Pegylated Interferon And Ribavirin Research Articles

Evolution of liver fibrosis after interferon-based anti-hepatitis C virus therapy failure in 3,049 chronic hepatitis C patients without cirrhosis

Background and study aimsLiver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart. Patients and MethodsThis was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs. ResultsA total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [−0.98 (2.93), p ≤ 0.001]. ConclusionFibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.

Antiviral therapy against chronic hepatitis C is associated with a reduced risk of oral cancer.

To identify the risk factors of oral cancer, we investigated the association between chronic hepatitis C (CHC) and oral cancer, and the development of oral cancer after anti-hepatitis C virus (HCV) therapy. We conducted a nationwide, population-based cohort study from 2004 to 2012 from the Taiwan National Health Insurance Research Database. CHC patients without anti-HCV therapy were matched with those non-HCV patients by age, sex and comorbidities. Moreover, CHC patients who underwent pegylated interferon and ribavirin (PegIFN/RBV) anti-HCV therapy were matched with CHC patients without anti-HCV therapy. A total of 100,058 patients were included in the HCV cohort and non-HCV cohorts, respectively. Their mean age was 59 years and 50% of these were male. CHC infection significantly increased the cumulative incidence of lichen planus and oral cancer. After adjustment for confounders and competing mortality, CHC infection significantly increased the risk of oral cancer (hazard ratio [HR]: 1.677, 95% confidence interval [CI]: 1.392-2.020, p < 0.001). Another 23,735 CHC patients without anti-HCV therapy were matched with 23,735 CHC patients in the treatment cohort. After adjustment for confounders and competing for mortality, the risk of oral cancer was significantly reduced in CHC patients receiving anti-HCV therapy (HR: 0.652, 95% CI: 0.479-0.887, p = 0.007). To minimize the inclusion of pre-existing unidentified oral cancer, we excluded oral cancer developed within the first year of CHC or anti-HCV therapy and found these associations remained statistically significant. In conclusion, CHC significantly increases the risk of oral cancer. Moreover, PegIFN/RBV antiviral therapy significantly reduces the risk of HCV-related oral cancer.

Early antiviral therapy reduces the risk of lymphoma in patients with chronic hepatitis C infection.

Chronic hepatitis C infection is linked to lymphoma development. To investigate whether antiviral therapy prevents the risk of HCV-related lymphoma. Patients diagnosed with chronic hepatitis C were retrieved from the Taiwan National Health Insurance Research Database during 2004-2012. We included patients who received pegylated interferon and ribavirin (PegIFN/RBV) antiviral therapy for ≥24weeks (PegIFN/RBV cohort) or hepatoprotectants for ≥90days without antiviral therapy (HCV-untreated cohort). Both cohorts were matched by age, sex, and comorbidities through propensity scores and followed for newly diagnosed lymphoma or non-Hodgkin's lymphoma (NHL). In total, 24133 patients were included in both the PegIFN/RBV and HCV-untreated cohort. The lymphoma incidence was significantly higher in the untreated than in the treated cohort (66.48 vs 43.34 per 100000 person-years, P=0.029). After adjusting for confounders, the patients who received PegIFN/RBV therapy were at a lower risk of developing lymphoma compared with the untreated patients (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.43-0.96, P=0.030). Moreover, this beneficial effect was mainly observed in patients with chronic hepatitis C <60years old with a relative risk reduction of 51% for all lymphoma (HR: 0.49, 95% CI: 0.29-0.82, P=0.007) and 48% for non-Hodgkin's lymphoma (HR: 0.52, 95% CI: 0.30-0.91, P=0.022). The risk of all lymphoma or non-Hodgkin's lymphoma development after antiviral therapy was lowered to that of subjects without HCV. PegIFN/RBV-based antiviral therapy significantly reduced the risk of lymphoma, especially non-Hodgkin's lymphoma; the reduction was mostly among patients <60years old. Early antiviral therapy for chronic hepatitis C is suggested.

New Perspectives of HCV Infection: Focus on New Treatment Agents and Comorbidity Status, a Short Review

Chronic hepatitis C (CHC) is one of the main leading causes of mortality associated with liver disease worldwide. Different predominant modes of transmission in the local area play an important role for the disease burden. Several cofactors are identified to accelerate the disease progression. Besides, several comorbidities are common in patients with CHC and also have poor response to the traditional combination of pegylated interferon and ribavirin (PegIFN/RBV) treatment.

Use of next-generation sequencing in the CHAT study (acute HCV in HIV): effect of baseline resistance-associated NS3 variants on treatment failure

BackgroundThe epidemic of acute HCV infection among HIV-infected men who have sex with men (MSM) is ongoing. Transmission of drug-resistant variants (DRVs) after HCV treatment failure could pose a major threat to the effectiveness of future therapies. We determined the baseline prevalence of pre-existing DRVs in the HCV NS3 protease gene and their effects on the addition of telaprevir (TVR) to standard pegylated interferon and ribavirin (PEG-IFN/RBV) for acute HCV infection in individuals enrolled in a multicentre randomized controlled trial (2013 and 2014).MethodsThe HCV NS3 viral protease was analyzed using Sanger and next-generation sequencing (NGS) for DRVs at baseline (n = 31), and at viral breakthrough following TVR-based treatment (n = 3) or PEG-IFN/RBV alone (n = 2).ResultsSequence analysis indicated that all individuals were infected with HCV genotype 1a. Complete (100%) concordance was seen between Sanger and NGS for high levels of mutant viral populations. The simeprevir-associated Q80K variant was present at high frequency in the German samples (7/11–64%) and infrequently in the UK samples (1/20–5%). In the three TVR-based treatment failures, V36M/l and R155K/T emerged, but not R155G which was detectable at low levels in two individuals at baseline. Failure rate at week 24 was 26.7% (with baseline DRVs) vs. 6.3% (without baseline DRVs), p = 0.17). Comparison of sequences pre- and post-therapy in 5 who failed therapy revealed the emergence of not previously described variants V193G, E176K, P189S (on TVR), and V181S in one instance each.ConclusionThe presence of baseline DRVs for the NS3 protease gene of HCV genotype 1a did not appear to predict treatment failure in our patient cohort. Where detected, Q80K was present at high levels (>98%), but had no effect on outcomes and remained high after failure.

Factors Affecting the Virological Response Among Chronic Hepatitis C Virus Patients in Yemen.

Hepatitis C virus (HCV) infection is increasingly seen as a major public health problem, threat, and concern worldwide. In Yemen about 1.7% of the population is infected with chronic hepatitis C. This study aimed to detect the predictors for response to pegylated interferon and ribavirin (Peg-IFN/RBV) in chronic HCV Yemeni patients. The study was conducted on 100 patients with chronic HCV who received Peg-IFN/RBV in the 48th Military Hospital in Sana'a Yemen, from 2011 to 2013. All patients were subjected to complete history taking, thorough clinical examinations, routine laboratory investigation, and abdominal ultrasonography. The HCV RNA was assessed at week 72 of treatment to detect whether the patient achieved sustained virological response (SVR). The SVR was achieved in 64% of the samples. Age above 40, Khat chewing, and obesity were the sociodemographic factors that predict good response for Peg-IFN/RBV combined therapy. Platelet count, alpha feto-protein (AFP), aspartate transaminase (AST), and alanine transaminase (ALT) levels were the basic laboratory investigations that gave favorable response. Significant predictors of sustained response included: older than 40 years (OR = 0.136, P = 0.042), Khat chewer (OR = 0.016, P = 0.008), body mass index (BMI) (OR = 0.055, P = 0.029) and increase in fasting blood glucose (OR = 0.925, P = 0.004), alkaline phosphatase (OR = 0.969, P = 0.001), total and bilirubin (OR = 0.058, P = 0.017), AST (OR = 1.033, P = 0.002), and albumin (OR = 6.490, P = 0.021). Studying the independent variables of response, we revealed that male gender, BMI, ALT >40, AFP >10, viremia >600, and hemoglobin and thyroid stimulating hormone (TSH) levels are variables associated with failure of end of treatment response (ETR) and SVR.

Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience.

The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n=74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n=1) in the NS3, and at L31 (n=4), Y93 (n=4), and L31/Y93 (n=1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n=12). Univariate analysis showed that a history of SMV (P<.01) and the presence of mutations in NS5A (P=.02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.

Serious Adverse Events with Sofosbuvir Combined with Interferon and Ribavirin: Real-Life Egyptian Experience.

Viral hepatitis is a serious problem worldwide that was under-recognized till recently. The prevalence of chronic hepatitis C virus (HCV) is estimated to be 180 million people worldwide. Treatment of chronic HCV using combined pegylated interferon and ribavirin (PEG/RIBA) has long been the standard of care with modest response. In our study, we will report the real-life experience of serious adverse events (SAEs) that were reported by the National Committee for Control of Viral Hepatitis (NCCVH, Cairo, Egypt) program while treating chronic HCV using the triple therapy, sofosbuvir combined with pegylated interferon and ribavirin (PEG/RIBA/SOF), which led to premature discontinuation of treatment. This retrospective analysis included a total of 6,989 chronic HCV patients who were treated by the NCCVH. They received the triple antiviral therapy in 26 treatment centers in Egypt using PEG/RIBA/SOF for 12 weeks. Among 6,989 patients who were treated in 26 treatment centers related to NCCVH, 406 cases (5.9%) reported SAEs and prematurely stopped their treatment. Triple therapy PEG/RIBA/SOF was an important intermediate milestone between interferon-based therapy and the interferon-free all-oral direct acting antiviral agents (DAAs). Results of this study were the leading cause of discontinuation of interferon-based therapy and introduction of interferon-free all-oral treatment protocols, incorporating DAAs from different classes as soon as they gain approval.

Treatment of Hepatitis C Infection with Direct-Acting Antiviral Agents in Liver-Transplant Patients: A Systematic Review and Meta-Analysis

Context: Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) can be prevented, using antiviral therapy and new treatment regimens. Combination of protease, NS5A, and NS5B inhibitors, with or without pegylated-interferon and ribavirin (PEG-IFN/RBV), results in significantly high rates of sustained virologic response (SVR) among post-LT patients with HCV infection. In this study, we aimed to assess the efficacy of direct-acting antiviral (DAA) regimens in post-LT patients with HCV infection. Evidence Acquisition: We conducted a systematic search in electronic databases to detect eligible studies on DAA treatments after LT. We evaluated English-language studies, including clinical trials and cohort studies, which used antiviral DAA regimens (with or without PEG-IFN/RBV) and reported SVR rates at 12 weeks after the end of treatment (SVR12). After data extraction, the pooled SVRs were calculated, using STATA version 11. Results: A total of 35 studies with various HCV genotypes were included in our analysis. Due to the small sample size and lack of suitable data on HCV genotypes 2 - 6, the meta-analysis was only conducted among patients with HCV genotype 1; the results of other studies were also obtained. SVR12 rates ranged from 91% to 97% in patients with 12- or 24-week sofosbuvir (SOF)/simeprevir (SMV) ± RBV, SOF/ledipasvir (LDV) ± RBV, and SOF/daclatasvir (DCV) ± RBV regimens. The minimum SVR12 rate was found in patients receiving SMV plus PEG-IFN/RBV (59%; 95% Confidence Interval, 49 - 68). Conclusions: Administration of new HCV DAA regimens can prevent post-LT HCV infection. The combination of SOF/DCV and SOF/LDV, with or without RBV, for 12 or 24 weeks can produce high rates of SVR12 in post-LT HCV patients in different settings.

Effectiveness of triple therapy with direct-acting antivirals for hepatitis C genotype 1 infection: application of propensity score matching in a national HCV treatment registry

BackgroundObservational studies are used to measure the effectiveness of an intervention in non-experimental, real world scenarios at the population level and are recognised as an important component of the evidence pyramid. Such data can be accrued through prospective cohort studies and a patient registry is a proven method for this type of study. The national hepatitis C (HCV) registry was established in Ireland in 2012 with the aim of monitoring the clinical and economic outcomes from new, high cost regimens for the treatment of HCV infection. A sustained virological response (SVR) 24 weeks following completion of therapy with interferon-containing regimens is considered a cure. Non-randomisation in these studies can result in confounding or selection bias. Propensity score (PS) matching is one of a number of statistical tools that can be used to mitigate the effects of confounding in observational studies.MethodsWe analysed the data of 309 patients who underwent triple therapy treatment with telaprevir (TPV) in combination with pegylated-interferon and ribavirin (PR) or boceprevir (BOC)/PR between June 2012 and December 2014. The decision to initiate treatment and the selection of the treatment regimen was at the discretion of the physician. To adjust for confounding, three approaches to propensity score matching were assessed Adjusted sustained-virological response rates (SVR), odds ratios, p-values and 95% confidence intervals were calculated from the three PS matched dataset.ResultsPrior to matching, the unadjusted sustained virological response rates 24 weeks after treatment complete (SVR24) were 74% (n = 158/215) and 61% (n = 57/94) for telaprevir/PR and boceprevir/PR, respectively. After matching, adjusted SVR24 rates were between 73–74% and 60–61% for telaprevir/PR and boceprevir/PR, respectively.ConclusionEfficacy rates were comparable with those reported in pivotal clinical trials and real world studies. After adjusting for confounding, we conclude that there was no difference in treatment effect after PS matching. The small sample size limits the conclusions that can be made about the effect of PS matching. Propensity score adjustment remains a tool that can be applied to future analysis, however, we suggest, where possible, using a larger sample size in order to reduce the uncertainty around the outcomes.

ANTIVIRAL TREATMENT OF CHRONIC HEPATITISС: AVAILABLE RESULTS AND FUTURE PROSPECTS

Objective : to evaluate the effectiveness of two interferon (IFN)-based antiviral therapy of chronic hepatitis C (IFN/RBV or PEG-IFN/RBV)depending on HCV genotype, IL-28B gene mutations and to determinethe group of patients who need treatment with direct antiviral agents. Material and methods. The study involved 844 patients with chronic hepatitis C (60.6 % men; 51.9 % with genotype 1 virus) in two infectious diseases hospitals. 324 patients received treatment with standard interferon and ribavirin (IFN/RBV), 520 patients - with pegylated interferon and ribavirin (PEG-IFN/RBV). Polymerase chain reaction was applied to determinesingle nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 of IL-28B gene. Results. The effectiveness (sustained virologic response, SVR) of the scheme IFN/RBV in patients with HCV genotype 1 was 23.9 %, and of PEG-IFN/RBV - 48.4 %. The highest frequency rate of SVR was recorded in patients with CC variant of SNP rs12979860 - 73.3 and 82.1 % (for IFN/RBV and PEG-IFN/RBV schemes, respectively). Schemes IFN/RBV (SVR 70.8 %) and PEG-IFN/RBV (SVR 86.5 %) were highly effective for patients with HCV genotypes 2 and 3. The treatment was not effective in patients with genotype 1 HCV having gene IL-28B SNPs rs12979860 CT or TT and rs8099917 TG or GG and in patientsover 40. Conclusion. It is prospectiveto use non-IFN regimens based on direct-acting antiviral agents to treat patients with 1 HCV genotype with genotype CT/TT (rs12979860) and TG/GG (rs8099917), as well as those who did not respond previously to the antiviral treatment with PEG-IFN/RBV.The implementation of the non-IFN regimens should be accelerated by means of registration or development of production of generic drugs.

Clinical Evaluation of Terap C Vaccine in Combined Treatment with Interferon and Ribavirin in Patients with Hepatitis C

BackgroundAn estimated 170 million individuals worldwide are infected with the hepatitis C virus (HCV). Although treatment options using a combination of pegylated interferon and ribavirin (P-IFN/RBV) are available, sustained clearance of the virus is only achieved in approximately 40% of individuals infected with HCV genotype 1. Recent advances in the treatment of HCV using directly acting antiviral agents have been achieved; however, treatment can be very expensive and is associated with substantial side effects. The development of a new treatment modality is needed. One possible modality could be specific immunotherapy. Terap C is a therapeutic vaccine candidate composed of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120. ObjectiveTo assess the safety and efficacy of concomitant therapy with the candidate vaccine, Terap C, IFN α-2b and ribavirin in untreated individuals with HCV genotype 1 infection. MethodsThis was a Phase II randomized, placebo-controlled, double-blind clinical trial evaluating the safety and efficacy of Terap C concomitant with IFN α-2b/RBV in 92 treatment-naïve patients with HCV genotype 1 infection. The study was conducted at the Gastroenterology Institute in Havana, Cuba. Patients were randomly assigned to 1 of 5 groups. The control group (Group 1) received IFN α-2b/RBV and placebo for 48 weeks. Groups 2 and 3 were administered Terap C 6 and 9 times, respectively, in addition to standard IFN α-2b/RBV treatment. In groups 4 and 5, Terap C was introduced 12 weeks after the initiation of IFN α-2b/RBV and administered 6 and 9 times, respectively, concomitant with IFN α-2b/RBV. ResultsAll patients showed some adverse events. Out of 3615 adverse events, only 18.8% were considered to be probably associated with administration of Terap C. Most events (47.4%) were considered to be improbably associated with of administration Terap C. Only 33.8% were considered possibly temporarily associated with Terap C, and can be explained by the use of conventional IFN α-2b + RBV or by HCV itself. The most common adverse events (≥65%) observed were pain at the injection site, headache, asthenia, psychiatric disturbances, fever, and gastrointestinal symptoms. Regarding sustained virological response, a 20% superiority was observed in the patients who received concomitant Terap C treatments from the beginning of the study compared with those who started after Week 12. ConclusionsVaccination with Terap C in patients with chronic HCV infection was safe and well tolerated. Clinical trial protocol code: IG/VHI/HC/0701; Public Register Code: RPCEC00000074.

Cost-Effectiveness of Hepatitis C Treatment for People Who Inject Drugs and the Impact of the Type of Epidemic; Extrapolating from Amsterdam, the Netherlands

BackgroundPeople who inject drugs (PWID) are disproportionally affected by the hepatitis C virus (HCV) infection. The efficacy of HCV treatment has significantly improved in recent years with the introduction of direct-acting antivirals (DAAs). However, DAAs are more costly than pegylated-interferon and ribavirin (PegIFN/RBV). We aimed to assess the cost-effectiveness of four HCV treatment strategies among PWID and treatment scale-up.MethodsAn individual-based model was used describing HIV and HCV transmission and disease progression among PWID. We considered two epidemiological situations. A declining epidemic, based on the situation in Amsterdam, the Netherlands, and a stable HCV epidemic, as observed in other settings. Data on HCV incidence, prevalence, treatment setting and uptake were derived from observed data among PWID in Amsterdam. We assessed the incremental cost-effectiveness ratio (ICER, costs in €/quality-adjusted life year (QALY)) of four treatment strategies: 1) PegIFN/RBV; 2) sofosbuvir/RBV for genotype 2–3 and dual DAA for genotype 1–4; 3) Dual DAA for all genotypes; 4) Dual DAA with 3x treatment uptake.ResultsIn both types of epidemic, dual DAA therapy was most cost-effective strategy. In the declining epidemic, dual DAA yielded an ICER of 344 €/QALY while in the stable epidemic dual DAA led to cost-savings. Scaling-up treatment was also highly cost-effective. Our results were robust over a range of sensitivity analyses.ConclusionHCV treatment with DAA-containing regimens is a highly cost-effective intervention among PWID. Based on the economic and population benefits of scaling-up treatment, stronger efforts are needed to achieve higher uptake rates among PWID.

ASSOCIATION BETWEEN THE IL28B rs12979860 POLYMORPHISM AND THERAPY RESPONSE IN PATIENTS INFECTED WITH GENOTYPE 1 OF HEPATITIS C VIRUS IN CENTRAL BRAZIL

Polimorfismos de nucleotídeo único (SNPs) relacionados ao gene IL28B têm sido associados à eliminação espontânea do vírus da hepatite C (VHC) e à resposta virológica sustentada (RVS) no tratamento da infecção pelo VHC. Este estudo teve como objetivo investigar a associação entre o SNP IL28B rs12979860 e a RVS em pacientes com hepatite C no Brasil Central. Um total de 101 pacientes crônicos monoinfectados com o genótipo 1 do VHC, tratados com interferon peguilado e ribavirina (PEG-IFN/RBV), foi estudado na cidade de Goiânia, estado de Goiás, Brasil Central. A análise de rs12979860 mostrou que o genótipo mais prevalente foi CT (57,4%), seguido por CC (23,8%) e TT (18,8%). A taxa global de 28,7% (IC 95%: 20,4-38,7) para a RVS foi encontrada na população estudada. Na análise multivariada, somente o genótipo CC para o SNP rs12979860 (OR: 3,77; IC 95%: 1,13- 12,60; p = 0,031) mostrou-se independente associado à RVS. Estes achados mostram que o SNP IL28B rs12979860 é um forte preditor de RVS no tratamento com PEG-IFN/RBV nos pacientes infectados com o genótipo 1 do VHC no Brasil Central.

PREVALENCE OF DEPRESSION;

With recent availability of Sofosbuvir, Chronic Hepatitis C treatment paradigmhas changed considerably. However for a resource constrained country like Pakistan, still thestandard treatment of Chronic Hepatitis C remains the combination of Interferons and Ribavirin.Depression, sometimes major, is a recognized side effect of this combination. Objective: Theobjective of our study was to analyze the prevalence of depression during treatment with pegylatedinterferon 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 FatimaMemorial Hospital and Alshafi Hospital Lahore. Duration of study: Duration of our study wastwo years and 3 months from January 2010 to April 2012. Patients and Method: We included180 patients in our study. We confirmed the diagnosis of chronic hepatitis C in all these willinglyparticipated patients. All these participants were put on combination of pegylated interferonand ribavirin. Serial follow ups were done for the assessment of development of depressionduring the treatment of Hepatitis C. Results: 46.8 (26%) patients developed depression duringtreatment. Depression was more common in the middle of treatment which gradually improvednear the end of treatment. Conclusion: We reached at a conclusion in our study that there isdefinite correlation of depression with pegylated interferon and ribavirin therapy in hepatitis Cpatients.

New approaches in the treatment of hepatitis C.

About 130-170 million people, is estimated to be infected with the hepatitis C virus (HCV). Chronic HCV infection is one of the leading causes of liver-related death and in many countries it is the primary reason for having a liver transplant. The main aim of antiviral treatment is to eradicate the virus. Until a few years ago the only treatment strategy was based on the combination of pegylated interferon and ribavirin (PEG/RBV). However, in genotypes 1 and 4 the rates of viral response did not surpass 50%, reaching up to 80% in the rest. In 2011 approval was given for the first direct acting antiviral agents (DAA), boceprevir and telaprevir, for treatment of genotype 1, in combination with traditional dual therapy. This strategy managed to increase the rates of sustained viral response (SVR) in both naive patients and in retreated patients, but with greater toxicity, interactions and cost, as well as being less safe in patients with advanced disease, in whom this treatment can trigger decompensation or even death. The recent, accelerated incorporation since 2013 of new more effective DAA, with pan-genomic properties and excellent tolerance, besides increasing the rates of SVR (even up to 100%), has also created a new scenario: shorter therapies, less toxicity and regimens free of PEG/RBV. This has enabled their almost generalised applicability in all patients. However, it should be noted that most of the scientific evidence available is based on expert opinion, case-control series, cohort studies and phase 2 and 3 trials, some with a reduced number of patients and select groups. Few data are currently available about the use of these drugs in daily clinical practice, particularly in relation to the appearance of side effects and interactions with other drugs, or their use in special populations or persons with the less common genotypes. This situation suggests the need for the generalised implementation of registries of patients receiving antiviral therapy. The main inconvenience of these new drugs is their high cost. This necessitates selection and prioritization of candidate patients to receive them, via strategies established by the various national organs, in accordance with the recommendations of scientific societies.

HCV viral load at baseline and at week 4 of telaprevir/boceprevir based triple therapies are associated with virological outcome in HIV/hepatitis C co-infected patients

BackgroundAs first generation HCV-specific protease inhibitors, boceprevir (BOC) or telaprevir (TVR) can achieve 60% to 70% sustained virological response (SVR) for HCV infected patients with genotype 1 infections, they could remain temporary a therapeutic option in patients living in resources limited countries with limited access to the new anti-HCV direct acting antiviral (DAA) drugs, such as sofosbuvir. Objectives and Study designHere we evaluated in a routine practice setting, the treatment responses, tolerance and factors associated with SVR of a triple therapy with BOC or TVR, combined with pegylated interferon and ribavirin (PegIFN/RBV) in HIV/HCV co-infected patients, included in a large cohort of HIV/HCV coinfected patients (ANRS CO13-HEPAVIH). ResultsAmong the 89 HIV/HCV coinfected patients treated, 65% of whom were previous non-responders to PegIFN/RBV therapy, 65%, 55% and 41% had at baseline genotype 1a, a high baseline HCV-RNA (≥800,000IU/ml) and a cirrhosis, respectively. The SVR12 rate was 63% overall, 53% for BOC-based regimen and 66% for TVR-based regimen. In multivariate analysis, two factors were significantly associated with HCV SVR: HCV viral load <800,000IU/mL at treatment initiation versus ≥800,000IU/mL (OR 4.403, 95% CI 1.29–15.04; p=0.018) and virological response at W4 (HCV-RNA undetectable after 4 weeks of triple therapy) (OR 3.35, 95% CI 1.07–10.48; p=0.038). ConclusionsOverall SVR12 was 63% and our results suggest that HIV/HCV coinfected patients with low HCV viral load (<800,000IU/mL) and undetectable HCV-RNA after 4 weeks of triple therapy with TVR or BOC-based regimen have a higher probability of treatment success.

Study of the effect of combined interferon and ribavirin therapy on the hearing profile of hepatitis C virus patients

Abstract This study aimed to study the effect of combined pegylated interferon and ribavirin (Peg-IFN/RBV) therapy on the hearing profile of patients with hepatitis C virus (HCV). The auditory system of a total of 74 chronic HCV patients was assessed using pure tone audiometry (conventional and high frequency) and distortion product otoacoustic emissions (DPOAEs in the form of a DP-gram) immediately before therapy and at the end of the 12th and 24th weeks. Vestibulocochlear adverse effects including hearing loss, tinnitus, vertigo, and otalgia were also considered. Significant elevations in hearing thresholds were found on comparing thresholds at the 12th and 24th weeks with those at the onset of the study. The elevations were mostly at higher frequencies (3000, 4000, 6000, 8000, 9000, 10 000, 11 200, and 12 500 Hz), and did not affect speech perception. For DPOAE, significant differences were observed at all F2 frequencies on comparing both amplitudes and signal to noise ratios at the 12th and 24th weeks with those before therapy, with significance appearing earlier for higher F2 frequencies. Otologic complaints were insignificant, except for tinnitus; a significant increase in tinnitus was observed from 0 to 31.1% by the end of the study. Significant auditory adverse effects may result from combined Peg-IFN/RBV therapy in HCV patients, highlighting the importance of prompt monitoring of auditory functions in these patients.

Simplified diagnostic monitoring for hepatitis C, in the new era of direct-acting antiviral treatment.

Approximately 150-175 million people are infected with hepatitis C virus (HCV). Until very recently, the complexity, cost and poor efficacy and tolerability of pegylated interferon and ribavirin (PEG-RBV) treatment have hindered scale up in low-income and middle-income countries (L&MICs). Similarly, the diagnostic and monitoring algorithm associated with PEG-RBV has been expensive and complicated because of the poor efficacy and frequency of adverse drug effects of PEG-RBV therapy. This article provides an overview of the potential changes to the diagnosis and monitoring algorithm and describes key promising tools in the diagnostics pipeline. Interferon-free direct-acting antiviral (DAA) therapy sets the stage to significantly simplify laboratory requirements and make the overall diagnostic package much less expensive. Diagnostic simplification and cost-reduction will be key to enable implementation of HCV screening and treatment in L&MICs. There is the potential to introduce simplified monitoring for hepatitis C. Antigen testing could be used as a replacement for HCV RNA PCR tests, to establish active infection and then to prove cure after stopping DAA treatment. If new DAA treatments can be shown to be pan-genotypic, genotyping may no longer be required.

The complete title: The effect of interleukin-28B rs12979860 polymorphism on the therapeutic response of Moroccan patients with chronic hepatitis C

Background/aimsThere is increasing evidence for the effect of rs12979860 IL28B polymorphism in response to the standard treatment PEG-IFN/RBV (i.e. combination of pegylated interferon and ribavirin) in chronic hepatitis C virus (HCV) infection. The present study aimed to determine the impact of IL28B associations in interferon responsiveness in 187 Moroccan patients with chronic HCV infection. MethodsHCV RNA levels were measured with a real-time RT-PCR assay and treatment efficacy was assessed by sustained virological response (SVR) and patients were classified as responders or non-responders. IL28B rs12979860 polymorphism genotyping was achieved by PCR-HRM technique. ResultsThe results demonstrated that SVR was achieved in 102 patients (55%); while 69 were non-responders (37%) and 16 relapsed (8%). Genotype 1 was the predominant HCV genotype detected in 112 patients followed by genotype 2 in 56 patients. The genotype CC was observed in 42 cases (25%); CT in 69 (41%) and TT in 57 (34%) demonstrating a C allele frequency of 46%. The SVR was observed in 32 patients with genotype CC accounting for 76%. The frequencies of rs12979860 CC type in infected individuals with HCV genotype 1 were 47% and 12% respectively in SVR and non-SVR groups. A highly statistically significant association between this SNP and SVR was found (p<0.001). Using multivariate logistic regression analysis, CC genotype was an independent factor for SVR. In the group of patients infected with genotype 2, SVR rate was 79%. The frequency of rs12979860 CC type in SVR group (n=4) was 9% and rs12979860 non-CC genotype was highly associated with SVR (p=0.001). ConclusionThis finding adds evidence that genotyping for the IL-28B rs12979860 SNP can be a good parameter for the prediction of treatment success in patients with chronic hepatitis C before initiation of antiviral therapy in Morocco.