Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?

Between 5 and 10% of adults infected with the hepatitis B virus (HBV) develop a chronic infection lasting longer than 6 months, which may lead to advanced liver disease. HBV can be classified into six genotypic families: A, B, C, D, E and F, but only genotypes A and D are significantly represented in western Europe, where they account for some 90% of cases of infection with HBV. In the present study, we investigated a possible association between HBV genotype A or D and clinical outcome of the infection. We compared the prevalence of these genotypes in a group of patients with chronic active hepatitis to that of a group with acute resolving hepatitis. In patients with chronic active hepatitis, genotype A was found in 28 of 35 patients and genotype D in only four. The remaining three patients were infected with genotype non-A, non-D. In contrast, genotype D was found in 24 of 30 patients with acute hepatitis, whilst genotype A was found in only three patients of this group. Three were infected with genotype non-A, non-D. Our results show a clear association between genotype A and chronic outcome (Ficher's exact test: two-sided P-value, P < 0.0001). They suggest that HBV genotypes may play a role in the virus-host relationship. Possible mechanisms for such a role are discussed.

Mutations in the basal core promoter and precore/core gene of hepatitis B virus in patients with chronic active but not acute hepatitis B.

Around 5-10% of adults infected with hepatitis B virus (HBV) develop a chronic liver disease such as chronic active hepatitis (CAH), and it is unclear whether the clinical outcome depends solely on the immune response or whether viral factors also play a role. In this study, a search was therefore made for nucleotide mutations in the basic core promoter (BCP) and amino-acid substitutions in the precore/core region of HBV infecting patients with CAH or with acute hepatitis. The nucleotide sequences of the BCP and of the precore/core region were determined in virus from ten patients with CAH and ten with acute hepatitis. The precore/core sequences were also analysed in 14 additional patients (6 with CAH, 8 with acute hepatitis). In seven of the ten patients with CAH, five types of mutations were found in the BCP. Deletions in the precore/core region were observed in six patients. In all six patients where only the precore/core region was studied, amino-acid substitutions were present. In contrast, in the ten patients with acute hepatitis studied for BCP, a mutation was found in the BCP of one patient only. Of the 18 patients in whom the precore/core was studied, three had an amino-acid substitution in this region. The results show a clear link between CAH and both HBV BCP and precore/core region mutations, suggesting these mutations may play a role in the persistence of HBV infection.

Comparison of a competitive combined reverse transcription-PCR assay with a branched-DNA assay for hepatitis C virus RNA quantitation.

We have developed a sensitive and reproducible one-step competitive reverse transcriptase (RT) PCR assay, which allows hepatitis C virus (HCV) RNA quantitation in plasma over a broad range of values. The RNA samples and a constant amount of an internal standard were reverse transcribed and coamplified with the same primers in the same tube. A standard curve was obtained from an additional series of tubes containing both the internal standard and known amounts of a wild-type HCV RNA transcript, thus eliminating the need for titrating samples with the competitor. Eighty-eight anti-HCV-positive samples were tested by RT-PCR and a branched-DNA (bDNA) assay which has a detection limit of 3.5 x 10(5) copies per ml. Fifty-five samples were quantifiable by both methods (correlation coefficient, 0.72), the ranges of values found by the RT-PCR and bDNA assays being, respectively, 0.127 x 10(6) to 18.4 x 10(6) and 0.44 x10(6) to 38 x 10(6) copies per ml. Six samples that had indeterminate values by the bDNA assay had RT-PCR values between 0.37 x 10(5) and 9.6 x 10(5) copies per ml. Twenty-two samples that had values below the cutoff value by the bDNA assay had RT-PCR values between 2.5 x 10(3) and 10.4 x 10(5) (18 less than and 4 more than the limit of 3.5 x 10(5) copies per ml). The remaining five samples were negative by both assays. The level of RT-PCR interassay reproducibility was high (correlation coefficient between duplicate values, 0.94). Our method, with a detection limit of 2,500 copies per ml, was markedly more sensitive than the bDNA assay. This method is convenient for following up patients with low viremia, a common situation with alpha interferon treatment.

[Inflammatory myopathy: unusual presentation of a case of Wegener disease]. / Myopathie inflammatoire: présentation inhabituelle d'un cas de maladie de Wegener.

The case is presented of a 66-year-old man who developed an inflammatory myopathy picture predominantly consisting in leg weakness. Wegener's granulomatosis was diagnosed on the basis of suggestive thoracic imaging, microhematuria and necrotizing arteritis with granulomas in muscular biopsy. An increasing titer of anti-neutrophilic cytoplasm auto-antibodies (ANCA) confirmed the diagnosis. Rapid resolution was obtained by classic immunosuppressor treatment (cyclophosphamide and corticoids), without worsening of renal function. In discussion we emphasize the importance of ANCA measurement for diagnosis and follow-up.