Peginterferon Α2a Research Articles

The outcome of the sofosbuvir Based Therapy in the treatment of Hepatitis C Virus Genotype 4 in Egyptian patients

Background and aim There have been significant advancements during the last few years with large numbers of ongoing trials with various direct-acting antivirals (DAA) showing high potency against hepatitis C virus (HCV). The aim was to show the effectiveness and side effects of Sofosbuvir based therapy in the treatment of HCV genotype 4 in Egyptian patients and compare its results with the international results. Methods The study included 740 patients with chronic HCV. The study population consisted of three groups: Group (1): included 240 patients who were treated with sofosbuvir 400 mg plus Peginterferon α2a and weight-based ribavirin for 12 weeks. Group (2): included 250 patients who were treated with sofosbuvir 400 mg and weight-based ribavirin for 24 weeks. Group (3): involved 250 patients who were treated with sofosbuvir 400 mg and simeprevir 150 mg once daily for 12weeks. Results Sustained virological response (SVR) occurred in 83.3% of the triple therapy group. In the dual therapy group, SVR occurred in 64% of patients. In the Simeprevir-Sofosbuvir group, SVR was achieved in 96% of patients with a statistically significant difference among the studied groups (p=0.015). Multivariate logistic regression analysis showed that treatment with simeprevir and sofosbuvir was associated with higher rates of SVR with an odds ratio of 12.5. Serum creatinine shows a negative correlation with an odds ratio of 3.1; MELD score showed a negative correlation with an odds ratio of 1.5. Conclusion Sofosbuvir-based therapy has satisfactory results for the treatment of hepatitis C virus genotype 4 with lesser complications

Population pharmacokinetics of peginterferon \u03b12a in patients with chronic hepatitis B

There were significant differences in response and pharmacokinetic characteristics to the peginterferon α2a treatment among Chronic Hepatitis B (CHB) patients. The aim of this study is to identify factors which could significantly impact the peginterferon α2a pharmacokinetic characteristics in CHB patients. There were 208 blood samples collected from 178 patients who were considered as CHB and had been treated with peginterferon α2a followed by blood concentration measurement and other laboratory tests. The covariates such as demographic and clinical characteristics of the patients were retrieved from medical records. Nonlinear mixed-effects modeling method was used to develop the population pharmacokinetic model with NONMEM software. A population pharmacokinetic model for peginterferon α2a has been successfully developed which shows that distribution volume (V) was associated with body mass index (BMI), and drug clearance (CL) had a positive correlation with creatinine clearance (CCR). The final population pharmacokinetic model supports the use of BMI and CCR-adjusted dosing in hepatitis B virus patients.

Randomized trial of combined triple therapy comprising two types of peginterferon with simeprevir in patients with hepatitis C virus genotype 1b.

Hepatitis C virus genotype 1b patients were randomly assigned to receive SMV (100mg QD) with P2aR for 12weeks, then P2aR alone for 12 or 36weeks; or SMV (100mg QD) with P2bR for 12weeks, then P2bR alone for 12 or 36weeks. The primary endpoint was a sustained virologic response 24weeks after completing treatment (SVR24). In total, 151 patients were randomly assigned to the P2aR (n = 76) or P2bR group (n = 75). Six patients dropped out. Sustained virologic response 24weeks after completing treatment was achieved in 55 (75.3%) of 73 P2aR patients and 55 (76.4%) of 72 P2bR patients. There was no difference in the rate of SVR24 between the two groups (P = 0.88). No differences in the proportion of patients who became HCV RNA-negative were detected between the P2aR and P2bR groups. The two groups had comparable numbers of adverse events, which led to the discontinuation of treatment in 9.6% and 8.3% of participants in the P2aR and P2bR groups, respectively. Peginterferon α2a or α2b in combination with SMV + ribavirin therapy showed identical antiviral effects in patients with chronic hepatitis C. Also, the incidence of adverse events was identical for both regimens.

The Clinical Significance of Autoantibodies in Hepatitis C Patients Submitted to Interferon Treatment

Hepatitis C virus is associated with several immune-mediated phenomena, presented usually as extra-hepatic hepatitis C manifestations. A predisposition to autoimmunity associated with the presence of baseline autoantibodies has been demonstrated in interferon mediated autoimmune diseases. We report a male patient, 34 years old, with genotype 1, chronic hepatitis C (hepatitis C viremia 1.432.463UI/mL) and family history of psoriasis. He had high levels of transaminases and immunology showed positive antinuclear antibodies (1/320) and anti-smooth-muscle antibodies, with elevated immunoglobulin G (1740mg/dL). Liver biopsy revealed a F1/2 Metavir score, histologic activity index of 3 and mild piecemeal necrosis. Antiviral treatment was started with peg-interferon α2a 180mcg plus ribavirin 1200mg, and the patient had rapid virologic response, normalization of transaminases, negativation of antinuclear antibodies positivity and decrease of immunoglobulin levels. However, at week 22, he developed psoriatic-like eczema and arthritis with functional limitation. Due to suspicion of latent psoriatic arthritis not previously diagnosed, he was started on methotrexate 10mg/weekly with improvement of psoriatic plaques, arthritis and functional limitation. Patient achieved sustained virologic response, with normal transaminases and no significant changes in immunology. Post-treatment median hepatic elastography was 3.6kPa. Autoimmunity in hepatitis C infection is not limited to surrogate autoantibody seropositivity, but may embrace the full spectrum of autoimmune disorders.

Incidence rates of tuberculosis in chronic hepatitis C infected patients with or without interferon based therapy: a population-based cohort study in Taiwan.

BackgroundIt is debated whether interferon-based therapy (IBT) would affect the incidence of active tuberculosis (TB) among hepatitis C virus (HCV) infected patients. Although some case reports have demonstrated a possible association, the results are currently inconclusive. Therefore, we conducted a nation-wide population study to investigate the incidence of active TB in HCV infected patients receiving IBT in Taiwan.MethodsThis 9-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 ( >23.7 million). This insurance program covers all citizens in Taiwan. We conducted a retrospective cohort study that identified subjects with HCV infection. IBTs were defined as regimens that included interferon α, peginterferon α2a and peginterferon α2b for at least 2 months. Among them, 621 subjects received IBT, and 2,460 age- and gender-matched subjects were enrolled for analysis. The Cox proportional hazards models were used to estimate the hazard ratio (HR) for active TB, and associated confidence intervals (CIs), comparing IBT cohort and untreated cohort. The endpoint in this study was whether an enrolled subject had a new diagnosis of active TB.ResultsDuring the 9-year enrollment period, the treated and untreated cohorts were followed for a mean (± SD) duration of 6.97 ± 0.02 years and 8.21 ± 0.01 years, respectively. The cumulative incidence rate of active TB during this study period was 0.150 and 0.151 per 100 person-years in the IBT treated and untreated cohorts, respectively. There was no significant difference in the incidence of active TB in either cohort during a 1-year follow-up (Adjusted Hazard Ratio (AHR): 2.81, 95% Confidence Interval (95% CI): 0.61–12.98) or the long-term follow-up (AHR: 1.02, 95% CI: 0.28 – 3.78). The Cox proportional hazards model demonstrated that IBT was not a risk factor for active TB . The only risk factor for active TB was the occurrence of hepatic encephalopathy.ConclusionOur results showed that IBT is associated with increased hazard of active TB in HCV infected patients in 1-year follow-up; however, the effect sizes were not statistically significant.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0705-y) contains supplementary material, which is available to authorized users.

Simeprevir Increases Rate of Sustained Virologic Response Among Treatment-Experienced Patients With HCV Genotype-1 Infection: A Phase IIb Trial

Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV. We analyzed data from patients who did not respond (null response), had a partial response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66). All patients were followed for 24 weeks after planned end of treatment; the primary end point was the proportion of patients with sustained virologic response (SVR; undetectable HCV RNA) at that time point. Overall, rates of SVR at 24 weeks were significantly higher in the groups given simeprevir than those given placebo (61%-80% vs 23%; P < .001), regardless of prior response to PegIFN and RBV (simeprevir vs placebo: prior null response, 38%-59% vs 19%; prior partial response, 48%-86% vs 9%; prior relapse, 77%-89% vs 37%). All groups had comparable numbers of adverse events; these led to discontinuation of simeprevir or placebo and/or PegIFN and RBV in 8.8% of patients given simeprevir and 4.5% of those given placebo. In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR at 24 weeks compared with patients given placebo, PegIFN, and RBV and was generally well tolerated. ClinicalTrials.gov number: NCT00980330.

Impact of the peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV‐co‐infected patients with the unfavourable non‐CC IL28B genotypes

Studies on the association between the peginterferon-α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon-α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV-co-infected patients according to IL28B genotype. This was a cohort study of HCV-1/HIV-co-infected patients who were HCV-treatment naïve and for whom the efficacy of peginterferon-α 2a plus ribavirin was evaluated by per-protocol analysis. The peginterferon-α 2a and ribavirin levels were measured by ELISA and HPLC-UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon-α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P=0.001 and 4.0; CI95 , 1.08-14.7; P=0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN-α 2a and ribavirin plasma levels were greater than 3400pg/mL and 1.6μg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR.

Evaluation of the therapeutic response of hepatitis C in coinfected patients (HIV/HCV): a study of cases from a hospital for chronic liver diseases in the Eastern Brazilian Amazon

The aim of this study was to evaluate the therapeutic response of hepatitis C in patients coinfected with human immunodeficiency virus (HIV-1). A retrospective study of 20 patients coinfected with HIV-1/HCV who were treated in the outpatient liver clinic at the Sacred House of Mercy Foundation Hospital of Pará (Fundação Santa Casa de Misericórdia do Pará - FSCMPA) from April 2004 to June 2009. Patients were treated with 180 µg PEG interferon-α2a in combination with ribavirin (1,000 to 1,250 mg/day) for 48 weeks. The end point was the sustained virological response (SVR) rate (HCV RNA negative 24 weeks after completing treatment). The mean age of the patients was 40 ± 9.5 years, of which 89% (n = 17) were male, and the HCV genotypes were genotype 1 (55%, n = 11/20), genotype 2 (10%, n = 2/20) and genotype 3 (35%, n = 7/20). The mean CD4+ lymphocyte count was 507.8, and the liver fibrosis stages were (METAVIR) F1 (25%), F2 (55%), F3 (10%) and F4 (10%). The early virological response (EVR) was 60%, the end-of-treatment virological response (EOTVR) was 45% and the SVR was 45%. The median HCV viral load was high, and in 85% of cases in which highly active antiretroviral therapy (HAART) was used, none of the patients with F3-F4 fibrosis responded to treatment. Of the twenty patients treated, 45% achieved SVR and 45% achieved EOTVR. Studies that include cases from a wider region are needed to better evaluate these findings.

Tumid Lupus Erythematosis Complicating Hepatitis C Therapy with Interferon: A Report of 2 Cases

Background: Tumid lupus erythematosis (TLE) is a rare subtype of cutaneous lupus. Interferon (IFN) therapy has been known to induce autoimmune and injection-site reactions, but TLE has not previously been described to complicate hepatitis C (HCV) treatment. Herein are two cases of histologically-proven TLE in the context of HCV treatment with two forms of injectable IFN. Case 1: A 35 y/o woman with HCV, genotype 1a, stage 2 fibrosis, treated with Peg interferon α2 + ribavirin. 30 weeks into treatment she developed several pruritic, pink, crusted papules on the extensor surfaces of the arms, thighs, back and extensor surfaces of the shins. Right elbow punch biopsy showed dermal mucin with superficial and deep perivascular and peri-eccrine lymphocyte dominant infiltrates sparing the epidermis, consistent with TLE. She completed IFN therapy and achieved a sustained virologic response. Her TLE was treated successfully with topical Fluocinonide 0.05% (Lidex®) with residual hyperpigmented macules and papules. Prior to IFN, she had a (+) ANA >1:1280 speckled pattern, (+) dsDNA without features of SLE. Case 2: A 55 Y/O man with HCV, genotype 1a, stage 1-2 fibrosis; a prior non-responder to Peg interferon α2-a + ribavirin, retreated with consensus interferon + ribavirin. 12 weeks into treatment, he developed several painful, dull red, ulcerated plaques with central crusting at the abdominal injection site. Punch biopsies revealed superficial and deep perivascular and periappendageal lymphoplasmacytic inflammatory infiltrate sparing the epidermis with increased dermal mucin deposition, again consistent with TLE. These lesions were disabling compelling early IFN termination. Despite negative systemic auto-antibodies and topical Fluocinonide, he developed diffuse arthralgias and persistent ulcerated, nonhealing plaques. Skin lesions have since improved via systemic anti-malarial, hydroxychloroquine (Plaquenil®). Discussion: TLE is characterized clinically by erythematous, edematous, non-scarring papules or plaques usually on sunexposed skin. Histopathologically it resembles classic lupus erythematosis by superficial and deep lymphocytic inflammatory infiltrates and dermal mucin, however, there is little or no epidermal or dermo-epidermal involvement and ANA antibodies are usually negative. Although there is a single case series of “lupus-like” injection site reactions from IFN treatment of malignant melanoma and multiple sclerosis, as well as one report of “cutaneous mucinosis” complicating IFN treatment of HCV, TLE has not been previously reported as an adverse effect of HCV therapy. Gastroenterologists ought to be aware of this potential treatment-limiting dermatologic side effect.

Effect of Telaprevir on the Pharmacokinetics of Tacrolimus in the Treatment of Hepatitis C After Liver Transplantation Presidential Poster

Purpose: Limited data are available on using telaprevir (TVR)-based triple therapy to treat HCV recurrence post-liver transplantation (LTx). A study in healthy volunteers shows that TVR leads to major increase in tacrolimus (TAC) blood concentration. We report our preliminary experience on the effects of TVR on TAC pharmacokinetics (PK) and the safety of TVR-based therapy in the post-LTx setting. Methods: Patients with HCV genotype 1 recurrence post-LTx on stable dose of TAC for at least 6 months prior to starting the antiviral regimen were included in this study. TVR-based triple therapy was started with TVR 750 mg TID, ribavirin 600 mg daily, and peg-interferon α2a 180 mcg weekly. On day 1 of treatment, TAC at half the pre-treatment daily dose was given and levels were checked at 12 and 24 hours and every other day thereafter for 2 weeks to assess TAC PK. No additional TAC was given until the level was around 4-6 ng/mL. Once the maintenance dose of TAC was established, levels were assessed weekly. Results: Four patients (1F, 3M), mean age 56.3 years, mean time from LTx 3.25 years, and mean fibrosis stage of 2.5 were treated. Two were HCV treatment naïve and two were prior null-responders post-LTx. The mean duration of treatment was 10.75 weeks (range 8-16 weeks). The pre-treatment TAC dose ranged from 1-3 mg twice daily. The TAC dose required to maintain therapeutic levels was found to be approximately ¼- ½ the pre-treatment daily dose at a frequency of once weekly. The mean area under the concentration time curve (AUC) for TAC while on TVR was 1353.46 ng.hr/mL (range 685.25-2040.05) compared to an expected AUC of 67 ng.hr/mL without TVR. The highest TAC level that we encountered in our study was 16.2 ng/mL (at 12-hour level after the initial dose). Clinically significant anemia (Hb <10 g/dL) developed in 2, requiring a decrease of the ribavirin dose to 400 mg daily and starting epoietin. No significant neurologic toxicity was encountered. The mean creatinine increased from 1.12 to 1.35 mg/dL. We did not encounter any infections or episodes of acute rejection. Conclusion: 1. TVR had a profound effect on TAC metabolism; 2. Dose reduction of TAC based on blood levels is associated with normal TAC blood levels; 3. TVR therapy for HCV recurrence post-OLT in patients on TAC-based immunosuppression appears feasible; 4. The effect on renal function requires additional study. Longer follow-up is needed to demonstrate efficacy in achieving control of HCV. Disclosure: Naim Alkhouri, MD - Speaker's Bureau and Advisory Board Member of Vertex (makers of telaprevir). Nizar N Zein - Speaker's Bureau and Advisory Board Member of Vertex (makers of telaprevir).

Acute inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alfa-2a in a patient with chronic hepatitis C virus infection: a case report

IntroductionThe combination of polyethylene glycol (PEG)ylated interferon (pegylated interferon) and ribavirin has been shown to be an effective treatment for chronic hepatitis C virus. In general, common side effects related to this combination therapy are mild and are well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to PEG-interferon α2a (pegylated interferon alfa-2a) is extremely rare. In the literature, only one case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a has been published previously.Case presentationTo the best of our knowledge we present only the second case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a, occurring in a 63-year-old Caucasian man. He developed tingling, numbness, and weakness of his upper and lower extremities with acute neurological deficits after five weeks of a combination therapy with PEG-interferon α2a and ribavirin for chronic hepatitis C virus infection. His clinical course, neurological findings, and his electromyogram results were all consistent with acute inflammatory demyelinating polyneuropathy. Our patient recovered completely after interferon was stopped and symptomatic treatment and a further electromyogram showed a disappearance of neuropathy. Four weeks later, PEG-interferon α2a was reintroduced with a gradually increasing dose without any reappearance of neurological symptoms allowing hepatitis C seroconversion.ConclusionsRecognition of this rare yet possible presentation is important for early and accurate diagnosis and treatment. This case report also suggests that the reintroduction of PEGylated interferon in patients who had presented with acute inflammatory demyelinating polyneuropathy related to interferon α may be safe, but this must be confirmed by further studies.

Do HIV/HCV co-infected patients need haematopoietic growth factors earlier than non-co-infected during HCV treatment?

BackgroundHepatitis C treatment (HCVt) with peg-interferon and ribavirin is limited by haematological side-effects. Haematopoietic growth factors (HGF) allow to maintain standard antiviral doses in order to achieve sustained virological response...

Influence of IL28B Polymorphisms on Response to a Lower-Than-Standard Dose peg-IFN-α 2a for Genotype 3 Chronic Hepatitis C in HIV-Coinfected Patients

BackgroundData on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.Methods and FindingsPilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed.Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.ConclusionsWeekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.Trial Registration:ClinicalTrials.gov NCT00553930

Comparative trials of peginterferon α2a and peginterferon α2b for chronic hepatitis C

Standard of care for patients with chronic hepatitis C is pegylated interferon (pegIFN) combined with ribavirin (Rbv). It results in persistent viral eradication and prevents the progression of liver disease and the associated complications in about 50% of treated patients. Currently, two PegIFNs are available that differ significantly in terms of pharmacokinetic and pharmacodynamic profiles as a consequence of different pegylation chemistries. While the registration trials of the two therapeutic regimens demonstrated the superiority of each PegIFN vs the native IFN α2b, the superiority of one regimen over the other in terms of treatment efficacy remains unknown. Retrospective cohort studies and randomized prospective head-to-head trials have attempted to resolve the considerable controversy over this issue and support evidence-based treatment decisions.

Development and Progression of Portal Hypertensive Gastropathy in Patients With Chronic Hepatitis C

The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC). A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon α2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of ≥1 point. During a median follow-up of 3.85 years, 50% of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices. New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors.

Together … to Take Care: Multidisciplinary Management of Hepatitis C Virus Treatment in Randomly Selected Drug Users With Chronic Hepatitis

Hepatitis C Virus (HCV) infection is treated with peg-interferon α2a or α2b and ribavirin. International studies show that drug user adherence to treatment is 40% to 60% and increases if the patient is in addiction treatment. The aim of the Together To Take Care (TTTC) study was to achieve better adherence to HCV therapy in randomly selected drug users, who are considered "difficult to treat." The secondary aim of the TTTC Study Group was to standardize a method for a multidisciplinary management of the liver disease in drug users. The TTTC group data were matched with a control group. Adherence: The 93.7% of patients followed therapy prescribed; of the patients infected by HCV genotype (gt) 3, all completed therapy as scheduled. For the 48-week treatment group, 66.7% of patients completed therapy (2 of 9 patients stopped treatment for breakthrough). Toxicological results: 10 (62.5%) patients were negative in the toxicological tests (opiates, cocaine, and alcohol). Virological results: 8 of 16 patients were infected by HCV gt 1, and 8 were infected by gt 3; 2 of 16 (12.5%) patients were human immunodeficiency virus (HIV) coinfected (1 HCV gt 1a and 1 HCV gt 3). All patients: 11 of 16 (68.75%) patients were HCV ribonucleic acid undetectable 24 weeks after completing therapy (sustained virological response, SVR). Gt 1: 4 of 8 (50.0%) showed SVR. Gt 3: 7 of 8 (87.5%) showed SVR. Overall, the HCV gt 3 patients had 87.5% probability of SVR, whereas gt 1 patients had 50% probability of SVR (gt 3/gt 1 patients odds ratio = 7). The results were analyzed by Fisher exact test. Our results show that good healthcare management plays an important role in increasing patients' adherence to therapy. In the project "TTTC," the patients work with the physicians to take responsibility for their health and acquire self-efficacy and self-awareness, thanks to the special care.

Superior response to pegylated interferon and ribavirin in Asians with chronic hepatitis C.

Reported sustained virological response (SVR) rates in Asians with chronic hepatitis C (CHC) exceed those of other ethnic groups, but differences in body weight across races potentially confound this observed superior response. Our aim was to determine whether Asian race independently predicts SVR within a multicultural clinic setting. Patients with genotype 1, 2 and 3 CHC prescribed peginterferon and weight-based ribavirin were included in this retrospective study. Logistic regression was performed to identify factors associated with SVR. Three-hundred ninety-two patients (BMI 26.9±5.0kg/m(2), genotype 1 66%, viral load 5.9±0.66log(10)IU/ml, advanced fibrosis 53%) were included in this study. Caucasians comprised 81%, South Asians 9% and Asians (Non-South) 10%. SVR was achieved by 54% overall, but was highest amongst Asians (Non-South) (79%) compared with South Asians (56%, P=0.04) and Caucasians (50%, P<0.001) despite a predominance of genotype 3 infection amongst the South Asians. Asians (Non-South) had the highest SVR rate even amongst those infected with genotype 1 (75%) and those with advanced fibrosis (77%). Independent of viral genotype, Asian (Non-South) race was a strong predictor of SVR (OR 5.10 vs. Caucasians, 95% CI 1.72-17.71, OR 7.84 vs. South Asians, 95% CI 1.62-37.84), as were treatment naïve status (OR 3.85, 95% CI 1.76-8.89), non-diabetic status (OR 3.70, 95% CI 1.30-11.11), non-obesity (OR 2.13, 95% CI 1.06-4.35), peginterferon α2a (2.08 vs. α2b, 95% CI 1.16-3.85), steatosis <10% (OR 2.0, 95% CI 1.05-3.85) and ribavirin exposure (mg/kg/day) (OR 1.13, 95% CI 1.01-1.28). Asian (Non-South) race is a strong independent predictor of SVR.

This Month in Gastroenterology

This Month in Gastroenterology

Polymorphism in the Human Major Histocompatibility Complex and Early Viral Decline during Treatment of Chronic Hepatitis C

The dynamics of the viral decline immediately after the start of therapy for chronic hepatitis C virus (HCV) infection may have prognostic potential for ultimate sustained virologic response. Considerable interindividual variability in the decline has been reported, including differences by race. The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in the immune response to viral infections. We examined whether carriage of specific human MHC alleles are associated with the rate of the early viral decline. Longitudinal viral level data (baseline and days 1, 2, 7, 14, and 28 of treatment), medium resolution MHC genotyping, and random coefficients models were used to examine associations between MHC class I and class II allele carriage and the dynamics of the viral decline in 180 African-Americans (AAs) and 194 Caucasian Americans (CAs) with genotype-1 HCV infection over the first 28 days of treatment with peginterferon alpha2a plus ribavirin. Baseline viral levels were similar by race, irrespective of allele carriage. However, the rate of change in the viral decline was associated with both allele and race. Among the four subgroups defined by race and specific allele, the fastest rates of decline were observed (in terms of estimated mean viral declines log(10) IU/ml during the first four weeks) in CA noncarriers for A*03 (2.75; P = 0.018), in CA carriers for Cw*03 (2.99; P = 0.046), and in CA noncarriers for DQA1*04 (2.66; P = 0.018) or DQB1*0402 (2.65; P = 0.018). MHC alleles are associated with the viral decline during the first 28 days of peginterferon therapy.

Phase II trial of branched peginterferon-α 2a (40 kDa) for patients with advanced renal cell carcinoma

BackgroundPeginterferon-α 2a (40 kDa), PEGASYS™ (PEG-IFN), is a modified form of recombinant human interferon (IFN)-α 2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase II trial was conducted in previously untreated patients with advanced renal cell carcinoma (RCC) to assess efficacy, toxicity and pharmacokinetic profile. Patients and methodsForty previously untreated patients with advanced RCC were enrolled on this multicenter trial. The median age was 60 years and 63% had prior nephrectomy. PEG-IFN was administered at a dose of 450 µg/week on a weekly basis by subcutaneous injection. Serial venous blood samples were drawn to assess concentrations of PEG-IFN. ResultsFive (13%) patients achieved a major response (four partial and one complete). The median time to progression was 3.8 months, and 63% of patients were alive at 1 year. The toxicity profile was mostly mild to moderate in intensity. Toxicity higher than grade 2 included neutropenia (six patients), fatigue/asthenia (four patients), nausea/vomiting (three patients) and elevated hepatic transaminase concentrations (four patients). Serum drug levels were studied in all patients; mean Cmax at week 1 was 19 ng/ml, and levels were sustained at close to peak over 1 week. With chronic dosing, drug concentration was increased 3-fold, and steady state was achieved in 5–9 weeks. ConclusionsThe sustained maintenance of serum levels of PEG-IFN allows once-weekly dosing. The efficacy and tolerability profile was qualitatively similar to standard IFN-α, and adverse events were mostly mild to moderate in nature.