Objective We used an informatics approach to identify and validate genes whose expression is unique to hepatic stellate cells and assessed the prognostic capability of their expression in cirrhosis. Design We defined a hepatic stellate cell gene signature by comparing stellate, immune and hepatic transcriptome profiles. We then created a prognostic index using a combination of hepatic stellate cell signature expression and clinical variables. This signature was derived in a retrospective–prospective cohort of hepatitis C-related early-stage cirrhosis (prognostic index derivation set) and validated in an independent retrospective cohort of patients with postresection hepatocellular carcinoma (HCC). We then examined the association between hepatic stellate cell signature expression and decompensation, HCC development, progression of Child–Pugh class and survival. Results The 122-gene hepatic stellate cell signature consists of genes encoding extracellular matrix proteins and developmental factors and correlates with the extent of fibrosis in human, mouse and rat datasets. Importantly, association of clinical prognostic variables with overall survival was improved by adding the signature; we used these results to define a prognostic index in the derivation set. In the validation set, the same prognostic index was associated with overall survival. The prognostic index was associated with decompensation, HCC and progression of Child–Pugh class in the derivation set, and HCC recurrence in the validation set. Conclusions This work highlights the unique transcriptional niche of stellate cells, and identifies potential stellate cell targets for tracking, targeting and isolation. Hepatic stellate cell signature expression may identify patients with HCV cirrhosis or postresection HCC with poor prognosis.

The inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) is a complex disease with multifactorial etiology. The intestinal dysbiosis have been investigated to play an important role in IBD pathogenesis and disease activity. The aim of our study was to analyze the intestinal microbiota composition in IBD across different severity levels and the impact of biologic therapy on microbiota modulation. In this study, 27 IBD patients were recruited, including 14 patients undergoing biologic therapy for moderate to severe disease activity and 13 controls with inactive disease. The gut microbial composition was determined by 16 S ribosomal RNA gene sequencing of stool samples. Biologic therapy led to significant clinical improvement in IBD disease activity after 48 weeks. About species richness, community alpha diversity was significant lower in active CD patients and enriched gradually after biologic therapy. The beta-diversity regard to the difference of bacterial community composition showed significant difference between patients in biologic and control group. A decrease in Firmicutes and increase in Bacteroidetes abundance were observed in patients with active disease, both in CD and UC. Biologic treatment induced shifts in gut microbiota, with increased Firmicutes and decreased Bacteroidetes, as well as improved F/B ratio gradually after treatment, correlating with disease activity. Our study suggested that gut microbiota differences changed after biologic therapies among IBD with different disease activity, and a rising Firmicutes/Bacteroidetes ratio could be a potential predictor for disease activity and treatment response monitoring.

The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus Ruminococcaceae UCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.

Antiviral therapy can prevent the development of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. However, HCC still develops in patients achieving sustained virological response (SVR). We proposed to evaluate the risk factors and derive a novel risk score for HCC (score_HCC) by summation of products of clinical weights based on the regression coefficients in the final proportional hazards model. From March 2002 to October 2009, we enrolled 871 patients with biopsy-proven CHC, who received combined pegylated interferon and ribavirin therapy and achieved SVR. Cox regression analysis showed that old age [hazard ratio (HR) 3.82, 95% CI 1.74–8.37, P = 0.001], high α-fetoprotein levels (HR 3.15, 95% CI 1.60–6.19, P = 0.001), low platelet counts (HR 2.81, 95% CI 1.22–6.44, P = 0.015) and high fibrotic stage (HR 3.95, 95% CI 1.46–10.70, P = 0.007) were independent risk factors. The cut-off level of risk scores was a derived value of 10 and was able to predict the HCC risk with 89.2% sensitivity and 69.5% specificity. The AUC value for the prediction was 0.848. The score_HCC values were further categorized into three risk groups: low risk (score_HCC ≤10), intermediate risk (score_HCC 11–15) and high risk (score_HCC ≥16). The proportion of HCC development increased from 1.37% (9/657) in the low-risk group to 9.14% (16/175) in the intermediate-risk group and 30.77% (12/39) in the high-risk group (P < 0.001). With the novel risk scores, we can estimate the chance of HCC development more exactly and practically. This approach can be used for HCC screening in CHC patients achieving SVR.

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)

Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies. From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed. Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13-2.65 for aged 60-69 and aHR=2.20, 95% CI=1.43-3.37 for aged ≥ 70), Male gender (aHR=1.74, 95% CI=1.26-2.41), platelet count <150 × 10(9)/l (HR=1.91, 95% CI=1.27-2.86), α-fetoprotein ≥ 20 ng ml(-1) (HR=2.23, 95% CI=1.58-3.14), high fibrotic stage (HR=3.32, 95% CI=2.10-5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10-2.14), and non SVR (HR=2.40, 95% CI=1.70-3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively. The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.