Hisashi Nakashima

Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection.

Background and Aim:  Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than genotype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome.

Hepatitis C virus (HCV) RNA level determined by second-generation branched-DNA probe assay as predictor of response to interferon treatment in patients with chronic HCV viremia

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype 1b and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-α treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype 1b patients [5.4 × 106 HCV genome equivalent (Meq)/ml] than in genotype 2a patients (0.9 Meq/ml) (P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype 1b patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level ≦1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype 1b patients with level ≤1.0 Meq/ml (57.6%) than in those with level >1.0 Meq/ml (3.8%) (P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level ≤1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of ≦1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN treatment.

TT-Virus Infection in Japanese General Population and in Hemodialysis Patients

To determine TT virus (TTV) prevalence and the persistence of viremia, we prospectively did cross-sectional and longitudinal studies using by the polymerase chain reaction to test the successive sera of 150 Japanese hemodialysis patients and compared these with those of 166 residents of a rural Japanese area endemic for hepatitis C virus (HCV). TTV DNA positivity was significantly higher in 50 (30.1%) of the residents than in 25 (16.7%) of the patients in 1997 (P < 0.05). TTV DNA positively in the patients was not associated with HCV RNA positivity and also increased with the number of blood transfusions and decreased with the duration of hemodialysis, but not significantly. Longitudinal study from 1997 to 1999 showed that persistent TTV DNA positivity was found significantly more often in 35 (21.1%) of the residents than in 13 (8.6%) of the patients (P < 0.05), and that persistent TTV DNA negativity was found significantly more often in 103 (68.7%) of the patients than in 91 (54.8%) of the residents (P < 0.05). Of the 25 patients and 50 residents TTV DNA positive in 1997, TTV DNA was eliminated more often in 12 (48.0%) patients than in 15 (30.0%) residents over the three years, but the difference was not significant. The route of TTV transmission might differ from HCV in that it could be nonparenteral. TTV was less prevalent in hemodialysis patients than residents, and the virus was more often eliminated by hemodialysis patients than by residents during the three-year observation period, possibly because of the effect of the hemodialysis procedure.