The median age of the cohort was 56 years and the majority were male. As expected, HCV was the predominant etiology of liver disease in this U.S. cohort. Epacadostat Most patients (88%) had evidence of cirrhosis. The median MELD score was 9.2 and most patients had normal performance status and were ambulatory. A majority of patients had a single lesion with a wide range in the size of the tumors with half of the patients meeting the so-called Milan criteria. Vascular invasion or extrahepatic spread was relatively infrequent. Curative therapy was employed including resection in 17% (n = 71) and liver transplantation in 31% (n = 133). Local ablation was used in 9%

(n = 37), transarterial therapy in 25% (n = 106), and systemic chemotherapy in 5% (n = 22). In 56 patients (13%), only comfort care was possible. In patients who underwent liver transplantation, their median MELD score were

9 (interquartile range [IQR] = 7-13). As expected, nearly all (88%) were within the Milan criteria. The median follow-up was 23 months and 295 (62%) died during the follow-up. The univariate Cox proportional hazards analysis was performed in the derivation cohort (Table 2a). All of the data elements that represent liver disease severity and tumor extent were significantly associated with risk of mortality, whereas age had a marginal effect. HTS assay Family history and liver disease etiology (HBV or HCV) had no apparent impact on survival. When variables with univariate significance were considered in a multivariate model, age, medchemexpress MELD, serum albumin, and the four radiographic variables that reflect the tumor extent (the size of the largest tumor nodule, the number of nodules, vascular invasion, and metastasis) as well as AFP were selected as independent predictors of survival. Figure 1 illustrates the relation between MELD and risk of death after adjusting for other variables in the multivariate model.

There was little change in mortality risk with low MELD scores. The risk started to increase demonstrably at a score of 13, beyond which a one-point increase in the MELD score was associated with a 10% rise in mortality in a largely linear fashion. For this reason, we instituted a lower bound of MELD score at 13 in the development of the survival model. Results of similar analysis on age, albumin, serum AFP, tumor size, and tumor numbers are illustrated in Supporting Figures 2-6. Based on the multivariate model, a risk score (MESIAH; Model to Estimate Survival in Ambulatory HCC patients score, MESIAH henceforth) can be calculated using the formula shown in Table 2b. Further, Table 2c illustrates expected survival for patients with the median MESIAH score in the derivation cohort. Application of the risk score in individual patients allows calculation of expected survival. For example, the 1- and 3-year survival probability in patients in the lowest quartile (MESIAH score <3.62), was 85.8%, 68.1%, respectively. In the highest quartile (MESIAH score >5.05), survival decreased to 52.