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Summary. Genetic factors can influence the outcome of antiviral therapy in chronic hepatitis C (HCV). We evaluated the role of interleukin-28B single nucleotide polymorphisms (SNPs) and inosine triphosphatase (ITPA) gene variants in HCV cirrhosis treated with Peg-Interferon and ribavirin. A prospective cohort of 233 patients with compensated cirrhosis received 1–1.5 μg/kg/week of Peg-Interferon alpha-2b plus 1000–1200 mg/day of RBV for 48 weeks. A sustained virologic response (SVR) was achieved in 27% of patients. On multivariate logistic analysis, the absence of oesophageal varices (OR 3.64 CI 95% 1.27–10.44 P = 0.016), infection with genotype 2 or 3 (OR 4.06, CI 95% 1.08–15.26, P = 0.038), C/C alleles of rs12979860 SNP (OR 7.04, CI 95% 2.40–20.72, P

Background and Aims: Current histological scoring systems do not subclassify cirrhosis. Computer-assisted digital image analysis (DIA) of Sirius Red-stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG). Methods: In 121 consecutively-transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded. Results: Sixty-two patients were analyzed. The median HVPG was 8 mmHg (interquartile range [IQR]: 5–10). Portal hypertension (HVPG ≥ 6

Hepatitis C virus (HCV) is the leading cause of liver transplantation in Europe and is associated with an increased risk of hepatocellular carcinoma (HCC). Because of the chronic nature of the disease, estimates suggest that the burden on healthcare will increase dramatically for this entity. Clinical care of patients with HCV-related liver disease has advanced considerably in the last two decades, thanks to increasing knowledge about the mechanisms of the disease, development of diagnostic procedures, and advances in therapeutic and preventive approaches. HCV RNA testing, HCV genotyping and staging of liver disease are essential for the diagnosis and the management of HCV therapy. Furthermore, the important role of host polymorphisms of the IL28B gene on virological response to treatment with pegylated interferon (PEG-IFN) alpha and ribavirin (RBV) has recently been clearly demonstrated. In relation to treatment, although numerous drugs for HCV are in various stages of preclinical and clinical development, the current standard of care (SoC) is the combination of PEG-IFN-α and RBV for chronic hepatitis C. With SoC, a sustained viral response (SVR) is achieved in approximately 45% of patients infected with HCV genotype 1 and in approximately 80% of patients infected with HCV genotypes 2 and 3. The EASL HCV guidelines recommend treating all naïve patients with compensated disease from HCV without contraindications to treatment and strongly suggest initiating SoC promptly in patients with advanced fibrosis. Further recommendations on monitoring treatment efficacy, treatment duration, dose reduction indications and the role of co-factors are provided.

Introduction: Differentiation between steatosis and non-alcoholic steatohepatitis (NASH) in non-alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy. Patients and methods: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%. Results: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and ASTwere independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86‐0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85. Conclusion: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis.

Recurrent hepatitis C is a common cause ofgraft loss in patients undergoing liver transplantation,and serial protocol liver biopsies have been used to identifypatients at risk of graft loss from rapid fibrosis progression.The aim of this study was to derive a simple non-invasive index to predict fibrosis in patients with recurrenthepatitis C post-transplant. A retrospective study wasperformed assessing serial liver biopsies for post-transplantchronic hepatitis C infection. One hundred eighty-fivepatients were included in the analysis; median age 53 years(interquartile range 48–59) and 140 (76%) were male.Liver histology showed 53 (29%) had Ishak fibrosis stagesF0/F1, 31 (17%) had F2, 29 (16%) had F3, 19 (10%) hadF4 and 53 (29%) had F5/F6. The London TransplantCentres (LTC) score was derived combining aspartateaminotransferase (AST IU/L), time from liver transplant(TFLT months), international normalized ratio and platelets.Diagnostic accuracy of the LTC score was assessed usingarea under receiver-operating characteristic (ROC) curves.The area under the ROC curve for moderate fibrosis (F ‡ 2)was 0.78 (95% CI, 0.70–0.86; P < 0.0001), for advancedfibrosis (F4–6) was 0.80 (95% CI, 0.72–0.87; P < 0.0001)and for cirrhosis was 0.80 (95% CI, 0.72–0.88;P < 0.0001). An optimal cut-off value of 6.3 distinguishedpatients with no or mild fibrosis (F £ 1) odds ratio 10.8 (95%CI, 5.1–22.9); P < 0.0001), sensitivity 88%, specificity 60%,negative predictive value 67% and positive predictive value84%. The LTC score can identify patients with Hepatitis Cvirus recurrence following liver transplant with a low risk ofsignificant fibrosis, thus avoiding the need for protocolbiopsy.Keywords: fibrosis, hepatitis C, liver transplantation, nonin-vasive marker.

Historically, liver biopsy (LB) was the sole methodto evaluate the severity of hepatic fibrosis in patients withchronic hepatitis C infection. However, LB is expensive andassociated with a risk of severe complications. Therefore,noninvasive tests have been developed to assess the severityof liver fibrosis. The accuracy of Fibroscan (FS) and Kingsscore (KS) was evaluated individually and in combinationusing liver histology as the reference standard. One hundredandeighty-sevenpatientswereidentifiedwhohadundergonea biopsy with a diagnosis of chronic hepatitis C virus (HCV)mono-infection (HCV RNA-positive by RT-PCR), attendingKings College Hospital (n = 88) or the Royal Free Hospital(n = 99) (London) between May 2006 and December 2007.Liver fibrosis was scored using the Ishak method; significantfibrosis was defined as Ishak fibrosis stage F3–F6, and cir-rhosis defined as Ishak fibrosis F5–F6. The diagnostic accu-racyofeachtestwasassessedbyareaunderreceiveroperatorcharacteristic curves (AUROC). Median age was 49 years(43–54) and 115 (61%) were male. The AUROC for FS, KSand FS + KS for the diagnosis of Ishak F3–F6 were 0.83,0.82 and 0.85, respectively and for the diagnosis of cirrhosis(‡F5) were 0.96, 0.89 and 0.93, respectively. The negativepredictive values for the diagnosis of cirrhosis using theoptimal cut-off results for fibrsocan (10.05 kPa), KS (24.3)and the two combined (26.1) were 98%, 91% and 94%,respectively. The noninvasive markers and, particularly, FSwere effective tests for the prediction of cirrhosis in chronichepatitis C. Both KS and FS also had clinical utility for theprediction of Ishak fibrosis stages F3–F6.Keywords: fibrosis, hepatitis C, Kings score, transient elas-tography.