A new Child-Turcotte-Pugh class 0 for patients with hepatocellular carcinoma: determinants, prognostic impact and ability to improve the current staging systems

Abstract

Background/aim: Majority of patients with hepatocellular carcinoma (HCC) belonged to Child-Turcotte-Pugh (CTP) class A. We aimed to identify a new class of patients with very well-preserved liver function and analyze its impact on outcome prediction, tumor staging and treatment allocation.

Methods: A total of 2654 HCC patients were retrospectively analyzed. The prognostic ability was compared by the Akaike information criterion (AIC).

Results: The CTP class 0 was defined by fulfilling all criteria of albumin ≧4 g/dL, bilirubin ≦0.8 mg/dL, prothrombin time prolongation <0 seconds, no ascites and encephalopathy. A total of 23% of patients of CTP class A were reclassified as CTP class 0. Patients with CTP class 0 had a higher serum sodium level, lower serum creatinine, alanine aminotransferase, α-fetoprotein levels, shorter prothrombin time, better general well-being, smaller tumor burden with more solitary nodules, lower rates of vascular invasion, ascites formation, hepatic encephalopathy, more frequently treated with curative interventions and better Barcelona Clinic Liver Cancer (BCLC) stages (all p<0.001). In the Cox proportional hazards model, the adjusted hazard ratios for CTP class A, B and C were 1.739, 3.120 and 5.107, respectively, compared to class 0 (all p<0.001). Reassigning patients with CTP class 0, A, B, B and C to stage 0, A, B, C and D, respectively, provided the lowest AIC score among all BCLC-based models.

Conclusions: The proposal of CTP class 0 independently predicted better survival in HCC patients. Modification of tumor staging systems according to the modified CTP classification further enhances their prognostic ability.

Figure 1. Comparison of survival distributions between patients of different CTP classifications.

Patients with the new CTP class 0 were associated with a better long-term survival (panel B; p<0.001). Pairwise comparison between each CTP and modified CTP classes showed significant survival differences (panel A p<0.001).

Figure 2. Comparison of survival between stages in the original and modified models BCLC, CLIP and TIS with the lowest AIC score.

Patients with a more advanced stage were associated with a worse long-term survival in the original (panel A) and modified model B (panel B) BCLC systems, the original (panel C) and modified model A (panel D) CLIP systems, the original (panel E) and modified model A (panel F) TIS systems (all p<0.001). Pairwise comparison of survival differences between all stages in the modified BCLC, CLIP and TIS staging systems showed significant differences between each stage (all p<0.05), except for patients with modified BCLC stage 0 and A (p = 0.08).