PEG-IFN Alfa-2b Research Articles

Pegylated interferon-α-2b combined with tenofovir disoproxil fumarate, granulocyte-macrophage colony-stimulating factor, and hepatitis B vaccine treatment for naïve HBeAg-positive chronic hepatitis B patients: A prospective, multicenter, randomized controlled study.

Hepatitis B surface antigen (HBsAg) loss or seroconversion is an ideal treatment endpoint for patients with chronic hepatitis B but is rarely achievable inhepatitis B e-antigen(HBeAg)-positive patients using existing treatment strategies. In this study, the effect of pegylated interferon (peg-IFN) alfa-2b plus tenofovir disoproxil fumarate (TDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatitis B vaccine was evaluated.This randomized controlled trial was conducted at nine liver centers in Chinese university hospitals from May 2018 to July 2020. Patients (n = 303) enrolled were randomly administered peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine (experimental group); peg-IFN-α-2b plus TDF (control group 2); or interferon-α-2b alone (control group 1). The primary efficacy endpoint was HBsAg seroconversion at 48 weeks and the secondary endpoint included safety.No differences in baseline HBsAg levels were observed among the groups. The primary endpoint was achieved in three (3.0%), one (1.03%), and one (1.19%) patient in the experimental group, control group 2, and control group 1, respectively. The incidence of HBsAg seroconversion at week 48 was not significantly different among the three groups (p = 0.629). However, the decrease in serum levels of HBsAg at week 48 was significantly higher in the experimental and control group 2 compared with that in control group 1 (p = 0.008 and 0.006, respectively). No significant difference between the experimental and control group 2 was observed (p = 0.619). Adverse events were not significantly different among the groups except for the lower incidence of neutropenia in the experimental group.Peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine is not superior to peg-IFN-α-2b combined with TDF in HBeAg-positive naïve patients. Clinical Trials Registration:ChiCTR1800016173.

Sustained serological and complete responses in HBeAg-positive patients treated with Peginterferon alfa-2b: a 6-year long-term follow-up of a multicenter, randomized, controlled trial in China

BackgroundPegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial.MethodsEligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 μg/kg/wk. 24 weeks or 1.5 μg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL.ResultsThe proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 μg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2–29.9%) and sustained CR (14.8–18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU.ConclusionsPEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.

Telaprevir with peginterferon/ribavirin for retreatment of null responders with advanced fibrosis post‐orthotopic liver transplant

Aggressive recurrence of hepatitis C remains problematic post-orthotopic liver transplant (OLT). There are limited data on treatment of HCV infection with telaprevir/boceprevir therapy with peginterferon/ribavirin (PR) post-OLT. To review our experience with telaprevir addition to peginterferon/ribavirin in treatment of aggressive hepatitis C in null responders to PR post-OLT. Adult patients with recurrent HCV infection post-OLT with null response to peginterferon/ribavirin for 12 wk (<2 log reduction) received four-wk lead-in PEG-IFN alfa-2b (1.0 μg/kg/wk) plus RBV (600-1000 mg/d) followed by addition of telaprevir 750 q8. All patients were converted to cyclosporine from tacrolimus (TAC). Seven patients (3 M, 4 F), mean age 56 yr, were treated. Three were <1 yr post-OLT, six had cirrhosis and one bridging fibrosis. Three of seven achieved sustained virologic response. All patients required RBV dose reduction, 6/7 required erythropoietin, 5/7 required filgrastim, and 2/7 required eltrombopag for platelets <20 000 μL. There were no supratherapeutic/subtherapeutic CYA levels encountered, no episodes of renal insufficiency. Conversion to CYA followed by four-wk peginterferon/ribavirin lead-in with addition of telaprevir can lead to significant clearance rates at week 24 in null responders with advanced fibrosis although high rates of anemia/RBV dose reduction, growth factor, and transfusion requirements were noted.

Infections During Peginterferon/Ribavirin Therapy Are Associated With the Magnitude of Decline in Absolute Lymphocyte Count: Results of the IDEAL Study

Myelosuppression due to pegylated interferon (peg-IFN) is common during treatment for hepatitis C virus. The relationship between infection risk and decreases in leukocyte lines, however, is not well established. The objective of this analysis was to determine the incidence of and risk factors for infections during peg-IFN/ribavirin (RBV) therapy. A total of 3070 treatment-naive, chronic hepatitis C genotype 1-infected patients were treated for up to 48 weeks with peg-IFN alfa-2b 1.5 µg/kg/week or 1 µg/kg/week, or peg-IFN alfa-2a 180 µg/week plus RBV. On-treatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 10(9) cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 10(9) cells/L. Granulocyte colony-stimulating factor was prohibited. Data on infections were captured at each study visit and categorized according to MedDRA version 13.0. A total of 581 (19%) patients experienced moderate, severe, or life-threatening infections as assessed by the investigator; 648 (21%) patients had at least 1 neutrophil count <0.75 × 10(9) cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 × 10(9) cells/L at any time while on treatment. Twelve patients had severe or life-threatening infection and grade 3/4 neutropenia, but only 4 had temporally related infections. In a multivariate logistic regression model, nadir lymphocyte count, history of depression, and female sex, but not nadir neutrophil count, were associated with moderate, severe, or life-threatening infection. Nadir lymphocyte count, not nadir neutrophil count, was independently associated with moderate, severe, or life-threatening infections in the IDEAL study. Clinicians should be aware of their patients' absolute lymphocyte counts during peg-IFN/RBV therapy; peg-IFN dose reductions may be a consideration in patients with significant lymphocytopenia (<0.5 × 10(9) cells/L).

Comparative efficacy, pharmacokinetic, pharmacodynamic activity, and interferon stimulated gene expression of different interferon formulations in HIV/HCV genotype‐1 infected patients

The effect of different formulations of interferon on therapeutic response in patients coinfected with HIV and HCV is unclear. In this study, the safety, tolerability, viral kinetics (VK) modeling and host responses among HIV/HCV coinfected patients treated with pegylated-IFN or albinterferon alfa-2b (AlbIFN) with weight-based ribavirin were compared. Three trials treated 57 HIV/HCV coinfected genotype-1 patients with PegIFN alfa-2b (1.5 µg/kg/week) (n = 30), PegIFN alfa-2a (180 µg/week) (n = 10), and AlbIFN (900 µg/q2week) (n = 17) in combination with weight-based ribavirin (RBV). HCV RNA, safety labs, and interferon stimulated gene expression (ISG) was evaluated. Adverse events were documented at all study visits. HCV viral kinetics using a full pharmacokinetic/pharmacodynamic model was also evaluated. Baseline patient characteristics were similar across the three studies. All three formulations exhibited comparable safety and tolerability profiles and efficacy. VK/PK/PD parameters for all three studies as measured by mean efficiency and rate of infected cell loss were similar between the three groups. Host responses (ISG expression and immune activation markers) were similar among the three groups. All three regimens induced significant ISG at week 4 (P < 0.05) and ISG expression strongly correlated with therapeutic response (r = 0.65; P < 0.01). In summary, a comprehensive analysis of responses to three different interferon formulations in HIV/HCV coinfected patients demonstrated similar effects. Notably, interferon-based therapy results in a blunted host response followed by modest antiviral effect in HIV/HCV coinfected patients. This suggests that future treatment options that do not rely on host immune responses such as direct antiviral agents would be particularly beneficial in these difficult to treat patients.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

BackgroundTolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. MethodsA multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p=0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. ConclusionTreatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.

The Effect of Peginterferon Alpha-2a vs. Peginterferon Alpha-2b in Treatment of Naive Chronic HCV Genotype-4 Patients: A Single Centre Egyptian Study

BackgroundEgypt has one of the highest (16-8%) prevalence rates of HCV infection in the world. Approximately 90% of Egyptian HCV isolates belong to a single subtype (4a), which responds less successfully to interferon therapy than other subtypes. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naive HCV-infected patients have shown conflicting results.ObjectivesAssessing the effects of Peginterferon alpha-2a versus Peginterferon alpha-2b on the sustained virological response in naive chronic HCV genotype-4 Egyptian patients.Patients and MethodsThis retrospective study cohort consists of 3718 chronic HCV patients admitted to a large, Egyptian medical center. 1985 patients had been treated with PEG-IFN alfa-2a plus RBV and 1733 patients with PEG-IFN alfa-2b plus RBV between years 2007-2011. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects.ResultsThe ETR & SVR in patients treated with PEGIFN alfa-2a was 64.1% and 59.6% as compared to treatment with PEGIFN alfa-2b where these parameters were 58.2% and 53.9% respectively (P < 0.05). Treatment discontinuation rates, were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Significant dose reduction was evident with peginterferon alfa-2b (35.3%) than peginterferon alpha-2a (27.3 %) (P < 0.01). Patients with lower base line AFP and ALT were most likely to achieve SVR using INF alpha 2-a.ConclusionsPeginterferon alpha-2a has a higher efficacy regarding ETR and SVR as compared to Peginterferon alfa-2b in treatment of naive chronic HCV genotype-4 patients.

Efficacy and Safety of Pegylated Interferon Alfa-2a or Alfa-2b Plus Ribavirin for the Treatment of Chronic Hepatitis C in Children and Adolescents: A Systematic Review and Meta-analysis

A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin (RBV) in children and adolescents with chronic hepatitis C virus (HCV). Medline, Embase, and Cochrane Central Register of Controlled Trials were searched. Clinical trials examining peg-IFN alfa-2a or peg-IFN alfa-2b plus RBV among persons ages 3-18 years with HCV were included. Data were abstracted for complete early virologic response (EVR), sustained virologic response (SVR), relapse, treatment discontinuations, hematologic and dermatologic adverse events, and growth inhibition. Eight trials met the inclusion criteria. Results indicate that 70% of subjects (95% confidence interval [CI], 58%-81%) achieved EVR, and 58% (95% CI, 53%-64%) achieved SVR. EVR and SVR were higher for those with HCV genotypes 2/3 than 1/4. Discontinuation due to adverse events and discontinuation due to viral breakthrough were each 4%, discontinuation due to a lack of response was 15%, and relapse was 7%. Anemia, neutropenia, leukopenia, and thrombcytopenia were 11%, 32%, 52%, and 5%, respectively. Alopecia, injection site erythema, and pruritus were 13%, 27%, and 10%, respectively. Small growth inhibitions were observed during treatment. The results of this meta-analysis indicate that peg-IFN/RBV combination treatment is effective and safe in treating children and adolescents with HCV.

Baseline Serum Cholesterol Is Associated with a Response to Pegylated Interferon Alfa-2b and Ribavirin Therapy for Chronic Hepatitis C Genotype 2

Background. HCV infection is associated with lipid disorders because this virus utilizes the host lipid metabolism to sustain its life cycle. Several studies have indicated that higher concentrations of serum cholesterol and LDL before treatment are important predictors of higher rates of sustained virological response (SVR). However, most of these studies involved patients infected with HCV genotype 1. Thus, we performed a multi-institutional clinical study to evaluate the impact of lipid profiles on SVR rates in patients with HCV genotype 2. Methods. A total of 100 chronic hepatitis C patients with HCV genotype 2 who received peg-IFN alfa-2b and ribavirin therapy were consecutively enrolled. The significance of age, sex, BMI, AST level, ALT level, WBC, hemoglobin, platelet count, gamma-glutamyltransferase, total cholesterol level (TC), LDL level, HCV RNA, and histological evaluation was examined for SVR using logistic regression analysis. Results. The 100 patients infected with HCV genotype 2 were divided into 2 groups, an SVR group and a non-SVR group. Characteristics of each group were subsequently compared. There was no significant difference in the level of HCV RNA, BMI, platelet, TG, or stage of fibrosis between the groups. However, there were significant differences in the levels of TC and LDL-C. In multivariate logistic regression analysis using baseline characteristics, high TC level was an independent and significant risk factor (relative risk 18.59, P = 0.015) for SVR. Conclusion. Baseline serum total cholesterol levels should be considered when assessing the likelihood of sustained treatment response following the course of peg-IFN and ribavirin therapy in patients with chronic HCV genotype 2 infection.

Adjuvant peginterferon alfa-2b therapy in stage III melanoma

Stage III melanoma, defined as regionally advanced disease based on the presence of either microscopic or gross lymph node involvement, remains a challenge for clinicians to treat secondary to the limited therapies that have clearly shown any benefit in overall survival compared with observation alone. The US FDA approved peginterferon alfa-2b (pegIFN alfa-2b) in March 2010 for use in the adjuvant setting to treat stage III malignant melanoma. The approval of pegIFN alfa-2b was based on results from the EORTC 18991 trial, which showed pegIFN alfa-2b had superior relapse-free survival compared with observation alone. PegIFN alfa-2b is administered subcutaneously and, aside from the nonpegylated IFN-α, is the only systemic therapy approved by the FDA to treat stage III melanoma. In this review, emphasis will be placed on describing the history of the use of IFN-α in regionally advanced melanoma, with a primary focus on the efficacy and safety profile of pegIFN alfa-2b as an adjuvant therapy in treating mali...

151 LIVER COLLAGEN PROPORTIONATE AREA CORRELATES WITH ESOPHAGEAL VARICES AND SVR IN PATIENTS WITH COMPENSATED HCV CIRRHOSIS

Background: Albeit cirrhosis evolves through clinical stages to decompensation and death, the relation between the amount of fibrosis and the disease course is unknown. Digital image analysis of stained biopsy sections quantifies fibrosis, using segmentation of digital images to measure areas of collagen and to produce a collagen proportionate area (CPA). Aim: To correlate CPA with esophageal varices (EV) at baseline and SVR to SoC therapy in patients with compensated HCV cirrhosis. Patients and Methods: Eighty-six HCV-RNA positive, compensated patients with an histology of cirrhosis (Scheuer’s stage 4) were included. Biopsies were stained with Sirius-red to calculate CPA, excluding samples <15mm. All patients underwent endoscopic screening for EV before SoC treatment with Peg-IFN alfa-2b and Ribavirin. Mean follow up was 37±12 months. Results: Twenty-nine patients (33.7%) had EV. Seven biopsies were suboptimal. In 79 assessable patients, the mean value of CPA was 15.6±6.7%. Mean CPA was significantly different among patients with or without EV (17.9±7.9 vs 13.7±5.9; p = 0.010). By univariate analysis CPA (p =0.007) and albumin (p =0.096) were associated to EV but by multivariate logistic analysis CPA was the only variable associated with EV (OR: 1.086 95%CI: 1.005–1.172; p =0.036). By AUROC the best CPA cut-off value for EV was 14.1% (Sensitivity:80%; Specificity:70%; PPV:60%; NPV 83%). Nineteen patients (24.1%) had SVR. Mean CPA value in patients with SVR was lower than in nonSVR patients (16.6±6.4% vs 12.5±6.9%, p = 0.021). The best CPA cut-off value for SVR was 13% (Sensitivity:74%; Specificity:67%; PPV:40%; NPV:89%). At univariate analysis, CPA and PLT were associated to SVR, but only CPA was associated with SVR at multivariate analysis (OR: 1.012, 95%CI: 0.82–0.99; p = 0.046). Conclusion: The amount of fibrosis in a cirrhotic liver, quantified by CPA, correlates closely to the degree of portal hypertension. The inverse relation between CPA and likelihood of SVR to SoC may suggest use of the former as an additional parameter to indicate which patients with compensated HCV cirrhosis should receive therapy.

Simple formula to predict response to peginterferon alpha2b and ribavirin combination therapy in genotype 1 chronic hepatitis C patients with high viral loads

We advocate a simple formula which can conveniently predict the outcome of Peg-interferon (IFN) alpha2b and ribavirin (RBV) combination therapy for genotype 1 chronic hepatitis C (CH-C) with high viral load. A total of 338 (group A: 230, Group B: 108) genotype 1 CH-C patients treated with Peg-IFN alfa-2b and RBV were enrolled. Clinical parameters differing significantly between sustained virological responders (SVRs) and non-SVRs in group A were categorized, then a simple formula to predict SVR was constructed and re-evaluated in group B. Another formula containing hepatitis C virus amino acid mutations/substitutions also was constructed. In group A, gender and HCV RNA load <1000 KIU were significant predictors of SVR by multivariate logistic regression analysis. A simple formula was constructed (formula A): male gender (point 2) + HCV RNA load <1000 KIU (3) + platelet counts ≥15 × 10(4) /mm(3) (1) + age <60 (1). In group A, score (0-1) predicted SVR rate 23.8% (2-4): 48.1% and (5-7): 70.2%. According to this formula, score (0-1) predicted SVR rate 7.1% (2-4): 38.6%, and (5-7): 70.3% in group B. Information on HCV amino acid mutations/substitutions seemed to add some accuracy. This simple formula can be used to roughly determine, at the patients' first/second visit, the probability of response to Peg-IFN alpha2b and RBV combination therapy for genotype 1 CH-C with high viral load.

Impact of past HBV exposure on virological response to combined interferon ribavirin therapy in patients with chronic HCV genotype 4

Aim: is to investigate if past exposure to HBV in chronic HCV infection promotes the progression of liver disease and influences Interferon (INF) response or not. Methods: 185 patients with chronic HCV were recruited and randomized into 2 groups, group I was treated with PEG-IFN alfa-2b plus ribavirin and group II with 3 MU/TIW IFN alfa-2b plus ribavirin. All patients had HBsAg negative & patients had HBc Ab positive tested for HBsAb. Patients with HBc Ab (n = 37) were tested for serum HBV DNA. Pretreatment liver biopsy and Immunohistochemistry was performed for detection of HBsAg and HBcAg using monoclonal antibodies. Demographic and laboratory data were collected. Results: 70/185 (38%) patients had Anti-HBc, 37 (20%) had isolated anti-HBc and none of the 37 subjects with isolated anti-HBc had serum HBV DNA. Sustained Viral Response (SVR) was achieved in 32/70 (46%) and 46/115 (40%) in anti-HBc seropositive and seronegative patients respectively, in conventional IFN group SVR was 37% and 39% in past HBV exposed patients and unexposed respectively, in PEG IFN group SVR was 59% and 41% in past HBV exposed patients and unexposed respectively. Among anti-HBc and anti-HBs seropositive patients SVR was 10/12 [83%] and 4/21 [19%] p = 0.004 in PEG and conventional IFN respectively. Marked fibrosis was diagnosed in 20% past HBV exposed patients versus 10% in unexposed patients (p = 0.01). Conclusion: past HBV exposure promotes the progression of liver disease but has no effect on the SVR to antiviral therapy in chronic HCV genotype 4 patients.

FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC 3 program

EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy. Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3, and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p ≤ 0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p ≤ 0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5). FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12 weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin.

Quantitative serum HBsAg and HBeAg are strong predictors of sustained HBeAg seroconversion to pegylated interferon alfa‐2b in HBeAg‐positive patients

To evaluate the usefulness of quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for predicting HBeAg seroconversion in chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or PegIFN alfa-2b. Fifty-eight patients were enrolled; 29 for the training group and 29 for the validating group. Quantification of HBsAg and HBeAg was carried out at baseline, week 12, week 24, and then again at 12 and 24 weeks follow up, respectively, for two groups. Sixteen patients in the training group were followed up for 5 years. The cutoff of 1500 IU/mL in serum HBsAg at week 12 had a positive predictive value (PPV) of 33% and a negative predictive value (NPV) of 91%, and 2890 IU/mL at week 24 had a PPV of 43% and an NPV of 95% for HBeAg seroconversion at week 48. The cutoff of 17.55 Paul Ehrlich Institute units/mL (PEI-U/mL) in serum HBeAg at week 12 had a PPV of 38% and an NPV of 95%, and 8.52 PEI-U/mL at week 24 had a PPV of 44% and a NPV of 100% for HBeAg seroconversion at week 48. Moreover the HBsAg and HBeAg levels of PegIFN alfa-2b group were lower than those of the conventional IFN alfa-2b group. During follow up, patients with HBeAg seroconversion remained HBeAg negative and none of them progressed to cirrhosis, but among the patients with non-HBeAg seroconversion, two progressed to cirrhosis. Two additional patients with negative HBeAg were observed. On-treatment serum HBsAg and HBeAg had high predictive values to predict sustained HBeAg seroconversion by PegIFN alfa-2b. Patients who cleared HBeAg had better survival free of hepatic complications during long-term follow-up study.

Ability of treatment week 12 viral response to predict long-term outcome in genotype 1 hepatitis C virus/HIV coinfected patients

Guidelines recommendation to extend treatment duration in genotype 1 hepatitis C virus (HCV)/HIV-coinfected patients who clear the virus later than treatment week 4 is not evidence-based. Our main objective was to study the ability of week 12 viral response [early virologic response (EVR)] to predict long-term outcome in patients treated for 48 weeks. Multicenter retrospective cohort analysis. Genotype 1 HCV treatment-naive, HIV-coinfected adult patients with compensated liver disease who started combination therapy with fixed-dose pegylated-interferon (pegIFN) alfa-2a or weight-based pegIFN alfa-2b plus ribavirin were included. Univariate and forward stepwise logistic regression analysis were used to identify predictors of sustained viral response (SVR) and relapse. By intention-to-treat analysis, 31.3% (87/278) of patients achieved an SVR. SVR rate was more than three-fold higher in patients who cleared the virus by week 12 of treatment compared with late responders. Among 123 end-of-treatment responders, 36 (29.3%) relapsed. Relapse risk increased in patients with cirrhosis, in those with ribavirin dose reductions and in late responders: more than 65% of patients who cleared the virus between weeks 12 and 24 relapsed following 48 weeks of treatment compared with 10% of those attaining a complete EVR (<15 IU/ml) at treatment week 12 (risk ratio 6.4, 95% confidence interval 2.9-14.4). Viral response at treatment week 12 is a strong predictor of long-term outcome. Genotype 1 HCV/HIV-coinfected patients who achieve a complete EVR (<15 IU/ml) are at low risk of viral relapse after completing the standard 48 weeks of therapy.

272 EARLY VIRAL RESPONSE OF CONTROLLED-RELEASE INTERFERON ALPHA2B AND RIBAVIRIN VS. PEGYLATED-INTERFERON ALPHA2B AND RIBAVIRIN IN TREATMENT-NAIVE GENOTYPE1 HEPATITIS C: 12 WEEK RESULTS (SELECT-2 TRIAL)

Aims: Recently, several clinical trials analyzed if extended duration of treatment with pegylated interferon-alfa and ribavirin over 48 weeks can improve sustained virologic response (SVR) rates in HCV genotype 1-infected patients with slow virologic response. Because results of these clinical trials are conflicting, we performed a metaanalysis to determine the overall impact of extended treatment compared to standard treatment on virologic response rates in treatment-naive HCV genotype 1 slow responders. Methods: Literature search was performed independently by two observers using Pub Med, EMBASE, CENTRAL and abstracts presented in English at international liver and gastroenterology meetings. Randomized controlled clinical trials (RCTs; but studies that re-analyzed data retrospectively RCTs were also allowed) were considered if they included monoinfected treatment-naive HCV genotype 1 patients and compared treatment with pegIFN-alfa 2a or 2b in combination with ribavirin for 48 weeks versus extended treatment (up to 72 weeks) in slow responders. Primary and secondary end points were SVR rates and end-of-treatment (EOT) and relapse rates, respectively. In the present meta-analysis, study endpoints were summarized with a DerSimonian-Laird estimate for binary outcome basing on a random effects model. Results: Literature search yielded seven RTCs addressing the benefit of extended treatment with pegylated interferon-alfa and ribavirin in treatment-naive HCV genotype 1 slow responders. In total, 1330 slow responders were included in our meta-analysis. We show that extended treatment duration compared to the standard of care significantly improves SVR rates in HCV genotype 1 slow responders (12.4% improvement of overall SVR rate, 95%CI 0.055– 0.193, P =0.0005). In addition, we show that rates of viral relapse were significantly reduced by extended treatment (24.1% reduction of relapse, 95%CI −0.3332 to −0.1487, P < 0.0001), whereas no significant impact of extended treatment on EOT response rates was found. Though extended treatment was burdened with an enhanced rate of premature treatment discontinuation due to interferonalfaand ribavirin-related side effects, the frequency of serious adverse events was not increased. Conclusions: Treatment extension in HCV genotype 1 slow responders can improve SVR rates in difficult to treat patients and should be considered in patients who need to be treated before specific antivirals will be approved.

271 EXTENDED TREATMENT OF TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS C VIRUS (HCV) GENOTYPE 1-INFECTION AND SLOW RESPONSE TO PEGYLATED INTERFERON-ALFA AND RIBAVIRIN: A META-ANALYSIS

Aims: Recently, several clinical trials analyzed if extended duration of treatment with pegylated interferon-alfa and ribavirin over 48 weeks can improve sustained virologic response (SVR) rates in HCV genotype 1-infected patients with slow virologic response. Because results of these clinical trials are conflicting, we performed a metaanalysis to determine the overall impact of extended treatment compared to standard treatment on virologic response rates in treatment-naive HCV genotype 1 slow responders. Methods: Literature search was performed independently by two observers using Pub Med, EMBASE, CENTRAL and abstracts presented in English at international liver and gastroenterology meetings. Randomized controlled clinical trials (RCTs; but studies that re-analyzed data retrospectively RCTs were also allowed) were considered if they included monoinfected treatment-naive HCV genotype 1 patients and compared treatment with pegIFN-alfa 2a or 2b in combination with ribavirin for 48 weeks versus extended treatment (up to 72 weeks) in slow responders. Primary and secondary end points were SVR rates and end-of-treatment (EOT) and relapse rates, respectively. In the present meta-analysis, study endpoints were summarized with a DerSimonian-Laird estimate for binary outcome basing on a random effects model. Results: Literature search yielded seven RTCs addressing the benefit of extended treatment with pegylated interferon-alfa and ribavirin in treatment-naive HCV genotype 1 slow responders. In total, 1330 slow responders were included in our meta-analysis. We show that extended treatment duration compared to the standard of care significantly improves SVR rates in HCV genotype 1 slow responders (12.4% improvement of overall SVR rate, 95%CI 0.055– 0.193, P =0.0005). In addition, we show that rates of viral relapse were significantly reduced by extended treatment (24.1% reduction of relapse, 95%CI −0.3332 to −0.1487, P < 0.0001), whereas no significant impact of extended treatment on EOT response rates was found. Though extended treatment was burdened with an enhanced rate of premature treatment discontinuation due to interferonalfaand ribavirin-related side effects, the frequency of serious adverse events was not increased. Conclusions: Treatment extension in HCV genotype 1 slow responders can improve SVR rates in difficult to treat patients and should be considered in patients who need to be treated before specific antivirals will be approved.

Propensity Score Matching in the Evaluation of Drug Therapy Management Programs

This retrospective cohort analysis demonstrates the application of propensity score methods in the Be In Charge (BIC) program, a drug therapy management program for patients with hepatitis C. Data were drawn from BIC participant records and program utilization and from a longitudinal database of administrative claims for pharmacy and medical services. Eligible patients must have received peginterferon alfa-2b (PEG-IFN alfa-2b) and ribavirin, but analyses evaluated only PEG-IFN alfa-2b use; BIC enrollees were matched with patients not enrolled in BIC (controls). Adherence was measured on the basis of the number of injections dispensed and the proportion of patients for whom an average of at least 1 injection per week was dispensed during follow-up. BIC subjects refilled 1.2 more injections than did controls (P < .001) within 12 weeks, 2.7 more (P < .001) within 24 weeks, and 6.7 more (P < .001) within 48 weeks. BIC enrollees were more likely than controls to refill the indicated dose (1 injection per week) within 12 weeks (72% vs 64%, P < .001), 24 weeks (52% vs 41%, P < .001), and 48 weeks (22% vs 13%, P = .002) of initiation. These data suggest that the BIC program may significantly improve adherence to PEG-IFN alfa-2b.

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