Teresa Ferraro

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.

Epstein-Barr virus as a trigger for autoimmune hepatitis in susceptible individuals

During follow-up of healthy relatives of 13 patients with autoimmune hepatitis, seven cases of infectious mononucleosis due to Epstein-Barr virus (EBV) occurred. In two of these seven, before EBV 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 two, antibodies to this autoantigen persisted and increased after infectious mononucleosis, and autoimmune hepatitis developed within 4 months. In susceptible individuals, EBV is a trigger for autoimmune hepatitis.

Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus.

BACKGROUND Fulminant hepatitis on withdrawal of chemotherapy has been described in chronic hepatitis B virus infection, but not in hepatitis C virus (HCV) infection. The relation between HCV and immune response to this virus, and disease severity, has not been examined. We present two patients with HCV who developed fulminant liver failure after chemotherapy was stopped. PATIENTS AND FINDINGS Two patients with chronic HCV infection and malignant lymphoma received chemotherapy (cyclophosphamide, adriamycin, vincristine, bleomycin, etoposide, and prednisolone in patient 1; doxorubicin, bleomycin, vinblastine, and dacarbazine in patient 2), on withdrawal of which both developed fulminant hepatitis. Alanine aminotransferase (ALT) concentrations were greatly raised (6030 and 3870 IU/L in patients 1 and 2, respectively), and serum HCV-RNA was low in both patients when severe disease developed (10(2) genome equivalents per mL). Patient 1 died, and necropsy showed massive liver necrosis. INTERPRETATION The findings suggest an immune-mediated mechanism for hepatocyte damage in HCV infection. Careful monitoring of ALT concentrations is necessary in such patients during and after chemotherapy.

Lack of Sustained Efficacy of Interferon in Patients with Chronic Hepatitis C

To the Editor: The hepatitis C virus (HCV) has been shown to cause progressive and chronic liver damage.1 Interferon therapy apparently eradicates HCV in 20 to 30 percent of patients, but the follo...

Role of IL28B Gene Polymorphism and Cell-Mediated Immunity in Spontaneous Resolution of Acute Hepatitis C

BACKGROUND  A single-nucleotide polymorphism (SNP; rs12979860) near the IL28B gene has been associated with spontaneous and treatment-induced hepatitis C virus clearance. We investigated predictors of spontaneous disease resolution in a cohort of patients with acute hepatitis C (AHC), analyzing epidemiological, clinical and virological parameters together with IL28B.rs12979860 genotypes and cell-mediated immunity (CMI). METHODS  Fifty-six symptomatic AHC patients were enrolled and followed prospectively. CMI was measured in 31 patients at multiple time points by interferon-γ enzyme-linked immunospot assay and was correlated to the IL28B.rs12979860 SNP. RESULTS  Eighteen patients had a self-limiting AHC that was associated with female sex (P = .028), older age (P = .018), alanine aminotransferase level >1000 U/L (P = .027), total bilirubin level >7 mg/dL (P = .036), and IL28B.rs12979860 genotype CC (P = .030). In multivariate analysis, only CC genotype was independently associated with self-limiting AHC (odds ratio, 5.3; 95% confidence interval, 1.1-26.5). Patients with the CC genotype with self-limiting AHC had a stronger (P = .02) and broader (P = .013) CMI than patients with the CT genotype with chronically evolving AHC. In patients with chronically evolving disease, CC genotype was associated with a broader CMI compared to CT genotype (P = .028). A negative CMI was more frequently associated with CT genotype among persistently infected patients (P = .043) and with persistent infection among CT patients (P = .033). CONCLUSIONS . Self-limiting AHC was independently associated with CC genotype. The correlation between IL28B.rs12979860 genotypes and CMI is suggestive of a possible important role of CMI in favoring hepatitis C virus clearance in CC patients.