Interferon And Ribavirin Research Articles

European mitochondrial haplogroups predict liver-related outcomes in patients coinfected with HIV and HCV: a retrospective study

BackgroundMitochondrial DNA (mtDNA) haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Our aim was to determine whether mtDNA haplogroups are associated with liver-related events (LREs) in HIV/HCV-coinfected patients.MethodsWe carried out a retrospective cohort study in HIV/HCV-coinfected patients who were potential candidates for therapy with interferon and ribavirin (IFN/Rib) between 2000 and 2009. The primary endpoint was the occurrence of LREs (decompensation or hepatocellular carcinoma). mtDNA genotyping was performed using the Sequenom MassARRAY platform. We used Fine and Gray proportional hazards model to test the association between mtDNA haplogroups and LREs, considering death as a competitive risk.ResultsThe study population comprised 243 patients, of whom 40 had advanced fibrosis or cirrhosis. After a median follow-up of 7.7 years, 90 patients treated with IFN/Rib achieved sustained viral response (SVR), 18 patients had LREs, and 11 patients died. Patients with haplogroup H had lower cumulative incidence than patients with other haplogroups (p = 0.012). However, patients with haplogroup T had higher cumulative incidence than patients with other haplogroups (p = 0.074). In the multivariate analysis, haplogroup T was associated with an increased hazard of developing LREs [adjusted subhazard ratio (aSHR) = 3.56 (95% CI 1.13;11.30); p = 0.030]; whereas haplogroup H was not associated with lower hazard of LREs [aSHR = 0.36 (95% CI 0.10;1.25); p = 0.105]. When we excluded patients who achieved SVR during follow-up, we obtained similar SHR values.ConclusionsEuropean mitochondrial haplogroups may influence the natural history of chronic hepatitis C.

Interferon-Free Regimen: Equally Effective in Treatment Naive and Experienced HCV Patients

Introduction and aim. Interferon-free regimen has been reported to be highly efficient in treatment of HCV infection, including patients with compensated cirrhosis. We compared the efficacy of Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir and Ribavirin (OBT/PTV/r, with DSV and RBV) therapy in patients with chronic HCV genotype 1b infection and compensated cirrhosis with and without prior treatment experience with pegylated interferon and ribavirin (IFN/RBV).Material and methods. A prospective two-center study was conducted in Mures County Hospital and Brasov County Hospital, Romania in period November 2015-July 2016. Both treatment naïve and PegIFN/RBV experienced patients with chronic HCV genotype 1b infection received 12 weeks of OBT/PTV/r, with DSV and RBV. Sustained virologic response 12 weeks after the treatment and eventual discontinuation of therapy due to adverse events were assessed in order to estimate safety and efficiency of therapeutic regimen.Results. Fifty nine patients were included in study, 35 (59.3%) of them were previously treated with IFN/RBV. Forty four (74.5%) patients were previously diag-nosed with cirrhosis Child Pugh score 5, while 15 (25.4%) with Child Pugh score 6. All 59 patients achieved a SVR12 of 100% and one patient from treatment naïve cohort discontinued the therapy due to hyperbilirubinemia and encephalopathy. However viral load assessed at 12 weeks after discontinuation of therapy in this patient was undetectable.Conclusion An all-oral regimen of co-for-mulated OBT/PTV/r with DSV and RBV results in high rate of sustained virologic response at post-treatment week 12 among HCV GT1b infected patients associated with compensated cirrhosis, regardless of previous treatment experience with PegIFN/RBV.

Interferon-Free Regimen: Equally Effective in Treatment Naive and Experienced HCV Patients

Introduction and aim: Interferon-free regimen has been reported to be highly efficient in treatment of HCV infection, including patients with compensated cirrhosis. We compared the efficacy of Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir and Ribavirin (OBT/PTV/r, with DSV and RBV) therapy in patients with chronic HCV genotype 1b infection and compensated cirrhosis with and without prior treatment experience with pegylated interferon and ribavirin (IFN/RBV). Methods: A prospective two-center study was conducted in Mures County Hospital and Brasov County Hospital, Romania in period November 2015–July 2016. Both treatment naïve and PegIFN/RBV experienced patients with chronic HCV genotype 1b infection received 12 weeks of OBT/PTV/r, with DSV and RBV. Sustained virologic response 12 weeks after the treatment and eventual discontinuation of therapy due to adverse events were assessed in order to estimate safety and efficiency of therapeutic regimen. Results: Fifty nine patients were included in study, 35 (59.3%) of them were previously treated with IFN/RBV. Forty four (74.5%) patients were previously diagnosed with cirrhosis Child Pugh score 5, while 15 (25.4%) with Child Pugh score 6. All 59 patients achieved a SVR12 of 100% and one patient from treatment naïve cohort discontinued the therapy due to hyperbilirubinemia and encephalopathy. However viral load assessed at 12 weeks after discontinuation of therapy in this patient was undetectable. Conclusion: An all-oral regimen of co-formulated OBT/PTV/r with DSV and RBV results in high rate of sustained virologic response at post-treatment week 12 among HCV GT1b infected patients associated with compensated cirrhosis, regardless of previous treatment experience with PegIFN/RBV.

The Incidence of Hepatocellular Carcinoma Is not Increased in Individuals with Chronic Hepatitis C After Treatment with Interferon-free Regimens: an ERCHIVES Study

BackgroundSustained virologic response (SVR) after interferon-based treatment for chronic hepatitis C virus (HCV) infection has been strongly linked with decreased incidence of hepatocellular carcinoma (HCC). Surprisingly, several recent studies have reported higher rates of HCC in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. As such, we sought to investigate whether DAA use is associated with increased rates of incident HCC.MethodsUsing the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified 17,836 patients without a prior diagnosis of HCC and divided them into 3 groups based on treatment: (a) pegylated interferon and ribavirin (IFN) (n = 3,534); (b) DAA-based therapy (n = 5,734); and (c) an untreated control group (n = 8,468). Predictors of HCC were identified using multivariate Cox proportional hazards analysis. HCC-free survival in cirrhotics was assessed by Kaplan–Meier analysis.ResultsSVR was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. In our cohort, the incidence rate of HCC was not different between IFN and DAA groups (7.48/1000 vs. 7.92/1000 patient-years of follow-up; P = 0.72). Moreover, DAA treatment was not associated with an increased risk of HCC (HR 1.16; [95% CI: 0.79, 1.71]) compared to IFN treatment. Other risk factors for HCC included older age, alcohol abuse/dependance history, smoking history, HCV genotype 3 infection, proton-pump inhibitor use, AFP > 20, and cirrhosis. Notably, among cirrhotics who achieve SVR, HCC-free survival was not different between IFN and DAA treated groups, and both groups had significantly improved HCC-free survival compared with untreated patients.ConclusionAmong cirrhotic patients with HCV, DAA treatment is associated with a comparable risk of HCC to IFN treatment. Furthermore, the rate of HCC after SVR by any treatment was significantly lower than for those untreated or who failed to achieve SVR. Previously reported increases in HCC associated with DAA treatment appear to be explained by the presence of pre-existing risk factors for HCC.Disclosures R. T. Chung, Gilead: Investigator, Research grant; Abbvie: Investigator, Research grant; Merck: Investigator, Research grant; Janssen: Investigator, Research grant; A. Butt, Merck: Investigator, Grant recipient

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.

Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin.

The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been associated with neurocognitive and psychiatric abnormalities. The goal of this research was to prospectively evaluate neurocognitive functioning among a group of HCV mono-infected and HIV/HCV co-infected patients during the first 24weeks of IFN/RBV treatment while accounting for practice effects, normal variations in change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective study of patients beginning on IFN/RBV for chronic HCV infection. Patients were administered a depression inventory, a measure of fatigue, a structured psychiatric interview, and a neurocognitive battery at baseline and 24weeks after initiation of treatment. Analyses were conducted to explore possible associations between neurocognitive functioning and the following: HIV/HCV co-infection vs. HCV mono-infection, IFN and RBV treatment exposure, psychiatric status, liver disease stage, and other medical characteristics. At baseline, there were no significant differences between the two groups' neuropsychiatric or neurocognitive function other than the mono-infected group had significantly higher reports of fatigue (p=0.033). Over the course of 24weeks of treatment after controlling for practice effects, the HIV/HCV co-infected patients experienced significantly greater declines in memory (t(56)=2.14, p=0.037) and global neurocognitive functioning (t(53)=2.28, p=0.027). In a well-characterized sample of mono-infected and co-infected patients, it appears that persons with HIV/HCV co-infection are potentially more vulnerable to neurocognitive sequalae during HCV treatment.

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.

Persistent neurocognitive decline in a clinic sample of hepatitis C virus-infected persons receiving interferon and ribavirin treatment.

Treatment of hepatitis C virus (HCV) with pegylated interferon and ribavirin (IFN/RBV) can be associated with neuropsychiatric side effects, which may necessitate dose reductions or treatment discontinuation. This study aimed to characterize the time course and predictors of cognitive and affective/mood symptoms after IFN/RBV treatment initiation. Forty individuals enrolled in a longitudinal project underwent comprehensive cognitive, medical, and psychiatric assessment at baseline and 10 weeks, 6 months, 12 months, and 18 months after treatment initiation. Analyses were conducted to determine the prevalence of neurocognitive impairment over time; explicate the relationship between neurocognitive impairment, neuropsychiatric symptoms, and liver disease at each time point; and identify predictors of neurocognitive decline as well as cognitive effects of viral clearance. By 10 weeks after initiating IFN/RBV, the prevalence of neurocognitive impairment rose from 22.5 to 47.4% (p < 0.05). Infection with genotype 1 and premorbid depression were associated with more severe declines (p < 0.05). After 18 months, 42.5% remained neurocognitively impaired, independent of viral clearance, severity of liver disease, and current depressive symptoms. Undetectable viral load was not associated with improvement 18 months after initiating treatment (p > 0.10). Results of the current study indicate that IFN/RBV treatment-emergent neurocognitive declines are significant, prevalent, and may persist long after treatment cessation. Clinicians should monitor cognition throughout the course of treatment for HCV, noting that early declines may indicate individuals at elevated risk for persistent neurocognitive impairment. Longer-term studies are needed to determine whether lasting declines may remit over longer intervals or with newer direct acting agents.

Impact of Donor and Recipient Single Nucleotide Polymorphisms of IL28B rs8099917 in Living Donor Liver Transplantation for Hepatitis C

Single nucleotide polymorphisms of interleukin-28B (IL28B) rs8099917 are reported to be associated with virologic clearance in interferon-and ribavirin -based treatment for hepatitis C virus (HCV)-infected patients. We examined virologic response in accordance with IL28B polymorphisms in our living donor liver transplantation series under a preemptive interferon and RBV treatment approach. Adequate DNA samples from both the recipient and donor for the study of single nucleotide polymorphisms of IL28B were available from 96 cases and were the subjects of the present study. Various clinical factors related with virologic response including early virologic response (EVR) and sustained virologic response (SVR) were examined. Totally 51% presented with EVR and 44% achieved SVR. Presence of the major allele (TT) in either the recipient or the donor corresponded to SVR of 53% and 48%. Presence of the minor allele (TG or GG) corresponded to SVR of 26% and 32%. Multivariate analysis revealed that genotype of HCV or EVR, but not IL28B polymorphisms in either the recipient or donor, was an independent factor for achieving SVR. When virologic response to treatment was incorporated into analysis, the impact of IL28B polymorphism on virological clearance remained relative to other factors and was not significantly independent.

Effect of Combination of Some Natural Products and Chloroquine on HCV Infection in Egyptian Patients: Pilot Study

Background: Studies using safe natural products {Blue green® tablet (Rhodiola rosea L. root dry extract; Eleutherococcus senticosus Maxim. root dry extract; Ginkgo biloba L. leaf dry extract; Klamath microalgae Aphanizomenon flos aquae (AFA) 50 mg)} showed its antiviral effect. As well as vitamin D3, linolenic acid, black seeds and honey. The aim of the study was to determine the efficacy of combination of these natural products and chloroquine in treatment of HCV patients refusing or unfit for combined Interferon and Ribavirin (INF/RBV) therapy or HCV patients who failed to achieve sustained virological response to INF/RBV. Methods: Patients with detectable HCV RNA with different stages of fibrosis and cirrhosis refusing or unfit for combined Interferon Ribavirin (INF/RBV) therapy or patients who failed to achieve sustained virological response to INF/RBV from April 2009 to March 2012 were included in this study. All the patients were treated first from coinfection as schistosomiasis and helicobacter pylori if present then received combination Blue green® tablet-original natural company, Italy; 2 tablet/30 kg once daily; Vitamin D: 1000 IU/day; tablespoon filled with paste made of linolenic acid, black seeds powder and honey; and 250 mg chloroquine once daily for 10 days and then every 3 days through the duration of therapy. Results: 195 patients with chronic HCV were included; mean age 47.8 ± 9.03 years, 67.7% males. All patients have chronic hepatitis. 24 patients had cirrhosis. 82 (42.1%) achieved negative HCV RNA after 6 months of treatment. After 12 months of treatment, 107 (54.9%) patients had negative HCV RNA. 125 (64.3%) patients achieved ETR after 18 months of treatment. Moreover, 4/6 (66.6%) patients with combined HCV and HBV showed undetectable HBV after 3 months. Two out of 8 (25%) patients who failed to achieve SVR with previous (INF/RBV) have ETR. Conclusion: Combination of safe natural products (Blue green® tablet, vitamin D3, linolenic acid, black seeds and honey) and chloroquine may have a role to achieve SVR in combination with recent direct acting antiviral drugs for HCV infection.

Numerical detection, measuring and analysis of differential interferon resistance for individual HCV intra-host variants and its influence on the therapy response

Hepatitis C virus (HCV) is a major cause of liver disease world-wide. Current interferon and ribavirin (IFN/RBV) therapy is effective in 50%-60% of patients. HCV exists in infected patients as a large viral population of intra-host variants (quasispecies), which may be differentially resistant to interferon treatment. We present a method for measuring differential interferon resistance of HCV quasispecies based on mathematical modeling and analysis of HCV population dynamics during the first hours of interferon therapy. The mathematical models showed that individual intra-host HCV variants have a wide range of resistance to IFN treatment in each patient. Analysis of differential IFN resistance among intra-host HCV variants allows for accurate prediction of response to IFN therapy. The models strongly suggest that resistance to interferon may vary broadly among closely related variants in infected hosts and therapy outcome may be defined by a single or a few variants irrespective of their frequency in the intra-host HCV population before treatment.

Treatment options in the management of thrombocytopenia in patients infected with HCV

) inpatients with chronic hepatitis has been associated with twofactors: the first is hypersplenism resulting from splenomegalyin portal hypertension [1]. The spleen continuouslysequesters one-third of circulating platelets, so thatsplenomegaly increases the fraction of platelets trapped inthe splenic sinusoids, especially when resulting from passivecongestion or an increase in venous portal pressure [1].Hypersplenism seems to be the most common cause ofthrombocytopenia associated with liver cirrhosis and portalhypertension.The second mechanism is related to the decreasedproduction of thrombopoietin, a hormone produced byhepatocytes, which regulates the development of themegakaryocyte. In cirrhosis, due to the reduction in the massof functioning hepatocytes, there can be a reduction ofthrombopoiesis in the bone marrow, leading tothrombocytopenia in the peripheral blood [1].In some situations, patients who are otherwise eligible forHCV treatment with interferon and ribavirin cannot be sotreated because their platelets counts are low, whichjeopardizes the treatment [2,3].Nevertheless, hepatitis C patients treated with interferon andribavirin also present a drop in the platelet count as a sideeffect [2,3].There is as yet no treatment consensus in the literature forthe management of these patients. We therefore present somerelated studies that address the management of these patients,in the pre-treatment and intra-treatment phases.Patients receiving interferon alpha or peginterferon alphacan present a 30-50% reduction in the baseline platelet count,and a dose reduction is necessary in approximately 4% of thepatients [2,3]. We should consider possible reduction of thedose when platelet counts drop to < 50,000/mm

Interferon-Based Combination Anti-Viral Therapy for Hepatitis C Virus After Liver Transplantation: A Review and Quantitative Analysis

Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. However, the efficacy, tolerability and safety of combination interferon and ribavirin (IFN-RIB) or peginterferon and ribavirin (PEG-RIB) anti-viral therapies post-LT are uncertain. We performed a comprehensive search of major medical databases (1980-2005) and conference proceedings (1996-2005). The main outcome measure was sustained virological response (SVR, undetectable HCV RNA) at 6 months. Summary estimates were calculated using random-effects models. Twenty-seven IFN-RIB and 21 PEG-RIB studies were included. IFN-RIB was associated with a pooled SVR rate of 24% (95% CI, 20-27%), while PEG-RIB was associated with an SVR rate of 27% (23-31%). Pooled discontinuation rates were 24% (21-27%) with IFN-RIB and 26% (20-32%) with PEG-RIB. The pooled rate of acute graft rejection was 2% (1-3%) with IFN-RIB and 5% (3-7%) with PEG-RIB. IFN-RIB and PEG-RIB therapies in HCV infection post-LT were associated with similar but overall low SVR and were poorly tolerated. The rate of acute rejection was small. The therapeutic advantage of PEG-RIB therapy observed in non-transplant chronic HCV infection appears to be attenuated post-LT. Clinical trials are needed to evaluate reasons for this post-transplant therapeutic disadvantage and to find strategies to ameliorate them.