Enhanced efficacy of pegylated interferon alpha-2a over pegylated interferon and ribavirin in chronic hepatitis C genotype 4A randomized trial and quality of life analysis.

AIM: The therapy of chronic hepatitis C genotype 4 (HCV-4) has not been optimized yet. This randomized, prospective, parallel-group clinical trial compared the efficacy and safety of pegylated interferon α-2a (PEG-IFN α-2a) plus ribavirin and PEG-IFN α-2b plus ribavirin and assessed the health-related quality of life (HRQOL) in patients with chronic HCV-4. METHODS: Eligible patients with proven chronic HCV-4 were randomized to receive either a weekly dose of PEG-IFN α-2a (180 µg) or PEG-IFN α-2b (1.5 µg/kg) and a daily dose of ribavirin (1000-1200 mg) for 48 weeks with 24 weeks post-treatment follow-up. The primary end point was sustained virological response (SVR) defined by undetectable HCV RNA 24 weeks after treatment. The Short form-36 Health Survey version 2 (SF-36v2) and the Chronic Liver Disease questionnaires (CLDQ) were assessed before, during and after therapy. RESULTS: The overall SVR rate of the entire cohort was 59.9%. The SVR rates were significantly higher in patients treated with PEG-IFN α-2a and ribavirin (Group A; n=109) compared with those treated with PEG-IFN α-2b and ribavirin (Group B; n=108, 70.6 vs. 54.6%, respectively; P=0.017). The relapse rates were 5.1% for PEG-IFN α-2a and 15.7% for PEG-IFN α-2b (P=0.0019). The SF-36v2 and CLDQ were low during therapy and improved significantly after therapy successful therapy. CONCLUSION: Pegylated interferon α-2a plus ribavirin was significantly more effective than PEG-IFN α-2b and ribavirin therapy in the treatment of chronic HCV-4 patients. The tolerability and adverse events were comparable between the two regimens. The HRQOL improved significantly after successful PEG-IFN α-2a plus ribavirin therapy.

Risk of non-melanoma skin cancer in autoimmune hepatitis.

BACKGROUND: Most patients with autoimmune hepatitis (AIH) require long-term immunosuppressive therapy (IS). While it is well established that solid organ transplant recipients have a high risk of developing non-melanoma skin cancer (NMSC) as a result of immunosuppression, little is known about the risk of NMSC associated with IS in patients with AIH. OBJECTIVES: The aim of this study is to determine the incidence and risk factors for NMSC in patients on IS for AIH. METHODS: We reviewed the medical records of all patients with AIH seen at a tertiary care medical center between 1998 and 2008. We compared the incidence of NMSC to an age- and sex-matched control population and analyzed risk factors for NMSC. RESULTS: A total of forty-five patients with AIH were identified. Twenty NMSC lesions were found in eight patients. Compared to the age and sex-matched general population, the risk of SCC and BCC were increased as quantified by elevated standardized incidence ratios (28.5 and 5.0, respectively). Patients who developed NMSC were on average 24 years older (78.4 vs. 54.2 years old, p < 0.0001) and had AIH diagnosed at a more advanced age (66.0 vs. 45.4 years old, p = 0.0003). CONCLUSION: The risk of NMSC is significantly increased in patients with AIH on immunosuppression. Independent risk factors include current age and age at diagnosis of AIH.

Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of intraarticular hyaluronic acid with corticosteroids for knee osteoarthritis (OA). METHODS: Our data sources were Medline, EMBASE, CINAHL, BIOSIS, and the Cochrane database, as well as hand- searched reviews, manuscripts, and supplements. For unpublished data we used author contacts. Randomized trials that reported effects of intraarticular hyaluronic acid versus corticosteroids on knee OA were selected based on inclusion criteria. Two reviewers extracted data independently. Using a random-effects model, we computed effect sizes for pain change from baseline at 2, 4, 8, 12, and 26 weeks. We also performed multivariate analyses accounting for within and between-study covariance. We performed sensitivity analyses for trials that reported intent-to-treat (ITT) analysis and blinding, and directly compared Hyalgan with methylprednisolone. RESULTS: The 7 eligible trials included 606 participants. Five reported ITT analyses. At week 2 the effect size was -0.39 (95% confidence interval [95% CI], -0.65, -0.12) favoring corticosteroids; at week 4 it was -0.01 (95% CI -0.23, 0.21) suggesting equal efficacy. At week 8 the effect size was 0.22 (95% CI -0.05, 0.49) favoring hyaluronic acid, and at week 12 it was 0.35 (95% CI 0.03, 0.66) favoring hyaluronic acid. At week 26 the effect size was 0.39 (95% CI 0.18, 0.59), favoring hyaluronic acid. The multivariate analyses and sensitivity analyses generated consistent results. CONCLUSION: From baseline to week 4, intraarticular corticosteroids appear to be relatively more effective for pain than intraarticular hyaluronic acid. By week 4, the 2 approaches have equal efficacy, but beyond week 8, hyaluronic acid has greater efficacy. Understanding this trend is useful to clinicians when treating knee OA.