Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir.

UNLABELLED: Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with PEG-IFN, RBV, and telaprevir are not known. Triple therapy for 12 weeks, followed by PEG-IFN and RBV for 12 weeks, was given to 49 patients with RBV-sensitive (CC at rs1127354) and 12 with RBV-resistant (CA/AA) ITPA genotypes who had been infected with hepatitis C virus (HCV) of genotype 1. Decreases in hemoglobin levels were greater in patients with CC than CA/AA genotypes at week 2 (-1.63 ± 0.92 vs. -0.48 ± 0.75 g/dL, P = 0.001) and week 4 (-3.5 ± 1.1 vs. -2.2 ± 0.96, P = 0.001), as well as at the end of treatment (-2.9 ± 1.1 vs. -2.0 ± 0.86, P = 0.013). Risk factors for hemoglobin <11.0 g/dL at week 4 were female gender, age >50 years, body mass index (BMI) <23, and CC at rs1127354 by multivariate analysis. RBV dose during the first 12 weeks was smaller in patients with CC than CA/AA genotypes (52 ± 14% vs. 65 ± 21% of the target dose, P = 0.039), but the total RBV dose was no different between them (49 ± 17% and 54 ± 18% of the target, P = 0.531). Sustained virological response (SVR) was achieved in 70% and 64% of them, respectively (P = 0.724). CONCLUSION: ITPA polymorphism influences hemoglobin levels during triple therapy, particularly during the first 12 weeks while telaprevir is given. With careful monitoring of anemia and prompt adjustment of RBV dose, SVR can be achieved comparably frequently between patients with CC and CA/AA genotypes.

An open pilot study exploring the efficacy of fluvastatin, pegylated interferon and ribavirin in patients with hepatitis C virus genotype 1b in high viral loads.

OBJECTIVE: Response to pegylated (PEG) interferon (IFN) and ribavirin is achieved only in 40-50% of patients infected with hepatitis C virus (HCV) of genotype 1 in high viral loads, which needs to be improved. METHODS: In an open-label pilot study, fluvastatin (HMG-CoA reductase inhibitor), 20 mg daily, was given along with PEG-IFN/ribavirin to 21 patients with chronic hepatitis C. They were followed for HCV RNA in serum. RESULTS: During treatment for 48 weeks, HCV RNA was lost from serum in 93% of the patients. In the 15 patients who received 48-week therapy, a sustained virological response (SVR) with loss of HCV RNA 24 weeks after completion was achieved in 10 (67%), including 7 of the 9 (78%) male and 3 of the 6 (50%) female patients. In the remaining 6 patients who received 72-week therapy, SVR was gained in 4 (67%), including 1 of the 2 male and 3 of the 4 female patients aged 56, 58 and 62 years, respectively. CONCLUSION: Fluvastatin could be used safely to increase the response to PEG-IFN and ribavirin, especially in aged women who respond poorly to combined PEG-IFN/ribavirin.

Poor response to pegylated interferon and ribavirin in older women infected with hepatitis C virus of genotype 1b in high viral loads.

BACKGROUND: Response to treatment in patients with chronic hepatitis C, with reference to age and gender, has not been examined fully. AIM: The influence of gender and age on treatment with pegylated interferon (PEG-IFN) and ribavirin was evaluated in a retrospective study. METHODS: PEG-IFN and ribavirin were given for 48 weeks to 179 men and 121 women infected with hepatitis C virus (HCV) of genotype 1b in high viral loads (>100 kIU/ml). RESULTS: Sustained virological response at 24 weeks after treatment was poorer in women than men who were aged >or=50 years (22% vs 53%, P < 0.001). Among the patients aged >or=50 years who had received >or=80% of the doses of PEG-IFN, ribavirin, or both, women responded less often than men (26% vs 64%, P < 0.001; 33% vs 61%, P = 0.022; and 32% vs 63%, P = 0.016; respectively). In multivariate analysis, male gender, retention of indocyanine green, ribavirin dose and compliance with therapy increased sustained virological response. CONCLUSIONS: Response to combined PEG-IFN and ribavirin is poorer in female than male patients with hepatitis C who are aged >or=50 years, irrespective of compliance with treatment. Low estrogen levels in older women could be responsible for their impaired response to PEG-IFN and ribavirin.

Prediction of response to pegylated interferon and ribavirin in hepatitis C by polymorphisms in the viral core protein and very early dynamics of viremia.

OBJECTIVE: To evaluate power of amino acid polymorphisms in core protein of hepatitis C virus (HCV) for predicting sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin, when they were combined with virological response. METHODS: Peg-IFN/ribavirin was given to 118 patients infected with HCV genotype 1b in high viral loads. Amino acid polymorphisms (Arg70 vs. Gln70 and Leu91 vs. Met91) in combination with on-treatment virological responses were correlated with SVR. RESULTS: End-of-treatment response (ETR) was achieved in 71% and SVR in 47% of the 118 patients. In multivariate analysis, Arg70 and Leu91, and higher ribavirin dose were independently associated with ETR. In patients with Gln70 and/or Met91, SVR was more frequent in those with than without prompt virological response (PVR) for a decrease in viral load >or=1.0 log by 48 h. Specificity in predicting patients without ETR and SVR, in combination with core polymorphisms, was not different between PVR and early virological response at 12 weeks. CONCLUSION: Core polymorphisms combined with PVR would be useful in promptly identifying the patients who will not respond to Peg-IFN/ribavirin, thereby avoiding unrewarding side effects and high costs.

Eight genotypes (A-H) of hepatitis B virus infecting patients from San Francisco and their demographic, clinical, and virological characteristics.

Clinical lines of evidence have been accumulated that hepatitis B virus (HBV) genotypes have characteristic geographical distributions and distinct clinical impact on liver diseases. The distribution of HBV genotypes was determined with reference to hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) levels in 165 patients with hepatitis B in San Francisco. HBV genotypes were determined by enzyme-linked immunosorbent assay (ELISA) and the unclassified samples were sequenced within the S region for phylogenetic analysis. Genotype A occurred in 60 (36%) patients, B in 16 (10%), C in 56 (34%), D in 19 (12%), E in 1 (1%), F in 1 (1%), G in 8 (5%), and H in 4 (2%). Caucasians were infected predominantly with HBV genotype A (HBV/A) (38 of 57 [67%]), Asians with HBV/C (45 of 63 [71%]), and Hispanics with HBV/F and HBV/H (4 of 9 [44%]). Serum ALT levels were higher in the patients infected with HBV/A (P = 0.03) or HBV/G (P = 0.02) than HBV/C. HBeAg was more frequent in patients infected with HBV/G than HBV/C or HBV/D (7 of 8 [88%] vs. 25 of 56 [45%] or 6 of 19 [32%], P = 0.03 or 0.01). In conclusion, eight genotypes (A-H) were identified in San Francisco in association with various ethnicities and then influenced ALT levels as well as the prevalence of serum HBeAg. HBV genotype H might be identified by combination of preS2 serotpe bksf and HBsAg serotype adw.