K.-C. Chang

A novel predictive score for hepatocellular carcinoma development in patients with chronic hepatitis C after sustained response to pegylated interferon and ribavirin combination therapy

OBJECTIVESnAntiviral 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.nnnMETHODSnFrom March 2002 to October 2009, we enrolled 871 patients with biopsy-proven CHC, who received combined pegylated interferon and ribavirin therapy and achieved SVR.nnnRESULTSnCox regression analysis showed that old age [hazard ratio (HR) 3.82, 95% CI 1.74-8.37, Pu200a=u200a0.001], high α-fetoprotein levels (HR 3.15, 95% CI 1.60-6.19, Pu200a=u200a0.001), low platelet counts (HR 2.81, 95% CI 1.22-6.44, Pu200a=u200a0.015) and high fibrotic stage (HR 3.95, 95% CI 1.46-10.70, Pu200a=u200a0.007) 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 (Pu200a<u200a0.001).nnnCONCLUSIONSnWith 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.

Role of hepatitis C virus substitutions and interleukin-28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response-guided therapy.

Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity‐determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin‐28B (IL‐28B) locus affect the outcome of interferon (IFN)‐based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response‐guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV‐1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non‐EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts ≥ 15 × 104/μL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.

MicroRNA-122 as a predictor of HBsAg seroclearance in hepatitis B and C dual infected patients treated with interferon and ribavirin

It has been demonstrated that microRNA-122 (miR-122) plays key roles in the modulation of hepatitis B virus (HBV) replication. This study examined the role of miR-122 in patients with hepatitis C virus (HCV)-HBV dual infection with active hepatitis C who received pegylated interferon-α and ribavirin dual therapy. We enrolled 121 patients with HCV-HBV dual infection after dual therapy. Stored serum was collected before treatment. RT-PCR was used to analyze miR-122. HBsAg seroclearance was noted in 37 (30.1%) cases during a median follow-up period of 5.4u2009years. miR-122 was significantly lower in HBsAg seroclearance patients than in non-HBsAg seroclearance patients (Pu2009<u20090.014). Multivariate analysis showed that miR-122 was an independent factor of HBsAg seroclearance (OR: 0.30, 95% CI: 0.09–0.98, Pu2009=u20090.046). miR-122 was significantly higher in patients who were qHBsAgu2009>u2009100u2009IU/mL versus ≤100u2009IU/mL (Pu2009<u20090.001). We concluded that in patients with HBV-HCV dual infection with active hepatitis C, miR-122 was associated with HBsAg seroclearance after therapy and qHBsAg level before therapy, indicating that miR-122 plays key roles in modulating HBV replication.

P566 THE CLINICAL-GUIDE RISK PREDICTION MODEL OF HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC HEPATITIS C PATIENTS AFTER INTERFERON-BASED THERAPY

defined eIF3 subunit (eIF3m) has not characterized. Recently, reported that eIF3m expression affects cell proliferation and cell cycle progression in colon cancer and one of tumorigenesis-related genes, macrophage migration inhibitory factor (MIF) is affected by eIF3m. We investigated expressions of eIF3m and MIF in human HCCs via immunohistochemistry and their relations with clinicopathological parameters. Methods: Surgically resected HCCs from 114 patients were selected. Immunohistochemistry for anti-eIF3m and anti-MIF processed, using auto-immunostainer. Results: One hundred HCCs (87.7%) expressed eIF3m, low grade 20.2%, intermediate 45.6% and high 21.9%. eIF3m expressed predominantly at peripheries and invasive fronts of tumor nests. Higher expression significantly associated with high preoperative AFP, poor differentiation and septal formation (P = <0.0001, 0.0001, 0.0055). Fatty change, mononuclear cell infiltration, vascular invasion and progression tended to be associated with higher expression. MIF expressed in 103 of 114 HCCs (90.4%), low grade 43.0% and high 47.4%. High expression was significantly associated with high preoperative AFP and encapsulation (P =0.0123, 0.0142). Vascular invasion tended to be associated with high expression. Significant positive correlation was found between eIF3m and MIF expressions (P =0.0048). Higher MIF expression tended to be related with high recur probability. eIF3m or MIF expression was not an independent predictive factor for recur throughout multivariate analysis. Conclusions: eIF3m expression suggested to have a pivotal role in HCC progression and invasion with downstream regulation of MIF expression. MIF expression may be an important factor for prediction of HCC recur.

648 VALIDATION OF 2010 AASLD GUIDELINE IN THE DIAGNOSIS OF HEPATOCELLULAR CARCINOMA FOR NON-CIRRHOTIC LIVER

in staining patterns is seen in 5% of cases. One case has features of both I-HCA and b-HCA and also contains a focus of hepatocellular carcinoma. A subset of H-HCA also shows immunoreactivity for SAA and CRP. Interestingly, 20% of H-HCA does not show the typically described steatosis. We have examined 61 resected HCA at our institution in the US, confirming the practical use of IHC in the accurate classification of HCA. The important recognition of b-HCA for patient management is also reemphasized.

717 THE EXPRESSION AND PROGNOSTIC ROLE OF CHIBBY GENE IN HUMAN HEPATOPCELLULAR CARCINOMA

716 PROGNOSTIC GENE-EXPRESSION SIGNATURE FOR HEPATITIS C-RELATED EARLY-STAGE LIVER CIRRHOSIS Y. Hoshida, A. Villanueva, A. Sangiovanni, M. Sole, C. Hur, K.L. Andersson, R.T. Chung, J. Gould, K. Kojima, S. Gupta, B. Taylor, A. Crenshaw, S. Gabriel, B. Minguez, M. Iavarone, S.L. Friedman, M. Colombo, J.M. Llovet, T. Golub. Broad Institute of Harvard and MIT, Dana-Farber Cancer Institute, Boston, MA, USA; Laboratori de Reserca Translacional d’Oncoloǵia Hepatica, IDIBAPS, Ciberehd, Hospital Clinic, Barcelona, Spain; Division of Gastroenterology, Fondazione Ca Granda IRCCS Ospedale Maggiore Policlinico, Universita degli Studi di Milano, Milan, Italy; Dept. of Pathology, Hospital Cĺinic, Barcelona, Spain; Massachusetts General Hospital-Harvard Medical School, Boston, MA, USA; Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Barcelona, Spain; Department of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA E-mail: hoshida@broadinstitute.org