Serologic markers with fulminant hepatitis in persons positive for hepatitis B surface antigen. A worldwide epidemiologic and clinical survey.

Of 377 cases of fulminant hepatitis in persons positive for hepatitis B surface antigen (HBsAg) in Greece, Italy, the United States, the United Kingdom, the Central African Republic, Taiwan, Egypt, and India, only 52% could be attributed to infection with hepatitis B virus, which was defined as the presence of the IgM antibody to the hepatitis B core antigen (IgM anti-HBc) and the absence of serum markers of infection by extraneous viruses. Thirty percent of cases were caused by coinfection with hepatitis B virus and hepatitis delta virus or by infection with hepatitis delta virus superimposed on carriers of chronic HBsAg. In 18.5% of the patients, the absence of IgM anti-HBc indicated that they were not known to carry HBsAg, but no obvious superimposed factor of hepatitis could be identified. The cause of fulminant hepatitis is complex, and major risk factors are a pre-existing HBsAg state and hepatitis delta virus infection. Superinfection of HBsAg carriers by non-A, non-B viruses seems to be the cause in a consistent proportion of cases.

Diagnostic significance of IgM antibody to hepatitis delta virus in fulminant hepatitis B.

The prevalence of hepatitis delta virus (HDV) infection was studied in 25 adult patients with fulminant hepatitis who were admitted consecutively to our unit from February, 1986, to September, 1988. Enzyme and radioimmunoassays were used for the detection of serological markers of HAV, HBV, and HDV (HDAg, IgM anti-HD, total [IgG] anti-HD) infections. Two hundred twenty-nine serum samples (three to 19 samples/patient) were tested for serological markers of HDV infection. Of the 25 patients, 17 (68%) were HBsAg-positive, and the remaining eight (32%) were HBsAg-negative on admission to the hospital. All patients were seropositive for IgM anti-HBc. Serological markers of HDV infection were detected in 13 (52%) of the 25 patients. In particular, HDV infection was observed in nine (53%) of the 17 HBsAg-positive and in four (50%) of the eight HBsAg-negative patients with type B fulminant hepatitis. Survival was 16.7% for patients with hepatitis B and 57.8% for patients with B and D coinfection. Coinfections were responsible for fulminant hepatitis in 100% of drug addicts and 40% in patients who were not drug addicts. All patients with HBV/HDV coinfections became seropositive for IgM anti-HD. The results show that HDV infection has a significant role (52%) in type B fulminant hepatitis in an area with a moderate prevalence of HBV infections, that it should be tested in cases with early clearance of HBsAg, and that it does not seem to be accompanied by a high fatality rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Monomeric (7S) immunoglobulin M antibodies to hepatitis delta virus in hepatitis type D.

The pattern of the immunoglobulin M antibody to the hepatitis delta virus distinguishes acute from chronic hepatitis D. Expression of the immunoglobulin M antibody to the hepatitis delta virus is relatively weak and short-lived in self-limited hepatitis but strong and persistent in chronic forms. To study the nature of the immunoglobulin M antibody to the hepatitis delta virus in acute hepatitis D and in chronic hepatitis D, antibody-positive sera were submitted to rate zonal centrifugation to separate monomeric 7S from pentameric 19S immunoglobulin M antibodies. Sera were from 6 patients with acute self-limited hepatitis, 4 patients with chronic hepatitis D, and 6 patients with hepatitis D progressing to chronicity. The immunoglobulin M reactivity was measured by a specific immunoassay based on capture of mu-chains by anti-mu linked on a solid phase. Only 19S antibody was found in acute hepatitis D. In contrast, all patients with chronic hepatitis D circulated 7S antibody in addition to the 19S antibody. In patients with progressive hepatitis D, both the 7S and 19S antibody variants were present at the onset of the disease. The difference in the antibody response between acute hepatitis D and chronic hepatitis D is not only temporal and quantitative but also qualitative. The expression of 7S antibody seems to be an immunologic event specific for chronic hepatitis D.

Serological response to the hepatitis delta virus in hepatitis D.

Sera from 74 hepatitis B surface antigen-positive individuals, who presented with acute hepatitis delta virus (HDV) infection which ran a self-limited course in 58 and progressed to chronicity in 16, were tested over time for HDV markers. In self-limited disease the serum pattern varied from early HD-antigenaemia followed by IgM and IgG anti-HD seroconversion, to the appearance of IgM and IgG anti-HD without antigenaemia, or the isolated expression of either the IgM or the IgG antibody. The typical case of IgM anti-HD was transient and appeared with a mean delay of 10-15 days from admission in the different serological subgroups. The IgG antibody usually developed several weeks later during convalescence. In contrast, patients with disease destined to become chronic had a brisk IgM antibody response and IgG anti-HD was detectable with a mean delay of 15 days; generally, the IgM and the IgG antibody persisted over the follow-up time. IgM antibody to HDV is often the only serological test positive in the clinical stage of hepatitis D and repeated testing for this marker is necessary to diagnose acute HDV co-infection. The serological follow-up provides important prognostic information: waning of IgM confirms resolution of HDV infection, persistence predicts chronicity.

Liver transplantation in hepatitis delta virus disease.

Seven patients with hepatitis delta virus (HDV) cirrhosis underwent liver transplantation. In every case the HDV infection was florid but accompanied by an inactive hepatitis B virus (HBV) infection. The patients were given anti-HB surface antigen (HBsAg) serum globulins and HBV vaccine. Two patients cleared the HBsAg and the HDV, and are alive and well 14 and 15 months, respectively, after transplantation. HDV infection recurred in the other five patients: hepatitis developed in three, another died, and the fifth was re-transplanted for causes unrelated to viral hepatitis (reinfection was shown by the presence of HD antigen in the graft). Liver transplantation is feasible in patients with HDV disease but involves a high risk of HDV reinfection that cannot be predicted by the virological pattern of the native HBV infection or prevented by conventional HBV prophylaxis.