Ribavirin Combination Therapy Research Articles

Pegylated interferon plus ribavirin combination therapy in postliver transplant recipients with recurrent hepatitis C virus infection

Posttransplant hepatitis C virus (HCV) recurrence is universal in chronic hepatitis C recipients. Antiviral therapy is suggested after liver transplant to halt disease progression. Pegylated interferon plus ribavirin therapy remains the standard of care in many areas where direct antiviral agents are poorly accessible. This study aimed to assess the treatment efficacy and safety of the regimen for Taiwanese patients with post-transplant HCV recurrence. Nine patients with HCV recurrence postliver transplantation were allocated. Patients received either pegylated interferon α-2a 180 μg/wk or pegylated interferon α-2b 1.5 mg/kg/wk plus ribavirin for 24–48 weeks. The primary endpoint was the achievement of sustained virological response (SVR), defined as undetectable HCV RNA throughout 6 months of follow-up after the end of treatment. The safety profiles were also documented. The rates of rapid virological response, early virological response, end-of-treatment virological response, and SVR were 33%, 63%, 75%, and 56% respectively. Of the four patients who failed antiviral treatment, the treatment responses were nonresponse (n = 1), loss of follow-up (n = 1), and relapse (n = 2). Three patients terminated therapy early due to severe adverse events, including severe anemia, intra-abdomen infection, and hepatocellular carcinoma recurrence. One of the three patients who terminated treatment early at Week 6 experienced rapid virological response followed by SVR. Pegylated interferon/ribavirin combination allowed a chance for cure with a fair SVR rate in Taiwanese chronic hepatitis C patients postliver transplantation. Early identification of side effects and careful monitoring during therapy might enhance the treatment efficacy.

Identification of treatment-experienced hepatitis C patients with poor cost-effectiveness of pegylated interferon plus ribavirin from a real-world cohort.

Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads >400,000IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.

Clinical timing and benefit of antiviral treatment for hepatitis C

Current treatments for hepatitis C include pegylated interferon-α (Peg-IFNα) and ribavirin (RBV) combination therapy and direct antiviral agents (DAAs). Antiviral treatment can be initiated after 4 to 6 months of clinical observations for patients with acute infections, but should be started as early as possible for those with chronic infections. However, for patients who are ineligible for Peg-IFN and RBV combination therapy and have no unrestricted access to DAAs, it is advised that they wait for the approval of DAAs in China if their medical condition is under control. Though, antiviral therapy should be started immediately if the disease progresses. It has been reported that there are numerous clinical benefits of antiviral treatment for hepatitis C. However, the long-term impact of DAAs treatment including efficacy and safety is limited and remains to be explored.

Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy

The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy. This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated. Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7% (13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92K at baseline. This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.

ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin.

Sofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV-induced anemia is a troublesome side-effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV-induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment and ITPA gene variants. Ninety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms of ITPA and the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed. Overall SVR at 12weeks was 94.4% (85/90). Patients with the ITPA CA/AA genotypes had a lower degree of anemia throughout the therapy than those with the ITPA CC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with the ITPA CA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was <12g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR. Patients with the ITPA CA/AA genotype were less likely to develop anemia than those with the ITPA CC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug-induced adverse events, particularly in patients with pre-existing anemia.

Association of IFNL3 Genotype with Hepatic Steatosis in Chronic Hepatitis C Patients Treated with Peginterferon and Ribavirin Combination Therapy.

Background: Genetic variation near the interferon lambda 3 (IFNL3) is known to be associated with response to pegylated interferon (pegIFN) and ribavirin combination therapy in patients with chronic hepatitis C virus (HCV) infection which is often accompanied by hepatic steatosis.Aims: We examined whether this genetic variation is associated with host lipids and treatment response.Methods: A total of 101 Japanese patients who had underwent liver biopsy before treatment with pegIFN and ribavirin for HCV genotype 1b infection were retrospectively analyzed for association between IFNL3 genotypes (rs8099917) and clinical factors including histopathological features of the liver. The presence of >5% steatosis in the liver specimen was defined as hepatic steatosis.Results: Forty patients (40%) had liver steatosis before therapy. Patients with IFNL3 minor genotype (non-TT) showed lower low-density lipoprotein cholesterol level (p=0.0045), higher γ-glutamyl transpeptidase level (p=0.0003) and higher prevalence of hepatic steatosis (p=0.0002). Advanced fibrosis [odds ratio (OR) 4.63, p=0.03] and IFNL3 major genotype (OR 0.13, p=0.001) were 2 independent factors for determining the presence of hepatic steatosis. Among the factors associated with sustained virological response, IFNL3 genotype was the most significant predictor, as per multivariate analysis.Conclusions: Our results confirmed that IFNL3 genotype is associated with hepatic steatosis as well as IFN response.

Is the 25-year hepatitis C marathon coming to an end to declare victory?

Hepatitis C virus (HCV) which was originally recognized as posttransfusion non-A, non-B hepatitis has been a major global health problem affecting 3% of the world population. Interferon/peginterferon and ribavirin combination therapy was the backbone of chronic HCV therapy for two decades of the journey. However, the interferon based treatment success rate was around 50% with many side effects. Many chronic HCV patients with psychiatric diseases, or even cytopenias, were ineligible for HCV treatment. Now, we no longer need any injectable medicine. New direct-acting antiviral agents against HCV allowed the advance of interferon-free and ribavirin-free oral regimens with high rates of response and tolerability. The cost of the medications should not be a barrier to their access in certain parts of the world. While we are getting closer, we should still focus on preventing the spread of the disease, screening and delivering the cure globally to those in need. In the near future, development of an effective vaccine against HCV would make it possible to eradicate HCV infection worldwide completely.

A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges.

Background:The estimated hepatitis C virus (HCV) carriers are approximately 10 million in Pakistan which usually progresses to chronic hepatitis, with rare cases of spontaneous viral eradication. The present article reviews the treatment status of HCV infection in Pakistani population and various factors associated with the treatment response rates.Methods:Literature on anti-HCV therapy was searched in PubMed, Google Scholar and PakMediNet. Thirty three different studies representing different geographic regions of Pakistan published from 2002 to 2016 were included in the present review. Weighted mean, standard error estimates (SE) and standard deviation (SD) were determined for each population group.Results:Mean value for sustained virological response (SVR) for standard IFN plus ribavirin (RBV) combination therapy was 68.38% ± 14.13% (range 33.8%–87.10%; SE 3.08) and pegylated-IFN plus RBV combination therapy 64.38% ± 8.68% (range 55.0%–76.00%; SE 3.88). The lowest value for SVR has been reported to be 24.3% (for genotype 1; administering INF-α 2b 3MU 3 times/week and RBV 1000–1200 mg/day for 48 weeks) while highest of 87.5% (genotype 3a; INF-α 2a 3MU 3 times/week and RBV 1000–1200 mg/day for 24 weeks). The mean value for rapid virological response (RVR) was found to be 48.18% ± 29.20% (SE 9.73). As PEG-interferon and direct acting antivirals (DAAs) are relatively expensive, interferon-alfa (IFN-α) and RBV combination therapy have been used widely to treat HCV infected patients in Pakistan for the last one and half decade. On average, 2.45% of the patients discontinued treatment due to severe side effects.Conclusion:We encourage further studies on understanding host and viral factors associated with specific focus on harder to treat viral variants (relapsers and nonresponders). These variants are currently rising in the country.

Interleukin 10 gene single nucleotide polymorphisms in Polish patients with chronic hepatitis C: Analysis of association with severity of disease and treatment outcome

It is suggested that interleukin 10 (IL-10), as a modulator of immune response, is likely to influence the elimination of hepatitis C virus (HCV), the progression of chronic hepatitis C (CHC) and the response to interferon-based therapy in CHC patients. The aim of the study was to analyze the association of single nucleotide polymorphisms (SNPs) of IL-10 gene with severity of liver disease (degree of inflammation and stage of fibrosis) and outcome of pegylated interferon alpha and ribavirin combined therapy (sustained virological response (SVR) and relapse) in 196 Polish CHC patients infected with HCV genotype 1. The analysis included IL-10 promoter SNPs: −1082(A/G) rs1800896, −819(C/T) rs1800871, −592(C/A) rs1800872 and SNP in the 3′ UTR of IL-10 gene: +4529(A/G) rs3024498. Genotyping was performed using PCR-RFLP and HRM analysis. It was demonstrated that the −592C allele is associated with mild hepatic inflammation. Moreover, it was found that the −819C allele might be associated with SVR and that the ACCA haplotype and intermediate IL-10 producer ACC haplotype are associated with SVR and non-relapse. It can be concluded that IL-10 SNPs are associated with severity of disease and response to therapy and may be considered as potential prognostic and predictive markers in CHC.

Impact ofIFNL4rs12979860 and rs8099917 polymorphisms on response to Peg-Interferon-α and Ribavirin in patients with congenital bleeding disorder and chronic hepatitis C

The aim of this study was to determine whether two polymorphisms of the human interferon lambda 4 (IFNL4) gene (rs12979860 and rs8099917) can predict sustained virologic response (SVR) following antiviral therapy in patients with inherited bleeding disorder and chronic hepatitis C (CHC). This retrospective study was conducted on 294 patients with congenital bleeding disorder and CHC who were treated with Peg-Interferon-α (PegIFN) and Ribavirin (RBV). Baseline patient and viral parameters were measured and analyzed statistically to assess their combined and individual contributions to SVR prediction. The most prevalent variants of rs12979860 and rs8099917 identified among the study patients were CT (45.9%) and TT (57.6%), respectively. Overall, SVR was achieved in 69% of the study patients. The rate of SVR was lower in patients with HCV genotype-1 than in those with HCV genotype-3 (62% vs 88%; P<.001; OR=0.23). Multivariate analysis of SVR predictors in patients with HCV genotype-1 infection included age (<24years), BMI (<25), absence of cirrhosis, HCV RNA level (<400000IU/mL), rs8099917 TT and rs12979860 CC, all of which were associated with a higher SVR rate. In HCV genotype-3 infection, only rs12979860 CC was significantly associated with SVR. These results demonstrate that polymorphisms of the IFNL4 gene are highly associated with SVR to PegIFN and RBV combination therapy in patients with a congenital bleeding disorder and CHC. Assessment of rs12979860 and rs8099917 genotypes can guide physicians in choosing an optimal treatment regimen, including less expensive therapies that may only be available in many geographic locales.

Hepatitis C viral dynamics during ribavirin priming differ according to prior treatment response and HCV type

The mode of action of ribavirin is not completely understood. Ribavirin monotherapy has a measurable antiviral effect, which shows great variability. It might lead to an earlier steady state of plasma concentration and therefore enhance the effect of following combination treatment. The aim of this study was to evaluate the antiviral effect of ribavirin priming and its influence on sustained virologic response after combination treatment in a group of patients with different hepatitis C virus (HCV) types with or without prior treatment experience. Retrospective analysis of 75 patients (37 treatment naïve, 20 prior relapse, 16 prior nonresponse, genotype 1 present in 60 patients) from five centres who received ribavirin priming as part of an individual strategy in order to improve treatment outcome. All patients received ribavirin monotherapy with a mean dose of 14.5mgkg-1 body weight for a mean of 28days. After ribavirin priming, dual combination treatment with pegylated interferon alfa and ribavirin was started. The mean HCV RNA decline after ribavirin priming was 0.6 log10 IUmL-1 (P<.001). The initial viral decline depended on HCV type and previous treatment status being highest among prior relapsers (0.8 log10 IUmL-1 ; P=.002) and HCV type 2/3 (1.2 log10 IUmL-1 ; P=.05) and lowest among those with prior nonresponse (0.3 log10 IUmL-1 , P=.01). IFNL4 (formerly IL28B) genotype for rs12979860 and IFNL3 genotype rs8099917 did not influence the initial viral decline. The study demonstrates a significant variability in the viral dynamics and antiviral efficacy of ribavirin monotherapy, which is mainly influenced by prior treatment status. The fact that the lowest response pattern was observed in prior nonresponder patients to pegylated interferon alfa plus ribavirin combination therapy can be taken as a hint that not only the individual interferon, but also the ribavirin sensitivity contributes significantly to the nonresponsive state.

Mouse Systems to Model Hepatitis C Virus Treatment and Associated Resistance.

While addition of the first-approved protease inhibitors (PIs), telaprevir and boceprevir, to pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy significantly increased sustained virologic response (SVR) rates, PI-based triple therapy for the treatment of chronic hepatitis C virus (HCV) infection was prone to the emergence of resistant viral variants. Meanwhile, multiple direct acting antiviral agents (DAAs) targeting either the HCV NS3/4A protease, NS5A or NS5B polymerase have been approved and these have varying potencies and distinct propensities to provoke resistance. The pre-clinical in vivo assessment of drug efficacy and resistant variant emergence underwent a great evolution over the last decade. This field had long been hampered by the lack of suitable small animal models that robustly support the entire HCV life cycle. In particular, chimeric mice with humanized livers (humanized mice) and chimpanzees have been instrumental for studying HCV inhibitors and the evolution of drug resistance. In this review, we present the different in vivo HCV infection models and discuss their applicability to assess HCV therapy response and emergence of resistant variants.

Dermatological Manifestations of Pegylated Interferon alfa2a and Ribavirin Combination Therapy in Chronic HCV Patients

Background and study aim: Dermatological adverse events are an existing concern during treatment of chronic hepatitis C virus infection. Pegylated Interferon (peg –IFN- alfa2a) and ribavirin combination therapy is associated with well-characterized dermatological lesions tending towards a uniform entity of dermatitis. A prospective observational study was designed to evaluate the frequency and clinical pattern of cutaneous side effects in a cohort of patients receiving combination therapy of (pegylated interferon alfa2a) and ribavirin for chronic hepatitis C infection. Patients and Methods: This study was carried out at Alahrar Center for treating chronic hepatitis C patients which is one of the centers of the national committee for treating chronic hepatitis C patients (HCV), Zagazig, Sharkia governorate, Egypt over a period of one year starting from January, 2014 to December 2014. A cohort of 116 consecutive, HCV-positive patients to be treated with pegylated interferon alfa2a and ribavirin with standard doses, were prospectively enrolled. After taking an informed consent, detailed history and cutaneous examination, before treatment and then monthly follow up for one year(during the course of treatment) were performed and recorded .All patients were subjected to throughout, routine laboratory investigations before enrollment including, CBC, random blood sugar, complete liver and renal function tests, TSH, Alfa fetoprotein, antibilharzial Ab titre, ANA, P.T, INR, quantitative PCR for HCV-RNA, pregnancy test was performed for the ladies. Results: 113/116 patients (97%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 69 cases (Session [CurrentTestPartTermID]%). Pigmented Oral lichen planus was noted in 50 cases (43%) and generalized pigmentation in 32 (27%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 42 (36%) and 40 (34%) cases respectively. Pruritus occurred in 50 cases (43%), aphthous stomatitis was observed in 33 cases (38%), 19 patients (22%) either developed or had worsening of melasma and 23 (27%) developed urticaria. Brittle nails (10 cases), cheilitis (8 cases), glossitis (3 cases), actinic lichen planus (9 cases), greying of hair (3 cases), discoloration of moustache hair (1 case), and photo-sensitivity (3 cases) were also observed. Preexisting psoriasis (8 cases), and lichen planus (5 cases) aggravated. Eruptive seborrhoeic keratosis was reported in 1 case. Conclusion: 113/116 patients (97%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 69 cases (Session [CurrentTestPartTermID]%). Pigmented Oral lichen planus was noted in 50 cases (43%) and generalized pigmentation in 32 (27%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 42 (36%) and 40 (34%) cases respectively. Pruritus occurred in 50 cases (43%), aphthous stomatitis was observed in 33 cases (38%), 19 patients (22%) either developed or had worsening of melasma and 23 (27%) developed urticaria. Brittle nails (10 cases), cheilitis (8 cases), glossitis (3 cases), actinic lichen planus (9 cases), greying of hair (3 cases), discoloration of moustache hair (1 case), and photosensitivity (3 cases) were also observed. Preexisting psoriasis (8 cases), and lichen planus (5 case) aggravated. Eruptive seborrhoeic keratosis was rep case).

Evidence-based clinical practice guidelines for liver cirrhosis 2015.

The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for liver cirrhosis in 2015. Eighty-three clinical questions were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. Manual searching of the latest important literature was added until August 2015. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This digest version in English introduces selected clinical questions and statements related to the management of liver cirrhosis and its complications. Branched-chain amino acids relieve hypoalbuminemia and hepatic encephalopathy and improve quality of life. Nucleoside analogues and peginterferon plus ribavirin combination therapy improve the prognosis of patients with hepatitis B virus related liver cirrhosis and hepatitis C related compensated liver cirrhosis, respectively, although the latter therapy may be replaced by direct-acting antivirals. For liver cirrhosis caused by primary biliary cirrhosis and active autoimmune hepatitis, urosodeoxycholic acid and steroid are recommended, respectively. The most adequate modalities for the management of variceal bleeding arethe endoscopic injection sclerotherapy for esophageal varices and the balloon-occluded retrograde transvenous obliteration following endoscopic obturation with cyanoacrylate for gastric varices. Beta-blockers are useful for primary prophylaxis of esophageal variceal bleeding. The V2 receptor antagonist tolvaptan is a useful add-on therapy in careful diuretic therapy for ascites. Albumin infusion is useful for the prevention of paracentesis-induced circulatory disturbance and renal failure. In addition to disaccharides, the nonabsorbable antibiotic rifaximin is useful for the management of encephalopathy. Anticoagulation therapy is proposed for patients with acute-onset or progressive portal vein thrombosis.

Meta-Analysis of Combination Therapy of Chinese Herbs Plus Interferon and Ribavirin in Patients with Chronic Hepatitis C.

BackgroundWe aimed to evaluate the combination therapy of Chinese herbs plus interferon and ribavirin in treatment of patients with chronic hepatitis C (CHC).Material/MethodsRelated databases were searched to identify randomized controlled trials (RCTs) that evaluated biochemical response, virological response, histological response, and/or adverse reactions to combination therapy of interferon and ribavirin with and without Chinese herbs. The RR (relative risk) with a 95% confidence interval (CI) was calculated. Sensitivity analysis was conducted by omitting one study at a time. Publication bias among the eligible studies was evaluated by Egger’s test.ResultsA total of 17 RCTs matched the selection criteria. Overall, combination therapies of Chinese herbs plus interferon and ribavirin achieved significantly higher ALT (alanine transaminase) and ETVR (the end-of-treatment viral response), and significantly lower levels of HA (hyaluronic acid), LN (laminin), PC III (procollagen iii peptide), IV-C (type IV collagen), decreased LC (decreasing leukocyte count), ATF (abnormal thyroid function), psychosis, and anemia in CHC patients compared with those treated without Chinese herbs. Sensitivity analysis showed no changes and no potential publication bias was found.ConclusionsThe current evidence suggests that combination therapy of Chinese herb plus interferon and ribavirin yields better outcome and fewer adverse events in CHC patients than that of interferon plus ribavirin therapy.

The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients

BackgroundThe hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries.ObjectivesThe aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients.Patients and MethodsA total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay.ResultsIn this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006).ConclusionsThe data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in Azerbaijani patients with chronic hepatitis C. Moreover, host genetic polymorphisms, such as those of the IL28B locus, might be useful for predicting the responsiveness to Peg-IFNα-2a/RBV combination therapy against HCV.

Treatment Response of Chronic Hepatitis C Patients and Health-Related Quality of Life

Objective(s): The objectives of present study were to investigate the response of chronic hepatitis C (CHC) patients to pegylated interferon alpha plus ribavirin (PEG-INF/RBV) combination therapy, to identify factors that could predict their response to treatment and to assess their health-related quality of life (HRQOL) before, during and after PEG-INF/RBV combination therapy. Methods: An intervention study (one group pre-test - post-test design) was used. Data were collected from 300 CHC patients who attended the Hepatology and Interferon Therapy Unit at Gamal Abd El Naser Insurance Hospital using a pre-designed structured interviewing questionnaire and viral hepatitis C quality of life questionnaire. Review of the patients’ medical records and their laboratory investigations was also carried out. Results: The cumulative seronegativity rate of treated patients was 74%. The proportion of CHC patients who survived seronegativity was 0.270 at the 12 th week, 0.261 at the 24 th week and 0.250 at the 48 th week of treatment. Patients’ age and viral load significantly affected seronegativity. Significant univariate main effects for age were statistically associated with poor HRQOL in the domains of physical functioning, role limitations due to physical health, emotional problems and pain. Presence of chronic diseases and HC viral load had a significant effect on physical functioning, role limitations due to physical health problems, emotional problems and pain. All domains of the HRQOL short form (SF36) decreased by the end of the 4 th week and started to increase at the 24 th and 48 th weeks of the follow up period. Conclusion: The proportion of CHC patients who survived seronegativity was 0.250 at the 48 th week of treatment. Factors associated with seroconversion were age and hepatitis C virus (HCV) load. CHC patients aged 55 years and above, those with chronic diseases and those with HC viral load of ≥ 900,000 IU/ml were found to be statistically associated with poor HRQOL. All the domains of the SF36 decreased by the end of the 4 th week and started to increase at the 24 th and 48 th weeks of follow up period. Keywords: hepatitis C, treatment, quality of life.

Impact of ribavirin dosage in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin combination therapy.

The factors associated with sustained virologic response (SVR) in chronic hepatitis C (CH-C) genotype 1 patients treated with simeprevir (SMV), pegylated interferon (Peg-IFN) plus ribavirin (RBV) triple therapy have not been fully investigated. Two hundred and twenty-nine treatment-naïve CH-C patients treated with SMV triple therapy were enrolled in this study. The overall SVR rate was 87% in per-protocol analysis. In multivariate analysis, the interleukin (IL) 28B genotype (rs8099917, TT vs. non-TT, odds ratio [OR]: 0.044, P = 0.001) and RBV dose (< 10/10-12/ ≥ 12 mg/kg/day, OR: 4.513, P = 0.041) were significant factors associated with SVR. In patients with the IL28B non-TT genotype, RBV dose affected SVR dose-dependently in stratified analysis of RBV dose (P = 0.015); it was 44% (8/18) for patients administered <10 mg/kg/day of RBV, 78% (14/18) for those administered 10-12 mg/kg/day of RBV, and 100% (3/3) for those administered ≥12 mg/kg/day of RBV, whereas in patients with the IL28B TT genotype, a significant correlation between SVR and RBV dose was not observed (P = 0.229). Regarding RBV dose reduction of less than 10 mg/kg/day, the inosine triphosphate pyrophosphatase (ITPA) genotype (rs1127354, CC vs. non-CC, OR: 0.239, P = 0.003) and age (by 1 y.o., OR: 1.084, P = 0.002) were significant independent factors. RBV dosage affected SVR dose-dependently in patients with the IL28B non-TT genotype treated with SMV triple therapy. Special attention to anemia progression and RBV dosage should be paid to aged patients with the ITPA CC genotype. J. Med. Virol. 88:1776-1784, 2016. © 2016 Wiley Periodicals, Inc.

JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2.

JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2.

The Role of Polymorphisms Near the IL28B Gene on Response to Peg-Interferon and Ribavirin in Thalassemic Patients With Hepatitis C.

BackgroundHepatitis C Virus (HCV) is the major cause of liver failure in thalassemic patients. In these patients, iron overload and their comorbidities make difficulties during Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) therapy.ObjectivesWe aimed to assess the impact of polymorphisms near the IL28B gene on virological response in HCV - infected thalassemic patients, who were treated with PEG-IFN and RBV.Patients and MethodsThis cross - sectional study was conducted on 143 thalassemic patients with chronic hepatitis C, who were treated with a combination of PEG-IFN and RBV regimen. The rs12979860 and rs8099917 polymorphisms were assessed as the most common polymorphisms near the IL28B gene by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.ResultsThe rate of sustained virological response (SVR) was significantly lower in thalassemic patients with HCV genotype-1 infection compared to patients with HCV genotype-3 infection. Among baseline predictors, rs12979860 and rs8099917 polymorphisms were found to be the only parameters associated with achievement of SVR in thalassemic patients with HCV genotype-1 infection however, there was no association between these polymorphisms and the rate of SVR in thalassemic patients with HCV genotype-3 infection.ConclusionsIn HCV genotype-1- infected thalassemic patients with rs12979860 CC genotype and without severe comorbidities, PEG-IFN and RBV combination therapy can be tried yet in those with rs12979860 CT/TT it may be reasonable to treat cases with new direct-acting antivirals.