Ribavirin Therapy For Chronic Hepatitis Research Articles

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Incidence, risk factors and impact on virological response of anemia in chronic genotype 2 hepatitis C receiving sofosbuvir plus ribavirin

The major dose-limiting toxicity of ribavirin is hemolytic anemia. We investigated the incidence, risk factors and impact on virological response of anemia in chronic hepatitis C genotype 2 patients receiving sofosbuvir plus ribavirin therapy. This was a retrospective real-world analysis of a single center including 293 chronic hepatitis C genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks. Severe anemia was defined as hemoglobin concentration <10g/dl. Treatment was completed in 285 (97%) of patients, of whom one withdrew due to severe anemia. Ribavirin dose reduction was required in 88 (30%) of patients. After excluding those with baseline hemoglobin <10g/dl, 79 (29%) patients had developed severe anemia during therapy. Stepwise logistic regression analysis identified that chronic kidney disease (odds ratio [OR]=3.970, p<0.001), baseline hemoglobin level (OR=0.475, p<0.001) and baseline platelet count (OR=0.992, p=0.022) were independent factors. The sustained viral response 12 weeks off therapy (SVR12) rate was 93.9% in the per-protocol population. Multivariate analyses showed that history of hepatocellular carcinoma significantly reduced the efficacy of sofosbuvir plus ribavirin therapy (OR=0.172, p=0.001). Severe anemia, dose reduction or average dose (mg/kg/day) of ribavirin was not associated with SVR12. Severe anemia was not uncommon during sofosbuvir plus ribavirin therapy for chronic hepatitis C genotype 2 patients. Careful monitoring of anemia is necessary in patients with chronic kidney disease and low baseline hemoglobin level and platelet count.

Efficacy and safety of ribavirin therapy for chronic hepatitis E after kidney transplantation.

Hepatitis E virus (HEV) infection has been recognized as an acute condition. However, recent reports have shown that immunocompromised patients, such as those receiving solid-organ transplantation, can develop chronic hepatitis with HEV infection. We report two cases of chronic hepatitis E after kidney transplantation (KT) who were successfully treated with ribavirin monotherapy. Several years after KT, both patients had sustained elevations in the levels of liver enzymes for a period of more than 6months. Both patients had HEV infection, genotype 3a. Histological studies showed infiltration of inflammatory cells without fibrosis. Treatment included ribavirin monotherapy at a dosage of 600mg daily for 3months. One month after therapy initiation, HEV-RNA turned to negative, and remained negative at 24weeks after ribavirin therapy without severe complications. Although the treatment of chronic hepatitis E is not fully established, ribavirin therapy can be a safe and effective treatment for chronic hepatitis E.

Comparative Antiviral Efficacy of Generic Sofosbuvir versus Brand Name Sofosbuvir with Ribavirin for the Treatment of Hepatitis C.

Background Chronic hepatitis C infection is a major cause for liver failure and liver cancer and can be treated with highly effective all oral directly acting antiviral (DAA) drugs. Generic versions of these DAAs are available in India. Method This was an open-label, single-center, prospective, nonrandomized observational study for the comparative safety and efficacy of generic versus brand name sofosbuvir with ribavirin therapy for chronic hepatitis C infection (all genotypes). Between December 2014 and December 2015, 66 patients received either generic sofosbuvir (400mg) or brand name SOLVALDI (400mg) with weight based ribavirin for 24 weeks in a single multispecialty hospital in Mumbai. Monitoring viral loads and safety labs was performed as per national guidelines. Results Sustained virologic response was 72.4% versus 75.7% (p=0.78) among patients treated with generics and SOVALDI, respectively. At 4 weeks on-treatment, approximately 90% of patients from both groups had undetectable or below the lower limit of quantification. Change in hemoglobin was comparable in both groups (p=0.26). Conclusion Generic versions of sofosbuvir reported in this study are safe and efficacious to treat hepatitis C. However, bioequivalency studies of all generic DAAs need to be performed before wider use of such drugs for the treatment of hepatitis C.

Interleukin-28B Polymorphism is a Pharmacogenetic Predictor during Sofosbuvir Plus Pegylated Interferon and Ribavirin Therapy for Chronic Hepatitis C Egyptian Patients

Background and Aim: Interleukin-28B (IL-28B) polymorphism is a predictor of sustained virologic response (SVR), spontaneous clearance and personalizing therapy of hepatitis C virus (HCV). This study aimed to determine IL28B rs12979860 polymorphism among chronic hepatitis C (CHC) Egyptian patients as a step in personalized HCV therapy and pharmacogenomics. Methods: CHC Egyptian patients were received sofosbuvir (SOF) plus pegylated interferon (PEG-IFN) and ribavirin (RBV) for 12 weeks. A total of 82 HCV infected Egyptian patients and 27 healthy individuals were included in the present study. CHC Patients were classified as achieving SVR if plasma HCV-RNA was undetectable (group A) and non-responders if plasma HCV-RNA was detectable (group B). IL28B genotypes were analyzed and their associations with SVR were selected. Results: The end of treatment response (ETR) rate was 100%. However, SVR12 was 76.8% (group A) and 23.2% relapsed (group B). Among studied CHC patients, 50% were IL-28B TT, 40.2% CT, and 9.8% CC. while the percentage of their frequencies in the healthy persons were 18.5%, 51.8%, and 29.6%, respectively. These results showed that the frequencies of TT genotypes were more prevalent in HCV patients. The genotype CC (n=8) achieved higher rates of SVR in group A (87.5%) than relapsed patients in group B (12.5%) and it had the least prevalence in group B compared with the frequencies of CT (21.2%) and TT (26.9%) genotypes. These results showed that CC genotype was associated with SVR. Conclusions: It can be concluded that the individuals with IL28B TT genotype are more susceptible to HCV infection in Egyptian patients and relapse. Moreover, IL-28B CC is useful for pretreatment prediction of the outcome of HCV treatment. Hence, IL28B polymorphism could be considered as a pharmacogenetic predictor in personalized HCV therapy and pharmacogenomics during SOF plus PEG-IFN and RBV therapy for chronic hepatitis C Egyptian patients.

Elevated on-treatment levels of serum IFN-gamma is associated with treatment failure of peginterferon plus ribavirin therapy for chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response.

Nitric oxide level and CD3-ζ expression in response to Interferon- Ribavirin Therapy in chronic Hepatitis C Egyptian patients.

Hepatitis C virus (HCV) infection is one of the major causes of liver diseases all over the world; it is considered one of the leading causes of cirrhosis, hepatic failure and hepatocellular carcinoma (HCC) in developed countries including Egypt. Since, the discovery of the virus, the main drug used in all antiviral protocols was interferon- α (IFN- α) but, which is not effective in 60% of these patients. The goal of this study was to measure nitric oxide synthase (NOS), and CD3-ζ in chronic HCV patients which could explain the failure from therapy. 5ml of peripheral blood were collected from 30 patients with chronic HCV infection and 10 healthy control volunteers. Patients were categorized in to responders and non-responders according to viral titre upon IFN-α treatment. CD3-ζ expression was measured in the peripheral blood by using flow_cytomery and NOS levels were assessed in the sera. Significant decreases (P˂0.001) in the expression of CD3-ζ in IFN-α non- responder was recorded when compared to responder patients and with healthy volunteers. In contrast, there were significant increases (P˂0.001) in the expression of NOS in IFN-α responder as compared to non-responder patients and healthy volunteers. Conclusion: these findings can be suggestedNitric oxide level and CD3-ζ expressionthat have immune suppressive function can be reversed and enhance responsive of HCV patients to interferon- α and ribavirin.

Correlation between Serum Levels of TNFR and IL6 with Treatment Response to Pegylated Interferon and Ribavirin Therapy in Chronic Hepatitis C Egyptian Patients

Correlation between Serum Levels of TNFR and IL6 with Treatment Response to Pegylated Interferon and Ribavirin Therapy in Chronic Hepatitis C Egyptian Patients

Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection

Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world—in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.

On-treatment predictions of success in peg-interferon/ribavirin treatment using a novel formula.

To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. We analyzed the clinical data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy, derived a predictive formula to assess a sustained virological response of the individual patient using a logistic regression model and confirmed the validity of this formula. The formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients. Sustained virological response was obtained in 83 (47.2%) of the patients and we derived formulae to predict sustained virological response at pretreatment and weeks 4, 12 and 24. The likelihood of sustained virological response could be predicted effectively by the formulae at weeks 4, 12 and 24 (the area under the curve of the receiver operating characteristic: 0.821, 0.802, and 0.891, respectively), but not at baseline (0.570). The formula at week 48 was also constructed and validation by test data achieved good prediction with 0.871 of the area under the curve of the receiver operating characteristic. Prediction by this formula was always superior to that by viral kinetics. These results suggested that our formula combined with viral kinetics provides a clear direction of therapy for each patient and enables the best tailored treatment.

Is the use of IL28B genotype justified in the era of interferon-free treatments for hepatitis C?

In 2009, several groups reported that interleukin-28B (IL28B) genotypes are associated with the response to peginterferon plus ribavirin therapy for chronic hepatitis C virus (HCV) infection in a genome-wide association study, although the mechanism of this association is not yet well understood. However, in recent years, tremendous progress has been made in the treatment of HCV infection. In Japan, some patients infected with HCV have the IL28B major genotype, which may indicate a favorable response to interferon-including regimens; however, certain patients within this group are also interferon-intolerant or ineligible. In Japan, interferon-free 24-wk regimens of asunaprevir and daclatasvir are now available for HCV genotype 1b-infected patients who are interferon-intolerant or ineligible or previous treatment null-responders. The treatment response to interferon-free regimens appears better, regardless of IL28B genotype. Maybe other interferon-free regimens will widely be available soon. In conclusion, although some HCV-infected individuals have IL28B favorable alleles, importance of IL28B will be reduced with availability of oral interferon free regimen.

Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C.

Background and AimThe accuracy for predicting virological outcomes of peginterferon-α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL28B genotyping. Our in vitro study revealed that the numbers of (TA) dinucleotide repeats [(TA)n] of rs72258881, which is located in the promoter region of IL28B gene, might regulate IL28B transcription. We aimed to evaluate the usefulness of these host factors for predicting virological outcomes of this therapy in response-guided clinical settings.MethodsA nationwide, multi-center prospective study in Japan determined IL28B (rs8099917) genotype, (TA)n of rs72258881, and amino acid substitutions of hepatitis C virus and used these for multivariate analysis together with other parameters at pretreatment.ResultsAfter enrolling 215 patients with genotype 1 and high viral load from 23 hospitals between October 2009 and February 2011, intent-to-treat analysis identified 202 patients in whom the final virological outcomes could be determined. Non-virological response by non-TT genotype was predicted with 79.7% accuracy. When combined with the (TA)n, the incidences of virological response tended to be higher in the longer (TA)n group, regardless of rs8099917 genotype. Multivariate logistic regression analysis revealed that rs8099917 non-TT genotype (P < 0.001), shorter (TA)n (P = 0.011), mutation of amino acid 70 in the virus core region (P = 0.029), and lower levels of serum albumin (P = 0.036) were independently associated with non-virological response.ConclusionsIL28B genotype and (TA)n of rs72258881 may independently affect virological outcomes of peginterferon-α and ribavirin as host factors, even in response-guided therapy.

The real impact of telaprevir dosage on the antiviral and side effects of telaprevir, pegylated interferon and ribavirin therapy for chronic hepatitis C patients with HCV genotype 1.

Triple therapy with telaprevir, pegylated interferon and ribavirin has been reported to improve antiviral efficacy but have potentially severe adverse effects in patients with chronic hepatitis C. To avoid the severe effects of telaprevir, lowering the dose has been suggested. However, impact of dosage changes on antiviral and adverse effects remains unclear. One hundred and sixty-six Japanese patients with HCV genotype 1 were treated with triple therapy. The drug exposure of each medication was calculated by averaging the dose actually taken. The overall SVR rate was 82%. The telaprevir discontinuation rate was 26%. The factors associated with discontinuation were an older age (≥65 y.o.) and a higher average dose during treatment. The telaprevir discontinuation rates were 42%, 25% and 14% in patients at ≥35, 25-35 and <25 mg/kg/day of telaprevir and 58% in older patients at ≥35 mg/kg/day of TVR. The factors associated with SVR were treatment-naïve, relapse to previous treatment, higher average telaprevir dose during treatment and completion of treatment. The SVR rate was higher, at 91%, in patients at 25-35 mg/kg/day of telaprevir than the 71% and 78% observed in those at <25 and ≥35 mg/kg/day of drug. In Japanese patients, a mean telaprevir dose of 25-35 mg/kg/day during treatment can augment its efficacy in triple therapy for patients with HCV genotype 1.

Efficacy and safety of pegylated interferon plus ribavirin therapy for chronic hepatitis C genotype 6: a meta-analysis.

BackgroundHepatitis C genotype 6 (HCV-6) is prevalent in Southeast Asia. Data on the efficacy of direct-acting antiviral agents in chronic HCV-6 patients is limited and pegylated interferon (Peg-IFN) plus ribavirin (RBV) combination therapy remains standard therapy for those patients.AimMeta-analysis was performed to assess the efficacy and safety of Peg-IFN plus RBV combination therapy for chronic HCV-6 patients.MethodsRelevant studies were found by database search through Medline, Embase, Web of Science and The Cochrane Library. All published clinical trials assessing the efficacy of Peg-IFN plus RBV combination therapy for chronic HCV-6 patients were included. Sustained virological response rate (SVR) was pooled. We performed additional meta-analyses to compare the SVR outcomes of 24 versus 48 weeks of treatment in four head-to-head trials. Another second meta-analysis was also conducted to compare the efficacy of combination Peg-IFN plus RBV therapy in HCV-6 versus HCV-1 patients.ResultsThirteen studies met the inclusion criteria. The pooled SVR of all single arms was 75% (95% CI: 0.68–0.81). The SVR of 24 weeks treatment was significantly lower than that at 48 weeks, with a risk difference of −14% (95% CI: −0.25 to −0.02, p = 0.02). However, when restricted to the patients with rapid virological response (RVR), there was no significant effect on SVR between these two treatment groups, with a risk difference of −1% (95% CI: −0.1 to 0.07, p = 0.67). The SVR in HCV-6 patients was significantly higher than that in HCV-1 patients, with a relative risk of 1.35 (95% CI: 1.16–1.57, p<0.001). Side effects were common, but rarely caused treatment discontinuation.ConclusionsThe results of this meta-analysis suggest that Peg-IFN plus RBV is effective and safe for HCV-6 patients. Shortening treatment seems to be feasible in HCV-6 patients with RVR when tolerance to treatment is poor. However, this decision should be made cautiously.

Restoration of natural killer cell activity by pegylated interferon‐alpha/ribavirin therapy in chronic hepatitis C patient

The combination therapy of pegylated interferon-α and ribavirin (PEG IFN/RBV) is one of the effective treatments for chronic hepatitis C (CHC) patients. Natural killer (NK)-cell activity was reported to be impaired in patients with hepatitis C virus (HCV). The aim of this study was to examine whether PEG IFN/RBV therapy could restore NK activity in CHC patients. In 19 CHC patients, PEG IFN/RBV therapy was performed. Just before (0M), at 3 months of the therapy (3M) and at 6 months after completion of the therapy (6M), NK activity and the frequency of NK cells, CD56(dim) NK cells and CD56(bright) NK cells in peripheral blood was estimated by creatinine release assay and flow cytometry. Statistical analysis was performed by anova and Mann-Whitney U-test. anova showed that NK activity significantly improved at 6M (vs 0M, P < 0.05) in the patients studied and in the patients with sustained virological response (SVR). It also showed that frequency of CD56(bright) NK cells was significantly increased at 6M (vs 0M, P < 0.05) in the patients studied and in the SVR group. However, no significant change in NK activity and frequency of CD56(bright) NK cells were detected in non-SVR group. Furthermore, NK activity ratio (6M/0M) in the SVR group was revealed to be higher compared with that in the non-SVR group by analysis using Mann-Whitney U-test (P < 0.05). PEG IFN/RBV therapy in CHC patients could improve NK activity by increasing the frequency of CD56(bright) NK cells in SVR patients. Our study also revealed that eradication of HCV could restore NK-cell activity.

Treatment efficacy of pegylated interferon plus ribavirin therapy in chronic hepatitis C patients with mixed genotype 1/2 infection

The treatment efficacy of patients with mixed hepatitis C virus (HCV) genotype 1/genotype 2 (HCV-1/2) remains unknown. We aimed to elucidate the sustained virological response (SVR) rate in patients with HCV-1/2 infection. One hundred and ten HCV-1/2 patients treated with response-guided peginterferon/ribavirin therapy (24 weeks for patients with a rapid virological response [RVR] and low viral loads; 48 weeks for patients without a RVR or high viral loads) were allocated. Two hundred HCV-1 patients were selected as a historical control. Interleukin-28B (IL-28B) rs8099917 genotype was tested for the association with an SVR. The rates of RVR, sustained virologic response (SVR), and relapse rate were 71.8%, 87.3%, and 11.1%, respectively. The SVR rate was significantly higher in patients with an abbreviated regimen as compared with those with 48-week regimen (95.5% vs 75.0%, P = 0.002), and both were similar to the HCV-1 historical control. Stepwise logistic regression analysis revealed that lower baseline viral loads were the single factor predictive of an RVR (odds ratio/95% confidence intervals [OR/CI] of 41.62/9.72-178.19, P < 0.001). The achievement of an RVR was the single best factor predictive of an SVR (OR/CI: 7.5/1.33-42.27, P = 0.02). Nevertheless, an abbreviated regimen became the single factor associated with an SVR if treatment regimen was taken into consideration (OR/CI: 11.0/1.25-96.79, P = 0.03). The SVR rate did not differ between patients with rs8099917 TT and TG/GG genotype (91.7% vs 87.5%, P = 0.63). The treatment efficacy of patients with HCV-1/2 was satisfactory. The role of IL-28B genetic variants in the population with response-guided therapy was limited.

Assessment of health‐related quality of life and how it predicts the outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C

Chronic infection with hepatitis C virus (HCV) decreases health-related quality of life (HRQOL). The present study was planned to investigate the impact of HRQOL of patients with chronic hepatitis C (CHC) on the outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to IL28B polymorphisms. The present study enrolled 228 CHC patients and assessed their HRQOLs prospectively with the 36-item short-form health survey. The patients with CHC have lower physical HRQOL status than the general population (P = 0.037, the Z-test). The patients with advanced liver diseases exhibited further decreases in HRQOL (P = 0.036, Spearman's rank correlation coefficient). The score of total HRQOL was significantly lower in the group with sustained virological response (SVR) to the therapy with pegylated interferon and RBV than the non-SVR group (P = 0.031, the Mann-Whitney U-test), with significantly lower scores of mental component and its comprising subscales in the SVR group. Stepwise multivariate logistic regression analysis showed that low HRQOL score ≤ 400 points was significantly associated with SVR (odds ratio = 2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients with low HRQOL score will have significantly less decrease in HRQOL score by 4 weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045). HRQOL is one of the significant predictor of the outcomes of therapy with pegylated interferon and RBV independently from IL28B polymorphism.

Neutrophil-to-lymphocyte ratio as a predictor of response to peginterferon plus ribavirin therapy for chronic hepatitis C.

We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR) could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, n = 263; genotype 2, n = 297; others/unknown, n = 42) receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR) and sustained virological response (SVR) were achieved in 436 (73%) and 458 (76%) of the patients, respectively. Higher NLR (≥1.42) was found to be associated with higher prevalence of DM (P = 0.039) and higher hepatitis C viral load (P = 0.002) and white cell count (P < 0.001). NLR was significantly lower in patients with RVR and SVR compared to those without (P = 0.032 and 0.034, resp.). However, NLR was not an independent factor by multivariate analysis. In the subgroup analysis, higher NLR (≥1.42) (odds ratio, 0.494, P = 0.038) was an independent poor predictor of SVR in genotype 2 patients but was not in genotype 1 patients. In conclusion, NLR is a simple and easily accessible marker to predict response to peginterferon plus ribavirin therapy for chronic hepatitis C genotype 2.

End treatment response and sustained viral response in hepatitis C virus genotype 3 among Pakistani population

BACKGROUND AND OBJECTIVESThis study aimed to determine the end treatment response (ETR) and sustained viral response (SVR) to interferon (IFN) and ribavirin in hepatitis C virus (HCV) genotype 3 in the Pakistani population.DESIGN AND SETTINGSThis is an interventional study conducted from January 2010 to December 2012 in Lyari General Hospital and Abbasi Shaheed Hospital, Karachi, outpatients department.METHODSAll patients with chronic hepatitis C genotype 3 infections were included. Patients with decompensated chronic liver disease, or having coexisting hepatitis B virus/human immunodeficiency virus were excluded. All patients received IFN alpha, 3 million international units (MIU), subcutaneously 3 times weekly and ribavirin >800 mg/d for a period of 6 months. Outcome parameters included ETR (negative polymerase chain reaction [PCR] at the end of therapy), SVR (negative PCR both at the end of treatment and 6 months later), and relapse (PCR negative at the end of treatment but positive 6 months later) were determined.RESULTSA total of 1170 patients were included with a female to male ratio of 1.64:1 and a mean age of 31.6 (8.4) years. Among 1170 patients, 985 completed the therapy as per the protocol, 119 were defaulted (treatment abandoned before completion), and 66 had to stop treatment due to side effects. ETR was 74.1%, SVR was 98%, relapse rate was 1.5%, and 10.1% were nonresponders. SVR was seen only in patients who had achieved an ETR (n=867). SVR was achieved in 848 patients (out of 867) (98%), relapse was seen in 13 (1.5%), and 6 (0.7%) patients lost follow-up after stopping treatment. Patients achieving ETR and SVR had a mean serum alanine aminotransferase of 71.3 (57.1) and 71.0 (56.5), respectively, which is approximately twice the upper normal limit.CONCLUSIONThe conventional IFN and ribavirin therapy in genotype 3 chronic HCV-infected patients gives an ETR and SVR of 74.1% and 98%, respectively.

Influence of Vitamin D-Related Gene Polymorphisms (CYP27B and VDR) on the Response to Interferon/Ribavirin Therapy in Chronic Hepatitis C

Background and AimsVitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus (HCV). This study was performed to assess the putative influence of polymorphisms in vitamin D-related genes on the response to antiviral therapy in patients with chronic hepatitis C (CHC).MethodsSingle nucleotide polymorphisms (SNPs) in CYP27B-1260 gene promoter (rs10877012AC) and in vitamin D receptor (VDR) gene rs2228570TC, rs1544410CT, rs7975232AC and rs731236AT were analyzed in a cohort of 238 Caucasian CHC patients treated with pegylated interferon (Peg-IFN) plus ribavirin (RBV). Multivariate analyses were performed to exclude confounding effects of well-known baseline predictors of response to therapy (HCV genotype and load, IL28B genotype, age, and GGT and serum cholesterol).ResultsThree SNPs at the VDR gene (rs1544410, rs7975232 and rs731236) were in strong linkage disequilibrium, with the CCA haplotype predicting therapeutic failure [Odds ratio 2.743; (95% C.I. 1.313–5.731), p = 0.007]. The carrier state of the VDR rs2228570 T allele was inversely related to the probability of therapeutic failure [Odds ratio 0.438; 95 C.I. (0.204–0.882), p = 0.021]. No relation existed between CYP27B-1260 rs10877012 polymorphism and response to therapy. The area under the operating curve (AUROC) based on the model including all variables significantly related to the response to therapy was 0.846 (95% confidence interval = 0.793–0.899).Conclusion VDR gene polymorphisms are independently related to the response to Peg-IFN+RBV therapy in chronic hepatitis C and could be used as complementary biomarkers of response when included in a prediction algorithm in association with demographic, virologic, biochemical and genetic traits.