Prognostic factors of survival in patients with non-resectable hepatocellular carcinoma: Hepatitis C versus miscellaneous etiology

Objective: To identify prognostic determinants of survival in patients with non-resectable hepatocellular carcinoma (HCC), determine the effect of transarterial chemoembolization (TACE) on prognosis, compare hepatitis C related HCC with mixed etiologies and evaluate the prognostic value of different staging systems. Methods: This cohort study included129 patients (male = 97, 75%) with non-resectable HCC. Data was collected from 2002 until August 2006. A series of demographic, clinical and biochemical and radiological data were collected. Cases were staged according to the Child's, Okuda, Cancer Liver Italian program (CLIP), Barcelona Clinic Liver Cancer (BCLC) and Chinese University Prognostic Index (CUPI) systems. Survival analysis was performed. Any effect of TACE on prognosis was recorded. Results: Median age of patients was 52 years (range 18 - 82). Median follow-up 11 months (range 2-36). At the time of analysis, 102 patients had died (79%). Etiology of HCC was hepatitis C virus (HCV) in 66 (51.2%), hepatitis B virus (HBV) 31 (24%), HBV + HCV 10 (7.8%), HBV + delta hepatitis 02 (1.6), and non-B non-C 20 (15.4%). Forty-one patients (31%) were offered TACE. Univariate analysis for HCV related HCC showed that age > 52 years (p<0.05), bilirubin >1.17 mg /dl (p<0.01), INR > 1.3 (p<0.01), alpha fetoprotein > 400 ng / ml (p<0.05), splenomegaly (p<0.01), ascites (p<0.001), portal vein thrombosis (p<0.01), splenic varices (p<0.01), and TACE not offered (p<0.01) were the prognostic factors while in miscellaneous etiology female sex (p<0.05), haemoglobin < 11.0 gm/dl (p<0.01), alkaline Phosphatase > 169 IU/L (p<0.05), ascites (p<0.05) and multifocality (p<0.05) were adversely effecting prognosis. Overall independent determinants were Hepatitis C etiology, female sex and multifocality of tumour (Hazard ratios 3.0, 3.0 and 1.9 respectively). Mean survival was 17.2 vs. 12.8 months for patients offered vs. not offered TACE respectively (p value = 0.015). Okuda, CLIP, BCLC, CUPI and Child's staging systems retained their performance as judged by chi square values in regression analysis. Discriminatory ability for death evaluated by receiver operating characteristic curve was better for Okuda system in the first year. Conclusion: Hepatitis C as the etiology of HCC, female sex and multi-focality are associated with poor prognosis. HCV related HCC may differ in prognostic factors from non-HCV HCC. Simple staging system by Okuda predicts prognosis effectively in non-resectable HCC.