0000000000347653
AUTHOR
Christian Bréchot
Identification of cyclin A as a molecular target of antinuclear antibodies (ANA) in hepatic and non-hepatic autoimmune diseases.
Abstract Background/Aims: Antinuclear antibodies (ANA) are a diagnostic of various autoimmune diseases and also of autoimmune hepatitis type 1. The designation ANA describes a heterogeneous group of autoantibodies. In liver diseases, only a few nuclear target antigens have been molecularly identified and characterized. Cyclins play a central role in a cell cycle regulation, DNA transcription, and cell proliferation. Cyclin A was also identified as an integration site of the hepatitis B virus in a patient with hepatocellular carcinoma. In this study we identify cyclin A as a novel nuclear target protein of ANA. Methods: Sera of patients with autoimmune hepatitis (AIH) type 1 ( n =61), type 2…
Impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action.
Abstract Background/Aims: To investigate the impact of hepatitis B (HBV) and C (HCV) infections on hepatocellular carcinoma (HCC) in Europe. Methods: Five hundred and three patients with HCC, from six liver centers, were included. All 503 sera and 80 liver samples were tested for HBV DNA and HCV RNA by polymerase chain reaction. GBV-C/HGV RNA was also tested in 57 sera. Results: HBsAg and anti-HCV were detected in 19% and 40.1% of the patients, respectively. Serum and liver HBV DNA were detected in 82% and 91% of the HBsAg positive subjects. HBV DNA was also detected in the serum and liver of 33% and 47% of HBsAg negative patients. In this group, serum HBV DNA was more prevalent in anti-HBs…
Cost effectiveness of peginterferon α-2b plus ribavirin versus interferon α-2b plus ribavirin for initial treatment of chronic hepatitis C
Background: Peginterferon α-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. Aims: To estimate the cost effectiveness of treatment with peginterferon α-2b plus ribavirin compared with interferon α-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. Methods: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We u…
Significance and relevance of serum preS1 antigen detection in wild-type and variant hepatitis B virus (HBV) infections
These studies assessed whether the serum expression of preS1 antigen could be a useful HBV marker for monitoring the progress of antiviral therapy in the treatment of chronic active hepatitis B (CAH-B) virus infections. Our findings indicate that: 1) the rearrangements we observed in the preS region of mutated HBV DNA molecules during chronic infection did not effect the preS1 sequence (21–47) critical for HBV infectivity; 2) the persistence or even the rebound of preS1 antigen expression during follow-up in responders to antiviral therapy may indicate virus persistence, suggesting the possibility of relapse through wild-type HBV or the emergence of HBV variants following the immunoeliminat…
Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship to Pre-S- and S-encoded viral surface antigens
The polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic hepatitis B virus carriers. Hepatitis B virus DNA was detectable in the serum of HBsAg—positive virus carriers using aliquots as small as 100 al. The detection limit for cloned hepatitis B virus DNA was 100 ag. Primer pairs for different regions of the HBV genome resulted in different sensitivity. Detection of the amplified hepatitis B virus DNA by Southern blotting and subsequent scintillation counting or densitometry allowed a semiquantitative assay. Using several primer pairs in parallel for optimal detection, all HBeAg-positive HBsAg carriers, 80% of HBe antibody—positive symptomatic HBsAg carriers and 57% of…
Failure of acyclovir to enhance the antiviral effect of α lymphoblastoid interferon on HBe-seroconversion in chronic hepatitis B
Serum HBeAg levels and HBe-seroconversion were investigated in patients with chronic HBeAg-positive hepatitis who were randomized to receive either alpha lymphoblastoid interferon (5 megaunits subcutaneously daily for 16 weeks) plus acyclovir (2 g intravenously daily during weeks 1 and 2 and weeks 9 and 10) (n = 49) or no treatment (n = 48). HBeAg levels in serial dilutions of patient serum were assessed quantitatively by radioimmunoassay and compared with the values found for negative control serum. One year after the start of therapy 44 treated patients and 43 control patients were available for follow-up. A complete response (HBe-seroconversion) occurred in 11 treated patients (25%) and …
Hepatitis B defective virus with rearrangements in the preS gene during chronic HBV infection.
We have found a defective form of HBV2 in a HBsAg- and anti-HBe-positive patient with liver cancer. Viral deletions were identified in the preS coding region using PCR. The presence of deleted HBV forms was observed in serum, PBMC, and liver samples. After sequencing 12 clones were analyzed (subtype adr). In 9 out of 12 clones a 183-bp in-frame deletion was recorded in the preS1 region (2995 to 3177). Three out of 9 clones also yielded rearrangements of the preS2 N-terminal part. Four out of 9 showed numerous point mutations in the preS1 and preS2 sequence. In addition, 3 out of 12 clones, which did not show the 183-bp preS1 deletion were found to have small deletions and insertions in the …