Joel E. Gallant, MD, MPH and Christopher J. Hoffmann MD, MPH
- HAV is highly endemic in Zambia due to contaminated drinking water and food.
- Average age of HAV infection in Africa is estimated to be 5 years old. Most adults have had HAV during childhood and are immune to re-infection.
- Unclear if immunity is lost during severe HIV-mediated immunosuppression
- Acute HAV may be underdiagnosed among adults in Africa with acute icteric disease.
Zambia Information Author: Christopher Hoffmann MD, MPH
- Hepatitis A virus (HAV): non-enveloped, icosahedral, positive-stranded RNA virus
- Spread via fecal-oral route; more prevalent in low and middle-income countries.
- Transmission through contaminated food & water & some sexual practices (oral-anal & digital-anal sex).
- Pathogenesis from robust HAV-specific CD8+ T-cell, NK T-cell, and IFN response leading to hepatocyte destruction
- Avg. incubation period 30 days (range 15-50); illness begins in symptomatic patients with abrupt onset of malaise, N/V, anorexia, fevers, hepatomegaly, & RUQ pain followed by icteris & pruritis. Rash & leukocytoclastic vasculitis may occur.
- ALT usually > 1000 IU/dL but lower in HIV+ than HIV-; Alk phos elevated in HIV+, up to 1000 IU/dL.Total bilirubin (>10 common) & direct bilirubin elevated (ALT peak precedes bili elevation).
- Typically acute, self-limited illness with resolution of Sx in 4 wks and normalization of ALT in 8 to 12 wks.
- Fulminant hepatic failure rare (1/100); occurs more commonly in patients with underlying liver disease, particularly HCV.
- Chronic infection does not occur, but serum viremia and fecal shedding persist longer in HIV+ (viremia may last up to 36 wks & fecal shedding >15 wks).
- Anti-HAV IgM diagnostic of acute infection, remains + for 4-6 mos; total HAV Ab useful for evidence of past exposure or immunization
- Other lab abnormalities include nonspecific elevations of ESR, CRP and increased immunoglobulins.
- Usually self-limited. Treatment supportive. No pathogen-specific Rx available.
- ART management during acute HAV not well-studied. Some providers stop ART until ALT normalizes, while others continue ART. Stopping ART may have its own risks for reasons unrelated to hepatitis as well as increase in risk of liver disease (SMART study) and resistance. Thus, it is prudent to follow 2 or 3 ALT measurements before deciding. If ALT stable or declining, continue ART. If ALT high and rapidly rising, consider discontinuation.
- Pts with fulminant hepatitis require aggressive supportive therapy, and should be transferred to center capable of performing liver transplantation. ART should generally be stopped.
- Prevent exposure with good hygiene, proper food preparation, and avoidance of unboiled water and uncooked foods from HAV-endemic areas.
- Hepatitis A vaccination should be offered to all at higher risk for HAV infection or of fulminant hepatic failure (international travelers, IDUs, MSM, homeless, HCV or HBV co-infected) . In addition, consider revaccination after CD4 recovery, as preservation of immunity uncertain even with previous vaccination or exposure. In low-income settings, most people exposed to HAV early in life & have immunity.
Hepatitis A vaccine (Havrix): contains 1,440 EL.U. of HAV antigen/mL, is used in patients over 2 yo. Recommended dose for adults 1 mL IM followed by a booster dose in 6-12 mos (consider 3 dose schedule (0,1,6 months) for improved vaccine response; 88% v 72% seroconversion); Combined hepatitis A/B vaccine (Twinrix): contains 720 EL.U. of HAV antigen and 20 mcg of HBV antigen. Recommended dose: 3 doses (1 mL each) given on a 0, 1, and 6 month schedule
- HIV+ pts have poorer response to vaccination, especially with lower CD4 (<400) & higher HIV viremia (>1000), but should still be vaccinated if indicated.
Post-exposure prophylaxis: If exposed and unvaccinated, efficacy of immune globulin (IG) for prevention of HAV infection well-documented. ACIP recommends administration of single IM dose of 0.02 mL/kg as soon as possible but not more than 2 wks after last exposure. Persons who have received at least 1dose of hepatitis A vaccine at least 1 month before exposure do not need IG.