Pegylated Interferon Plus Ribavirin Research Articles

Low Incidence of Hepatocellular Carcinoma after Antiviral Therapy in Patients with Chronic Hepatitis C and Hemophilia.

Background: Hepatocellular carcinoma (HCC) rarely develops in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). We assessed the incidence of HCC in CHC patients with hemophilia after treatment with pegylated interferon plus ribavirin (PegIFN/RBV) and direct-acting antivirals (DAAs). Methods: Patients (n = 202) were enrolled between March 2007 and July 2019. A total of 139 patients were treated with PegIFN/RBV (genotype 1, n = 98; genotype 2, n = 41). Sixty-three patients were treated with DAAs (genotype 1, n = 44; genotype 2, n = 19). The cumulative incidence rates of HCC were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: For genotype 1, SVR was achieved in 78.6% (77/98) and 90.9% (40/44) of patients in the PegIFN/RBV and DAAs groups, respectively. For genotype 2, SVR was achieved in 95.1% (39/41) and 94.7% (18/19) of patients in the PegIFN/RBV and DAAs groups, respectively. Six HCC cases were identified. The cumulative incidence of HCC was 4.1% at 14 years in PegIFN/RBV and 1.7% at 5 years in DAAs. The 14-year cumulative incidence of HCC was 1.9% in the SVR group and 21.7% in the no-SVR group in the PegIFN/RBV group (p < 0.001). Conclusions: Treatment with PegIFN/RBV led to stable SVR and a low incidence of HCC. Although the follow-up period was short, DAAs led to more stable SVR than PegIFN/RBV and a low incidence of HCC in CHC patients with hemophilia.

Non-alcoholic fatty liver disease is a risk factor for occurrence of hepatocellular carcinoma after sustained virologic response in chronic hepatitis C patients: A prospective four-years follow-up study

Background and aimThe incidence of hepatocellular carcinoma (HCC) decreases significantly in chronic hepatitis C (CHC) patients with sustained virologic response (SVR) after pegylated-interferon plus ribavirin (PR) or direct-acting antiviral (DAAs) therapy. We follow-up a single cohort of CHC patients to identify risk factors associated with HCC development post-SVR. MethodCHC patients with SVR in Beijing/Hong Kong were followed up at 12–24 weekly intervals with surveillance for HCC by ultrasonography and alpha-fetoprotein (AFP). Multivariate Cox proportional hazards regression analysis was used to explore factors associated with HCC occurrence. ResultsBetween October 2015 and May 2017, SVR was observed in 519 and 817 CHC patients after DAAs and PR therapy respectively. After a median post -SVR follow-up of 48 months, HCC developed in 54 (4.4%) SVR subjects. By adjusted Cox analysis, older age (≥55 years) [HR 2.4, 95% CI (1.3–4.3)], non-alcoholic fatty liver diseases [HR 2.4, 95%CI (1.3–4.2), higher AFP level (≥20 ng/ml) [HR 3.4, 95%CI (2.0–5.8)], higher liver stiffness measurement (≥14.6 kPa) [HR 4.2, 95%CI (2.3–7.6)], diabetes mellitus [HR 4.2, 95%CI (2.4–7.4)] at pre-treatment were associated with HCC occurrence. HCC patients in the DAAs induced SVR group had a higher prevalence of NAFLD as compared with those in the PR induced SVR group, 62% (18/29) vs 28% (7/25), p = 0.026. A nomogram formulated with the above six independent variables had a Concordance-Index of 0.835 (95% CI 0.783–0.866). ConclusionUnderlying NAFLD is associated with increased incidence of HCC in chronic HCV patients post-SVR, particularly in those treated with DAA.

Cost-effectiveness of new antiviral treatments for non-genotype 1 hepatitis C virus infection in China: a societal perspective

ObjectiveThis study aimed to estimate the cost-effectiveness of direct-acting antivirals (DAAs) among patients with non-genotype 1 for the eradication of hepatitis C virus (HCV) infection in China.MethodsA decision-analytic Markov model...

Cost-Utility Analysis of Direct-Acting Antivirals for Treatment of Chronic Hepatitis C Genotype 1 and 6 in Vietnam.

ObjectiveVery few cost-utility analyses have either evaluated direct-acting antivirals (DAAs) on hepatitis C virus (HCV) genotype 6 patients or undertaken societal perspective. Recently, DAAs have been introduced into the Vietnamese health insurance drug list for chronic hepatitis C (CHC) treatment without empirical cost-effectiveness evidence. This study was conducted to generate these data on DAAs among CHC patients with genotypes 1 and 6 in Vietnam.MethodsA hybrid decision-tree and Markov model was employed to compare costs and quality-adjusted life-years (QALYs) of available DAAs, including (1) sofosbuvir/ledipasvir, (2) sofosbuvir/velpatasvir, and (3) sofosbuvir plus daclatasvir, with pegylated-interferon plus ribavirin (PR). Primary data collection was conducted in Vietnam to identify costs and utility values. Incremental cost-effectiveness ratios were estimated from societal and payer perspectives. Uncertainty and scenario analyses and value of information analyses were performed.ResultsAll DAAs were cost-saving as compared with PR in CHC patients with genotypes 1 and 6 in Vietnam, and sofosbuvir/velpatasvir was the most cost-saving regimen, from both societal and payer perspectives. From the societal perspective, DAAs were associated with the increment of quality-adjusted life-years by 1.33 to 1.35 and decrement of costs by $6519 to $7246. Uncertainty and scenario analyses confirmed the robustness of base-case results, whereas the value of information analyses suggested the need for further research on relative treatment efficacies among DAA regimens.ConclusionsAllocating resources for DAA treatment for HCV genotype 1 and 6 is surely a rewarding public health investment in Vietnam. It is recommended that the government rapidly scale up treatment and enable financial accessibility for HCV patients.

Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma.

The elimination of chronic hepatitis C infection (CHC) by pegylated interferon plus ribavirin (Peg-IFN/RBV) decreases hepatocellular carcinoma (HCC) recurrence rate. However, the tertiary prevention of HCC recurrence by direct acting antiviral agents (DAA) remains controversial. This study aims to compare the tertiary prevention effect between DAA and Peg-IFN/RBV in CHC-HCC patients. Three hundred and one patients who received curative HCC treatment were retrospectively recruited. The recurrence incidence rate (IR) was compared among patients either receiving Peg-IFN/RBV or DAA regimen or untreated by three timeframes (I: from HCC treatment to antiviral therapy; II: during antiviral therapy; III: after antiviral therapy). The prevention effect between Peg-IFN/RBV and DAA were compared in frame II and III after propensity score matching (PSM) with age, tumor staging, HCC treatment modality, and cirrhotic status. Before PSM, the recurrence IRs in three arms were comparable in frame I, while being lower in the Peg-IFN/RBV and DAA arm compared to the untreated arm in frame II. In frame III, the tertiary prevention effect lasted in the Peg-IFN/RBV arm (p < 0.001), but diminished in the DAA arm (p = 0.135) compared to untreated patients. After PSM, the HCC recurrence IR was higher in the DAA arm than the Peg-IFN/RBV arm in frame II (2724 vs. 666 per 104 person-years, log-rank p = 0.042) and III (5259 vs. 3278 per 104 person-years, log-rank p = 0.048). Preantiviral ALBI grade therapy is the only predictor for postantiviral therapy HCC recurrence. In conclusion, the tertiary prevention effect of HCC recurrence was not durable in DAA-treated patients, but persisted in Peg-IFN/RBV treatment patients.

Hepatitis C virus cure with direct acting antivirals: Clinical, economic, societal and patient value for China.

About 10 million people in China are infected with hepatitis C virus (HCV), with the seroprevalence of anti-HCV in the general population estimated at 0.6%. Delaying effective treatment of chronic hepatitis C (CHC) is associated with liver disease progression, cirrhosis, hepatocellular carcinoma, and liver-related mortality. The extrahepatic manifestations of CHC further add to the disease burden of patients. Managing CHC-related advanced liver diseases and systemic manifestations are costly for both the healthcare system and society. Loss of work productivity due to reduced well-being and quality of life in CHC patients further compounds the economic burden of the disease. Traditionally, pegylated-interferon plus ribavirin (PR) was the standard of care. However, a substantial number of patients are ineligible for PR treatment, and only 40%–75% achieved sustained virologic response. Furthermore, PR is associated with impairment of patient-reported outcomes (PROs), high rates of adverse events, and poor adherence. With the advent of direct acting antivirals (DAAs), the treatment of CHC patients has been revolutionized. DAAs have broader eligible patient populations, higher efficacy, better PRO profiles, fewer adverse events, and better adherence rates, thereby making it possible to cure a large proportion of all CHC patients. This article aims to provide a comprehensive evaluation on the value of effective, curative hepatitis C treatment from the clinical, economic, societal, and patient experience perspectives, with a focus on recent data from China, supplemented with other Asian and international experiences where China data are not available.

Increase in Incidence of Hepatocellular Carcinoma in Chronic Hepatitis C Chinese After Sustained Virologic Response with Direct Acting Antiviral Agents as Compared to Pegylated Interferon Plus Ribavirin Therapy: A Prospective Open-Label Study

Background: The incidence of hepatocellular carcinoma (HCC) decreased significantly in persons with chronic hepatitis C (CHC) who achieved sustained virologic response (SVR) after pegylated-interferon plus ribavirin (PR) therapy. It remains controversial whether there is any difference in HCC incidence after SVR using direct-acting antiviral agents (DAAs), as compared to PR therapy. We report a prospective observational study which compare the SVR and post-SVR HCC incidence in CHC Chinese who had completed either DAAs or PR therapy. Methods: This prospective observational study (NCT02578693) was conducted at two sites in Beijing and Hong Kong, to evaluate SVR in CHC Chinese with completion of DAAs or PR therapy. Those with SVR were followed up at 12-24 weekly intervals with surveillance for HCC performed by ultrasonography and alpha-fetoprotein at each visit. Multivariate Cox analysis was used to explore factors associated with post-SVR occurrence of HCC. Findings: Between October 2015 and May 2017, SVR was observed in 519 of the 533 (97.4%) and 817 of 1202 (68.0%) CHC patients with completion of anti-HCV therapy (p = 0.0001), respectively. Subjects that achieved SVR were followed with a median duration of 3 years. During the follow-up period, HCC developed in 28 (5.8%) and 25 (3.3%) post-SVR patients treated with DAAs and PR therapy, respectively (p = 0.036). The use of DAAs, older age (≥55 years), diabetes mellitus, higher LSM (≥17.5 kPa), and higher AFP level (≥30 ng/ml) at SVR were associated with increased risk of HCC (hazard ratios: 1.9, 3.1, 3.9, 4.9 and 5.2 respectively). Interpretation: After a median follow-up of 3 years, a lower incidence of HCC was observed in CHC patients who had SVR with PR therapy compared to those treated with DAAs. HCC surveillance in CHC patients with SVR should be performed more stringently in those with high risk factors and treated with DAAs. Clinical Trial Registration: The clinical protocol was registered at ClinicalTrials.gov (NCT02578693). Funding Statement: This is an investigator-initiated study supported by Chinese medical association (Grant No.13071110496) and capital characteristic clinic project of the Beijing municipal science and technology commission (Grant No. Z181100001718034). RFS is supported by the Emory Center for AIDS Research NIH grant 2P30-AI-050409. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Approval was obtained from the Ethics Committees in Hong Kong (Hong Kong Clinical Research Ethics Committee, HKCREC) and Beijing (Ethics Committee of Beijing 302 hospital). Informed consent was obtained from all patients and the study was conducted in compliance with the 1975 Declaration of Helsinki, Good Clinical Practice guidelines, and local regulatory requirements.

Real-world anti-viral treatment decisions among chronic hepatitis C patients in Taiwan: The INITIATE study

While direct-acting antiviral regimens have been approved for chronic hepatitis C (CHC) patients in Taiwan, reimbursement is limited to certain populations. Thus, pegylated interferon plus ribavirin (PEG-IFN/RBV) remains the standard of care for many patients. The aim of this study was to investigate the percentage of CHC patients who were recommended and willing to receive PEG-IFN/RBV, and to identify reasons why patients were not recommended or unwilling to receive treatment. 822 Taiwanese CHC patients were enrolled from May-August 2016 in this cross-sectional study. PEG-IFN/RBV recommendation and patient willingness to receive treatment were evaluated through surveys. Patient characteristics associated with treatment recommendation and willingness were assessed. 311 (37.8%) patients were recommended PEG-IFN/RBV while 102 (12.4%) were willing to follow treatment recommendation. Rates of recommendation and willingness were lower in treatment-experienced, hepatitis C virus genotype 1 (GT1) and cirrhotic patients, and those treated in Northern Taiwan. Multivariate analyses found factors such as prior treatment experience, GT1, cirrhosis and low hemoglobin levels to be associated with lower recommendation rates while advanced age, GT1 and low baseline viral loads were associated with lower willingness rates. Physicians' top reasons for not recommending PEG-IFN/RBV included the wish to wait for better treatment options (60.3%), prior treatment failure (21.3%) and patients' advanced age (20.9%). Patients were unwilling to receive treatment mainly due to concerns about side effects (91.4%), the wish to wait for better treatment options (71.3%) and inconvenience (25.4%). A minority of Taiwanese CHC patients were recommended PEG-IFN/RBV, of which few were willing to receive treatment.

The role of biochemical variations and genotype testing in determining the virological response of patients infected with hepatitis C virus

Background:In hepatitis C virus (HCV), infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R) therapy and progression to chronic hepatitis C (CHC).Aims:The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype.Settings and Design:The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24–48 weeks including 250 HCV infected patients.Materials and Methods:Biochemical parameters were determined by Beckman Coulter AU680 automated analyzer. HCV and Interleukin 28B (IL28B) genotyping were carried out by polymerase chain reaction-restriction fragment length polymorphism and viral load was determined by quantitative real-time PCR.Results:Wild outnumbered the variant genotypes in rs12979860, rs12980275, and rs8099917 SNP of IL28B gene. Sustained virological response (SVR) SVR and viral genotype were significantly associated with age, hepatic steatosis, low-grade varices, and serum aspartate transaminase levels (at the end of treatment) (P < 0.05). In addition, SVR was significantly influenced by body mass index (BMI), insulin resistance, serum low-density lipoprotein , and ferritin levels (P < 0.05). Viral genotype 1 infected patients had higher serum cholesterol and triglyceride levels (P < 0.05).Conclusions:Although the IL28B sequence variation is the major factor that can influence response rates to antiviral therapy, viral and biochemical factors also have a definite role to play in the diagnosis, etiology, and treatment outcome in HCV-infected patients.

Antiviral therapy in hepatitis C-infected patients prevents relapse of diffuse large B cell lymphoma.

IntroductionHepatitis C infection (HCV) is highly prevalent worldwide and has a well-known association with B-cell lymphoid malignancies. While several studies have demonstrated that antiviral therapy (AT) is effective to induce a complete hematological response in HCV-related low-grade B cell lymphoma, in HCV-related high-grade B cell non-Hodgkin lymphomas such as diffuse large B cell lymphoma (DLBCL) chemotherapy is the only possible choice. However, the role of AT to reduce relapse of DLBCL after an effective chemotherapy containing rituximab (CT-R) has not been analyzed in previous studies. Therefore we analyzed whether patients with a sustained virological response (SVR) to AT had over time a reduction of lymphoma relapse compared to no-SVR patients.Material and methodsThe study included 21 consecutive HCV-infected patients affected by DLBCL. The patients were treated with AT (direct-acting antivirals or pegylated interferon alfa plus ribavirin) concomitantly or after CT-R. Over time, we evaluated relapse of DLBCL in patients treated with CT-R according to response to AT.ResultsAn SVR was achieved in 16 of 21 patients. Five patients relapsed on AT with PegIFN/R (pegylated interferon plus ribavirin). Over time lymphoma relapse was more frequent in patients without a virological response compared with patients with an SVR (RR = 12.0, 95% CI: 1.66-86, p < 0.01 Fisher’s exact test).ConclusionsAT during or after CT-R is an important strategy to prevent relapse of DLBCL in HCV patients when the patients have achieved an SVR. Our results suggest that eradication of HCV infection may result in long-term prevention of B-cell non-Hodgkin’s lymphoma relapse.

Optimal Duration of Pegylated Interferon Plus Ribavirin Therapy for Chronic Hepatitis C Genotype 3 Patients who do not Achieve Rapid Virological Response

Chronic hepatitis C (CHC) genotype-3 (G-3) patients treated with standard 24-week pegylated interferon plus ribavirin(PEG-RBV) therapy achieve sustained virological response(SVR) rate of 69-82%. Patients who do not achieve rapid virological response(RVR) have lower SVR rate. Data regarding optimal management of this subgroup is scarce. We aimed to determine the most appropriate treatment duration in CHC G-3 patients who do not achieve RVR. Treatment naïve CHC G-3 patients treated with PEG-RBV therapy were included in this retrospective analysis. Patients with cirrhosis were excluded. RVR was assessed in all patients beyond the year 2007. RVR non-achievers were advised extended treatment beyond 24 weeks. Of the total 685 patients started on treatment, 646 completed treatment (mean age 39.1±12 years, 68.3% males). In the pre-'RVR assessment' period (2004-2006), SVR with standard 24 week therapy was 72.3% (112/155). In post-'RVR assessment' period (2007-2013), 75.8% (402/530) patients achieved RVR; and 91.5% (368/402) of these achieved SVR with standard 24 weeks therapy. Among RVR non-achievers (n=128), 51 patients opted for extended 36 week therapy, 12 for 48 week therapy, while 65 stopped therapy at 24 weeks. Choice of treatment duration was dependent entirely on the affordability of the patient. SVR with extended therapy (36/48 weeks) was significantly higher than standard 24 week therapy in RVR non-achievers (82.5% vs. 52.3%; P=0.003). However, SVR rate in 36 week group was not significantly different from 48 week group (84.3% vs. 75%; P=0.425]. On multivariate analysis, duration of treatment (36/48 week vs. 24 week; P<0.001) was significantly associated with SVR. SVR rates in CHC G-3 patients treated with PEG-RBV in northern India were comparable to western data. Standard 24 week therapy is adequate for RVR-achievers. However, in RVR non-achievers, extended 36 week therapy significantly improves SVR, while further extension to 48 week does not provide any additional advantage.

The host HLA-A*02 allele is associated with the response to pegylated interferon and ribavirin in patients with chronic hepatitis C virus infection.

Human leukocyte antigen (HLA) alleles are associated with both the progression of chronic hepatitis C (CHC) and the sustained virological response (SVR) to antiviral therapy. HLA-A*02 is the most common HLA allele in people of European/Caucasian descent and the Chinese and Japanese population. Therefore, we investigated whether HLA-A*02 expression is associated with disease outcome in Chinese CHC patients. Three hundred thirty-one treatment-naïve CHC patients were recruited in this study. The expression of HLA-A*02 was tested by FACS and LABType SSO assays. All patients were treated weekly with pegylated interferon plus ribavirin (PEG-IFN/RBV) according to a standard protocol. Virological response was assessed by TaqMan assay at the 4th, 12th, 24th, and 48th week of therapy, and again at the 24th week post-therapy. By the end of the study, 293 CHC patients, including 144 HLA-A*02-positive patients and 149 HLA-A*02-negative patients, were evaluable for analysis. There were no statistical differences in clinicopathological parameters between HLA-A*02-positive and negative patients before antiviral therapy (P > 0.05). The HLA-A*02-positive patients had a higher rapid virological response (RVR, 74.3 % versus 62.4 %, P = 0.03) and SVR (78.5 % versus 64.4 %, P = 0.01) and a lower relapse rate (4.2 % versus 11.9 %, P = 0.03) than HLA-A*02-negative patients. Multivariable logistic regression analysis showed that HLA-A*02 expression, liver fibrosis stages <S3, HCV genotype 2a, IL-28B rs8099917 TT, and RVR were independent predictive factors of SVR (P < 0.05). Host HLA-A*02 allele expression is associated with SVR, highlighting the importance of considering HLA-A*02 as a predictor of the response to PEG-IFN/RBV treatment in the Chinese population with CHC.

MHC class I-related chain B gene polymorphism is associated with virological response to pegylated interferon plus ribavirin therapy in patients with chronic hepatitis C infection

The outcome of antiviral therapy is associated with viral and host factors. In the present study, the association between MHC class I-related chain B (MICB) genotypes and therapeutic response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy was investigated in hepatitis C virus (HCV)-infected patients. In total, 107 patients with chronic HCV infection (74 with HCV serotype 1 and 33 with serotype 2) were enrolled. Genotyping of MICB single-nucleotide polymorphism (SNP) rs3828913 and interleukin-28B (IL28B) SNP rs8099917 was performed using TaqMan® SNP genotyping assays. The genotype distribution of the MICB alleles was: CC, 79.4%; CA, 17.8%; and AA, 2.8%. Sustained virological response (SVR) was achieved by 55.1% (59/107) of the HCV patients. The SVR rate of patients with MICB major (CC) alleles was 62.3% and this rate was significantly higher than that of the patients with MICB minor (CA and AA) alleles (27.2%) (P=0.0068). A multivariate logistic model showed that the MICB major genotype was an independent factor contributing to SVR (OR, 4.47; 95% CI, 1.46-13.70; P=0.009). In addition, the MICB genotype was identified as the sole independent factor contributing to SVR and non-virological response in HCV serotype 1 patients with the IL28B major genotype. In HCV serotype 2 patients, the MICB genotype was the sole significant factor contributing to SVR (OR, 30.68; 95% CI, 2.72-346.3; P=0.006). In conclusion, the MICB genotype is a strong predictive factor for virological response to PEG-IFN/RBV therapy in HCV patients.

Treatment of chronic hepatitis C genotype 1 early responders with 36 week pegylated interferon and ribavirin therapy

Introduction. Standard treatment for patients with chronic hepatitis C genotype 1 (CHC G-1) infection includes pegylated interferon plus ribavirin (PEG-RBV) for 48 weeks. Shorter treatment regimen would be more acceptable due to lower cost and fewer side-effects. We aimed to compare the efficacy of 36 week PEG-RBV therapy with standard 48 week therapy in CHC G-1 patients who achieve complete early virological response (cEVR).Material and methods. Consecutive treatment-naïve patients with CHC G-1 were treated with pegylated interferon a2b (1.5 μg/kg/week) or α2a (180 μg/week) and weight based ribavirin. Patients who achieved cEVR at 12 weeks [undetectable HCV RNA irrespective of RVR (rapid virological response)] were randomized into- group A (48 weeks therapy) and group B (36 weeks therapy). Primary end-point was achievement of sustained virological response (SVR) at 24 weeks of follow up.Results. Out of the total 166 patients started on treatment, 112 (69.3%) achieved cEVR, and were randomized into group A (n = 59) and group B (n = 53). Fifty-five (93.2%) patients in group A and 50 (94.3%) in group B completed therapy. The overall SVR rate in group A was 79.6% (47/59) and group B was 84.9% (45/53) (p = 0.622). SVR rates in the two groups were comparable in all patient sub-groups according to factors like viral load (≤ or > 400,000 IU/mL), RVR (achieved/not achieved), age (≤ or > 40 years), body mass index (≤ or > 27) and cirrhosis (present/absent).Conclusion. In CHC G-1 patients who achieve cEVR, 36 weeks PEG-RBV therapy is as effective as standard 48 weeks therapy, irrespective of other host or virological factors.

Core amino acid variation at position 110 is associated with sustained virological response in Caucasian patients with chronic hepatitis C virus 1b infection.

The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 [86-118] mg/dL vs. 76 [54-88] mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.

Quantitation of substitutions at amino acid 70 in hepatitis C virus genotype 1b.

BackgroundSubstitutions of amino acid (aa) 70 in the core region of hepatitis C virus genotype 1b (HCV 1b) are a predictor of the non-virological response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy. The aim of our study was to develop quantitative real-time reverse transcription polymerase chain reaction (qPCR) assays to quantify wild-type (70 W) and mutant (70 M) strains of HCV 1b.MethodsWe used the TaqMan system to quantify strains 70 W and 70 M. Codon 70 in the HCV 1b core region can be either CGN or CAN, therefore degenerate TaqMan minor groove binder (MGB) probes with inosine were used. We determined detection limits, sensitivity and specificity of the methods developed. Direct sequencing and cloning of the HCV core region were used to confirm the reliability of our new system. Serum samples from 138 Chinese patients infected with HCV 1b were examined with the system we developed and compared with results obtained from the Roche TaqMan RT-PCR HCV RNA quantitation system.ResultsDegenerate MGB probes were able to clearly distinguish 70 W from 70 M. The detection limit was 103 copies/mL. Cross-reactivity tests confirmed the specificity of our method. Our system can effectively quantify 70 W and 70 M for 99.6% of patients with HCV 1b. Further tests involving cloning and sequencing confirmed the reliability of our system.ConclusionsWe developed an assay system using degenerate TaqMan MGB probes with inosine to quantify wild-type and mutant viral RNAs of the HCV 1b core region at aa 70. Our developed assay system had high levels of sensitivity and accuracy, and could prove useful in investigating dynamic changes during PEG-IFN/RBV therapy to assess virological responses.

Interferon-based anti-viral therapy for hepatitis C virus infection after renal transplantation: an updated meta-analysis.

BackgroundHepatitis C virus (HCV) infection is highly prevalent in renal transplant (RT) recipients. Currently, interferon-based (IFN-based) antiviral therapies are the standard approach to control HCV infection. In a post-transplantation setting, however, IFN-based therapies appear to have limited efficacy and their use remains controversial. The present study aimed to evaluate the efficacy and safety of IFN-based therapies for HCV infection post RT.MethodsWe searched Pubmed, Embase, Web of Knowledge, and The Cochrane Library (1997–2013) for clinical trials in which transplant patients were given Interferon (IFN), pegylated interferon (PEG), interferon plus ribavirin (IFN–RIB), or pegylated interferon plus ribavirin (PEG–RIB). The Sustained Virological Response (SVR) and/or drop-out rates were the primary outcomes. Summary estimates were calculated using the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analysis.ResultsWe identified 12 clinical trials (140 patients in total). The summary estimate for SVR rate, drop-out rate and graft rejection rate was 26.6% (95%CI, 15.0–38.1%), 21.1% (95% CI, 10.9–31.2%) and 4% (95%CI: 0.8%–7.1%), respectively. The overall SVR rate in PEG-based and standard IFN-based therapy was 40.6% (24/59) and 20.9% (17/81), respectively. The most frequent side-effect requiring discontinuation of treatment was graft dysfunction (14 cases, 45.1%). Meta-regression analysis showed the covariates included contribute to the heterogeneity in the SVR logit rate, but not in the drop-out logit rate. The sensitivity analyses by the random model yielded very similar results to the fixed-effects model.ConclusionsIFN-based therapy for HCV infection post RT has poor efficacy and limited safety. PEG-based therapy is a more effective approach for treating HCV infection post-RT than standard IFN-based therapy. Future research is required to develop novel strategies to improve therapeutic efficacy and tolerability, and reduce the liver-related morbidity and mortality in this important patient population.

Treatment of chronic hepatitis C with pegylated interferon plus ribavirin in treatment-naïve ‘real-life’ patients in India

Results of treatment of chronic hepatitis C (CHC) with pegylated interferon plus ribavirin (PEG-RBV) are mainly available from well-designed clinical trials, and only few 'real-life' studies which give a true picture of success of therapy are available. Such data in Indian patients is scarce. This prospective study aimed to evaluate the efficacy, safety, and factors associated with sustained virological response (SVR) in Indian CHC patients treated with PEG-RBV in 'real-life' setting. All treatment-naïve patients with CHC/compensated cirrhosis treated with PEG-RBV between January 2004 and December 2010 were included. Of 592 patients started on treatment, 524 (88.5%) completed therapy (mean ± SD age-42.0 ± 12.1years; 74.3% males). Genotype 3 (73.6%) was the commonest, followed by genotype 1 (19.3%). In intention to treat analysis, SVR rates for 'all' patients, genotype 1 and genotype 3 patients were 72.3% (428/592), 57% (65/114), and 78.2% (341/436), respectively (in per-protocol analysis-81.7 %, 69.1 %, and 85.3%, respectively). Noncirrhotics had better SVR rates compared to cirrhotics treated for the same duration. About 20% patients had both low viral load and achieved rapid virological response (RVR). Factors significantly associated with SVR were age <40years, absence of cirrhosis, RVR, and no reduction in interferon dose. SVR rates in CHC patients treated in 'real-life' setting in India were better than those reported in western population. Therapy should be prolonged for patients with cirrhosis, while one-fifth of patients may qualify for abbreviated therapy. Factors significantly associated with SVR were age <40years, absence of cirrhosis, RVR, and no reduction in interferon dose.

Efficacy of Pegylated Interferon Plus Ribavirin in Treatment of Chronic Hepatitis C Patients in India in ‘Real-Life’ Setting

Background: Results of treatment of chronic hepatitis C (CHC) with pegylated interferon plus ribavirin (PEG-RBV) are mainly available from well-designed clinical trials, and only few ‘real life’ studies which give a true picture of success of therapy are available. Such data in Indian patients is scarce.

Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: A metabolomics analysis

ObjectivesSerum samples from patients with chronic hepatitis C were subjected to metabolomics analysis to clarify the pretreatment characteristics of their metabolites and also changes in specific metabolites resulting from antiviral therapy with pegylated interferon plus ribavirin (PegIFN/RBV). Materials/MethodsThe serum levels of low-molecular-weight metabolites in the twenty patients before and 24weeks after completion of PegIFN/RBV therapy were analyzed using capillary electrophoresis and liquid chromatography–mass spectrometry. ResultsTen patients showed a non-virological response (NVR) and 10 achieved a sustained virological response (SVR) with eradication of viremia. The pretreatment levels of tryptophan were significantly higher in the patients of SVR than in those of NVR (p=0.010). The area under the curve (AUC) value of tryptophan calculated from the receiver operating characteristic (ROC) curve for discriminating SVR from NVR was 0.84 (95% confidential interval, 0.66–1.02, p=0.010). The ROC curve of multiple logistic regression model incorporating the pretreatment levels of tryptophan and γ-glutamate-arginine showed that the AUC value was highly significant (AUC=0.92, 95% confidential interval, 0.79–1.05, p=0.002). Twenty four weeks after completion of treatment, the levels of γ-glutamyl dipeptides, glutamic acid, 5-oxoproline, glucosamine and methionine sulfoxide were decreased, whereas those of 5-methoxy-3-indoleacetate, glutamine, kynurenine and lysine were increased significantly (p<0.05) in both the NVR and SVR patients. ConclusionsThe pretreatment serum levels of certain metabolites including tryptophan are associated with the response to PegIFN/RBV therapy. PegIFN/RBV therapy can ameliorate the oxidative stress responsible for glutathione metabolism.