Management of chronic hepatitis C virus infection: a new era of disease control.
ABSTRACT The management of chronic viral hepatitis has changed significantly with the availability of effective antiviral agents. There is now a high probability that timely intervention can arrest development of cirrhosis, thereby preventing mortality from portal hypertension, liver failure and liver cancer. This two-part review discusses the implications of this new era of antiviral therapy for physicians. The present review is about chronic hepatitis C virus (HCV); a similar review that considers the treatment of hepatitis B virus will be published in a later issue of the Internal Medicine Journal. Chronic HCV infection is common, but fibrotic progression of liver disease is slow and variable; many infected persons never develop cirrhosis. Case selection for antiviral therapy is crucial. The most effective therapy is a pegylated (long-acting) interferon with ribavirin. Sustained viral response (SVR) (absent viraemia 6 months after completing treatment) can be obtained in 40-60% of individuals infected with genotype 1 and in approximately 67% with genotype 4 after 12 months of treatment. Response rates are higher (75-85%) with genotypes 2 and 3 after only 6 months of treatment. Late relapse is negligible after SVR. This viral cure reverses hepatic fibrosis, reduces the risk of liver failure and of hepato-cellular carcinoma. Combination therapy requires a supportive setting to minimize the impact of side-effects and maximize therapeutic effectiveness. Overall management of HCV-infected persons must also embrace measures to improve quality of life by preventing or dealing with psychosocial issues and advocating lifestyle changes to counter comorbidity from alcohol, central obesity and insulin resistance. These latter factors favour fibrotic disease progression, complications of cirrhosis (such as hepatocellular carcinoma) and development of type 2 diabetes mellitus, as well as eroding the chances of SVR with antiviral therapy.
Article: The comparative efficacy and safety of peginterferon alpha-2a vs. 2b for the treatment of chronic HCV infection: a meta-analysis.[show abstract] [hide abstract]
ABSTRACT: Two types of peginterferon, alpha-2a (PEG-IFN-α2a) and 2b (PEG-IFN-α2b), are approved for the treatment of hepatitis C infection. Several high-quality studies have compared the efficacy of these two types of interferon, but it seems that any of these trials had inadequate statistical power on their own to find even a tiny difference between these two medicines. We pooled the available data in the literature to find any small difference between these two medicines. In a systematic review of the literature, randomized controlled trials comparing the use of PEG-α2a vs. 2b were assessed. The DerSimonian and Laird method was employed to run meta-analysis. The end points were virological responses. In 7 randomized controlled trials, 3518 patients were randomized to receive PEG-IFN-α2a + ribavirin (n=1762) or PEG-IFN-α2b + ribavirin (n=1756). Early virological response (EVR), early treatment response (ETR), and sustained virological response (SVR) were greater for patients treated with PEG-IFN-α2a. Odds Ratios (ORs) were 1.38 (95% confidence interval [CI] 1.11-1.71), 1.67 (95% CI 1.24-2.24), and 1.38 (95% CI 1.02-1.88) respectively. In the subset of naïve patients with genotype 1/4 and 2, ORs of SVR were 1.38 (95% CI 1.02-1.88) and 4.06 (95% CI 1.67-9.86) respectively. PEG-IFN-α2a had significantly higher rate of neutropenia OR=1.50 (95% CI 1.25-1.79) but pooled OR for withdrawal rates was not significant [OR=0.78 (95% CI 0.47-1.29)]. PEG-IFN-α2a with similar safety is more effective than PEG-IFN-α2b. A longer duration of maximum serum concentration compared with PEG-IFN-α2b (168 vs. 48-72 h.) yields a greater SVR and higher neutropenia in PEG-IFN-α2a recipients.Hepatitis Monthly 01/2010; 10(2):121-31. · 2.19 Impact Factor
Article: Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials.[show abstract] [hide abstract]
ABSTRACT: To compare interferon monotherapy with its combination with lamivudine for hepatitis B e antigen (HBeAg)-positive hepatitis B treatment. Two independent researchers identified pertinent randomized controlled trials. The trials were evaluated for methodological quality and heterogeneity. Rates of sustained virological and biochemical responses, and HBeAg clearance and seroconversion were used as primary efficacy measures. Quantitative meta-analyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. Greater sustained virological, biochemical and seroconversion rates were observed with addition of lamivudine to conventional [odds ratio (OR)=3.1, 95% confidence intervals (CI) (1.7-5.5), P<0.0001, OR=1.8, 95% CI (1.2-2.7), P=0.007 and OR=1.8, 95% CI (1.1-2.8), P=0.01 respectively], although not pegylated [OR=1.1, 95% CI (0.5-2.3), P=0.8, OR=1.0, 95% CI (0.7-1.3), P=0.94, and OR=0.9, 95% CI (0.6-1.2), P=0.34 respectively] interferon-alpha, with no significant affect on HBeAg clearance rates [OR=1.6, 95% CI (0.9-2.7), P=0.09, and OR=0.8, 95% CI (0.6-1.1), P=0.26 respectively]. Excluding virological response (P<0.001), pegylated interferon monotherapy and conventional interferon and lamivudine combination therapy were similarly efficacious (P>0.05), with the former studied in harder to treat patients, as evidenced by the superior virological response observed with conventional as compared with pegylated interferon monotherapy (P<0.0001). In comparable populations, pegylated interferon monotherapy is likely to be equally or more efficacious than conventional interferon and lamivudine combination therapy, thus constituting the treatment of choice, with no added benefit with lamivudine addition. However, when conventional interferon is used, its combination with lamivudine should be considered.Liver international: official journal of the International Association for the Study of the Liver 11/2007; 27(9):1185-93. · 3.82 Impact Factor
Article: Membranous nephropathy.[show abstract] [hide abstract]
ABSTRACT: Membranous nephropathy (MN) is a glomerular disease characterized by proteinuria, usually in a nephrotic range, and variable natural course. The etiology is unknown in many cases, while in some patients, MN may be secondary to infection, to other diseases, or to exposure to drugs and toxic substances. In idiopathic MN, the antigens are probably located at the base of podocytes, and the glomerular lesions occur by the local formation of immune complexes, with consequent activation of complement and inflammation triggered by the membrane attack complex C5b-9. Patients with severe proteinuria, those with advanced tubulointerstitial changes at renal biopsy and those with increased serum creatinine at presentation have a poorer prognosis, while patients showing complete or even partial remission of proteinuria have a favorable prognosis. The indications for and types of treatment are controversial. There is no good evidence in favor of therapies based on corticosteroids alone. Cyclophosphamide and chlorambucil may increase the probability of remission, but the prolonged use of these agents may cause disquieting adverse effects. Good results have been obtained by alternating corticosteroids and a cytotoxic agent every other month for 6 months. Other potential treatments are represented by cyclosporine, synthetic adrenocorticotropic hormone (ACTH), mycophenolate mofetil, rituximab and intravenous immunoglobulins. Further studies addressed to recognizing the responsible antigen(s), and interventions directed to interfere with the specific antibodies, with regulators of glomerular permeability, and/or with factors regulating the complement activity might allow us to better understand the physiopathology of MN and to organize more specific and effective treatments in the near future.Journal of nephrology 20(3):268-87. · 1.65 Impact Factor