AIM:To investigate the clinical course of untreatable hepatocellular carcinoma(HCC) identified at any stage and to identify factors associated with mortality.METHODS:From January 1999 to December 2010,320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy.Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score.The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging.Data were collected for each patient including all clinical,laboratory and imaging variables necessary for the outcome prediction staging systems considered.HCC staging was performed according Barcelona Clinic Liver Cancer(BCLC) and Cancer of the Liver Italian Program scores.Follow-up time was defined as the number of months from the diagnosis of HCC to death.Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival.RESULTS:Seventy-five per cent of patients had hepatitis C.Ascites was present in 169 patients(53%),while hepatic encephalopathy was present in 49 patients(15%).The Child-Pugh score was class A in 105 patients(33%),class B in 142 patients(44%),and class C in 73 patients(23%).One hundred patients(31%) had macroscopic vascular invasion and/or extrahepatic spread of the tumor.A single lesion > 10 cm was observed in 34 patients(11%),while multinodular HCC was present in 189 patients(59%).Thirty nine patients(12%) were BCLC early(A) stage,55(17%) were BCLC intermediate(B) stage,124(39%) were BCLC advanced(C) stage,and 102(32%) were endstage BCLC(D).At the time of this analysis(July 2011),28(9%) patients were still alive.Six(2%) patients who were lost during follow-up were censored at the last visit.The overall median survival was 6.8 mo,and the 1-year survival was 32%.The 1-year survival according to BCLC classes was 100%,79%,12% and 0%,for BCLC A,B,C and D,respectively.There was a significant difference in survival between each BCLC class.The median survival of patients of BCLC stages A,B,C and D was 33,17.4,6.9,and 1.8 mo,respectively(P < 0.05 for comparison between stages).The median survival of Child-Pugh A,B and C classes were 9.8 mo(range 6.4-13),6.1(range 4.9-7.3),and 3.7(range 1.5-6),respectively(P < 0.05 for comparison between stages).By univariate analysis,the variables significantly associated to an increased liklihood of mortality were Eastern Cooperative Oncology Group performance status(PS),presence of ascites,low level of albumin,elevated level of bilirubin,international normalized ratio(INR) and Log-[(α fetoprotein(AFP)].At multivariate analysis,mortality was independently predicted by bad PS(P < 0.0001),high INR values(P = 0.0001) and elevated Log-(AFP) levels(P = 0.009).CONCLUSION:This study confirms the heterogeneous behavior of untreated HCC.BCLC staging remains an important prognostic guide and may be important in decision-making for palliative treatment.