Pegylated Interferon Plus Research Articles

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin.

This retrospective cohort study aims to investigate interferon (IFN)-associated retinopathy incidence in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon (PegIFN) plus ribavirin (RBV). We selected 1688 patients undergoing PegIFN/RBV therapy for HCV (HCV-treated cohort), 3376 patients not receiving HCV treatment (HCV-untreated cohort) and 16,880 controls without HCV (non-HCV cohort) from the Taiwan Longitudinal Health Insurance Database. The patients were frequency-matched by age, sex, and index date at a 1:2:10 ratio, and followed up until the end of 2013. Cox proportional hazard regression models were used to compare the incidences of any retinal vascular events, including subtypes, among the three cohorts. Compared with the non-HCV cohort, the HCV-treated cohort had a significantly increased risk of retinopathy (hazard ratio (HR) = 4.98, 95% confidence interval (CI): 2.02–12.3). The risk was particularly prominent for retinal hemorrhage (HR = 12.7, 95% CI: 3.78–42.9). When the HCV-untreated cohort was used as the reference, the aforementioned HRs increased to 9.02 (95% CI: 3.04–26.8) and 32.3 (95% CI: 3.94–265), respectively. This study suggested that PegIFN/RBV therapy significantly increased the risk of retinal hemorrhage but not retinal vascular occlusions in the HCV-treated cohort.

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.

Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment.

Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, −1.33 versus 0.86, P < 0.001). The albumin levels and platelet counts significantly increased during the follow-up period after SVR (44.27 ± 4.09 versus 42.63 ± 4.37, P = 0.037 and 173.89 ± 87.36 versus 160.11 ± 77.97, P = 0.047). These data indicated that HCV-related cirrhotic patients with SVR after PegIFN + RBV may have a favorable clinical course and improvements in laboratory data. Moreover, HCC should be monitored.

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.

Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B.

In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.

Dual Treatment With Sofosbuvir Plus Ribavirin is as Effective as Triple Therapy With Pegylated Interferon Plus Sofosbuvir Plus Ribavirin in Predominant Genotype 3 Patients With Chronic Hepatitis C

Background and Aim Sofosbuvir (SOF) was the first directly acting antiviral made available for chronic hepatitis C (CHC) in India. We describe our “real life” experience of using SOF with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in predominant genotype 3 patients with CHC. Methods A total of 158 patients (men 99 [62.6%], mean age 40.3 ± 12.8 years) with CHC treated with dual therapy (SOF + RBV) for 24 weeks or triple therapy (Peg-IFN + SOF + RBV) for 12 weeks were included prospectively. Patients with co-infection, decompensated liver disease, and post-organ transplantation were excluded. Data were analysed for the preference of treatment regimen, end of treatment response (ETR), sustained virological response at 12 weeks, and side effects. Results Genotype 3 was the predominant genotype (105 [66.4%]) followed by genotype 1 (40 [25.3%]) and genotype 4 (13[8.2%]). Forty-eight (30.37%) patients had cirrhosis (LSM ≥ 13 kPa), and 30 (19%) were treatment experienced with Peg-IFN + RBV. A total of 103 (65.18%) patients received dual therapy, and 55 (34.81%) received triple therapy. Resentment to receive injections, inaccessibility to a facility, fear of injection or its side effects, and financial constraints were the reasons to refuse triple therapy. All patients in triple therapy group and all but two patients (98%) in the dual therapy group attained ETR. All those who achieved ETR achieved sustained virological response at 12 weeks in both groups. But for anemia in three patients (two in triple, one in dual therapy), there were no major side effects. Conclusions Most patients with CHC prefer an oral treatment with directly acting antivirals. Both oral and interferon-based regimens achieve high response rate.

MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response.

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose-binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.

Response to Pegylated Interferon Plus Ribavirin in Patients with Hepatitis C Virus Genotype 6a Infection from Guangdong and Guangxi Province of China.

Aim. Our aim is to survey the treatment effect of PEG-IFN plus ribavirin in patients infected with HCV genotype 6a in Guangdong and Guangxi province of China and investigate best course of antiviral treatment for patients with HCV-6a infection. Methods. 515 eligible patients received subcutaneous 180 μg PEG-IFNα-2a or 1.5 μg/kg PEG-IFNα-2b once weekly plus oral ribavirin. Primary outcome was SVR by intention-to-treat analysis. Secondary outcome was RVR, cEVR, ETR, and relapse rate. Results. SVR in patients with HCV-6a infection treated for 48 weeks was comparable to that in patients with HCV-2/3 infection (80.9% versus 82.5%, p = 0.812) and higher than that in patients with HCV-1b infection (80.9% versus 67.2%, p = 0.014). ETR (98.9% versus 90.6%, p = 0.016), virological response at month 3 of end-of- treatment (88.8% versus 76.6%, p = 0.044), SVR (80.9% versus 65.6%, p = 0.032), and virological response at month 12 of end-of-treatment (76.4% versus 60.9%, p = 0.04) in patients with HCV-6a infection treated for 48 weeks were higher than those in patients with HCV-6a infection treated for 24 weeks. Conclusion. SVR in patients with HCV-6a treated for 48 weeks was comparable to that in patients with HCV-2/3 infection and higher than that in patients with HCV-1b infection; patients with HCV-6a infection treated for 48 weeks had a superior treatment response than patients treated for 24 weeks.

Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With Pegylated Interferon Plus Ribavirin: A Randomized Study.

We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at treatment week 4) could be applied for active HCV/hepatitis B virus (HBV) dually infected patients, without compromised the treatment efficacy.A total of 203 patients, seropositive of HCV antibody, HCV RNA and HBV surface antigen (HBsAg), and seronegative for HBV e antigen for >6 months, were randomized to receive peginterferon-alpha/ribavirin by either genotype-guided therapy (GGT, n = 102: HCV genotype 1 [HCV-1], 48 weeks; HCV-2/3, 24 weeks) or RGT (n = 101: HCV-1, 48 or 24 weeks if patients with baseline VL <400,000 IU/mL and RVR; HCV-2/3, 24 or 16 weeks if patients with RVR). The primary endpoint was HCV-sustained virological response (SVR).The HCV SVR rate was comparable between the GGT (77.5%, 79/102) and RGT groups (70.3%, 71/101, P = 0.267), either among HCV-1/HBV (69.4% [43/62] vs 63.5% [40/63], P = 0.571) or among HCV-2/3/HBV (90.0% [36/40] vs 81.6% [31/38], P = 0.342) dually infected patients based on intention-to-treat analysis. In HCV-1/HBV dually infected patients, RVR (odds ratio [OR]: 6.05; 95% confidence intervals [CI]: 2.148–17.025, P = 0.001) and lower pretreatment blood glucose levels (OR: 0.97; CI: 0.944–0.989, P = 0.003) were independent predictors of HCV SVR. Although RVR (OR: 10.68; CI: 1.948–58.514, P = 0.006) was the only significant factor associated with HCV SVR in HCV-2/3/HBV dually infected patients. HBsAg loss at 1 year posttreatment was observed in 17 of 185 (9.2%) patients. The rates of discontinuation and adverse events were similar between the 2 groups.RGT with peginterferon-alpha/RBV may be considered for HBeAg-negative HBV/HCV dually infected patients.

Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With PEGylated Interferon Plus Ribavirin: A Randomized Study

Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With PEGylated Interferon Plus Ribavirin: A Randomized Study

Sofosbuvir plus pegylated interferon and ribavirin in patients with genotype 1 hepatitis C virus in whom previous therapy with direct‐acting antivirals has failed

Retreatment of patients who have not achieved sustained virological response (SVR) after treatment with investigational direct-acting antiviral agents (DAAs) has not been extensively studied. We conducted an open-label trial to assess the efficacy and safety of sofosbuvir (SOF) plus pegylated interferon (Peg-IFN) and ribavirin (RBV) in patients with genotype 1 hepatitis C virus (HCV) who participated in previous studies of one or more Gilead investigational DAAs in combination with RBV with or without Peg-IFN. We enrolled 80 patients at 40 sites. All patients received SOF 400 mg once daily plus Peg-IFN-α 180 μg/week and weight-based ribavirin (1,000 or 1,200 mg/day) for 12 weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks after discontinuation of therapy (SVR12). Of the 80 patients enrolled, 36 (45%) had received two or more courses of earlier treatment for HCV and 74 (93%) had at least one resistance-associated variant (RAV) at baseline. SVR12 was achieved by 63 of the 80 patients (79%) treated. Rates of SVR12 were similar across patient subgroups. Presence of RAVs at baseline did not appear to be associated with treatment failure. Seventy-one of eighty patients (89%) experienced at least one adverse event (AE), but most events were mild to moderate in severity. The most common AEs were fatigue, headache, and nausea. No patients discontinued all treatment because of AEs. These findings suggest that SOF plus Peg-IFN and RBV for 12 weeks is effective and safe in patients who have not achieved SVR with earlier regimens of one or more DAAs plus Peg-IFN and RBV.

Combination Therapies with Daclatasvir and Asunaprevir on NS3-D168 Mutated HCV in Human Hepatocyte Chimeric Mice

Although the frequency of emergent drug-resistant strains of HCV in patients who failed to respond to simeprevir plus pegylated interferon (PEG-IFN) and ribavirin (RBV) decreased after cessation of the treatment, it is not clear whether or not the NS3-D168 variants affect the outcome of NS5A and NS3 inhibitor combination therapy. In this study, we investigated the relationship between the effect of daclatasvir plus asunaprevir treatment and the frequencies of NS3-D168 variants. HCV genotype-1b-infected human hepatocyte chimeric mice with various frequencies of NS3-D168 amino acid substitutions were treated with asunaprevir alone or in combination with daclatasvir for 4 weeks. Frequencies of NS3-D168 substitutions at baseline were analysed by ultra-deep sequencing. Some mice with NS3-D168 substitutions were treated with PEG-IFN or telaprevir for 4 weeks. Mice with high frequencies of NS3-D168 showed low susceptibility to asunaprevir treatment and failed to respond to daclatasvir plus asunaprevir therapy. In contrast, mice with a low frequency (less than approximately 14%) of NS3-D168 showed a similar susceptibility to wild-type HCV-infected mice and achieved viral eradication with daclatasvir plus asunaprevir therapy. Although treatment with either telaprevir or PEG-IFN resulted in reduction of serum HCV RNA levels, no significant decrease in the frequency of NS3-D168 substitutions was achieved. Daclatasvir and asunaprevir treatment could eliminate NS3-D168 variant HCV if the frequency was low. It is necessary to confirm that the frequency of NS3-D168 variants has decreased sufficiently before adopting daclatasvir plus asunaprevir therapy in patients with simeprevir plus PEG-IFN/RBV treatment failure.

Su1413 MICB (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

Su1413 MICB (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

Effect of aging, glucose level, and HIV viral load on response to treatment with pegylated interferon plus ribavirin in HIV/HCV co-infected women.

This was a post-hoc analysis of the Optimized Pegylated interferons Efficacy and anti-Retroviral Approach (OPERA) study, originally designed to document routine clinical and treatment data in HIV/HCV coinfected patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV). The aim of this study was to define the impact of several variables, such as age, glucose metabolism, and HIV viral load, on PEG-IFN/RBV treatment outcomes, in HIV/HCV coinfected women. Female subjects from the OPERA database were retrospectively evaluated and factors associated with sustained virological response (SVR) were assessed and compared to the male population by logistic regression analysis. At baseline, clinical and demographic data were collected. Patients were then administered with PEG-IFN/RBV therapy for 48 weeks. After a 24-week follow-up period, SVR was evaluated. A total of 1523 patients were enrolled in 98 centers across Italy, 1284 of whom were IFN therapy naïve and were included in the post-hoc analysis. In the female group, factors associated with SVR were the presence of HCV genotype 2,3 (adjusted odds ratio [AOR]=6.87, p<0.0001), age ≤45 years (AOR=2.61, p=0.014), ≥80% exposure to PEG-IFN (AOR=3.85, p=0.019) and RBV (AOR=3.94, p=0.015) therapy. Also, increased glucose plasma level negatively correlated with SVR (AOR=0.98, p=0.066). In the male population, undetectable HIV-RNA (AOR=1.47, p=0.033) but not glucose level (AOR=1.0, p=0.95) predicted SVR. Findings from the present study demonstrate that several factors may be predictive of SVR when pegylated interferon plus ribavirin is used (i.e., age, gender, HIV viral load and HCV genotype) that need to be carefully considered prior to therapeutic intervention, since they may hinder successful therapy. Use of PEG-IFN/RBV with novel direct antiviral agents will likely be still maintained until less expensive and effective interferon-free strategies become available.

Impact of Body Weight Reduction via Diet and Exercise on the Anti-Viral Effects of Pegylated Interferon Plus Ribavirin in Chronic Hepatitis C Patients with Insulin Resistance: A Randomized Controlled Pilot Trial

Insulin resistance (IR) modifies the anti-viral effects of interferon (IFN) therapy in patients with chronic hepatitis C (CHC). This prospective study evaluated whether lifestyle interventions improve the anti-viral response to treatment with pegylated (PEG)-IFN plus ribavirin (RBV) in patients with CHC. The study cohort consisted of 60 patients chronically infected with a high viral load of hepatitis C virus genotype 1b and a homeostasis model assessment of IR (HOMA-IR) value above 2. The patients were divided into two groups, an intervention group (n=26) and a control group (n=34). The patients in the intervention group were prescribed diet and exercise treatment for 3-6 months to reduce their body weight by ≥5% before starting treatment with PEG-IFN plus RBV. Diet and exercise significantly reduced the HOMA-IR values in the intervention group, from 3.4 to 2.5 (p=0.0009), especially among the 15 patients who achieved a body weight reduction of ≥5%. The viral disappearance rate at 12 weeks was significantly higher in the intervention group among the patients with a ≥5% weight reduction than in the control group (53.3% vs. 23.5%, p=0.01). However, the sustained viral response (SVR) rates were similar. Improvements in IR achieved through weight reduction via lifestyle interventions may enhance the early viral response to PEG-IFN plus RBV in patients with CHC. However, this intervention program has no effect on the SVR rate.

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.

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.

Consensus Interferon Plus Ribavirin for Hepatitis C Genotype 3 Patients Previously Treated With Pegylated Interferon Plus Ribavirin

BackgroundNot enough data are available about the effectiveness of consensus interferon (CIFN) among HCV genotype 3 patients who failed to respond to pegylated interferon and ribavirin.ObjectivesWe aimed to assess the efficacy and safety of CIFN and ribavirin in non-responders and relapsers to pegylated interferon with ribavirin therapy.Patients and MethodsThis open-label investigator-initiated study included 44 patients who received CIFN 15 µg /day plus ribavirin 800-1200 mg daily. In patients with an early virological response (EVR), the dose of CIFN was reduced to 15 µg thrice a week for further 36 weeks. Patients with delayed virological response continued to receive daily CIFN plus ribavirin to complete 48 weeks. The patients were considered “non-responders” if there were less than 2 log reduction in HCV RNA at 12 weeks and detectable HCV RNA at 24 weeks.ResultsTwenty-four patients (55%) were non-responders and 20 patients were relapsers to the previous treatment with pegylated interferon plus ribavirin (mean age 43.6 ± 9.4 years, males 25 (57%)). Nine patients were clinically cirrhotic (Child A). End of treatment virological response was achieved in 19 (43.1%) patients and sustained virological response (SVR) occurred in 12 (27.3%). Out of these 12 patients, eight were non-responders and four were relapsers to the previous treatment. Advanced fibrosis or clinical cirrhosis was associated with low SVR. Adverse events were fever, myalgia, anorexia, depression, and weight loss. Two patients received granulocyte colony stimulating factor for transient neutropenia. Seven patients were given erythropoietin to improve hemoglobin, and six were treated for mild depression. Two patients developed portosystemic encephalopathy.ConclusionsMore than one-quarter of treatment-experienced patients with HCV genotype 3 achieved SVR after re-treatment with consensus interferon plus ribavirin.

Predictors of Early Virological Response of Viral Hepatitis C to Combination Therapy with Pegylated Interferon Plus Ribavirin

A combination therapy with pegylated interferon (PEG-IFN) plus ribavirin (RBV) has made it possible to achieve a sustained virological response (SVR) of 50% in refractory cases with genotype 1b and high levels of plasma HCVRNA. Several factors including virus mutation and host factors such as age, gender, fibrosis of the liver, lipid metabolism, innate immunity, and single nucleotide polymorphism (SNPs) are reported to be correlated to therapeutic effects. However, it is difficult to determine which factor is the most important predictor for an individual patient. Data mining analysis is useful for combining all these together to predict the therapeutic effects, It is important to analyze blood tests and to predict therapeutic effects prior to initiating treatment. Our aim is to determine the independent contribution of factors including age, gender, viral load, liver fibrosis, hepatitis activity index sore, and the homeostasis model assessment of insulin resistance (HOMA-IR) score in predicting response to therapy in chronic hepatitis C (CHC). Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment-naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study.