Development and validation of an IGF-1-modified Child-Pugh score to risk-stratify hepatocellular carcinoma patients

Background The Child-Turcotte-Pugh (CTP) score inaccurately predicts survival in patients with chronic liver disease, including hepatocellular carcinoma (HCC), yet remains the standard tool for assessing hepatic reserve and guiding therapeutic decisions. CTP scoring relies on objective laboratory values for albumin, bilirubin, and prothrombin time and subjective clinical grading of hepatic encephalopathy and ascites. As liver production of insulin-like growth factor-1 (IGF-1) is significantly reduced in patients with cirrhosis, we hypothesized that IGF-1 could be a valid surrogate for hepatic reserve to replace the subjective parameters in CTP scores. Materials and methods We prospectively enrolled patients and collected data and retrospectively tested plasma IGF-1 levels in four independent cohorts: two HCC cohorts from the USA [n = 310 (training set) and n = 99 (validation set 1)]; one HCC cohort from Korea [n = 188 (validation set 2)]; and one cirrhosis cohort from Egypt [n = 71 (validation set 3)]. Recursive partitioning identified within the training set three optimal IGF-1 ranges that correlated with survival: >50 ng/ml = 1 point; 26-50 ng/ml = 2 points; and <26 ng/ml = 3 points. We modified the CTP score by replacing ascites and encephalopathy grading with IGF-1 values, subjected both the resulting IGF score and the CTP score to log-rank analysis, and quantified the prognostic values with C-statistics to compare the scores′ performance in all cohorts. Results The IGF score was significantly more accurate in predicting survival and improved the stratification of all CTP classes in the training and validation cohorts. Conclusion The new IGF score is simple and blood-based, and validated well on multiple independent HCC cohorts. It could identify a subpopulation of patients who may benefit from active therapy because of their preserved hepatic reserve, as distinct from patients for whom therapy can be deferred or avoided.