIV-infected individuals, predominantly injection drug-users and hemophiliacs, has been increasing. Transmission, traditionally thought to occur solely through exposure to contaminated blood can also be attributed to non-parenteral routes. Eyster et al. has shown that the frequency of HCV sexual transmission is higher when HIV is present suggesting that HIV maybe a cofactor for the sexual transmission of HCV. Eyster has also shown that progression of HCV to cirrhosis and liver failure is hastened by HIV infection, though HCV has no effect on HIV.
Hepatitis D (Delta)
HDV can only replicate in the presence of HBV and occurs either as a co-infection with HBV or a superinfection in established HBV carriers. Clinically, HDV is a serious and often progressive disorder manifested by an unusually aggressive course.
Non-A, Non-B, Non-C Hepatitis (Hepatitis G) The term non-A, non-B non-C hepatitis (NANBNC) refers to infections not due to HAV, HBV, or HCV. The hepatitis G virus (HGV) appears to be the cause of most sporadic NANBNC hepatitis cases.
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Symptoms:
After an incubation period of 60 to 160 days, most HIV-positive patients infected with HBV develop acute inflammation of the liver characterized by diffuse or patchy hepatocellular necrosis. Cases often present with malaise, anorexia, fever, jaundice and mild splenomegaly. Infection is followed by recovery and subsequent immunity in more than 95 percent of infected persons. Approximately 5 percent will fail to eliminate the virus from the liver and become chronic carriers. Chronic hepatitis is more likely to develop in HIV-infected individuals with HBV because of reduced cell-mediated immunity. HBV-DNA levels can be followed are are prognostic.
With HCV, illness may develop following an average 50 day incubation period. At least 50 percent of these infections progress to chronic disease. Many remain asymptomatic yet present with cirrhosis and/or hepatocellular carcinoma after a 5-10 year follow up. Eyster et al. have shown that the presence of HIV can worsen the clinical course of HCV infection and contribute to the progression to liver disease.
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Diagnosis:
Elevated liver enzymes and urinary bile provide early indications of hepatocellular inflammation and may be clues to viral hepatitis infection. The HBV surface antigen is detected in serum and is usually the first indication of acute HBV infection. Core antigens may be found in infected hepatocytes. Corresponding antibodies develop after clinical recovery and usually persist throughout life; thus, their detection indicates past infection and immunity. Antibodies fail to develop in those cases which progress to chronic or asympto-matic carrier status.
Serum tests for HCV itself became available in 1989. HCV antigens can be
detected in the cytoplasm of infected hepatocytes. HCV antibodies may take several months to appear in serum after acute infection. HCV-RNA levels can
be followed at commercial laboratories and correlate with disease progression.
Chronic hepatitis diagnosis is by needle biopsy of the liver.
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Treatment:
Alpha interferon 2b (Infron A) is approved for the treatment of chronic hepatitis in individuals who are not HIV-infected. Infron A is typically administered by injection for either16 weeks (HBV) or for 52 weeks (HCV). In HIV-infected individuals, studies of alpha interferon 2b and AZT have shown only limited response rates with high relapse rates for responders who discontinued treatment. Common side effects include flu-like symptoms that make long-term administration difficult. Farci et al. showed favorable response rates (50%) for individuals with hepatitis-D who were treated with short-term, high-dose alpha interferon 2a (Roferon A) as compared to low-dose or no treatment.
3TC (lamivudine) is under investigation for the treatment of chronic hepatitis B. Dienstag et al. recently treated 32 HIV-negative patients with chronic hepatitis B (including 17 who had no response to earlier treatment with interferon) with either 25, 100, or 300 mg of 3TC every day for 12 weeks. Levels of HBV-DNA became undetectable (< 1.5 pg per mL) in 70 percent of the patients who received 3TC, 25 mg and 100 percent of the patients who received 3TC, 100 mg and 300 mg (P = 0.003). No data are yet available specifically in patients infected with HIV.
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REFERENCES:
Cribier B et al. High hepatitis C viraemia and impaired antibody response in patients with HIV. AIDS 9: 1131-1136, 1995.
Eskild A et al. Hepatitis B antibodies in HIV infected homosexual men are associated with more rapid progression to AIDS. AIDS 6: 571-574, 1992.
Eyster ME et al. Heterosexual Co-transmission of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Ann lnt Med 115: 764-768, 1991.
Dienstag JL et al. A preliminary trial of lamivudine for chronic hepatitis B infection. NEJM 333; 1657-61, 1995.
Farci P et al. Treatment of chronic hepatitis-D with interferon alph-2a. NEJM 330: 88-94,1994.
Hadler SC et al. Outcome of Hepatitis B Virus Infection in Homosexual Men and Its Relation to Prior Human Immunodeficiency Virus Infection. J Inf Dis 163: 454-459 1991.
Jia-Horng Kao et al. Sexual transmission of HCV. Lancet 342: 626, 1993.
Korenman J et al. Long-term Remission of Chronic Hepatitis B after Alpha-Interferon Therapy. Ann lnt Med 114: 629-634, 1991.
Scharschmidt BF et al. Hepatitis B in Patients with HIV Infection: Relationship to AIDS and Patient Survival. Ann Int Med 117: 837-838, 1992.
Stevenson M et al. Hepatitis B markers do not predict decline in CD4 count. Abstract PO-BO2-0947, IV Intl Conf AIDS, Berlin, 1993.
Zanetti AR et al. Mother-to-infant transmission of hepatitis C virus. Lancet 345: 289-90, 1995.
