In patients with cirrhosis with a 1-2 cm nodule detected during surveillance, a single imaging technique showing a typical contrast pattern confidently permits the diagnosis of HCC, thereby reducing the need for FNB examinations.

Steatosis has been reported to negatively influence the natural history of chronic hepatitis C (CHC), but controversy remains over its causal role due to the confounding effect of adiposity, insulin resistance, and diabetes. The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition. The aim of this study was to evaluate the effect of the rs738409 CG genotype on liver fat and fibrosis in CHC patients. We also explored the possible effect of PNPLA3 genotype on other steatosis-related complications, namely, treatment failure and hepatocellular carcinoma (HCC) development. To this end we considered two independent series of 325 and 494 CHC patients with available DNA and liver biopsy followed at tertiary referral centers in northern Italy. The rs738409 genotype was determined by a Taqman assay. The rs738409 GG genotype, observed in 10% of patients, was associated with steatosis independently of age, sex, body mass index (BMI), diabetes, alcohol intake, and viral genotype (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.4-2.7; P < 0.001). The association with rs738409 genotype was confirmed for severe steatosis, was independent of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) values, and was observed in all viral genotypes but the 3. The rs738409 GG genotype was associated with fibrosis stage and cirrhosis (OR 1.47, 95% CI 1.2-1.9; P 5 0.002), treatment response (n 5 470; OR 0.63, 95% CI 0.4-0.8; P 5 0.006), and HCC occurrence (n 5 325; OR 2.16, 95% CI 1.3-3.6; P 5 0.002), independently of confounders. Conclusion: The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other steatosis-related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC. (HEPATOLOGY 2011;53:791-799)

No abstract

Although annular fibrosis is the hallmark of cirrhosis, other microscopic changes that affect liver function such as sinusoid capillarization or loss of metabolic zonation are common. A sustained virological response (SVR) may halt fibrosis deposition in hepatitis C virus (HCV)-infected patients, but its impact on the other cirrhosis-associated lesions is unknown. The aim of this study was to assess the impact of an SVR on cirrhosis-related histopathological features. Paired pre-and posttreatment liver biopsies from 38 HCV patients with cirrhosis with an SVR were analyzed. Fibrosis was staged using the METAVIR scoring system, and the area of fibrosis was measured using morphometry. Ductular proliferation, metabolic zonation, sinusoid capillarization, and hepatic stellate cell activation were assessed by anti-cytokeratin-7, anti-glutamine synthetase (GS), anti-cytochrome P4502E1 (CYP2E1), anti-CD34, and anti a-smooth muscle actin (aSMA). After 61 months from an SVR, cirrhosis regression was observed in 61%, and the collagen content decreased in 89%. Although periportal and lobular necroinflammation vanished, portal inflammation persisted in 66%. Ductular proliferation decreased in 92%. Before treatment, metabolic zonation was lost, as shown by GS and CYP2E1, in 71% and 88%, respectively, with normalization in 79% and 73%, after an SVR. Conversely, no changes in sinusoidal capillarization were observed after treatment, as assessed by CD34 (P 5 0.41) and aSMA (P 5 0.95). Finally, no differences in all the immunohistochemical scores emerged whether or not cirrhosis persisted. Conclusion: Cirrhosis regression and decreased fibrosis are frequently observed among HCV patients with cirrhosis with an SVR. Despite ductular proliferation vanishing and lobular zonation restoration, portal inflammation and sinusoidal capillarization may not regress after viral eradication. (HEPATOLOGY 2012;56:532-543)

No abstract

Polymorphisms in the interleukin-28B (IL28B) region are associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at the IL28B locus influences the natural history of chronic HCV infection. Thus, we asked whether an association between IL28B polymorphisms and liver fibrosis progression existed. We studied 247 consecutive patients with chronic HCV, an accurate estimate of the date of infection, and a liver biopsy performed before any treatment. No patient had a history of alcohol abuse or coinfection with other viruses. We assessed the role of rs8099917 and rs12979860 polymorphisms and the effect of host and environmental factors on fibrosis progression. Blood transfusion (75%) was the main modality of infection. Median age at infection was 21 years, and median interval between infection and liver biopsy was 25 years. One hundred twenty-nine patients (52%) were infected by HCV-1, 74 (30%) by HCV-2, 34 (14%) by HCV-3, and 10 (4%) by HCV-4. Bridging fibrosis/cirrhosis (Ishak !4) was detected in 24% of patients. Age at infection had a marked effect on fibrosis progression by both a linear model and Cox proportionalhazard regression (P < 2E-16). A 12.1% increase in the hazard of advanced fibrosis was estimated for each additional year at infection, suggesting that this was the major explanatory variable in this cohort. Male gender (P < 0.05), HCV genotype 3 (P < 0.001) and steatosis (P < 0.05) were also associated with faster fibrosis progression. Conversely, the two IL28B polymorphisms had no impact on fibrosis progression. Conclusion: In HCV patients with a known date of infection, IL28B genotype was not associated with fibrosis progression rate or with the risk of developing advanced liver fibrosis.

Conflicting data exist regarding the relationship between hepatitis C virus genotype 1 and hepatic steatosis as well as the latter's role in the progression of fibrosis and treatment response. We assessed factors associated with hepatic steatosis in genotype 1 chronic hepatitis C and the impact of hepatic fat on fibrosis development and interferon responsiveness. Two hundred ninety-one non-diabetic patients with genotype 1 chronic hepatitis C were examined for the presence of steatosis and its correlation with clinical, virological, and biochemical data, including insulin resistance (

No abstract