Background

IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.

Methods

Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.

Results

Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.

Conclusions

IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype.

Background/Aims

Helicobacter pylori infection causes gastritis, peptic ulcers and gastric malignancies, and its eradication has been advocated by many groups. We determined the H. pylori carrier status and eradication rates of patients with chronic hepatitis C virus (HCV) infection.

Methods

In total, 76 chronically HCV-infected patients were enrolled for comparison with 228 HCV-noninfected, age- and sex-matched controls. H. pylori infection was confirmed by H. pylori antibody and urea breath testing.

Results

The H. pylori infection rate was significantly higher for HCV-infected patients (67 of 76, 88.2%) than for HCV-noninfected controls (158 of 228, 69.3%). Endoscopic findings showed that the rates of gastric ulcers and gastritis were significantly higher for the 67 HCV-infected patients with H. pylori infection (34.3% and 77.6%) than for the 158 HCV-noninfected controls with H. pylori infection (15.2% and 57.6%). Treatment to eradicate H. pylori had a significantly higher success rate for HCV-infected patients (61 of 67, 91.0%) than for HCV-noninfected controls (115 of 158, 72.8%).

Conclusions

The markedly high H. pylori eradication rate observed in this study shows that eradication of H. pylori holds promise for the improvement of the long-term health condition of patients with chronic HCV infection.

AIM: To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate (YMDD) mutants (reverse transcription; rtM204I/V) and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus (HBV) infection.

METHODS: The data of 61 consecutive Japanese patients with chronic hepatitis B who underwent continuous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo (mean, 50.8 mo; range, 24-90 mo).

RESULTS: A mixed mutant-type (YMDD + tyrosine-isoleucine-asparatate-asparatate: YIDD or tyrosine-valine-asparatate-asparatate: YVDD) or a mutant-type (YIDD or YVDD) were found in 57.4% of 61 patients at 1 year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 (92%) had mixed mutant- or a mutant-type. Only 5 (8%) had no mutants at each observation point. Virological breakthrough was found in 26 (46.4%) of 56 patients with YMDD mutants, 20 of whom had a hepatitis flare-up: the remaining 30 (53.6%) had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment.

CONCLUSION: Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.

AIM: To analyze the efficacy and safety of a combination therapy of pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) in older Japanese patients (65 years or older) infected with hepatitis C virus (HCV).

METHODS: This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk.

RESULTS: At 24 wk after the end of combination therapy, the overall sustained virological response (SVR) for genotypes 1 and 2 were 40.7% and 79.6%, respectively. The SVR rate decreased significantly with age in each genotype, and was markedly reduced in genotype 1 (P < 0.001). Moreover, the SVR was significantly higher in patients with genotype 1 who were less than 65 years (47.3% of 685) than in those 65 years or older (22.9% of 253) (P < 0.001) and was higher in patients with genotype 2 who were less than 65 years (82.9% of 252) than in those 65 years or older (65.6% of 61) (P = 0.004). When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV, the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older (P < 0.001). Adverse effects resulted in treatment discontinuation more often in patients with genotype 1 (14.4%) than in patients with genotype 2 (7.3%), especially by patients 65 years or older (24.1%).

CONCLUSION: PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.

Background

An early virological response (EVR) after the start of interferon (IFN) treatment for chronic hepatitis C leads to a successful virological outcome. To analyze an association between sustained virological response (SVR) and EVR by comparing TaqMan with Amplicor assays in HCV genotype 1-infected patients treated with pegylated (PEG)-IFN alpha-2b plus ribavirin (RBV).

Methods

We retrospectively analyzed a total of 80 HCV genotype 1 patients (39 SVR and 41 non-SVR patients), who received an enough dosage and a complete 48-week treatment of PEG-IFN alpha-2b plus RBV. Serum HCV RNA levels were measured by both TaqMan and Amplicor assays for each patients at Weeks 2, 4, 8 and 12 after the start of the antiviral treatment.

Results

Of the 80 patients with undetectable HCV RNA by Amplicor, 17 (21.3%) patients were positive for HCV RNA by TaqMan at Weeks 12. The quantification results showed that no significant difference in the decline of HCV RNA level between TaqMan and Amplicor 10-fold method assays within the initial 12 weeks of the treatment was found. However, the qualitative analysis showed significant differences of the positive predictive rates for SVR were found between TaqMan (100% at weeks 4 and 100% at weeks 8) and Amplicor (80.0% and 69.6%, respectively).

Conclusions

The COBAS TaqMan HCV assay is very useful for monitoring HCV viremia during antiviral treatment to predict a SVR in HCV genotype 1 patients.

Background

Lamivudine treatment has been recently demonstrated to increase the serum albumin levels in cirrhotic patients with hepatitis B virus (HBV) infection, but the precise mechanism remains unclear. We hypothesized that the improvement of hypoalbuminemia by lamivudine may be attributable to the reduction of HBV replication itself, rather than to cessation of hepatitis. In order to confirm this hypothesis, in this study we evaluated factors which correlated with the increase in serum albumin levels. Fifty-four patients (Child-Pugh A/B/C, 35/9/10) with HBV-related liver cirrhosis who had been treated with lamivudine for more than 12 months were evaluated. We analyzed the correlation between the increase in serum albumin levels at month 12 after starting treatment (Δ-albumin) and various pretreatment variables. We also analyzed the correlation between Δ-albumin and the reduction in serum levels of HBV-DNA (Δ-HBV-DNA) or alanine aminotransferase (Δ-ALT) at month 12.

Results

The average Δ-albumin was 0.38 g/dL and only serum HBV-DNA levels before treatment correlated significantly with Δ-albumin. We also analyzed the correlation in patients whose alanine aminotransferase levels were normalized after 12 months so that the possible influence of breakthrough hepatitis could be excluded. Even among this subgroup of patients, there was no significant correlation between Δ-albumin and either pretreatment alanine aminotransferase levels or Δ-ALT. In contrast, in patients whose serum HBV-DNA was undetectable at month 12, we found a significant correlation between Δ-albumin and both pretreatment serum HBV-DNA levels and Δ-HBV-DNA.

Conclusion

Our results demonstrated that albumin levels are associated with pretreatment HBV-DNA but not with alanine aminotransferase levels.