Gloria Moraleda

Analysis of hepatitis B precore region in serum and liver of chronic hepatitis B virus carriers

Using an oligonucleotide hybridization assay we studied the prevalence of wild-type and the predominant pre-core mutant hepatitis B virus in serum and liver of 49 antibody to hepatitis B e antigen carriers and three hepatitis B e antigen positive patients. Of the 45 serum samples from the anti-HBe carriers analyzed (no serum sample was available in four patients), 36 (80%) had hepatitis B virus DNA. In 26 of these 36 patients (72%) a mixed population was detected, wild-type genome alone was found in six patients (16%), the single mutant (nucleotide position 1896), in three cases (8%) and in one patient (2%) the viral DNA had the two nucleotide mutation (1896 and 1899). Of the liver biopsies from the 36 anti-HBe patients studied (no liver biopsy was available in 13 patients), 33 (92%) had hepatitis B virus DNA. A mixed viral population was detected in 23 patients (69%), only wild-type virus or a single mutation was found in eight (34%) and two patients (8%), respectively. In all cases, wild-type was the predominant genome. In serum and liver samples from the same patient, we found a concordance of the presence of wild-type HBV and the pre-core mutants studied in 23/26 (88%) of the patients. Alanine aminotransferase levels were higher (p < 0.01) and the duration of hepatitis B surface antigen carrier lower (p < 0.02) in patients with a predominance of precore mutant in comparison to wild-type.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B virus DNA in liver and peripheral blood mononuclear cells during reduction in virus replication.

Changes in hepatitis B virus DNA in blood cells and liver were studied in 34 patients (12 controls, 22 under therapy). There were no basal differences in the presence of the viral genome in blood cells between treated and control patients. A significant decrease in the percentage of patients with viral genome in blood cells was observed in patients who lost this marker in serum. Replicative intermediates of the viral genome were observed in the basal liver samples from all patients. In patients who lost the viral DNA in serum, hepatitis B virus genome became undetectable in the second liver sample in all but two patients who had viral sequences integrated in the host genome. Replicative intermediates were found in all patients with serum viral DNA. The results of this study suggest that there may be a relation between the disappearance of hepatitis B virus DNA in liver and blood cells.

Treatment of chronic hepatitis B with recombinant interferon alpha versus recombinant interferon alpha plus levamisole

To compare the efficacy and tolerance of the simultaneous administration of levamisole plus IFN versus treatment with IFN alone in chronic hepatitis B, 39 patients were randomly assigned into two groups. Nineteen patients received 15 million units of recombinant alpha interferon 2b (rIFN-alpha 2b) 3 times a week for 4 months. The other 20 patients were treated with the same dose and schedule of rIFN-alpha 2b and 150 mg of levamisole simultaneously given during the first 6 weeks of treatment. At the end of the study (thirteenth month), serum HBV-DNA was negative in 59% of patients treated with interferon alone and in 37% of those treated with interferon and levamisole. HBeAg was negative in a similar percentage in the two groups (41% vs. 37%). Serum alanine aminotransferase levels decreased in patients who lost viral DNA. These data demonstrate that the combination of alpha interferon and levamisole, at the doses and under the schedule used in this study, does not achieve better results than the treatment with alpha interferon alone. Although tolerance to the simultaneous administration of alpha interferon and levamisole is good, secondary effects may be hazardous.

Presence of HBV-DNA in peripheral blood mononuclear cells from anti-HIV symptomless carriers

The presence of hepatitis B virus DNA (HBV-DNA) in the peripheral blood mononuclear cells (PBMC) of 29 anti-HIV symptomless carriers (eleven HBeAg positive, eleven anti-HBe positive and seven HBsAg negative) and of 40 anti-human immunodeficiency virus (HIV)-negative patients (15 HBeAg positive, 15 anti-HBe positive and ten HBsAg negative) has been studied by dot-blot and Southern blot hybridization. HBV-DNA has been found in similar proportions in both anti-HIV-positive and negative patients (36% and 46%, respectively, in the HBeAg positive group and 27% and 37% in the anti-HBe positive group). No HBV-DNA was detected in the PBMC of the HBsAg-negative patients. No relation has been observed between the presence of HBV-DNA in the PBMC of the anti-HIV-positive patients and the detection of HIV antigen (HIV Ag), number of CD4 cells or the CD4/CD8 ratio. In summary, the presence of HBV-DNA in the PBMC of anti-HIV symptomless carriers does not seem to imply that the patients clinical state has worsened.

Detection of Antibody to Calmodulin in Chronic Viral Hepatitis: Lack of Correlation with Virus Replication and Hepatocellular Damage

We have analyzed the presence of IgG and IgM anti-calmodulin antibodies (anti-CaM) by ELISA in patients with chronic hepatitis due to B, delta and C viruses as well as in patients with other liver diseases. The specificity of the assay was demonstrated by preadsorption of positive serum with calmodulin (CaM) but not with myosin light chain. Among 164 patients with chronic viral hepatitis (B, delta and C) and 50 with non-viral hepatitis, 27 and 26%, respectively, had auto antibodies against CaM. There was a significantly increased frequency (37%) of these auto-antibodies in chronic delta infection as compared to that (21%) of patients with chronic B hepatitis (p less than 0.05). An intermediate incidence of anti-CaM, (24%) was found in chronic C infection. The frequency of anti-CaM was not related to the level of hepatitis B virus (HBV) or hepatitis delta virus (HDV) replication. A high occurrence of anti-CaM in the presence of liver membrane antibody (p less than 0.03) was observed. During follow-up of patients with chronic delta-hepatitis, the presence of anti-CaM was consistently observed, when the isotype was IgM, but transiently when it was IgG. The occurrence of anti-CaM correlated neither with ALT levels nor with histological diagnosis. Antibodies to CaM, are present in liver diseases especially in chronic delta-hepatitis, and do not play a pathogenic role on hepatocellular damage.