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.
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.
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.
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.
Adherence; hepatitis C virus; HCV; antiviral therapy
Today, combination antiviral therapy with pegylated interferon-alpha and ribavirin (RBV) allows many patients infected with hepatitis C virus (HCV) to achieve a sustained virological response, which is equivalent to cure. Data also support the clinical benefit of combination antiviral therapy in patients coinfected with HCV and HIV, and in patients who have received a liver transplant.
Antiviral therapy with pegylated interferon-alpha and RBV is, however, associated with a high incidence and significant magnitude of anemia. This anemia may have several mechanisms, including bone marrow suppression and hemolysis. In addition, patients coinfected with HIV may have both pre-existing and RBV-associated anemia. Management of anemia in patients with HCV through RBV dose reduction or treatment discontinuation may compromise the effectiveness of treatment, because studies have demonstrated that treatment adherence or maintenance of antiviral therapy dose is an important predictor of sustained virological response.
Anemia associated with combination antiviral therapy in patients with HCV is frequently associated with an inadequate or blunted endogenous erythropoietin response. Accumulating evidence now supports the use of recombinant human erythropoietin (rHuEpo) to manage anemia in these patients, with the objective of maintaining the RBV dose, but clinical standards are lacking. The present article reviews the data relevant to the use of rHuEpo in this patient population and proposes a set of clinical practice standards to assist clinicians in selecting patients for rHuEpo and in implementing rHuEpo therapy effectively.
Anemia; Hepatitis C virus; Recombinant human erythropoietin; Ribavirin
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.
injection drug users; HIV infection; discontinuation; pegylated interferon; therapy
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.
Antiviral therapy in HCV patients; Meta-analysis; Response to anti-HCV therapy; Tolerability of anti-HCV therapy
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.
pegylated interferon; ribavirin; hepatitis C virus; non-responders; relapsers
Hepatitis C is a major reason of morbidity and mortality among hemophilia patients. Although combination therapy with peginterferon (peg-INF) and ribavirin is considered as standard treatment for chronic hepatitis C (CHC), but more evidence of the efficacy and safety is needed.
In this study, efficacy and tolerability of combination therapy with peginterferon α-2a–ribavirin was investigated among hemophilia HCV infected patients.
Patients and Materials
In a quasi-experimental, 45 naive hemophilia patients with chronic HCV received 180 mg of pegylated interferon (Pegasys) by subcutaneous injection weekly plus an oral dose of 800-1200 µg ribavirin daily according to body weight. The treatment continued 48 weeks in patients with genotype one and 24 weeks in those with genotype 3. Sustained virological response (SVR) was considered as efficacy of treatment.
Forty three patients (95.6%) reached to end of treatment response (ETR); only two (4.4%) patients did not respond and were discontinued from treatment. None of 43 patients relapsed. SVR obtained in 43 of 45 patients (95.6%), in multivariate logistic regression model, third month’s treatment WBC (WBC > 2000) remained the only significant predictor of SVR. Regimen dose reduced in three patients; two of those because of ALT increasing and other one for his retinal bleeding. In repeated measurement analysis, alanine aminotransferase (ALT) and hemoglobin (Hb) decreased significantly during treatment, but reduction of platelet (PLT) was not significant.
Results show high efficacy and safety of combination therapy of Peg-IFN-α 2a plus ribavirin among hemophiliacs with chronic hepatitis C.
Hepatitis C; Hemophilia A; Hemophilia B; Peginterferon alfa-2a; Ribavirin; Iran
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.
Pegylated interferon plus ribavirin remains the first-line treatment for patients with hepatitis C virus (HCV). Interferon α has the most extensive clinical application and is used for the treatment of chronic hepatitis B virus and hepatitis D virus as well as acute and chronic HCV infections. The attachment of polyethylene glycol to interferon increases its half-life by reducing the rate of absorption after injection, reducing renal and cellular clearance and also decreasing immunogenicity. In this case report, we have described a patient with chronic hepatitis C who developed ischemic necrosis of her fingertips after completing her third course of pegylated interferon and ribavirin. The patient underwent a very extensive workup in order to determine the underlying cause of her digital ischemia which was finally determined to be secondary to the use of pegylated interferon.
Pegylated interferon; Interferon; Hepatitis C; Necrosis; Ischemia
The combination of pegylated interferon (PEG-IFN) and ribavirin is the standard treatment for chronic hepatitis C. Our recent clinical study suggests that ribavirin augments the induction of interferon-stimulated genes (ISGs) in patients treated for hepatitis C virus (HCV) infection. In order to further characterize the mechanisms of action of ribavirin, we examined the effect of ribavirin treatment on ISG induction in cell culture. In addition, the effect of ribavirin on infectious HCV cell culture systems was studied. Similar to interferon (IFN)-α, ribavirin potently inhibits JFH-1 infection of Huh7.5.1 cells in a dose-dependent manner, which spans the physiological concentration of ribavirin in vivo. Microarray analysis and subsequent quantitative polymerase chain reaction assays demonstrated that ribavirin treatment resulted in the induction of a distinct set of ISGs. These ISGs, including IFN regulatory factors 7 and 9, are known to play an important role in anti-HCV responses. When ribavirin is used in conjunction with IFN-α, induction of specific ISGs is synergistic when compared with either drug applied separately. Direct up-regulation of these antiviral genes by ribavirin is mediated by a novel mechanism different from those associated with IFN signaling and intracellular double-stranded RNA sensing pathways such as RIG-I and MDA5. RNA interference studies excluded the activation of the Toll-like receptor and nuclear factor κB pathways in the action of ribavirin.
Our study suggests that ribavirin, acting by way of a novel innate mechanism, potentiates the anti-HCV effect of IFN. Understanding the mechanism of action of ribavirin would be valuable in identifying novel antivirals
In this paper, we report the health related quality of life (HRQOL) data from patients with hepatitis C viral infection (HCV) who were refractory to prior therapy and had re-treatment with a combination of Pegylated interferon alpha-2b and ribavirin. We hypothesized that the HRQOL will improve in those patients who attain sustained viral response similar to naïve patients undergoing treatment for HCV.
HRQOL data was obtained from 152 patients enrolled into a randomized study for re-treatment of HCV refractory to prior therapy with interferon alpha-2b in combination with ribavirin. The treatment protocol was for 48 weeks and had a high and low dose arm. The HRQOL data was collected at baseline, weeks 24 and 48 of treatment, and at 24 week follow-up after treatment. A repeated measures statistical model was used for comparing the HRQOL domain scores between the responders and non-responders and the treatment groups. The responders and non-responders were also compared to the age and sex adjusted national mean scores.
Twenty-five of the 152 (17%) patients achieved a sustained viral response. At baseline, HRQOL is lower in HCV patients compared to national norms. The norm based HRQOL domain scores for the different domains of the SF-36 instrument were as follows: physical functioning = 47.13, role-physical = 46.87, bodily pain = 48.00, general health = 44.01, vitality = 45.39, social functioning = 47.05, role-emotional = 48.88, mental health = 48.76, physical component score 43.26 and mental component score = 46.17. The scores decreased during therapy in those who would be responders and non-responders, but the pattern of change was different. During the treatment, the HRQOL domain scores of responders decrease notably in the domain of vitality. At week 48 vitality scores were worst in responders. 5 of the 8 domain scores were lower compared to baseline in non-responders. At 24 weeks post treatment follow up, HRQOL in those refractory patients who respond to re-treatment tended to be better than the national average in the domains of vitality (p = .06), social functioning (p = .06) and role-emotional (p = .03) while the non-responders improved their scores in domains of physical function and bodily pain.
We conclude that patients who are to be responders and non-responders behave differently in terms of the HRQOL domain scores when re-treated with a combination of interferon alpha 2b and ribavirin. The responders sustained a significant decrease in the domain score of vitality while 5 of the 8 domain scores decrease in non-responders at the end of treatment. At the end of follow up, in responders, the HRQOL score tended to be better than the national average notably in the domains of role-emotional, vitality and social functioning. On the other hand, in non-responders, the domain scores of physical function improve, while that of role-emotional worsened.
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.
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.
Chronic hepatitis C; Genotype 4; Hansenula polymorpha; Pegylated interferon
Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States. Effective treatments are available, however adherence to treatment is challenging. Modified directly observed therapy (mDOT) with weekly administration of pegylated interferon might improve adherence and outcomes for patients infected with chronic HCV. To compare two treatment protocols and examine predictors of sustained virologic response (SVR). A retrospective review comparing chronic HCV treatment outcomes in two outpatient clinics at an urban academic medical center. Gastroenterology fellows provided standard treatment (SC) in one clinic; a nurse practitioner administered weekly pegylated interferon injections weekly in a primary care clinic. All patients received oral ribavirin. Data was extracted from the medical records of all treated patients over a 5-year period. 155 treatment-naïve, chronically infected HCV patients were treated. Ninety-seven patients received mDOT treatment and 58 received standard care. Mean age was 46 years. Genotype 1 represented 59 % of the sample. The mDOT patients were significantly more likely to be younger (44 vs. 50 years), have a history of injection drug use (93.1 vs. 50.0 %), and be HIV-infected (13.5 vs. 2 %) compared to SC patients. The overall SVR rate was 45.2 % and did not differ between the groups in unadjusted analyses (p = 0.95). Genotype was the only predictor of SVR. Patients treated by nurse practitioners trained in HCV care and seen weekly for interferon injections have comparable treatment outcomes to patients treated by specialists.
Primary care; Hepatitis; Urban health; Nursing; Disease management
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.
Sickle cell anemia; Chronic hepatitis C; Treatment
Background. Current treatment of chronic hepatitis C with pegylated interferon and ribavirin has the ability to eliminate viral infection in about half of the patients treated. Therapeutic options, for those with remaining chronic hepatitis, will remain limited until
novel antivirals become available in the future. Consensus interferon is currently available and has demonstrated clinical efficacy with superior invitro antiviral activity, but the maximum tolerated dose is not defined. Methods. We assessed the efficacy of daily high-dose (24 ug) consensus interferon with weight-based (1000–1200 mg daily) ribavirin in HCV genotype 1-infected non-responder patients. Results. Six adverse events were documented in five patients, and the trial was terminated with no subject achieving viral clearance. Conclusions. The occurrence of serious adverse events effectively defined the upper limit of acceptable dose, while also revealing that this dose did not offer enhanced sustained viral clearance.
This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes. Pegylated interferon combination therapy was stopped, and the retinopathy of the patient was treated with intravitreal bevacizumab injections and panretinal photocoagulations. This case shows that pharmacokinetically improved pegylated interferon has ocular complications for patients with chronic hepatitis C. Accordingly, patients undergoing pegylated interferon treatment for hepatitis C need regular eye examinations for protection of their vision.
Chronic hepatitis C; Interferon-associated retinopathy; Ocular vision; Pegyalted interferon
Hepatitis C virus (HCV) affects about 170 million people worldwide and is the most common chronic blood borne infection in the United States. Since the advent of blood screening protocols in the early 1990s, injection drug use has become the leading cause of infection. Hepatitis C can have both hepatic and nonhepatic manifestations of infection. Hepatic manifestations include hepatic fibrosis, cirrhosis, liver cancer, and liver failure. The standard treatment for chronic HCV is combination therapy with pegylated interferon-α and ribavirin. Although pegylated interferon and ribavirin has been used against HCV for close to a decade, advances in therapy have centered on doses and treatment durations. There has been increasing interest in applying on-treatment response or viral kinetics to predict antiviral response rates and shape therapeutic intervention. Protease inhibitors are a promising adjuvant to combination therapy, but their efficacy and safety are still under investigation.
Hepatitis C virus; Chronic hepatitis C; Pegylated interferon-α; Ribavirin; Viral kinetics; Protease inhibitors
Specific inhibitory mechanisms suppress the T-cell response against the hepatitis C virus (HCV) in chronically infected patients. However, the relative importance of suppression by IL-10, TGF-β and regulatory T-cells and the impact of pegylated interferon-alpha and ribavirin (PegIFN-α/ribavirin) therapy on these inhibitory mechanisms are still unclear. We revealed that coregulation of the HCV-specific T-cell responses in blood of 43 chronic HCV patients showed a highly heterogeneous pattern before, during and after PegIFN-α/ribavirin. Prior to treatment, IL-10 mediated suppression of HCV-specific IFN-γ production in therapy-naive chronic HCV patients was associated with higher HCV-RNA loads, which suggests that protective antiviral immunity is controlled by IL-10. In addition, as a consequence of PegIFN-α/ribavirin therapy, negative regulation of especially HCV-specific IFN-γ production by TGF-β and IL-10 changed dramatically. Our findings emphasize the importance of negative regulation for the dysfunctional HCV-specific immunity, which should be considered in the design of future immunomodulatory therapies.
Combination of pegylated-interferon (PEG-IFN) plus ribavirin (RBV) is the standard-of-care for hepatitis C virus (HCV) treatment in HIV coinfected individuals. In 2007, abacavir (ABC)-based antiretroviral therapy was for the first time reported to be associated with early virological failure during HCV treatment. The aim of our study was to evaluate the impact of ABC on the response rate to HCV-therapy.
Retrospective analysis of HIV-HCV-coinfected patients treated with PEG-IFN and weight-adjusted RBV in four hospitals in Spain was performed. A descriptive baseline variables analysis was conducted. Logistic regression models were used to test possible associations between non-response and pre-treatment characteristics including antiretroviral drugs.
A total of 244 HIV/HCV co-infected patients treated with pegylated-interferon and ribavirin were included. Eighty-five % of patients were on HAART and of them 24% received ABC-based regimens. The most frequent genotypes were 1 and 3. RBV dosing was ≥13.2 mg/kg/day in 97% of the patients. In the global intent-to-treat analyses, 46.3% of patients reached SVR (46.2% in ABC group vs. 46.7% in non-ABC group, p=1). The only two factors in the multivariate analysis statistically associated with an increased risk of failure to achieve SVR were HCV genotype 1/4 and older age. The use of ABC was not associated with failure to achieve SVR in none of the other time points evaluated.
Our data suggest that the use of ABC-based regimens in the context of HCV therapy does not negatively affects the outcome of this treatment.
ABACAVIR; RIBAVIRIN; SVR; HCV treatment
To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%–80%, and <60% dose peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given ≥80%, 60%–80%, and <60% dose ribavirin, respectively. SVR rate sharply fell when exposure to peg-IFN was below 80% whereas it decreased in a stepwise manner as for ribavirin. Therefore, ≥80% of peg-IFN and as much as possible dose of ribavirin are desired to achieve SVR in the treatment of genotype 1 high viral titer chronic hepatitis C.
Pegylated-interferon (PEG-IFN) and ribavirin (RBV), current standard treatment for hepatitis C virus (HCV) infection, is frequently associated with neutropenia and anemia, leading to high treatment discontinuation rates in HIV/HCV coinfected patients. Our objective was to compare the effectiveness of intervening with hematologic growth factors versus dose reductions of standard HCV therapy for the management of treatment-induced hematologic disorders.
Ninety-two HIV/HCV coinfected, therapy-naive subjects received PEG-IFN alfa-2b 1.5 μg/kg/wk and RBV 13 ± 2 mg/kg/day for up to 48 weeks. Before treatment initiation, subjects were randomized to subsequently receive growth factors, recombinant human erythropoietin (rHuEPO) and/or granulocyte-colony stimulating factor (G-CSF), or dose reduction (RBV and/or PEG-IFN) for anemia and neutropenia management, respectively. We analyzed the ability of each management strategy to control anemia and neutropenia and the percentage of subjects who achieved a successful treatment outcome among subjects according to the different management strategies.
During treatment, 43 subjects developed anemia (HuEPO, n=24; dose reduction, n=19) while 25 subjects developed neutropenia (G-CSF, n=10; dose reduction, n=15). Following the intervention, the increase in both hemoglobin and absolute neutrophil counts also did not differ between the two side effect management strategies. Sustained response percentages were similar comparing anemic and neutropenic subjects regardless of management strategy (anemia: rHuEPO, 29% versus dose reduction, 21%, p=0.92; neutropenia: G-CSF, 40% versus dose reduction, 20%, p=0.46).
Growth factor supplementation and dose reduction do not appear to differ as management strategies for anemia and neutropenia in HIV/HCV co-infected individuals treated with PEG-IFN/RBV.
Hepatitis C virus/HIV coinfection; anemia; neutropenia; recombinant human erythropoietin; granulocyte colony stimulating factor
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.
Consensus interferon; Hepatitis C; Ribavirin; Veterans Affairs