Tiziana Garofano

Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.

BACKGROUND Hepatitis A virus (HAV) infection rarely causes fulminant hepatic failure in people with no underlying liver disease. There are limited data on the course of this infection in patients with chronic hepatitis B and chronic hepatitis C. METHODS We prospectively followed, from June 1990 to July 1997, 595 adults with biochemical and histologic evidence of chronic hepatitis B (163 patients) or chronic hepatitis C (432 patients) who were seronegative for HAV antibodies. All were tested every four months for serum IgM and IgG antibodies to HAV. RESULTS Twenty-seven patients acquired HAV superinfection, 10 of whom had chronic hepatitis B and 17 of whom had chronic hepatitis C. One of the patients with chronic hepatitis B, who also had cirrhosis, had marked cholestasis (peak serum bilirubin level, 28 mg per deciliter [479 micromol per liter]); the other nine had uncomplicated courses of hepatitis A. Fulminant hepatic failure developed in seven of the patients with chronic hepatitis C, all but one of whom died. The other 10 patients with chronic hepatitis C had uncomplicated courses of hepatitis A. CONCLUSIONS Although most patients with chronic hepatitis B who acquired HAV infection had an uncomplicated course, patients with chronic hepatitis C had a substantial risk of fulminant hepatitis and death associated with HAV superinfection. Our data suggest that patients with chronic hepatitis C should be vaccinated against hepatitis A.

Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals

To identify factors contributing to the pathogenesis of autoimmune chronic active hepatitis (CAH) healthy relatives of 13 patients with the disorder were followed prospectively for 4 years. 58 relatives were monitored for various serological markers and for T-lymphocyte migration inhibitory activity every 2 months. 3 cases of subclinical acute hepatitis A occurred during the study. In 2 of the 3 subjects, before hepatitis A virus (HAV) infection, there was a defect in suppressor-inducer T lymphocytes specifically controlling immune responses to the asialoglycoprotein receptor, an antigen expressed on the hepatocyte surface. In these 2 subjects, specific helper T cells and antibodies to the asialoglycoprotein receptor persisted and increased after acute hepatitis A, and autoimmune CAH type 1 developed within 5 months. Thus, in susceptible individuals HAV is a trigger for autoimmune CAH.

Pneumocystis carinii pneumonia during primary HIV-1 infection

3 patients with severe CD4 lymphocytopenia (62-91 cells/microL) and inverted CD4/CD8 ratios (0.13-0.15) developed Pneumocystis carinii pneumonia during symptomatic, primary HIV-1 infection. Within four months of symptom onset, their CD4 counts and CD4/CD8 ratios returned to normal. Twenty-nine to forty-eight months after acquiring HIV-1 infection, they show no signs or symptoms of progression to AIDS. Pneumocystis carinii pneumonia can occur, therefore, in primary HIV-1 infection, and profound CD4 lymphocytopenia can revert to normal without antiretroviral therapy.