Polymorphisms of HLA-DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B.

BACKGROUND: Polymorphisms of the HLA-DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients. AIM: To investigate the association of HLA-DP polymorphisms with response to peginterferon (PEG-IFN) in Caucasian chronic hepatitis B (CHB) patients. METHODS: We studied 262 Caucasian chronic hepatitis B patients infected with HBV genotype A or D, treated with PEG-IFN for 1 year in two randomised controlled trials (HBV 99-01 and PARC study). Response was defined as an HBV DNA <2000 IU/mL at 6 months post-treatment. Variations at HLA-DPA1 and HLA-DPB1 were genotyped. RESULTS: Of the 262 patients, 58% was HBeAg-positive and HBV genotype A and D was observed in 32% and 68%, respectively. At 6 months post-treatment, 57 (22%) patients had achieved an HBV DNA <2000 IU/mL. HLA-DPB1 was independently associated with virological response [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI):1.1-3.0, P = 0.025], and with an undetectable HBV DNA (adjusted OR 2.4 95% CI: 1.2-4.7, P = 0.015) when adjusted for HBeAg status and other known response modifiers. In HBeAg-positive patients, combined HBeAg seroconversion with HBV DNA <2000 IU/mL was increasingly observed with each addition of an HLA-DPB1 G-allele (adjusted OR 2.7, 95% CI: 1.2-5.9, P = 0.012). Furthermore, HLA-DPA1 and HLA-DPB1 haplotype block GG showed comparable results for virological and combined response. CONCLUSION: In this large cohort of Caucasian chronic hepatitis B patients infected with HBV genotypes A or D, polymorphisms of HLA-DP are independently associated with both virological and serological response to PEG-IFN therapy at 6 months post-treatment.

Peginterferon alfa-2a (40 kDa) monotherapy: a novel agent for chronic hepatitis C therapy.

Current therapy for hepatitis C remains far from optimal. The modification of IFN by the attachment of a polyethylene glycol (PEG) moiety has produced long-lasting IFNs. A 40 kDa branched peginterferon alfa-2a (40 kDa) (PEG-IFN alfa-2a) has unique pharmacokinetic and pharmacodynamic properties. PEG-IFN alfa-2a is absorbed in a sustained manner and its clearance is reduced substantially compared with IFN alfa-2a, resulting in sustained serum drug concentrations. These constant serum drug levels stay above the EC(50) values (effective concentration 50%) needed for antiviral, antiproliferative and immunomodulatory actions. Sustained virological responses were significantly greater in patients who received PEG-IFN alfa-2a versus IFN alfa-2a, with a similar side effect profile. Histological improvements were seen in patients who achieved sustained virological responses and were frequently observed among patients who did not achieve a virological response. The advantages of PEG-IFN alfa-2a were also seen in patients with cirrhosis or hepatitis C virus (HCV) genotype 1.

Hepatitis C-related cirrhosis: a predictor of diabetes after liver transplantation.

Hepatitis C virus (HCV) infection has recently been suggested to be a risk factor for the development of diabetes mellitus. The aim of our study was to investigate whether the prevalence of diabetes is increased among liver transplant recipients infected with HCV. We compared the prevalence of diabetes among 278 liver transplant recipients whose original cause of liver failure was HCV infection (110 patients), hepatitis B virus infection (HBV; 53 patients), and cholestatic liver disease (CLD; 115 patients). The pretransplantation prevalence of diabetes was higher in the HCV group (29%) compared with the HBV (6%) and CLD (4%) groups (P <.001). The prevalence of diabetes remained higher in the HCV group 1 year after transplantation: 37%, 10%, and 5% in the HCV, HBV, and CLD groups, respectively (P <.001). The cumulative steroid dose during the first year of transplantation was significantly lower in the HCV group compared with the CLD group. Multivariate analysis revealed that HCV-related liver failure (P =.002), pretransplantation diabetes (P <.0001), and male sex (P =.019) were independent predictors of the presence of diabetes 1 year after transplantation. The high prevalence of diabetes persisted in the HCV group, with 41% diabetic at 5 years. The majority of patients with diabetes mellitus (89%) required insulin therapy after transplantation. Patient and graft survival rates were similar among patients with and without diabetes. In conclusion, our study shows that there is a high prevalence of diabetes among liver transplant recipients infected with HCV both before and after transplantation.