Epidemiology and clinical outcome of hepatitis D virus infection in Turkey.

The prevalence, the epidemiology, the clinical and biochemical characteristics of hepatitis delta virus (HDV) infection were studied in patients with HBsAg-positive acute hepatitis, in those with chronic liver disease, and in apparently healthy carriers in Turkey. Fifty-eight of the 242 carriers of HBsAg (23.9%) and 31 of the 237 (13.1%) patients with acute HBsAg-positive hepatitis had serological evidence of HDV infection. Eleven of these individuals were HBsAg carriers with acute HDV superinfection. The prevalence of HDV infection was significantly (p less than 0.001) higher in patients with chronic liver disease (54/165; 32.7%) than in asymptomatic carriers of HBsAg (4/77; 5.2%). The highest prevalence (26/57; 45.6%) of HDV infection was found in patients at high risk of acquiring hepatitis virus infection (health care workers, hemodialysis patients, polytransfused patients) with chronic liver disease. Whereas the frequency of "severe" or fulminant hepatitis was similar in HBV infected patients (7.8%) and in HBV/HDV coinfected individuals (10%), the frequency of biphasic hepatitis was significantly (p less than 0.005) higher in the latter patients (30%) than in those with classical hepatitis B (7.8%). Chronic evolution of the disease was observed in 3.9% of the patients with classical hepatitis B and in 5% of those who had evidence of simultaneous HBV/HDV infection. The 10 carriers of HBsAg who survived the acute HDV superinfection developed chronic delta hepatitis. These findings indicate that HDV is endemic in Turkey and that its prevalence is highest among chronic HBsAg-positive hepatitis patients, implicating HDV as a major cause of liver disease among urban Turkis.

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.

Problems in the management of chronic hepatitis B with interferon: experience in a randomized, multicentre study.

In a multicentre trial, 82 patients known to be hepatitis B e antigen and hepatitis B virus DNA positive for at least 1 year, with elevated serum alanine aminotransferase levels and chronic liver lesions on biopsy, were randomized to receive either recombinant interferon alfa-2a at a dose of 4.5 million units thrice weekly for 4 months or no treatment. At the end of therapy, viral DNA clearance and aminotransferase normalization were significantly (p less than 0.05) more frequent in treated patients than in controls. After 16 months' follow up, the difference was still significant for hepatitis B e antigen clearance and transaminase normalization. Hepatitis B virus DNA reactivation was observed during follow up in 43% of treated patients and 50% of controls. Improvements in liver inflammation were observed in patients on interferon. High pre-treatment serum aminotransferase levels, female sex and a low score for fibrosis in the initial biopsy were predictive factors significantly (p less than 0.05) associated with termination of hepatitis B virus replication in treated cases. These results indicate that interferon is effective in inducing clearance of HBV from serum and improvement of biochemical and histological parameters of liver disease. However, a more prolonged regimen of therapy may be required to obtain stable suppression of hepatitis B virus replication.

A possible misdiagnosis in patients presenting with acute HBsAg-negative hepatitis: the role of hepatitis delta virus.

We describe here two cases of delta hepatitis (a coinfection and a superinfection) presenting as acute HBsAg-negative hepatitis. The first patient, a parenteral drug abuser, had a biphasic course of the disease, with HBsAg detectable transiently only during the relapse. Testing for delta markers on stored sera gave evidence of HBV/HDV coinfection. The other patient, a hospital nurse, chronic asymptomatic carrier of HBsAg, developed fulminant hepatitis with the transient appearance of antibody to HBsAg. She survived massive liver necrosis, and serological analysis of HDV markers documented a hepatitis delta virus superinfection. These cases demonstrate the possible substantial repression of HBV gene products exerted by the replication of delta virus, with a likely misdiagnosis if delta markers are not determined in serial serum samples.

Rapidly progressive HBsAg-positive hepatitis in Italy. The role of hepatitis delta virus infection.

Serum or liver markers of hepatitis delta virus (HDV) infection were found in 20 of 22 (90%) Italian patients presenting with an ostensible type B hepatitis that ran an accelerated course to cirrhosis. The features of the illness conformed to a syndrome of HDV infection in young males carrying the hepatitis B surface antigen (HBsAg); a latent HBsAg state was documented in many patients by a history of prior exposure to the hepatitis B virus (HBV) or by the absence of IgM antibodies to the HB core antigen. Characteristic of the disease were the clinical overture as a severe hepatitis, the lobular involvement by an extensive necroinflammatory reaction, the exuberant expression of intrahepatic hepatitis delta antigen and an atypical HBV profile of inactive infection or accelerated seroconversion from HBeAg to anti-HBe. Superimposed upon HBV infection, HDV may create a rapidly progressive course which resembles very aggressive hepatitis B but is infrequently observed in hepatitis B alone.

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.

Milan as possible starting point of LAV/HTLV III epidemic among Italian drug addicts.

Sera collected between 1978 and 1985 from 716 parenteral drug-addicts admitted to our Clinic with viral hepatitis were tested for antibodies to HTLV III. None of the patients was showing symptoms suggestive of LAV/HTLV III infection at the time of sera collection. Positivity for HTLV III antibody was found and confirmed (by ELISA) in 212 subjects (29.6%). The earliest positivity appeared in a serum sample collected in February 1979. These and other data point to Milan as to the actual source of the Italian PDAs-linked LAV/HTLV-III epidemic.