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1.  adherence to medication for chronic hepatitis C – building on the model of human immunodeficiency virus antiretroviral adherence research 
Treatment of hepatitis C virus (HCV) infection with pegylated interferon/ribavirin achieves sustained virological response in up to 56% of HCV mono-infected patients and 40% of HCV/human immunodeficiency virus (HIV)-co-infected patients. The relationship of patient adherence to outcome warrants study.
To review comprehensively research on patient-missed doses to HCV treatment and discuss applicable research from adherence to HIV antiretroviral therapy.
Publications were identified by PubMed searches using the keywords: adherence, compliance, hepatitis C virus, interferon and ribavirin.
The term ‘non-adherence’ differs in how it is used in the HCV from the HIV literature. In HCV, ‘non-adherence’ refers primarily to dose reductions by the clinician and early treatment discontinuation. In contrast, in HIV, ‘non-adherence’ refers primarily to patient-missed doses. Few data have been published on the rates of missed dose adherence to pegylated interferon/ribavirin and its relationship to virological response.
As HCV treatment becomes more complex with new classes of agents, adherence will be increasingly important to treatment success as resistance mutations may develop with suboptimal dosing of HCV enzyme inhibitors. HIV adherence research can be applied to that on HCV to establish accurate methods to assess adherence, investigate determinants of non-adherence and develop strategies to optimize adherence.
PMCID: PMC3102513  PMID: 19416131
2.  Adherence to Hepatitis C Virus Therapy and Early Virologic Outcomes 
Suboptimal drug exposure attributable to physician-directed dosage reductions of pegylated interferon and/or ribavirin are associated with decreased sustained virologic response rates. However, data are limited with regard to suboptimal drug exposure that is attributable to missed doses by patients with chronic hepatitis C virus (HCV) infection. We examined the relationship between adherence to pegylated interferon and ribavirin therapy, measured by pharmacy refill, and HCV suppression during the initial 12 weeks of therapy.
We conducted a cohort study involving 188 patients with chronic HCV infection who were treated with pegylated interferon plus ribavirin. Adherence was calculated using pharmacy refill data and could exceed 100%. The primary outcome was decrease in HCV load at 12 weeks; early virologic response was a secondary outcome. Mixed-effects regression models estimated the association between adherence and HCV suppression during the initial 12 weeks. Subanalyses were performed among patients who received optimal weight-based dosages.
The mean decrease in HCV load at 12 weeks was 0.66 log IU/mL greater for patients with ⩾85% adherence than for those with <85% adherence (3.23 vs. 2.57 log IU/mL; P = 04). When patients who received a suboptimal ribavirin dosage were excluded, the decrease in viral load was 1.00 log IU/mL greater for persons with <85% adherence (3.32 vs. 2.32 log IU/mL; P = 01). Early virologic response was more common among patients with ⩾85% adherence than it was among those with <85% adherence to treatment with pegylated interferon (73% vs. 29%; P = 02) and ribavirin (73% vs. 55%; P = 08).
Adherence of ⩾85% to pegylated interferon and ribavirin treatment was associated with increased HCV suppression. Decreases in HCV load became greater when patients with ⩾85% adherence to their regimen continued to receive their recommended weight-based ribavirin dosage.
PMCID: PMC2668718  PMID: 19086908
3.  Adherence to treatment for recently acquired hepatitis C virus (HCV) infection among injecting drug users 
Journal of hepatology  2010;55(1):76-85.
Background and aims
Adherence to HCV therapy impacts sustained virological response (SVR), but there are limited data on adherence, particularly among injecting drug users (IDUs). We assessed 80/80 adherence (≥80% of PEG-IFN doses, ≥80% treatment), on-treatment adherence and treatment completion in a study of treatment of recent HCV infection (ATAHC).
Participants with HCV received pegylated interferon (PEG-IFN) alfa-2a (180 μg/week, n=74); those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n=35). Everyone received 24 weeks of therapy. Logistic regression analyses were used to identify predictors of PEG-IFN 80/80 adherence.
Of 163, 109 received treatment (HCV, n=74; HCV/HIV, n=35), with 75% ever reporting IDU. The proportion with 80/80 PEG-IFN adherence was 82% (n=89). During treatment, 14% missed ≥1 dose (on-treatment adherence=99%). Completion of 0-4, 5-19, 20-23 and all 24 weeks of PEG-IFN therapy occurred in 10% (n=11), 14% (n=15), 6% (n=7) and 70% (n=76), respectively. Participants with no tertiary education were less likely to have 80/80 PEG-IFN adherence (AOR 0.29,P=0.045). IDU prior to or during treatment did not impact 80/80 PEG-IFN adherence. SVR was higher among those with ≥80/80 PEG-IFN adherence (67% vs. 35%,P=0.007), but similar among those with and without missed doses during therapy (73% vs. 60%,P=0.309). SVR in those discontinuing therapy between 0-4, 5-19, 20-23 and 24 weeks was 9%, 33%, 43% and 76%, respectively (P<0.001).
High adherence to treatment for recent HCV was observed, irrespective of IDU prior to, or during, therapy. Sub-optimal PEG-IFN exposure was mainly driven by early treatment discontinuation rather than missed doses during therapy.
PMCID: PMC3117933  PMID: 21145855
injection drug users; HIV infection; discontinuation; pegylated interferon; therapy
4.  Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study 
Annals of Internal Medicine  2011;155(6):353-360.
Adherence to hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin has been incompletely examined.
To evaluate the relationship between adherence to HCV therapy and early and sustained virologic response, assess changes in adherence over time, and examine risk factors for non-adherence.
Retrospective cohort study.
National Veterans Affairs Hepatitis C Clinical Case Registry
5,706 HCV-infected patients (genotypes 1, 2, 3, or 4) with at least one prescription for pegylated interferon and ribavirin between 2003 and 2006 and HCV RNA results prior to and after treatment initiation.
Adherence was calculated over 12-week intervals using pharmacy refill data. Endpoints included early virologic response (decrease of ≥2 log10 HCV RNA at 12 weeks) and sustained virologic response (undetectable HCV RNA 24 weeks after end of treatment).
Early virologic response increased with higher levels of ribavirin adherence over the initial 12 weeks of therapy (genotype 1, 4: 25/68 [37%] with the lowest category [≤40% adherence] versus 1,367/2,187 [63%] with the highest category [91–100% adherence], p<0.001; genotype 2, 3: 12/18 [67%] with ≤40% adherence versus 651/713 [91%] with 91–100% adherence, p<0.001). Among genotype 1 and 4 patients, sustained response increased with higher ribavirin adherence over the second, third, and fourth 12-week intervals. Results were similar for interferon adherence. Mean adherence to interferon and ribavirin decreased 3.4% and 6.6% per 12-week interval, respectively (test for trend, p<0.001 for each drug). Patients prescribed growth factors or thyroid medications during treatment had higher mean antiviral adherence.
Observational study without standardized timing for outcomes measurements.
Early and sustained virologic responses increased with higher levels of adherence to interferon and ribavirin. Adherence to both antivirals declined over time, but more so for ribavirin.
PMCID: PMC3366635  PMID: 21930852
Adherence; hepatitis C virus; HCV; antiviral therapy
5.  Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics 
BMC Infectious Diseases  2011;11:315.
Most methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment. Physicians may be reluctant to treat HCV in IDUs because of concerns about treatment adherence, psychiatric comorbidity, or ongoing drug use. Optimal HCV management approaches for IDUs remain unknown. We are conducting a randomized controlled trial in a network of nine methadone clinics with onsite HCV care to determine whether modified directly observed therapy (mDOT), compared to treatment as usual (TAU), improves adherence and virologic outcomes among opioid users.
We plan to enroll 80 HCV-infected adults initiating care with pegylated interferon alfa-2a (IFN) plus ribavirin, and randomize them to mDOT (directly observed daily ribavirin plus provider-administered weekly IFN) or TAU (self-administered ribavirin plus provider-administered weekly IFN). Our outcome measures are: 1) self-reported and pill count adherence, and 2) end of treatment response (ETR) or sustained viral response (SVR). We will use mixed effects linear models to assess differences in pill count adherence between treatment arms (mDOT v. TAU), and we will assess differences between treatment arms in the proportion of subjects with ETR or SVR with chi square tests. Of the first 40 subjects enrolled: 21 have been randomized to mDOT and 19 to TAU. To date, the sample is 77% Latino, 60% HCV genotype-1, 38% active drug users, and 27% HIV-infected. Our overall retention rate at 24 weeks is 92%, 93% in the mDOT arm and 92% in the TAU arm.
This paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual. Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy (both pegylated interferon and ribavirin) for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs, and can also guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence.
Trial Registration NCT01442311
PMCID: PMC3227608  PMID: 22078241
6.  Pegylated interferon alfa and ribavirin for children with chronic hepatitis C 
AIM: To study current treatment options for pediatric hepatitis C infection and their associated success rates.
METHODS: We retrospectively reviewed charts of thirty children who had been treated with combination therapy of pegylated interferon alfa plus ribavirin for chronic hepatitis C infection. Patients had been treated with ribavirin (15 mg/kg per day) and either pegylated interferon alfa 2a (180 mg/m2 once weekly) or pegylated interferon alfa 2b (1.5 mg/kg once weekly). Patients’ follow-up included subjective assessment of complaints, physical examination including weight and height, as well as laboratory evaluations for viral load [before treatment, at 12 wk, and 6 mo following treatment completion, as determined by sustained viral response (SVR)], complete blood count, liver enzymes, alkaline phosphatase, bilirubin, renal function tests, and thyroid function tests. For patients not achieving a two log decrease in viral load at treatment week 12, treatment was discontinued and the patient was considered a treatment non-responder.
RESULTS: Thirty children aged 3-18 years were included in the study. Twenty patients (11 males, 9 females) received pegylated interferon alfa 2b and ten patients (6 males, 4 females) received pegylated interferon alfa 2a. Twenty-three patients were infected with genotype 1, six patients were infected with genotype 3, and one patient was infected with genotype 2. Twenty patients (67%) achieved SVR. Treatment success rates were 90% with pegylated interferon alfa 2a vs 55% with pegylated interferon alfa 2b. Although a trend was noted for improved outcomes in the group receiving pegylated interferon alfa 2a, there were no statistically significant outcome differences between the two treatment groups (P = 0.1). Treatment success was 56.5% for patients infected with genotype 1 virus, compared to 100% for patients infected with other genotypes (P = 0.064). There was no difference in treatment response between males and females. A cut-off age of twelve years was used to dichotomize younger vs older participants; however, no difference in treatment response was observed between these groups. Using multivariate regression analysis, we could not determine predictors for achieving SVR from among the variables we examined (age, sex, and viral genotype). Although we noted a trend toward SVR with peginterferon alfa-2a, there was no statistical difference between the two peginterferons. A high incidence of adverse reactions to treatment was noted. Twenty-five patients (83%) suffered from at least one adverse reaction, but most experienced more than one adverse reaction. All patients except one became leukopenic (white blood cell count less than 5500 leukocytes/μL), six (20%) became anemic (hemoglobin less than 110 g/L), and one (3.3%) became thrombocytopenic (platelets less than 100 000/μL).
CONCLUSION: Combination therapy to treat hepatitis C in children is as effective as in adults. There may be a benefit for treatment with pegylated interferon alfa 2a.
PMCID: PMC3581998  PMID: 23467199
Hepatitis C virus; Interferon alfa; Ribavirin; Children; Sustained viral response
7.  Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients 
AIDS Research and Treatment  2011;2011:903480.
Background. Hepatitis C (HCV) treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR). Results. Nearly half (46%) the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse), and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.
PMCID: PMC3205594  PMID: 22110904
8.  Depression During Pegylated Interferon-Alpha Plus Ribavirin Therapy: Prevalence and Prediction 
Interferon-alpha (IFN-alpha) plus ribavirin is used to treat hepatitis C virus (HCV) infection and is associated with a high rate of depression. Newer, pegylated preparations of IFN-alpha have a longer half-life, require once-per-week dosing, and may be associated with reduced neuropsychiatric burden. Limited data exist on depression during pegylated IFN-alpha therapy.
Depressive symptoms were assessed using the Zung Self-Rating Depression Scale (SDS) in 162 HCV-infected patients at baseline and after 4, 8, 12, and 24 weeks of treatment with pegylated IFN alpha-2b (PEG IFN) plus weight-based (N = 86) versus standard dose (N = 76) ribavirin. Data were collected from March 2001 to April 2003.
Compared with baseline, mean SDS index scores were significantly increased by week 4 and remained elevated throughout the study. Thirty-nine percent of the sample experienced moderate to severe depressive symptoms (SDS index score ≥ 60) at some point during PEG IFN/ribavirin therapy. Baseline depression scores significantly predicted severity of depressive symptoms during PEG IFN/ribavirin treatment (simple regression analysis: Y = 0.55X + 32.7, p < .0001). In addition, assignment to weight-based ribavirin treatment and history of depression were associated with increased likelihood of developing moderate to severe depressive symptoms (odds ratio [OR] = 2.7. 95% CI = 1.3 to 5.6, p < .01, and OR = 3.3, 95% CI = 1.3 to 8.1, p < .01, respectively).
Development of moderate to severe depressive symptoms occurred frequently during PEG IFN/ribavirin treatment and was predicted by baseline depression scores and higher doses of ribavirin. History of major depressive disorder was also a significant predictive factor, but only through association with elevated baseline depression status. All of these factors can be evaluated and addressed lo limit neuropsychiatric morbidity during HCV treatment.
PMCID: PMC1615913  PMID: 15669887
9.  Combination therapy with silibinin, pegylated interferon and ribavirin in a patient with hepatitis C virus genotype 3 reinfection after liver transplantation: a case report 
Hepatitis C virus reinfection occurs universally after liver transplantation with accelerated cirrhosis rates of up to 30% within 5 years after liver transplantation. Management of hepatitis C virus reinfection is complicated by drug interactions and pre-treatment. Dual antiviral therapy with pegylated interferon and ribavirin only reaches sustained virological response rates of approximately 30% after liver transplantation. With the approval of the viral NS3/4A protease and NS5B ribonucleic acid -dependent ribonucleic acid polymerase inhibitors, combination therapy offers new therapeutic options resulting in considerably higher sustained virological response rates in the non-transplant setting. However, silibinin has also shown potent antiviral activity in non-responders to dual therapy.
Case presentation
We report the first case of antiviral therapy with pegylated interferon and ribavirin in combination with silibinin post-liver transplantation in a 50-year-old Caucasian man with genotype 3 reinfection with prior non-response.
Silibinin was administered at a dose of 20mg/kg/day intravenously for 2 weeks and continued orally for 47 weeks in combination with a 48-week pegylated interferon and ribavirin therapy (180μg/week and 800mg/day), which was started on day 8. Pegylated interferon and ribavirin doses were adapted to 135μg/week and 600mg/day. After 4 weeks of therapy, the viral load declined 6 log10 and became undetectable in week 6, resulting in a sustained virological response 24 weeks after the end of therapy.
In general, antiviral therapy was well tolerated. Side effects included pruritus and anaemia leading to erythropoietin therapy.
Combination therapy with pegylated interferon, ribavirin and silibinin resulted in sustained virological response 24 weeks after the end of therapy in a patient reinfected with hepatitis C virus genotype 3 who was a prior non-responder after liver transplantation. Silibinin therapy may offer a new therapeutic option for patients reinfected with non-genotype 1 hepatitis C virus who have had a liver transplanted and are non-responders.
PMCID: PMC4110930  PMID: 25047566
Antiviral therapy; Liver transplantation; Silibinin
10.  Pegaferon in hepatitis C: Results of a Multicenter Study 
Chronic hepatitis C (CHC) is a major contributor to cirrhosis and hepatocellular carcinoma and major global public health problem that causes mortality in both developed and developing countries.For the past decade, treatment with pegylated interferon (peg interferon α) and ribavirin (RBV) has been associated with rates of sustained virologic response of ≤ 66% among patients with hepatitis C virus (HCV) infection. In this study, we report the response rate of Iranian treatment-naïve CHC patients to Pegaferon, a locally developed pegylated interferon-α2a (PEG-IFNα2a).
Patients diagnosed with CHC who referred to two university based outpatient clinics in Tehran from December 2007 to May 2011 were enrolled in a single-group, open-labeled experimental design. Eligible patients were above 15 years of age and had HCV infection with evidence of chronic hepatitis. Exclusion criteria included the presence of a debilitating disease, decompensated cirrhosis or refusal to participate in the study. Patients were treated with 180μg Pegaferon weekly in addition to 800-1200 mg daily, weight-based RBV for 24 or 48 weeks depending on genotype. Viral response and adverse effects were recorded.
A total of 216 patients were enrolled in the study of which 83.3% were male and 16.7% were female. In 93 (43.1%) patients, the HCV RNA viral load was ≥ 800,000 IU/ml before starting treatment. “As-treated analysis” indicated that a total of 168 (77.8%) patients achieved sustained viral response (SVR, undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment).
This study, with a larger number of participants, confirms the results of a previous study by the authors that Pegaferon, a PEG-IFNα 2a locally produced in Iran, is effective in treatment-naïve CHC patients.
PMCID: PMC4154913  PMID: 25197541
Hepatitis C virus; Pegylated interferon; Pegaferon; Ribavirin
11.  Efficacy and safety of a novel pegylated interferon alpha-2a in Egyptian patients with genotype 4 chronic hepatitis C 
Hepatitis C virus (HCV) genotype 4 is a common infection in Egypt and is the leading cause of liver disease.
To study the efficacy and safety of a novel 20 kD pegylated interferon alpha-2a derived from Hansenula polymorpha in combination with ribavirin for the treatment of Egyptian patients with genotype 4 chronic hepatitis C (CHC).
One hundred seven patients with genotype 4 CHC were involved in the present study. Liver biopsy was performed in all patients. All patients received a fixed weekly dose of 160 μg of a novel pegylated interferon in combination with ribavirin in standard and adjusted doses. Serum HCV RNA levels were assessed by a real-time sensitive polymerase chain reaction assay at four, 12, 48 and 72 weeks after the start of therapy. Patients demonstrating an early virological response (EVR) completed a 48-week course of treatment.
The overall sustained virological response (SVR) was 60.7%. The SVR in patients with a rapid virological response was significantly higher (91.7%) than in patients with complete EVR (67.74%) (P=0.033) and partial EVR (56.14%) (P=0.003). SVR was also significantly higher in patients with a low degree of liver fibrosis according to Metavir score (F1 and F2) (67.57%) compared with those with a high degree of liver fibrosis (F3 and F4) (45.45%) (P=0.017). The baseline viral load had no impact on SVR in the present series nor were any serious adverse events reported.
The novel pegylated interferon alpha-2a assessed in the present study was effective for the treatment of patients with genotype 4 CHC, and was safe and well tolerated.
PMCID: PMC2975472  PMID: 21037988
Chronic hepatitis C; Genotype 4; Hansenula polymorpha; Pegylated interferon
12.  Retreatment of hepatitis C non-responsive to Interferon. A placebo controlled randomized trial of Ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378] 
BMC Gastroenterology  2003;3:24.
Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published untill now.
One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%), HCV RNA above 2 × 106 copies/ml (55%) and cirrhosis (38%). Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw) and ribavirin (1000–1200 mg / day), 6 months ribavirin monotherapy (1000–1200 mg / day) or 6 months ribavirin placebo. The study was double blinded for the ribavirin / placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis.
At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin.
During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin monotherapy (p = 0.76). End of treatment WBC was significantly lower in patients treated with combination therapy, compared to ribavirin (p < 0.01) as well as for patients treated with ribavirin monotherapy compared to placebo (p < 0.01).
This belated report on the only placebo controlled study of interferon ribavirin combination therapy in non responders to standard doses of interferon monotherapy documents the effectiveness, be it limited, of this approach as well as the dynamics of the effects on blood counts.
PMCID: PMC222984  PMID: 12948399
Hepatitis C; Treatment; Randomised controlled trial; Interferon; Ribavirin; Non-responders; Monotherapy; Placebo
13.  U.S. Multicenter Pilot Study of Daily Consensus Interferon (CIFN) Plus Ribavirin for “Difficult-to-Treat” HCV Genotype 1 Patients 
Digestive Diseases and Sciences  2011;56(3):880-888.
Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection.
Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3–4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1–1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52–72 weeks (from time of viral response +48 weeks) (group B, n = 31).
Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8–12 weeks, and late virologic response from 16–24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients.
Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.
PMCID: PMC3041922  PMID: 21221804
Consensus interferon; Hepatitis C; Ribavirin; Veterans Affairs
14.  The Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents Chronic Hepatitis C 
Gastroenterology  2010;140(2):450-458.e1.
Background & Aims
Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized, controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5–17 years old with chronic hepatitis C.
HCV RNA-positive children from 11 university medical centers were randomly groups assigned to receive either the combination of peginterferon alfa-2a (PEG 2a; 180 μg/1.73 m2 body surface area, subcutaneously each week; n=59) and ribavirin (15 mg per kilogram orally in 2 doses daily) or PEG2a and placebo for 48 weeks (n=55). The primary endpoint was sustained virologic response (SVR, lack of detectable HCV RNA at least 24 weeks after stopping therapy).
An SVR was achieved in 53% of children treated with PEG 2a and ribavirin, compared with 21% of children who received PEG 2a and placebo (P<0.001). Early virologic response (> 2 log10 IU reduction in HCV RNA at 12 weeks) had a negative predictive value of only 0.89 in children with genotype 1, indicating that these children might benefit from 24 weeks of therapy before stopping treatment. Side effects, especially neutropenia, led to dose modification in 40% of children. Eighty-two percent of the PEG/ribavirin and 86% of the PEG/placebo group were in compliance with the year-2 follow-up visit; the durability of virologic response was 100% in both groups.
The combination of PEG and ribavirin is superior to PEG and placebo as therapy for chronic hepatitis C in children and adolescents.
PMCID: PMC3042126  PMID: 21036173
antiviral therapy; pediatric liver disease; multi-center pediatric trial
15.  Adherence to Hepatitis C Virus Therapy in HIV/Hepatitis C-Coinfected Patients 
AIDS and behavior  2013;17(1):94-103.
Adherence to hepatitis C virus (HCV) therapy has been incompletely examined among HIV-infected patients. We assessed changes in interferon and ribavirin adherence and evaluated the relationship between adherence and early (EVR) and sustained virologic response (SVR). We performed a cohort study among 333 HIV/HCV-coinfected patients who received pegylated interferon and ribavirin between 2001 and 2006 and had HCV RNA before and after treatment. Adherence was calculated over 12-week intervals using pharmacy refills. Mean interferon and ribavirin adherence declined 2.5 and 4.1 percentage points per 12-week interval, respectively. Among genotype 1/4 patients, EVR increased with higher ribavirin adherence, but this association was less strong for interferon. SVR among these patients was higher with increasing interferon and ribavirin adherence over the first, second, and third, but not fourth, 12-week intervals. Among HIV/HCV patients, EVR and SVR increased with higher interferon and ribavirin adherence. Adherence to both antivirals declined over time, but more so for ribavirin.
PMCID: PMC3514597  PMID: 22907288
Adherence; hepatitis C virus; HIV; antiviral therapy; pegylated interferon; ribavirin
16.  Effects of Host and virus related factors on Interferon-α+ribavirin and Pegylated-interferon+ribavirin treatment outcomes in Chronic Hepatitis C patients 
Virology Journal  2011;8:234.
Current standard therapy commonly followed for chronic Hepatitis C Virus (HCV) in Pakistan is interferon alpha plus ribavirin combination therapy (IFN α/ribavirin) and pegylated interferon plus ribavirin (PegIFN/ribavirin). PegIFN/ribavirin has increased rate of sustained virological response than standard IFN α/ribavirin therapy. Objective of current study was to analyze rate of early and delayed response to antiviral treatment as well as rate of relapse response in patients following standard treatment IFN α/ribavirin and in patients following pegylated interferon treatment.
Baseline serum samples of 153 patients enrolled for IFN α/ribavirin and 50 patients for PegIFN/ribavirin were collected. After total RNA extraction, genotyping was and HCV RNA viral load was done. Subsequently HCV RNA viral load was estimated at 4 weeks of treatment, at 12 weeks, at 24 or 48 weeks and finally after 6 months follow up period. All the data was statistically analyzed using fisher's exact test.
Total 86 patients out of 153 patients following conventional IFN α/ribavirin therapy completed treatment and 69% of them showed Rapid Virological Response (RVR). Whereas 50 patients following PegIFN/ribavirin treatment completed treatment and 80% of them achieved RVR. Total 64 out of 86 patients following IFN α/ribavirin therapy completed follow up period and 53.5% of them achieved Sustainded Virologcal Response (SVR). Forty-five out of total 50 patients who received PegIFN/ribavirin treatment completed 6 months follow up period and among these 70% achieved SVR. SVR rates were significantly associated with RVR (p < 0.001), age (p < 0.001) and gender (p < 0.01)
Rate of sustained virological response can be determined by factors like rapid virological response and age since they share significant association with one another. More over rate of SVR was more prominent in males than in females.
PMCID: PMC3113307  PMID: 21575275
17.  Acute hepatitis C virus (HCV) infection in the setting of HIV coinfection: a single-centre 10-year follow-up 
Journal of the International AIDS Society  2014;17(4Suppl 3):19638.
Acute hepatitis C virus (HCV) infection has emerged as a major cause of morbidity in the HIV-infected population. Most guidelines recommend early treatment with pegylated interferon and ribavirin due to higher cure rates. The impact of acute HCV and its treatment on the outcome of the HIV-infected population is unknown. With new treatment options for HCV, early treatment of acute HCV has to be questioned. Here, we report a long-term analysis on patients with acute HCV.
Retrospective analysis from an outpatient clinic from Berlin. All patients with the diagnosis of acute HCV according to The European AIDS Treatment Network (NEAT) criteria were included in the database at their date of HCV diagnosis and followed-up until the last medical contact. Demographic data was taken from the medical file. A fibrosis estimation was performed using transient elastography (Fibroscan(®). A Fibroscan value above 7 kPa was considered as significant fibrosis, above 12.4 kPa as liver cirrhosis. The following outcomes were documented: (a) liver-related: hepatic decompensation, cirrhosis, hepatocellular carcinoma. (b) non-liver-related: death, myocardial infarction, AIDS-defining event, psychiatric hospitalisation.
A total of 207 cases of acute HCV infection in HIV-infected patients were diagnosed between May 2002 and September 2013. All patients were male and declared homosexual contacts as their risk factor for having acquired HIV. The mean age was 39 years, 162 patients (78%) were on antiretroviral treatment, and the median CD4 cell count was 593/mm3 (IQR 443–749). At HCV diagnosis, the highest median alanine aminotransferase (ALT) level was 408 IU/mL (159–871), the HCV viral load was 800,000 IU/mL (45x103–2.8x106). 22 cases (11%) cleared their infection spontaneously, 161 (77%) underwent interferon-based treatment. Of those treated, 58% had a sustained virological response. 36 cases of HCV reinfection were documented. All patients were followed-up over an interval of 806 patient-years. The median liver stiffness was 5.3 kPa (4–7) after a median interval of 34 months. 33 patients developed significant fibrosis, and 11 patients (6%) developed cirrhosis. Nine (5%) patients died during follow-up, and 11 developed non-liver-related endpoints. All but one deceased patients had interferon-based treatment.
Severe hepatic disease and death rarely occurs in a highly treated HCV population. As interferon-based treatment may induce side effects, it is from now on justified to await new HCV treatment options.
PMCID: PMC4224944  PMID: 25394142
18.  Hepatitis C (chronic) 
Clinical Evidence  2010;2010:0921.
About 60% to 85% of people infected with hepatitis C virus will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions in treatment-naïve people with chronic hepatitis C infection, but without liver decompensation? What are the effects of interventions in people with chronic hepatitis C infection, but without liver decompensation, who have not responded to interferon treatment? What are the effects of interventions in people with chronic hepatitis C infection, but without liver decompensation, who relapse after interferon treatment? What are the effects of interventions in people with chronic hepatitis C infection who also have HIV? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: interferon monotherapy; interferon alfa plus ribavirin; peginterferon monotherapy; and peginterferon plus ribavirin.
Key Points
Chronic hepatitis C virus (HCV) infection is defined as persistent, detectable serum HCV RNA for a period greater than 6 months, with or without derangement in liver function tests. About 60% to 85% of people infected with HCV will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population.Complications of chronic HCV infection include cirrhosis, compensated and decompensated liver disease, and hepatocellular carcinoma.Many people chronically infected with HCV remain asymptomatic, including a significant proportion of those who progress to cirrhosis, so routine screening of people in high-risk groups is advisable.
Interferon monotherapy produces a sustained virological response in both treatment-naïve people and people with cirrhosis or advanced fibrosis compared with placebo or no treatment. Interferon also improves liver histology, although it may not be effective in preventing hepatocellular carcinoma in people with cirrhosis.Efficacy is dependent on duration of treatment, with treatment for 12 months seeming more effective than treatment for 6 months. However, treatment for 12 months is associated with an increase in adverse effects.A dose of 6 MU of interferon three times weekly seems no more effective at achieving sustained virological response than 3 MU three times weekly, and is associated with an increased risk of adverse effects.
Adding ribavirin to interferon regimens further increases the likelihood of achieving sustained virological response, but also increases the risk of anaemia. Efficacy of combination therapy depends on genotype, with genotype 1-infected people typically requiring longer duration of treatment compared with genotype 2- and genotype 3-infected people.
Peginterferon monotherapy increases the proportion of treatment-naïve people who achieve sustained virological response compared with standard interferon monotherapy.
Adding ribavirin to peginterferon increases the likelihood of achieving sustained virological response compared with either peginterferon alone or standard interferon plus ribavirin. This is currently the standard recommended therapeutic approach.
In people previously non-responsive to interferon monotherapy, treatment with interferon alfa plus ribavirin increases the likelihood of achieving sustained virological response compared with interferon alone. This effect seems greater when the interferon dose is higher than 3 MU three times weekly, or the duration of the treatment is 12 months or greater.We don't know whether peginterferon as a monotherapy, or in combination with ribavirin, is effective in non-responders to interferon monotherapy. We don't know whether peginterferon plus ribavirin is more effective than interferon alfa plus ribavirin.
In people who relapse after interferon monotherapy, treatment with interferon plus ribavirin is more likely than interferon treatment alone to achieve sustained virological response (SVR). There is general consensus that peginterferon plus ribavirin is likely to improve the probability of achieving SVR in people who relapse after interferon monotherapy.We don't know whether peginterferon alone is effective at achieving SVR in people who relapse after interferon monotherapy.
In people co-infected with HCV and HIV, peginterferon plus ribavirin seems more effective than standard interferon plus ribavirin treatment or peginterferon alone at achieving SVR. Although interferon plus ribavirin seems less effective than peginterferon plus ribavirin, the proportion of people achieving SVR suggests that interferon plus ribavirin may be effective in people with HCV and HIV. We don't know whether interferon alone is effective in people co-infected with HCV and HIV.
PMCID: PMC2907607  PMID: 21718581
19.  Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C 
World Journal of Hepatology  2014;6(7):520-526.
AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus (HCV).
METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin (800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.
RESULTS: Eighty-two patients (35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response (RVR): while the figures were 74.1% for early virologic response (EVR) and 44.4% for sustained virologic response (SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events (SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.
CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.
PMCID: PMC4110544  PMID: 25068004
Hepatitis C virus; Genotype; Peginterferon alfa-2b; Ribavirin; Treatment
20.  Effect of pegylated interferon on non-responders and relapsers with interferon 
To assess whether a combination of pegylated interferon (interferon conjugated with polyethylene glycol) and ribavirin can improve the response rate in patients with chronic hepatitis C who either did not respond to (Non-responders), or had relapsed after responding to (Relapsers) standard interferon and ribavirin combination therapy.
Patients and methods:
In this prospective study, 20 chronic hepatitis C patients (comprising 16 Non-responders and 4 Relapsers to previous treatment with alpha interferon and ribavirin), were treated with pegylated interferon-2b weekly and ribavirin daily for one year. Eleven patients had genotype 4, eight were of genotype 1 and one patient had genotype 3. Response to treatment was determined based on normalisation of liver enzymes and negative viral load (assessed using qualitative HCV RNA PCR) at end of treatment (ETR) and 6 months off treatment (SVR).
Seven patients (35%) achieved normalisation of liver enzymes and negative viral load at the end of treatment. However, only 2 patients (10%) managed to retain these levels after six months off treatment. The latter two patients had been previous Relapsers.
Combination of pegylated interferon and ribavirin may be beneficial in previous relapsers with standard interferon-ribavirin combination therapy, but is unlikely to achieve sustained virological response in non-responders.
PMCID: PMC3174716  PMID: 24019720
pegylated interferon; ribavirin; hepatitis C virus; non-responders; relapsers
21.  Clinical experience with nonstandard doses ofinterferon alfa-2b and ribavirin in the treatment of chronic hepatitis C infection: A retrospective analysis 
Hepatitis C virus (HCV) infection is the most common blood-borne virus in the United States. Several mono- and combination therapies have been approved by the US Food and Drug Administration for the treatment of HCV, but their routes of administration, dosing approaches, eras of introduction, and actual use in clinical practice and resulting effectiveness have not yet been reported.
The aim of this article was to characterize clinical use and virologic response (VR) of the HCV treatments interferon alfa-2b plus ribavirin (IFN + RBV) and peginterferon alfa-2b plus ribavirin (peg-IFN + RBV).
This retrospective chart review of office-based practices in theUnited States was conducted at 200 physicians' offices across the United States. We collected data concerning dosing patterns, VR (HCV RNA load, ≤1000 IU/mL or “negative” on polymerase chain reaction qualitative analysis), and adverse events (AEs) from the medical records of a geographically diverse sample of patients receiving treatment for chronic HCV infection in the United States from July 2001 to June 2002. For efficacy assessment, factors that were statistically different at baseline were adjusted using logistic regression. Providers also reviewed the medical records for symptoms or signs consistent with HCV treatment-related AEs.
Data from the records of 675 patients (423 men, 252 women; mean [SD] age of 45.5 [8.2] years; mean [SD] body weight, 80.8 [19.4] kg) were analyzed. At baseline, the IFN + RBV treatment group (330 patients) had significantly higher percentages of black patients (22.1% vs 15.7%; P = 0.032) and patients with hepatic disease based on clinician-reported cirrhosis and liver dysfunction (18.8% vs 9.9%; P < 0.001), and a significantly lower percentage of white patients (60.3% vs 69.6%; P = 0.012) compared with the peg-IFN + RBV treatment group (345 patients). The difference in log-transformed baseline HCV RNA loads between the 2 treatment groups in this study was <1 log unit. A significantly higher percentage of IFN + RBV-treated patients compared with peg-IFN + RBV-treated patients were prescribed HCV therapy on diagnosis (37.3% vs 29.9%; P = 0.041), and the mean (SD) duration of treatment was significantly different between the 2 treatment groups (52.5 [37.0] vs 27.5 [15.0] weeks; P < 0.001). Peg-IFN + RBV was associated with a higher rate of VR compared with IFN + RBV on univariate analysis (28.5% vs 17.5%; P = 0.018). Recommended doses of peg-IFN and higher-than-recommended doses of RBV were associated with an increased likelihood of VR. Higher-than-recommended doses of peg-IFN without a concomitant increase in RBV was not associated with an increased likelihood of VR. The incidences of the 3 most commonly reported AEs in the IFN + RSV group were significantly higher compared with those in the peg-IFN + RSV group: fatigue, 217 (65.8%) versus 185 (53.6%) patients (P = 0.001); depression, 147 (44.5%) versus 120 (34.8%) (P = 0.009); and anxiety, 87 (26.4%) versus 64 (18.6%) (P = 0.014). Nausea, however, was reported in a significantly higher number of patients in the peg-IFN group compared with the IFN + RBV group (74 [21.4%] vs 51 [15.5%]; P = 0.045). The frequencies of dose modification and treatment discontinuation due to AEs were similar between the 2 treatments and were similar to or less than those reported in other studies.
In this retrospective data analysis of US office-based practicesconcerning HCV treatment, clinicians were observed to prescribe IFN + RBV at doses that differ from recommendations in the product information (PI), as well as prescribe the RBV component of peg-IFN + RBV at doses that differed from PI recommendations. Although patients treated with peg-IFN + RBV appeared to achieve higher VR compared with those treated with IFN + RBV in our analysis of data from clinical practice, peg-IFN + RBV was associated with lower VR rates compared with those reported in clinical studies.
PMCID: PMC4003805  PMID: 24790244
hepatitis C; pegylated interferon; interferon alfa-2b and ribavirin; ribavirin; dosing; outcomes
22.  Hepatitis C Treatment: current and future perspectives 
Virology Journal  2010;7:296.
Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population. The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates. Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 & 3. As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematological complications. Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, < 0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age <40 years. New therapeutic approaches are under study like interferon related systems, modified forms of ribavirin, internal ribosome entry site (HCV IRES) inhibitors, NS3 and NS5a inhibitors, novel immunomodulators and specifically targeted anti-viral therapy for hepatitis C compounds. More remedial therapies include caspase inhibitors, anti-fibrotic agents, antibody treatment and vaccines.
PMCID: PMC2984595  PMID: 21040548
23.  Efficacy of pegylated interferon α-2a and α-2b in patients with genotype 1 chronic hepatitis C: a meta-analysis 
BMC Infectious Diseases  2012;12:357.
Two formulations of Pegylated interferon (Peg-IFN) are on the market for treatment of chronic hepatitis C virus (HCV) infection. The purpose of this meta-analysis was to assess the efficacy of Peg-IFN α-2a versus Peg-IFN α-2b in combination with ribavirin in anti-human immunodeficiency virus (HIV)-negative patients with genotype 1 chronic HCV infection.
The following criteria were to be met for inclusion in the meta-analysis: (a) original data from randomized and non-randomized clinical trials; (b) study on the efficacy of conventional doses of Peg-IFN α-2a (180 μg/week) versus Peg-IFN α-2b (1.5 μg/kg of body weight/week), both in combination with ribavirin, in antiviral therapy-naïve HCV-genotype 1 subjects; (c) at least one of these primary outcomes: Rapid Virological Response (RVR); Early Complete Virological Response (EVR); End of Treatment Response (ETR); Sustained Virological Response (SVR); (d) odds ratio estimates of relative risk (RR) and associated 95% confidence intervals (CIs) or at least data enabling them to be computed; (e) English language; and (f) published as a full paper up to December 2011.
Seven published studies met the inclusion criteria, allowing a meta-analysis on 3,026 patients. Peg-IFN α-2a and Peg-IFN α-2b showed similar rate of RVR (RR = 1.05; 95% CI = 0.87-1.27, p = 0.62) and SVR (RR = 1.08; 95% CI = 0.99-1.18, p = 0.098). Peg-IFN α-2a more frequently than Peg-IFN α-2b achieved EVR (RR = 1.11; 95% CI = 1.02-1.21, p = 0.013) and ETR (RR = 1.22; 95% CI = 1.14-1.31, p < 0.0001).
The standard schedules of Peg-IFN α-2a and Peg-IFN α-2b, both in combination with ribavirin, can be used indifferently for patients with chronic HCV genotype 1 who are anti- to eliminate HIV-negative and antiviral treatment-naïve.
PMCID: PMC3556138  PMID: 23245594
Antiviral therapy in HCV patients; Meta-analysis; Response to anti-HCV therapy; Tolerability of anti-HCV therapy
24.  Safety of pegylated interferon and ribavirin therapy for chronic hepatitis C in patients with sickle cell anemia 
World Journal of Hepatology  2010;2(5):180-184.
AIM: To evaluate the safety and efficacy of combined pegylated interferon and ribavirin for the treatment of chronic hepatitis C (HCV) in patients with sickle cell anemia (SCA).
METHODS: Fifty-two patients with SCA and HCV were treated over a period of 7 years from June 2002 to July 2009. Their medical records were reviewed for: age at treatment, sex, body mass index, Hb level at the start of therapy and on follow-up, hemoglobin electrophoresis, liver function tests, G6PD level, LDH, bilirubin, HCV-RNA viral load, HCV genotype, liver biopsy, duration of treatment, and side effects. All were treated with pegylated interferon and a standard dose of ribavirin. The treatment was continued for 24 wk for those with genotype 2 and 3 and for 48 wk for those with genotype 1 and 4.
RESULTS: Fifty-two patients (30 females and 22 males) were treated. Their mean age was 29.5 years (range 15-54 years). HCV genotype was determined in 48 and 15 had liver biopsy. Their mean pre-treatment HCV-RNA viral load was 986330 IU/mL (range 12762-3329282 IU/mL). The liver biopsy showed grade I in 6 and grade II in 9 and stage I in 13 and stage II in 2. Only 8 were receiving hydroxyurea at the time of treatment. All tolerated the treatment well and none experienced a decrease in their Hb which required blood transfusion pre, during or after therapy. There were no hematological side effects attributable to ribavirin at the usual recommended dose. Thirty-seven (71.2%) achieved SVR at 6 mo after the end of treatment. The remaining 15 were non-responders. Two of them showed an ETR but had a relapse. The remaining 13 had a relatively significant HCV-RNA viral load with a mean HCV-RNA viral load of 1829741.2 IU/mL (900000-3329282 IU/mL) and eight of them had HCV genotype 1, four had HCV genotype 4, and one had HCV genotype 5.
CONCLUSION: Patients with SCA and HCV can be treated with pegylated interferon and ribavirin at the usual recommended dose. This is even so in those who are not receiving hydroxyurea. The treatment is safe and effective and the response rate is comparable to those without SCA.
PMCID: PMC2998964  PMID: 21160993
Sickle cell anemia; Chronic hepatitis C; Treatment
25.  Effect of Ribavirin on Viral Kinetics and Liver Gene Expression in Chronic Hepatitis C 
Gut  2013;63(1):10.1136/gutjnl-2012-303852.
Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C.
70 treatment-naïve patients were randomized to 4 weeks of ribavirin (1000–1200 mg/d) or none, followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were also randomized to a liver biopsy 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10.
After four weeks of ribavirin monotherapy, HCV levels decreased by 0.5±0.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting ISG induction by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC.
Ribavirin is a weak antiviral but its clinical effect seems to be mediated by a separate, indirect mechanism, which may act to reset interferon-responsiveness in HCV-infected liver.
PMCID: PMC3778097  PMID: 23396509
Interferon-stimulated genes; hepatic gene expression; ribavirin mechanism; hepatitis C virus; viral kinetics

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