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Purpose: Chronic hepatitis B virus (CHB) infection is a worldwide health problem. Polyethylene glycol (PEG)ylated interferon (PEG-IFN) is an available therapy for CHB that has antiviral and immunomodulatory effects. However, PEG-IFN therapy is limited by the fact that only a subset of patients show a sustained response, its severe side effects, and high cost. The aim of this study was to explore novel biomarkers for the early prediction of PEG-IFN treatment response and to uncover its underlying mechanism., Patients and Methods: We enrolled 10 paired patients with Hepatitis B e antigen (HBeAg)-positive CHB who received PEG-IFN-α2a monotherapy. Patient serum samples were collected at 0, 4, 12, 24, and 48 weeks and serum samples were collected from eight healthy people as healthy controls. For confirmation, we enrolled 27 patients with HBeAg-positive CHB receiving PEG-IFN therapy and serum samples at 0 and 12 weeks were obtained. Serum samples were analyzed using Luminex technology., Results: Among 27 assessed cytokines, 10 cytokines were identified to have high expression levels. Among them, six cytokines had significant differences in their levels between the patients with HBeAg-positive CHB and the healthy controls (P < 0.05). Potentially, treatment response could be predicted using the early time points of 4, 12, and 24 weeks. Moreover, after 12 weeks of PEG-IFN treatment, increased levels of pro-inflammatory cytokines and decreased levels of anti-inflammatory cytokines were observed. The fold change of IP-10 between 12 weeks and 0 weeks correlated with the decrease in ALT levels from 0 to 12 weeks (r = 0.2675, P = 0.0024)., Conclusion: In patients with CHB, we observed a certain pattern in the levels of cytokines during treatment with PEG-IFN, and the cytokine IP-10 might be a potential biomarker for treatment response., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Chen et al.)

An open-level, randomized and treatment-controlled clinical trial has shown that a therapeutic vaccine containing hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (NASVAC) is endowed with antiviral and liver protecting capacity and is safer than pegylated interferon (Peg-IFN) in patients with chronic hepatitis B (CHB). The present study provides information about the role of the hepatitis B virus (HBV) genotype in this phase III clinical trial. From a total of 160 patients enrolled in this trial, the HBV genotypes of 133 patients were characterized, and NASVAC induced a stronger antiviral effect (HBV DNA reduction below 250 copies per mL) than Peg-IFN. The antiviral effects and alanine aminotransferase levels were not significantly different among different HBV genotypes in NASVAC-treated patients. However, a significantly higher proportion of genotype-D patients receiving NASVAC showed better therapeutic effects, compared to genotype-D patients receiving Peg-IFN, with a marked difference of 44%. In conclusion, NASVAC seems to be a better alternative to Peg-IFN, especially in patients with HBV genotype-D patients. This reflects the attractiveness of NASVAC in countries where genotype D is highly prevalent. The mechanisms underlying the effect of HBV genotype are being studied in a new clinical trial.

Although there are therapeutic advantages for hepatitis B virus (HBV) withpegylated interferon alpha (peg-IFNα) treatment compared with nucleos(t)ide analog (NAs) therapy, the effect difference in infected population at different phases has not been well established. We studied the clinical efficacy of peg-IFNα in two populations with HBV infection, including inactive HBsAg carrier (IHC) and chronic hepatitis B (CHB). A total of 328 HBV-infected patients were included in this real-world analysis. Patients were divided into two groups according to the infected stages. Peg-IFNα monotherapy or combination therapy with NAs were used in IHCs, and peg-IFNα added-on NAs therapy was applied to patients with CHB. The primary efficacy endpoint was HBsAg loss at Week 24. Results: The Kaplan-Meier cumulative rates of HBsAg loss were 39.50% (n = 47/119) in IHC group and 28.71% (n = 60/209) in CHB group at Week 24 (p < .05). After Propensity Score Matching (PSM), the HBsAg loss rates were 36.84% (n = 35/95) and 32.63% (n = 31/95), respectively (p > .05). Patients with baseline HBsAg level < 100 IU/ml achieved higher rates of HBsAg clearance in IHC and CHB group (before PSM: 47.44% vs. 42.86%, after PSM: 49.12% vs. 45.83%, all p values > .05). Baseline HBsAg level and its level decline from baseline to Week 12 can be as the predictors for HBsAg loss at Week 24 in both groups. Hence, the efficacy of HBsAg clearance was broadly similar between IHCs and NA-treated CHB patients during the early peg-IFNα therapy. A significant downward trend of HBsAg level was observed in both groups during peg-IFNα therapy., (© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Based on the pivotal trial showing no clinicallyrelevant differences between pegylated interferon α-2b (Peg-α-2b) and α-2a (Peg-α-2a) combined with ribavirin for treatment of chronic hepatitis C virus (HCV) genotype 1 infection in Ukraine, a cost-minimization analysis was performed using a 1 year time horizon and both a health care and patients’ perspective. A decision tree reflects treatment pathways. Drug costs were based on drug labeling and adjusted to the average body mass in Ukraine. Subgroup analysis was applied to deal with heterogeneity of patient’s weight causing dose changes. A break-even price of Peg-α-2a and Peg-α-2b (based on the average dose) was calculated. Univariate sensitivity analyses and probabilistic sensitivity analysis were carried out to reflect decision uncertainty. For an average body weight, total medical costs per patient differ from US$9220 for Peg-α-2b to US$9513 for Peg-α-2a from a health care perspective, and from US$15,212 to US$15,696 from a patients’ perspective. Sensitivity analyses show these results are robust. With average body weight, the break-even price of Peg-α-2b may be 7.3% higher than Peg-α-2a to have similar total costs.

Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 μg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects. [ABSTRACT FROM AUTHOR]

In hepatitis B 'e' antigen ( HBeAg) positive patients with hepatitis B virus ( HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (Peg IFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding Peg IFN to tenofovir ( TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus ( HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year Peg IFN intensification during TDF-containing antiretroviral therapy ( TDF+Peg IFN) were matched 1:1 to controls undergoing TDF without Peg IFN ( TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification ( qHBeAg) and hepatitis B surface antigen quantification ( qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months ( IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/ mL and 3.72 log10 IU/ mL, respectively ( P>.5 between groups). Median follow-up was 33.4 months ( IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (−0.066 vs −0.027 PEIU/ mL/month, P=.001) and qHBsAg (−0.049 vs −0.026 log10 IU/ mL/month, P=.09) were observed in patients undergoing TDF+Peg IFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups ( P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance ( TDF+Peg IFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates ( TDF+Peg IFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, Peg IFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN. [ABSTRACT FROM AUTHOR]

Purpose of Review: The goal of chronic hepatitis B (CHB) therapy is an improvement in clinical outcomes, but surrogate markers include viral suppression, hepatitis B e-antigen (HBeAg) seroconversion, and, more recently, hepatitis B surface antigen (HBsAg) clearance, labeled as 'functional cure.' The current therapy of CHB is based on two strategies: either a finite course of pegylated interferon (pegIFN) or an indefinite duration of oral nucleos(t)ide analogues (NAs). NAs with high antiviral potency and barrier to resistance have become the mainstay of therapy due to ease of use, tolerability, and cost. However, optimization of these two therapeutic modalities has not been fully explored to maximize outcomes, which include combination therapy. Recent Findings: Initial randomized control trials with approved NAs and pegIFN as de novo combinations did not appear to show benefit compared to pegIFN alone, but meta-analyses now show that there are significant improvements in undetectable HBV DNA, HBeAg loss and seroconversion, and HBsAg loss. However, many patients remain on long-term NA therapy, and a strategy to increase HBeAg seroconversion and preferably HBsAg clearance are needed. Such strategies include switch (sequential) or add-on pegIFN to patients already on NAs. An add-on pegIFN strategy in HBeAg-negative CHB (PEGAN study) has shown 8% HBsAg clearance after 48 weeks of therapy, and a switch strategy (OSST study) showed a similar result-8.5% HBsAg clearance. However, the ultimate goal of HBsAg seroclearance remains still <10% despite these strategies. Summary: It may be possible to improve these outcomes further by selecting patients with lower quantitative HBsAg (qHBsAg) levels and to predict outcomes based on on-treatment qHBsAg responses. [ABSTRACT FROM AUTHOR]

The therapeutic effect of pegylated interferon (peg-IFN) alfa-2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa-2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa-2a (160 μg) subcutaneous once weekly and oral weight-based ribavirin (1000-1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P < 0.001; respectively]. Along the study, the observed adverse events were mild and similar across treatment groups. Addition of hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170-2178, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Introduction:Sofosbuvir (SOF) with simeprevir (SIM) combination was the first interferon-free regimen that reached optimal results in terms of sustained viral response (SVR). Areas covered:A systematic review of the scientific literature concerning the effects that the SOF/SIM combination had on hepatitis C genotype 1 patients yielded 771 references. After the revision process, four clinical trials and 15 observational studies met the inclusion criteria; in total, these studies involved 5,766 patients. The SVR ranged from 67% to 100% depending on the patients’ viral subtype and cirrhosis status. Adverse effects were common, but treatment discontinuation related to drug toxicity occurred in less than 5% of cases. Expert commentary:The SOF/SIM combination exhibits efficacy and tolerability profiles that are similar to those of the other available interferon-free combinations used for non-cirrhotic genotype 1b patients. Meanwhile, for patients with advanced cirrhosis or genotype 1a, this approach cannot be considered a routine treatment option due to the unsatisfactory results. [ABSTRACT FROM PUBLISHER]

Background: The safety and efficacy of sofosbuvir-based treatment (sofosbuvir and ribavirin with or without pegylated interferon-α) for hepatitis C virus (HCV) infection has been established in clinical trials. However, there is limited data regarding safety and efficacy of sofosbuvir-based treatment for HCV infection in a 'real-life' cohort. We describe our experience with sofosbuvir-based treatment for HCV infection in a real-life cohort. Methods: This was a prospective, nonrandomized and observational study at a tertiary care centre in Surat, India. The primary end-point was proportion of the study patients who achieved a sustained virological response 12 weeks after cessation of treatment (SVR 12). Secondary end-points of the study include SVR 4, virological relapse and appearance of adverse events. Results: A total of 107 patients with chronic HCV who received sofosbuvir-based treatment were included in the study. During study period, two patients died due to severity of liver complications. Hence, overall rate of SVR 4 and SVR 12 was 98.1 % ( n = 103/105) and 94.3 % ( n = 99/105), respectively. Among 67 patients with HCV genotype-3 infection, the SVR 12 rate was 92.5 % ( n = 62/67), and among 38 patients with HCV genotype-1 infection, the rate of SVR 12 was 97.4 % ( n=37/38). A total of 32 (29.9 %) patients reported adverse events during the course of sofosbuvir-based treatment. None of the patient discontinued treatment due to adverse event. Conclusions: Sofosbuvir-based treatment is safe and efficacious in clinical practice in Indian patients with HCV genotype-1 and genotype-3 infection. [ABSTRACT FROM AUTHOR]

Fibrosis progression is common in hepatitis C. Both host and viral factors influence its natural history. Liver fibrosis is a key predictive factor for advanced disease including endpoints such as liver failure, cirrhosis and hepatocellular carcinoma (HCC). METAVIR fibrosis stages F3–F4 have been considered as the threshold for antiviral therapy. However, this aspect is controversial after the advent of new direct-acting antivirals (DAAs) because they show an excellent efficacy and safety profile. Moreover, in the DAA era, fibrosis stage seems not to be a predictive factor of a sustained virological response (SVR). Viral eradication decreases liver damage by improving the inflammation, as well as by regressing fibrosis irrespective of the treatment regimen. Non-invasive methods are useful in the assessment of liver fibrosis, replacing liver biopsy in clinical practice; but their usefulness for monitoring fibrosis after SVR needs to be demonstrated. Fibrosis regression has been demonstrated after the eradication of hepatitis C virus infection and is associated with a lower risk of hepatic cirrhosis and liver cancer. However, patients showing advanced fibrosis and cirrhosis must be followed-up after SVR, as risks of portal hypertension and HCC remain. [ABSTRACT FROM AUTHOR]

Background: Pegylated interferon alpha 2a, alpha 2b and ribavirin have been included to the National List of Essential Medicines (NLEM) for treatment of only chronic hepatitis C genotypes 2 and 3 in Thailand. This reimbursement policy has not covered for other genotypes of hepatitis C virus infection (HCV) especially for genotypes 1 and 6 that account for 30-50 % of all HCV infection in Thailand. Therefore, this research determined whether pegylated interferon alpha 2a or alpha 2b plus ribavirin is more cost-effective than a palliative care for treatment of HCV genotype 1 and 6 in Thailand.Methods: A cost-utility analysis using a model-based economic evaluation was conducted based on a societal perspective. A Markov model was developed to estimate costs and quality-adjusted life years (QALYs) comparing between the combination of pegylated interferon alpha 2a or alpha 2b and ribavirin with a usual palliative care for genotype 1 and 6 HCV patients. Health-state transition probabilities, virological responses, and utility values were obtained from published literatures. Direct medical and direct non-medical costs were included and retrieved from published articles and Thai Standard Cost List for Health Technology Assessment. The incremental cost-effectiveness ratio (ICER) was presented as costs in Thai baht per QALY gained.Results: HCV treatment with pegylated interferon alpha 2a or alpha 2b plus ribavirin was dominant or cost-saving in Thailand compared to a palliative care. The ICER value was negative with lower in total costs (peg 2a- 747,718vs. peg 2b- 819,921 vs. palliative care- 1,169,121 Thai baht) and more in QALYs (peg 2a- 13.44 vs. peg 2b- 13.14 vs. palliative care- 11.63 years) both in HCV genotypes 1 and 6.Conclusion: As cost-saving results, the Subcommittee for Development of the NLEM decided to include both pegylated interferon alpha 2a and alpha 2b into the NLEM for treatment of HCV genotype 1 and 6 recently. Economic evaluation for these current drugs can be further applied to other novel medications for HCV treatment. [ABSTRACT FROM AUTHOR]

Background: Sorafenib is a standard of care for advanced hepatocellular carcinoma (HCC). An in vitro study showed the synergistic effects of sorafenib and interferon for HCC. To clarify the efficacy, combination therapy with sorafenib and interferon was performed for patients with advanced HCC. Methods: Pegylated interferon α-2a was administered every 2 weeks for the initial 4 weeks. Subsequently, it was combined with sorafenib. We evaluated the anti-tumor effect and biomarkers during treatment period. Results: The subjects were 13 patients with advanced HCC complicated by hepatitis C virus (HCV)-related liver cirrhosis. A partial response, stable disease and progressive disease were noted in 4, 6, and 3 patients, respectively. The response rate, the disease control rate, the mean time to progression and the median survival time (MST) were 30.8 % (4/13), 76.9 % (10/13), 12.2 months, and 17.5 months, respectively. In 8 Child-Pugh class A and 5 Child-Pugh class B patients, the MST was 22.0 and 11.0 months, respectively ( p = 0.001). In plasma vascular endothelial growth factor (VEGF), serum alpha-fetoprotein (AFP), AFP-L3, a protein induced by vitamin K absence or antagonist-II (PIVKA II), and hepatocyte growth factor (HGF), there was no pretreatment factor and no biomarker during the combination therapy to predict therapeutic effect in the present study. Conclusions: The results of this study suggest that combination therapy with sorafenib and interferon could be effective and safe in advanced HCC patients with HCV-related liver cirrhosis. [ABSTRACT FROM AUTHOR]

There is no published study from India on hepatitis C virus (HCV) treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR). A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15-67) years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 106 copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54%) patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80%) patients required increase in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment-limiting). Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy. [ABSTRACT FROM AUTHOR]

Background/Aims: This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEGIFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. Methods: Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. Results: The patients' median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. Conclusions: Low-dose PEG-IFN plus ribavirin was a safe and costeffective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR. [ABSTRACT FROM AUTHOR]

Background/Aims: Despite the potent suppression of the hepatitis B virus with modern antiviral agents, only a minority of HBeAg-positive patients achieve hepatitis B e antigen seroconversion. We aimed to explore the potential efficacy of combination therapy consisting of pegylated interferon (p-IFN) and an oral antiviral agent in patients with HBeAgpositive chronic hepatitis B. Methods: The treatment protocol consisted of p-IFN-α-2a at 180 μg/wk for 48 weeks, with either entecavir or tenofovir added 8 weeks after the initiation of p-IFN and continued for at least 6 months after HBe seroconversion was achieved. Results: To date, 10 patients have been treated under the protocol (eight adults, mean age 36±8 years; two adolescents, aged 12 and 16 years). All eight adult patients experienced loss of HBeAg at a mean of 72.3±66.9 weeks, including six patients who also developed anti-HBe and one patient who had HBs seroconversion. Although both adolescents remain on therapy, one adolescent had HBs seroconversion without HBe seroconversion. A total of nine of our 10 patients experienced a favorable serological transition. Conclusions: The combination of p-IFN and a modern oral antiviral agent may be more effective than monotherapy with either class of agent in the treatment of HBeAg-positive chronic hepatitis B patients. [ABSTRACT FROM AUTHOR]

With recent availability of Sofosbuvir, Chronic Hepatitis C treatment paradigm has changed considerably. However for a resource constrained country like Pakistan, still the standard treatment of Chronic Hepatitis C remains the combination of Interferons and Ribavirin. Depression, sometimes major, is a recognized side effect of this combination. Objective: The objective of our study was to analyze the prevalence of depression during treatment with pegylated interferon and ribavirin in patients infected with Hepatitis C at two tertiary care hospitals Lahore. Setting: All these patients were selected randomly from outpatient departments at Fatima Memorial Hospital and Alshafi Hospital Lahore. Duration of study: Duration of our study was two years and 3 months from January 2010 to April 2012. Patients and Method: We included 180 patients in our study. We confirmed the diagnosis of chronic hepatitis C in all these willingly participated patients. All these participants were put on combination of pegylated interferon and ribavirin. Serial follow ups were done for the assessment of development of depression during the treatment of Hepatitis C. Results: 46.8 (26%) patients developed depression during treatment. Depression was more common in the middle of treatment which gradually improved near the end of treatment. Conclusion: We reached at a conclusion in our study that there is definite correlation of depression with pegylated interferon and ribavirin therapy in hepatitis C patients. [ABSTRACT FROM AUTHOR]

Background & Aims The role of quantitative serum hepatitis B core-related antigen ( HBcrAg) in patients with chronic hepatitis B ( CHB) receiving pegylated interferon ( PEG- IFN) is unclear. This study was aimed at comparing its usefulness with quantitative HBsAg in patients with HBeAg-positive CHB receiving PEG- IFN therapy. Methods A total 46 patients treated with PEG- IFN for 48 weeks were retrospectively analysed. Intrahepatic covalently closed circular DNA (ccc DNA) from paired liver biopsies and serial serum HBsAg and HBcrAg during therapy were assessed. Results Virological response ( VR), defined as HBeAg clearance and HBV DNA <2000 IU/ml at 24 weeks post treatment, was achieved in 15 (32.6%) patients. Responders had significantly higher ccc DNA decline from baseline compared with non-responders. Baseline HBsAg and HBcrAg were correlated with ccc DNA ( r = 0.424, P = 0.020 and r = 0.564, P = 0.001, respectively), and changes in the corresponding markers during therapy were correlated with ccc DNA reduction ( r = 0.579, P = 0.001 and r = 0.503, P = 0.005, respectively). Responders showed more rapid decline of both markers during therapy compared with non-responders. In multivariate analysis, serum HBcrAg at week 12 was identified as a predictor of VR. The optimal cut-off value for HBcrAg (log10 8.0 U/ml) provided negative predictive value ( NPV) of achieving VR at weeks 12 and 24 of 94.4 and 100%, respectively, while using HBsAg > 20 000 IU/ml provided NPV of 80 and 100% respectively. Conclusions The convenient quantitative HBcrAg represented a reliable marker of intrahepatic ccc DNA. Monitoring HBcrAg levels during PEG- IFN therapy may help identify patients with a very low probability of response comparable to, if not better than, quantitative HBsAg. [ABSTRACT FROM AUTHOR]

Objectives: We conducted a systematic review and metaanalysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6 (HCV-6) patients treated with pegylated interferon (PEGIFN) and ribavirin (RBV). Methods: Data were retrieved from Medline, Embase, PubMed and the Cochrane Library for 'genotype 6' studies published up to December 2014 and for abstracts from international scientific meetings. Inclusion criteria were efficacy of PEG-IFN+RBV based on SVR, 24- or 48-week therapy and treatment-naïve patients. Patients with hepatitis B, D and E and HIV coinfection or another concurrent liver disease were excluded. Pooled standard difference, odds ratio and confidence intervals (CIs) were calculated using a random-effect model with STATA 11. Results: Fourteen studies were included in the meta-analysis. The pooled SVR rate was 80% (95% CI: 0.78-0.83, p < 0.0001; I 2 = 71.2%). SVR of the PEG-IFN+RBV-treated HCV-6 patients was markedly higher than that of HCV-1 patients (80.1 vs. 55.3%). The SVR rate was significantly higher for the 48- than the 24- week treatment, but not different among HCV-infected patients with rs12979860 and ss469415590 polymorphisms of the ILFN4 gene (80.6% CC vs. 66.7% non-CC, p = 0.593; 81.1% TT/TT vs. 60% non-TT/TT, p = 0.288). Gender and type of PEG-IFN did not affect SVR rates. Conclusions: Treatment outcomes for HCV-6 patients are superior to those for HCV- 1 patients and comparable to those of HCV-2 and HCV-3 patients, especially at 48 weeks. The level of fibrosis affects treatment outcome, but SVR rates are not significantly different between genders. IL28B and IFNL4 polymorphisms are not significantly associated with HCV-6 treatment outcome. [ABSTRACT FROM AUTHOR]

Background: The 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-IFNo2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries. Objectives: The 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 Methods: A 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 nu-cleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Results: In 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 = 0.0 06). Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Dual hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is not rare in HBV or HCV endemic areas, and can be found in populations at risk of parenteral viral transmission. Clinical observatory studies suggest a higher risk of liver disease progression in patients with dual HCV/HBV infection than in HBV or HCV monoinfected patients. Recent trials confirmed that combination therapy of peginterferon alfa-2a or alfa-2b and ribavirin was effective and safe in dually infected patients with positive HCV RNA. Moreover, about 30% of the dually infected patients cleared hepatitis B surface antigen within 5 years after the start of peginterferon-based therapy. The optimal treatment strategies for dually infected patients with active hepatitis B, with decompensated cirrhosis, or in other clinical situations should be explored in further studies. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may lead to the development of strategies for the treatment of dually infected patients with active hepatitis C, particularly for those not tolerating or not eligible for peginterferon-based therapy. Notably, direct-acting antivirals would not have any activity against HBV infection; simultaneous or on-demand nucleos(t)ide analogs would be needed if clinically indicated. [ABSTRACT FROM AUTHOR]

Background: After treatment cessation, a high prevalence of relapse was reported in chronic hepatitis B (CHB) patients in China, especially in nucleot(s)ide analogues (NUCs)-experienced patients. Re-treatment for these patients remains unsolved. Objectives: This study aims to evaluate the efficacy of PEGylated interferon in HBeAg positive patients with exposure to antiviral therapy. Patients and Methods: A total of 55 treatment-experienced, HBeAg positive Chinese patients were enrolled in this study. Of these patients, 33 were NUCs-experienced and 22 were interferon-experienced. PEGylated interferon was administered to 34 patients; and 21 patients were retreated with conventional interferon. Results: Of the 34 treatment-experienced patients who received PEGylated interferon, 52.9% achieved virologic response, and 41.2% achieved HBeAg loss and seroconversion. Patients who were treated with PEGylated interferon for 48 weeks achieved higher virologic response (80%); HBeAg loss (60%); HBeAg seroconversion (60%); and HBsAg loss (5%) than patients treated for 24 weeks with PEGylated interferon. Their responses were also higher than those who were treated with conventional interferon. HBeAg seroconversion in treatment-experienced patients was independently associated with 48-week PEGylated interferon therapy duration. Conclusions: PEGylated interferon was effective in treatment-experienced patients with HBeAg positive CHB, and showed higher rates of virological response, HBeAg loss, and seroconversion. The results provide important information regarding the role of retreatment with PEGylated interferon in treatment-experienced HBeAg positive patients. [ABSTRACT FROM AUTHOR]

Pegylated interferon α-2a (Peg-IFN) has been shown to induce hematologic and molecular responses in patients with the Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET). We describe a series of patients with long-standing MPNs among whom Peg-IFN was initiated when they developed anemia and increased bone marrow reticulin fibrosis suggestive of early transformation to post-ET (PET) or post-PV (PPV) myelofibrosis (MF). Six patients were treated with Peg-IFN for a mean duration of 33.8 months (range 2-63 months). Five patients had long-standing ET (three were calreticulin (CALR)-positive, one janus kinase 2 (JAK2)-positive, and one JAK2-negative and CALR-negative), and one had long-standing JAK2-positive PV prior to starting Peg-IFN. This is the first study to report that, concurrent with the improvement in anemia, serial laboratory studies demonstrate an increase in serum LDH and left-shifted myeloid cells in the peripheral circulation over approximately 6 months, followed by a gradual normalization of these findings. Splenomegaly also increased and then resolved among responding patients. Serial bone marrow biopsies were available, which showed little change except for improvement in the grade of reticulin fibrosis in two patients. Among patients with early transformation to PET or PPV MF, our data support the efficacy of Peg-IFN in improving hemoglobin levels and reducing splenomegaly. These peripheral blood findings should not, therefore, be considered evidence of treatment failure within the first year of Peg-IFN therapy. [ABSTRACT FROM AUTHOR]

Background: The cost of interferon-free combination therapies remains high to provide widespread access to treatment, regardless of fibrosis stage.Aim: To estimate the cost-effectiveness of simeprevir/daclatasvir (SMV/DCV) therapy in treatment-naïve chronic hepatitis C genotype-1b patients with moderate fibrosis.Methods: A Markov model was developed to simulate the natural history of chronic hepatitis C progression. The model estimated lifetime healthcare costs and quality-adjusted life-years (QALY) for a cohort of patients from the Spanish National Healthcare System perspective. The cost-effectiveness threshold considered was €40,000/QALY. The treatment strategies analyzed were SMV/DCV, peginterferon/ribavirin/telaprevir, and peginterferon/ribavirin/boceprevir. A sensitivity analysis was carried out.Results: The incremental cost-effectiveness ratios of the SMV/DCV strategy were €23,774/QALY and €28,524/QALY compared with that of telaprevir or boceprevir triple therapy, respectively, for genotype-1b patients with moderate fibrosis.Conclusions: SMV/DCV combination compared with the standard of care previous to the arrival of second-generation direct-acting antivirals fell below generally accepted willingness-to-pay threshold. Results obtained should be supported by ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Aim Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non-TT. Among such treatment-refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non-TT. Methods Patients were randomly assigned to receive simeprevir (100 mg/day) for 12 weeks plus PEG IFN/ribavirin for 24 weeks (control group, n = 58), or vitamin D (2000 IU/day) for 16 weeks including a lead-in phase plus PEG IFN/ribavirin for 24 weeks (vitamin D group, n = 57). The primary end-point was sustainably undetectable viremia 24 weeks after the end of treatment (SVR). Results SVR rates were 37.9% in the control group and 70.2% in the vitamin D group. In subgroup analysis, SVR rates of prior null responders were 11.8% and 54.5%, respectively. SVR rates for advanced fibrosis were 28.6% and 65.4%. SVR rates for patients with vitamin D3 deficiency at the baseline were 25.0% in the control group and 66.7% in the vitamin D group. Overall, the SVR rate was significantly higher in patients with high serum 25(OH)D3 levels at the beginning of combination therapy than in those with low serum 25(OH)D3 levels. Conclusion Native vitamin D3 supplementation improved SVR rates in simeprevir with PEG IFN/ribavirin for chronic hepatitis C genotype 1b patients with refractory factors. [ABSTRACT FROM AUTHOR]

Context: Hepatitis C virus (HCV) infection is a major cause of liver-morbidity and mortality among patients with thalassemia. Peginterferon plus ribavirin is currently the recommended therapy for hepatitis C infection in patients do not have thalassemia, but using ribavirin in patients with thalassemia is restricted due to its hemolytic effect. To evaluate the efficacy and safety of adding ribavirin to peginterferon or interferon, authors performed a systematic review on the available literatures. Evidence Acquisition: Trials were identified through electronic database, manual searches of journals and bibliographies and approaching authors of trials. Randomized trials that enrolled patients with a diagnosis of thalassemia and chronic hepatitis C infection treated with interferon or peginterferon with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcomes were sustained virological response (SVR), liver-related morbidity, mortality and adverse events. The odds ratios from each trial were calculated individually and in the subgroup analysis of trials. Data were analyzed with fixed-effect model. Results: Three randomized clinical trials with 92 patients were included. All three trials had unclear risk of bias. Compared with peginterferon monotherapy adding ribavirin to peginterferon had significant beneficial effect on sustained virological response (OR = 3.44, 95% CI: 1.18 -10.06). There was no significant difference between combination therapy and monotherapy in the end of treatment achievement response. Other than about 30% increase in blood transfusion due to anemia that returned to normal level 2 - 3 months after treatment, there was no significant increase in side effects followed by adding ribavirin to pegylated interferon (Peg-IFN). Data were insufficient to determine the impact of genotype, viral load and age on the response to treatment. Conclusions: Compared with monotherapy, adding ribavirin to treatment is more effective in removing hepatitis C virus from the bloodstream in patients with thalassemia, it is also more effective in reducing the relapse rate after treatment. Except the increase in blood transfusion, there was no significant increase in side effects followed by adding ribavirin. [ABSTRACT FROM AUTHOR]

Background and aim Interferon-based therapy is known to be associated with significant side effects, including the cardiac complications; these may affect the patients’ adherence to therapy and consequently the response rate. The aim of this study was to detect types and predictors of interferon-induced cardiac complications in Egyptian hepatitis-C-virus-infected patients treated with pegylated interferon/ribavirin combination therapy. Methods A total of 194, chronic hepatitis C virus (HCV) patients were followed up from the time of receiving treatment till one year after end of treatment, to detect cardiac disorders and to determine the response status. Patients were assessed by through history taking, full clinical examination, full evaluation of laboratory parameters, and cardiac assessment using the standard 12-lead electrocardiography and Transthoracic Doppler Echocardiography. Patients in the final analysis were divided into: group A (patients who developed cardiac disorders) and group B (patients who did not develop cardiac disorders). Results The baseline clinical features (cardiovascular risk factors and hemodynamics) were comparable in both groups. Patients who developed cardiac disorders had higher baseline ALT level, hepatic fibrosis, and activity than patients without cardiac disorders ( p < 0.05). The confirmed cardiac complications represented 18.6% ( n = 36) and included left ventricular systolic and diastolic dysfunctions, pericardial effusion, arrhythmia, myocardial ischemia, and heart failure. Hepatic activity in the liver biopsy, ejection fraction, and left ventricular end-diastolic dimension were independent predictors for cardiovascular complications. Conclusion Pegylated interferon therapy of chronic HCV is associated with many types of cardiac complications, predictors of which are higher baseline ALT, viral load, hepatic fibrosis, and hepatic histological activity index. [ABSTRACT FROM AUTHOR]

Objective: We studied the effect of sustained virologic response (SVR) after treatment with pegylated-interferon (PEG-IFN) plus ribavirin on the development of liver cirrhosis in elderly patients with chronic hepatitis C (CHC). Patients and methods: This retrospective study enrolled 145 elderly CHC patients (aged $65 years) who were treatment-naive and were treated with PEG-IFN plus ribavirin for 6 months between January 2005 and December 2011. Abdominal sonography was performed and liver biochemistry was studied at baseline, at the end of treatment, and every 3-6 months thereafter. The development of liver cirrhosis and related complications was evaluated at the follow-ups. The aspartate aminotransferase-to-platelet ratio index was used as a noninvasive maker for fibrosis. Results: The mean patient age was 69.1±3.3 years, and the average follow-up time was 5.5 years (standard deviation: 2.5 years, range: 1.1-12.3 years). Ninety-five patients (65.5%) achieved SVR, and 26 (17.9%) discontinued treatment. Twenty-seven patients (18.6%) developed liver cirrhosis after treatment. Patients without SVR had significantly greater risk of liver cirrhosis than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312-8.761, P<0.012). The difference in 3-year cumulative incidence of liver cirrhosis was 24.8% greater for patients without SVR (35.2%, 95% CI: 13.0-57.5, P<0.012) compared with those with SVR (10.4%, 95% CI: 3.1-17.7). There was a trend of a higher baseline aspartate aminotransferase-to-platelet ratio index score in patients who progressed to liver cirrhosis compared with those who did not progress (2.1±1.2 vs 1.6±1.3, P<0.055), but the difference failed to reach significance by Cox regression (adjusted HR: 1.285, 95% CI: 0.921-1.791, P<0.14). Conclusion: An SVR following PEG-IFN combination treatment can reduce the risk of liver cirrhosis in elderly CHC patients. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin. Methods: This retrospective study consisted of 474 Japanese non-cirrhotic patients with chronic hepatitis C. The cumulative incidence of HCC was estimated using the Kaplan-Meier method, according to insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) and treatment outcome. Results: The overall sustained virological response (SVR) rate was 45.1 % (214/474, genotype 1: 35.4 % [129/364] and genotype 2: 77.3 % [85/110]). Twenty-one (4.4 %) patients developed HCC during the follow-up period. The 5-year cumulative incidence of HCC of the SVR group (2.6 %) was significantly lower than that of the non-SVR group (9.7 %) (log-rank test: P = 0.025). In multivariable logistic regression analysis, HOMA-IR (≥2.5) (hazard ratio [HR] 12.8, P = 0.0006), fibrosis status (F3) (HR 8.85, P < 0.0001), and post-treatment alanine aminotransferase (ALT) level (≥40 U/L) (HR 4.33, P = 0.036) were independently correlated to the development of HCC. Receiver operating characteristic analysis to determine the optimal threshold value of HOMA-IR for predicting the development of HCC in the non-SVR group showed that the areas under the curve was high (0.80, cutoff value: 3.0). Only three patients (1.4 %) who achieved SVR developed HCC. Two of them had severe insulin resistance and did not show improvement in HOMA-IR after achieving SVR. Conclusions: Insulin resistance has a strong impact on the development of HCC by non-cirrhotic patients who have PEG-IFNα2b and ribavirin treatment failure. [ABSTRACT FROM AUTHOR]

Repeated measurement of the HCV RNA level is essential for properly monitoring treatment efficacy. The aim of this study was to determine the utility of two HCV real-time assays in the evaluation of the impact of hepatitis C virus (HCV) kinetics on the outcome of triple therapy with NS3/4A protease inhibitors (PIs), telaprevir or simeprevir. This study consisted of 171 Japanese patients infected with HCV genotype 1. All 3266 serum samples taken during and post treatment were tested with both the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HCV Test v2.0 and the Abbott RealTime (ART) HCV Test. Of the 2597 samples undetectable (lower limit of detection [

Introduction: Treatment of HCV using a combination of pegylated interferon (PEG-IFN) and ribavirin fails in about 40% of the patients with HCV genotype 4 infections, and it is physically and economically demanding. Thus, it is highly important to identify factors that can help to predict the likelihood that a patient will respond to this treatment. Methods: In this study, five miRNAs, i.e., miRNA-122, miRNA-199, miRNA-192, miRNA-30, and miRNA- 128, were selected according to previous studies that demonstrated their noticeable functions in viral replication, indicating that they potentially could be used by host cells to control viral infections. The five miRNAs were measured using real-time, reverse transcription-polymerase chain reactions. The data were analyzed using the ttest and chi-squared test. Results: We found that the expression level of miRNA-122 was significantly increased in the responders' group (p < 0.01) over that in the non-responders' groups before and after treatment; both increased significantly (p < 0.01) compared with the normal control group. Conclusion: miR-122 might be a useful predictor for virological responses to treatment with PEG-interferon plus ribavirin therapy in patients with HCV. [ABSTRACT FROM AUTHOR]

Background: Pegylated interferon and ribavirin are currently one of the accepted treatment for chronic Hepatitis C. Dermatologic complications of interferon have been reported, but to date a few cases of bacterial cellulitis; a rare and severe complication, have been published. Cellulitis is a common infectious process affecting the skin and subcutaneous tissues which results in significant morbidity and holds considerable healthcare costs. Cases Report: Herein, we report a case of chronic hepatitis C genotype 1a who was on medication since 8 weeks prior to developing leg cellulitis, an uncommon pegylated interferon injection site. Considering no other possible risk factors were found to be in favor of bacterial cellulitis, our case is unique in its kind. Some reports reveal necrotizing vasculitis as basis for cutaneous lesions, which could be due to the high concentrations of drug at the injection site, a toxic effect of the diluents, or an immunological reaction. Conclusion: According to the latter mechanism patients could develop bacterial cellulitis in their different organs. Conclusively, we propose the hypothesis of a possible association between cellulitis to occur at any site as the complication of pegylated interferon Alfa 2b and would highlight the role of a careful skin examination that could be an asset in preventing local skin infections. [ABSTRACT FROM AUTHOR]

Background. There have been few reports of hepatitis C virus (HCV) treatment results with interferon-based regimens in indigenous populations. Objective. To determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI) population. Design. In an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined. Results. Sustained virologic response (SVR) with standard interferon was 16.7% (3/18) and with standard interferon and ribavirin was 29.7% (11/37). Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%), including 10 of 46 with genotype 1 (21.7%), 38 of 51 with genotype 2 (74.5%) and 13 of 22 with genotype 3 (59.1%). By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p =0.002), estimated duration of infection (p =0.034) and HCV genotype (p B0.0001). There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%). Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%). Conclusions. We had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1. [ABSTRACT FROM AUTHOR]

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

Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Traditionally, therapy has been focused on pegylated interferon in combination with ribavirin, with clinical trials demonstrating that HCV genotype 1 had the lowest response rate (40–50%), while genotype 3 had an intermediate response rate (60–70%). Recently, significant advances have been made with all-oral direct-acting antiviral (DAA) therapy, which have significantly improved cure rates for HCV genotype 1. Accordingly, HCV genotype 3 is now potentially the most difficult to treat. One of the most potent DAA medications is sofosbuvir, a pan-genotypic nucleotide analogue that inhibits the NS5B polymerase of HCV. Daclatasvir, a pan-genotypic inhibitor of the HCV NS5A replication complex, was recently approved in the United States for treatment of HCV genotype 3 in conjunction with sofosbuvir. This combination may provide a powerful tool in the treatment of HCV genotype 3. [ABSTRACT FROM PUBLISHER]

Objectives: to analyze the T1/T2 cytokine profile in CD8 T cells from peripheral blood mononuclear cells from patients with genotype-1 CHC during treatment with pegylated interferon (Peg-IFN) α2a plus ribavirin (RBV). To correlate Th1/Th2 balance with virological response. Patients and methods: in this prospective longitudinal study, a total of 28 naïve genotype-1 CHC patients received Peg-IFNα2a (180 µg/week) plus RBV (1-1.2 g/day) for 48 weeks. All patients (mean age 45 ± 8 years) completed treatment and follow-up: 12 (43%) achieved a sustained virological response (SVR), 13 relapsed after end of treatment (47%), and only 3 (10%) were non-responders. Sixteen healthy controls were also analyzed (mean age 39 ± 17 years). The production of IL-4, IIFNγ, and TTNFα by CD8 T cells was measured by intracytoplasmic detection using flow cytometry in both resting and stimulated cells with a phorbol ester. Statistics: Student's t test for independent values, χ2 test, and ANOVA test were used; relapsers and non-responders were joined to achieve a higher statistical power. Results: at third month during treatment, phorbol ester-stimulated-IL-4 levels tend to be lower in patients who presented with SVR versus those who did not (0.97 vs 2.58; p = 0.1). No statistically significant differences were found in IIFNγ and TTNFα levels at month 3. At EOT, the stimulated-IIFNγ production was significantly higher in patients with SVR (20 vs. 8; p < 0.05). Conversely, IL-4 production was higher in NR patients although these data did not reach statistical significance (p < 0.1). No significant differences were found in TTNFα (14 vs. 7; p < 0.2). Conclusions: Cytokine T1 induced-response maintenance during combination treatment, measured as IIFNgamma production by CD8+ T lymphocytes, is associated with SVR and suggests the replication control and later clearance of patients infected by genotype-1 HCV.Objetivos: analizar el perfil de citocinas T1/T2 producidas por los linfocitos T CD8+ de sangre periférica en pacientes con hepatitis crónica C (HCC) y genotipo 1 durante el tratamiento con interferón pegilado (Peg-IFN) α2a y ribavirina (RBV) y compararlos con controles sanos. Correlacionar el balance T1/T2 con la respuesta virológica al tratamiento combinado. Pacientes y métodos: en este estudio prospectivo longitudinal se incluyeron 28 pacientes naïve con HCC genotipo 1 tratados con Peg-IFNα2a (180 µg/semana) más RBV (1-1,2 g/día) durante 48 semanas. Los 28 pacientes (edad media 45 ± 8 años) finalizaron el tratamiento y seguimiento: 12 (43%) presentaron respuesta viral sostenida (RVS), 13 recidivaron (47%) y sólo 3 fueron no respondedores (10%). Se estudiaron 16 controles sanos (edad media de 39 ± 17 años). Se analizó mediante citometría de flujo la producción intracitoplásmica de IL-4, IFNγ y TNFα por los linfocitos T CD8+ en reposo y tras ser estimulados con un ιster de forbol. Anαlisis estadístico: t de Student, test de χ² y ANOVA; se agrupan los pacientes recidivantes y no respondedores para obtener mayor potencia estadística. Resultados: no se encontraron diferencias significativas entre los niveles de citocinas de controles sanos y pacientes con HCC. Al tercer mes de tratamiento, los niveles de IL-4 inducidos tendían a ser menores en los pacientes que obtuvieron una RVS que en el resto de pacientes (0,97 vs. 2,58; p = 0,1); tampoco se encontró significación estadística en relación a los niveles de IIFNγ y de TTNFα. Al final del tratamiento, la producciσn de IIFNγ estimulado fue significativamente mayor en los pacientes que obtuvieron una RVS (20 vs. 8; p < 0,05). Por el contrario, la producción de IL-4 fue mayor en los pacientes no respondedores, aunque estos datos no alcanzaron significación estadística (p < 0,1). No se encontraron diferencias en relación con los niveles de TTNFα (14 vs. 7; p < 0,2). Conclusiones: el mantenimiento de la respuesta inmune tipo T1 durante el tratamiento combinado, medida en función de la síntesis de IIFNγ por los linfocitos T CD8, se asocia con RVS y sugiere el control de la replicaciσn y el aclaramiento posterior de los pacientes infectados con el genotipo 1 del VHC.

Introduction: Treatment strategies for chronic hepatitis B (CHB) using either interferon or Lamivudine can achieve sustained response in 30-40 % in HBeAg positive CHB. Retreatment of treatment failure in CHB and treatment of HBeAg negative patients pose major therapeutic challenge. Because of success story of Peginterferon in hepatitis C and some preliminary data in CHB, we undertook this open-labeled prospective study to study the response of Peginterferon α-2b (PegIFN) and Lamivudine combination in patients of CHB. Materials and methods: Following 4 groups of patients of CHB with persistently elevated transaminases were treated with Lamivudine 100 mg PO daily and PegIFN 1.5 μg/ kg SC once a week-1) HBeAg negative treatment naïve patients-for 12 months 2) HBeAg negative patients who were nonresponsive to at least two treatment regimensfor 12 months, 3) HBeAg positive treatment naïve patients-for 6 months 4) HBeAg positive patients who were treatment failure at least with two regimens-for 6 months. Patients were tested for LFT, HBeAg, antiHBe, quantitative HBVDNA (only in HBeAg negative CHB) and liver biopsy when possible at inclusion. During treatment period, LFT was tested at monthly interval and HBeAg, antiHBe and HBVDNA (in HBeAg negative CHB) at 3 monthly intervals. End of treatment response (EOR) was assessed at end of treatment period and sustained response (SR) at 6 months post treatment. Treatment response was defined in HBeAg positive patients with normalization of enzymes and disappearances of HBeAg & in antiHBe positive patients with normalization of enzymes and loss of detectable HBVDNA. Results: Total 25 patients with CHB were included in this study with mean age of 37.9 ± 4.6 years (range 20-56) and male: female= 11.5:1. 1) In HBeAg negative treatment naïve patients, 4/6 patients achieved EOR (66.6%), whereas in 3/6 patients (50%) had SR. 2) In HBeAg negative treatment failure group, 4/5 patients had EOR (80%) and 3/5 patients achieved SR (60%), of which 1 patient lost HBsAg. 3) In HBeAg positive treatment naïve patients, 4/5 patients achieved EOR (80%) and 3/5 patients obtained SR (60%). One patient in this group lost HBsAg. 4) In HBeAg positive treatment failure group, 5/9 patients achieved EOR (55.5%), whereas 3/9 patients (33.3%) obtained SR. Conclusion: Overall, in difficult-to-treat patients (considering groups 1, 2 & 4-total 20 patients) with combination of PegIFN and Lamivudine, EOR was seen in 13 patients (65%), SR was obtained in 9 patients (45%) and loss of HBsAg was seen in 1 patient (5%).