B. Nalpas

The expression of hepatitis B spliced protein (HBSP) encoded by a spliced hepatitis B virus RNA is associated with viral replication and liver fibrosis

BACKGROUND/AIMSnWe have previously demonstrated the in vivo expression of a new spliced hepatitis B virus (HBV) protein (HBSP) encoded by a singly spliced pregenomic RNA. The present study was designed to evaluate the impact of HBSP expression on the clinical status and liver pathology of HBV infection.nnnMETHODSnSera from 125 chronic HBV carriers were tested for the presence of HBSP antibodies by an indirect enzyme-linked immunosorbent assay test. The severity of liver damage was evaluated using the Knodell score.nnnRESULTSnAnti-HBSP antibody prevalence in HBV chronic carriers was 46%. We highlighted the concomitant expression of HBSP protein and anti-HBSP antibody. An association between anti-HBSP antibody detection and serum markers of HBV replication was demonstrated. With respect to HBV-related liver disease, an association was only observed with the severity of fibrosis. Furthermore, an elevation of secreted tumor necrosis factor alpha (TNFalpha), but not of soluble TNFalpha receptor 75, was observed in anti-HBSP-antibody-positive patients. Multivariate analysis showed that anti-HBSP antibody detection was independently associated with viral replication, severity of fibrosis and elevated TNFalpha secretion.nnnCONCLUSIONSnOur data suggest the hypothesis that HBSP might play a role in the natural history of HBV infection and may be involved in the pathogenesis and/or persistence of HBV infection.

Hepatitis B virus multiplication in the absence of usual serological markers: A study of 146 chronic alcoholics

The possible role of HBV infection in the progression of alcoholic liver disease remains debated. However, serum HBV markers in alcoholics, although present with a high frequency, mainly consist of anti-HBs and/or anti-HBc antibodies. In order to detect an HBV multiplication that could be missed by the usual markers, we looked for HBV-DNA in the serum of 146 chronic alcoholics; the results were compared with those of the usual serological HBV markers. Sixty-eight of the 146 patients could be studied for HBV-DNA both in the liver and the serum. The 146 alcoholics were divided in 48 with normal liver function (group I); 67 with non-cirrhotic alcoholic liver disease (group II); 31 with alcoholic cirrhosis (group III). Among the 146 patients, 17 had a viral multiplication reflected by serum positive HBV-DNA, as against none of 100 healthy controls (P less than 0.01). Six of the 17 had a normal liver function (6/48 = 12.5%), 7 were of group II (7/67 = 10.4%) and 4 had cirrhosis (4/31 = 12.9%). Serum HBV-DNA was associated with HBsAg in 3 occasions; in addition serum HBV-DNA was also present in 5 HBsAg-negative patients with anti-HBc and/or anti-HBs and even in 9 without any usual HBV marker. The overall prevalence of HBV markers in the 146 patients went from 30.8% to 37.0% when serum HBV-DNA was taken into account; it was similar in the 3 groups studied. Eight patients, of the 68 studied, were liver HBV-DNA-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B vaccination in chronic alcoholics

Given the possible role of hepatitis B virus in the occurrence of hepatocellular carcinoma and the high prevalence of HBV infection in alcoholics, we attempted to prevent HBV infection in alcoholic patients with or without cirrhosis. Among 32 cirrhosis, 20 received three injections of hepatitis B vaccine at monthly intervals and 12 had a 4th injection one month later. Effectiveness was evaluated on the anti-HBs titer at the 6th month; it did not differ between the 3- and 4-injection groups. Two patients were good responders (anti-HBs greater than 300 mU/ml), 14 had a low response (m-30 mU/ml at the peak) and 16 (50%) had no detectable anti-HBs. All alcoholics without cirrhosis were given 4 injections; all had detectable anti-HBs but their mean antibody response was 97.7 +/- 4 SD. No obvious statistical difference in the response to the vaccine was noted on the basis of sex or age, or on the discontinuation or not of alcohol intake. Deficient antibody response to vaccines has not previously been demonstrated in patients with cirrhosis or in alcoholics. It remains to be determined whether this response is specific of HBV and how it could be related to the role of HBV in the occurrence of liver alterations in alcoholics.