Genetic predictors of response to treatment of chronic hepatitis C virus infection in patients from southern Italy

Various clinical and genetic factors affect response to antiviral treatment of chronic hepatitis C virus (HCV) infection. The IL28B single-nucleotide polymorphism (SNP) rs12979860 is associated with a sustained viral response (SVR), and the suppressor cytokine signaling 3 (SOCS3) gene is over-expressed in HCV-1b non-responders. The aim of this study was to look for correlations between genetic, clinical and viral factors implicated in response to antiviral treatment in chronic HCV infection. We evaluated 190 controls and 148 HCV-infected patients (102 HCV-1 and 46 HCV-2). Demographic, metabolic and histological features related to antiviral treatment were recorded. Univariate and multivariate analyses were used to identify correlations between the genetic and non-genetic features examined and response to antiviral treatment. IL28B expression was higher in CC SNPs versus other alleles in controls (P=0.01) and this difference was associated with viral infection (HCV vs controls P=0.006), particularly in HCV-2 patients (P=0.003). SOCS3 and IL28B expression was correlated with controls (P=0.011), whereas there was an inverse correlation between the expression of the two genes in HCV patients and HCV-1b non-responders (P=0.014 and P=0.03, respectively). Multivariate analysis showed that the only independent SVR predictive factor was rapid virological response. The frequency of IL28B rs12979860 SNP alleles in controls (C allele=71.1% and T allele= 28.9%) was comparable to that of the HCV population (C allele=66.6% and T allele=33.4%). Rapid virological response seems to be the only significant independent predictor of an SVR to antiviral treatment. The inverse correlation between SOCS3 and IL28B expression in genotype 1b non-responders suggests that SOCS3 may affect IL28B expression thereby influencing response to antiviral therapy

Antiviral therapy: Why does it fail in HCV-related chronic hepatitis?

HCV infection is a very common cause of chronic viral hepatitis. It is a worldwide health problem with approximately 170 million persons infected and areas of high endemicity in which the percentage of the population infected reaches 30%. It is a progressive disease that can lead to complications such as severe liver fibrosis and cirrhosis, ascites, esophageal varices, gastrointestinal bleeding and, in 30-50% of patients with cirrhosis, hepatocellular carcinoma. Extrahepatic pathologies such as mixed cryoglobulinemia, non-Hodgkin lymphoma and membrano-proliferative glomerulonephritis have been associated with HCV infection. Effective treatment exists, and is based on IFN-α. Sustained disappearance of the virus (sustained virological response) radically changes the natural history of chronic hepatitis C, with reduced or no disease progression and complications. Interferon-based treatment has improved over the years owing to the association with ribavirin and subsequently with 'pegylation' of interferon molecules. The present standard of care results in a response rate of up to 80% in some subpopulations. Nevertheless, some patients do not respond to this therapy. Several factors predicting nonresponse to interferon therapy have been investigated since it became available. These factors include the characteristics of the virus and of the subject infected, and the therapy used. The aim of this article is to provide an overview of these factors, and insights into the newly recognized causes of nonresponse to help clinicians select the most appropriate therapy for HCV viral hepatitis. © 2011 Expert Reviews Ltd

Association between non-alcoholic fatty liver disease, insulin resistance and Helicobacter pylori.

Here we report a case of a 55-year Caucasian man, who improved the metabolic profile after the treatment for Helicobacter pylori eradication. In particular, we report the changes in homeostatic model assessment of insulin resistance, fatty liver index and echographic liver pattern. We hypothesize the co-factorial role of H. pylori in the mechanisms involved in non-alcoholic fatty liver disease pathogenesis and insulin resistance, by the cytokine serum changes. If this correlation is confirmed, the H. pylori treatment may represent an option in the clinical management of liver steatosis

The diagnostic conundrum in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver alteration worldwide. It encompasses a spectrum of disorders that range from simple steatosis to a progressive form, defined non-alcoholic steatohepatitis (NASH), that can lead to advanced fibrosis and eventually cirrhosis and hepatocellular carcinoma. On liver histology, NASH is characterized by the concomitant presence of significant fat accumulation and inflammatory reaction with hepatocellular injury. Until now, liver biopsy is still required to differentiate simple steatosis from NASH and evaluate the degree of liver fibrosis. Unfortunately, this technique has well-known limitations, including invasiveness and expensiveness. Moreover, it may be biased by sampling error and intra- or inter-observed variability. Furthermore, due to the increasing prevalence of NAFLD worldwide, to program a systematic screening with liver biopsy is not imaginable. In recent years, different techniques were developed and validated with the aim of non-invasively identifying NASH and assess liver fibrosis degrees. The non-invasive tests range from simple blood-tests analyses to composite scores and complex imaging techniques. Nevertheless, even if they could represent cost-effective strategies for diagnosing NASH, advanced fibrosis and cirrhosis, their accuracy and consequent usefulness are to be discussed. With this aim, in this review the authors summarize the current state of non-invasive assessment of NAFLD. In particular, in addition to the well-established tests, the authors describe the future perspectives in this field, reporting the latest tests based on OMICS, gut-miocrobioma and micro-RNAs. Finally, the authors provide an accurate assessment of how these non-invasive tools perform in clinical practice depending on the clinical context, with the aim of giving the clinicians a useful tool to try to resolve the diagnostic conundrum of NAFLD