BackgroundPrognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.Methods and FindingsProspective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child–Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26–106 mo) and 39 mo for Taiwanese patients (interquartile range, 12–61 mo).The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2–3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4–5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort.The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score’s prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups.ConclusionsThe ITA.LI.CA prognostic system includes both a tumor staging—stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)—and a prognostic score—integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.

In comparison with the Child–Turcotte–Pugh (CTP) system, recent studies suggested that the model for end‐stage liver disease (MELD) may more accurately predict the survival for patients with cirrhosis. In the US, the liver allocation system was changed in 2002 from a status‐based algorithm utilizing CTP scores to one using continuous MELD severity scores as a reference system in prioritizing adult patients on the waiting list. Direct evidence that demonstrates the benefits of MELD is the fact that the mortality rates of transplant candidates on the waiting list have remarkably decreased after the implementation of the MELD. The MELD score is closely associated with the degree of portal hypertension as reflected by the hepatic venous pressure gradient. Hyponatraemia occurs as a result of advanced cirrhosis, and a serum sodium (Na) level <126 mEq/L at the time of listing for transplantation is a strong independent predictor of mortality. Several MELD‐derived prognostic models that incorporate serum Na into calculation have been proposed in the hopes of further improving the MELD's prognostic accuracy. Additionally, serum parameters such as creatinine and international normalized ratio are subject to interlaboratory variations and may need unifying standardizations. Patients with refractory complications of cirrhosis may need a priority MELD score to prioritize them on the waiting list. Appropriate modifications and the fine‐tuning of the MELD based on well‐designed prospective studies are necessary in solving the current controversial issues.

The model for end-stage liver disease (MELD) has a better predictive accuracy for survival than the Child-Turcotte-Pugh (CTP) system and has been the primary reference for organ allocation in liver transplantation. The CTP system, with a score range of 5-15, has a ceiling effect that may compromise its predictive power. In this study, we proposed a refined CTP scoring method and investigated its predictive ability. An additional point was given to patients with serum albumin Ͻ 2.3 g/dL, bilirubin Ͼ 8 mg/dL or prothrombin time prolongation Ͼ 11 seconds. The modified CTP system, containing class D, was compared to the MELD and original CTP system in 436 patients. There was a significant correlation between the MELD and modified CTP score (ϭ0.59, PϽ 0.001). Using mortality as the endpoint, the area under receiver operating characteristic curve for modified CTP system was 0.895 compared with 0.872 for MELD (Pϭ0.450) and 0.809 for original CTP system (P Ͻ 0.001) at 3 months; the area was 0.890, 0.837 and 0.756, respectively (Pϭ0.051 and Ͻ 0.001, respectively) at 6 months. The risk ratio per unit increase for the modified CTP score was 2.7 and 3.08 at 3 and 6 months respectively (P Ͻ 0.001). In conclusion, the modified CTP system can be proposed as an alternative prognostic model for cirrhotic patients. By extending the score range according to the influence of the laboratory-derived variables, the modified CTP system has a better performance than the original system and is as efficient as the MELD for outcome prediction. Patients with decompensated liver cirrhosis often have a limited survival, and liver transplantation is the only definite treatment modality to effectively prolong their lifespan. However, patients on the waiting list of transplantation far outnumber the potential cadaveric or living liver donors. As a result, the number of patients dying while on the waiting list is progressively increasing in recent years. 1The donor livers are allocated to the recipients according to the severity of underlying liver disease. The MELD (model for end-stage liver disease) score, which is based on the calculation from three biochemical parameters (serum bilirubin, prothrombin time, and creatinine), has been shown to more accurately predict the survival than the Child-Turcotte-Pugh (CTP) score in a recent multi-center study in the United States, 2 and the liver allocation system has changed from a statusbased algorithm to one using a continuous MELD severity scale to prioritize adult patients on the waiting list.3,4 Its accuracy for outcome prediction in patients with decompensated cirrhosis has also been validated in other centers and in Europe. 5-7Abbreviations: AUC, area under the curve; CTP, Child-Turcotte-Pugh; HBV, hepatitis B virus; HCV, hepatitis C virus; INR, international normalized ratio; MELD, model for end-stage liver disease; PT, prothrombin time; ROC, receiver operating characteristic curve.

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