Date Published: January 20, 2017
Publisher: Public Library of Science
Author(s): Dong Hyeon Lee, Jeong-Hoon Lee, Yong Jin Jung, Jungsoo Gim, Won Kim, Byeong Gwan Kim, Kook Lae Lee, Yuri Cho, Jeong-Ju Yoo, Minjong Lee, Young Youn Cho, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Sheng-Nan Lu.
Recently, a modified insulin-like growth factor-1 (IGF)–Child-Turcotte-Pugh (CTP) classification was proposed to improve the original CTP classification. This study aimed to validate the new IGF-CTP classification system as a prognostic maker for patients with hepatocellular carcinoma (HCC) in a hepatitis B virus endemic area.
We conducted a post-hoc analysis of a prospective cohort study. We used Harrell’s C-index and U-statistics to compare the prognostic performance of both IGF-CTP and CTP classifications for overall survival. We evaluated the relationship between HCC stage and the four components of the IGF-CTP classification (serum levels of IGF-1, albumin, and total bilirubin and prothrombin time [PT]) using nonparametric trend analysis.
We included a total of 393 patients in this study. In all, 55 patients died during the median follow-up of 59.1 months. There was a difference between IGF-CTP class and CTP class in 14% of patients. Overall, the IGF-CTP classification system had a higher prognostic value (C-index = 0.604, 95% confidence interval [CI] = 0.539–0.668) than the CTP system (C-index = 0.558, 95% CI = 0.501–0.614), but the difference was not statistically significant (P = .07 by U-statistics). A lower serum level of IGF-1 was related to a more advanced cancer stage (P < .01). The remaining components of the IGF-CTP classification were not significantly related to tumor stage (P = .11 for total bilirubin; P = .33 for albumin; and P = .39 for PT). The IGF-CTP classification was slightly better than the original CTP classification for predicting survival of patients with HCC in a chronic hepatitis B endemic area. This is most likely due to the fact that serum IGF-1 levels reflect underlying HCC status.
Most cases of hepatocellular carcinoma (HCC) occur in the setting of chronic hepatitis and liver cirrhosis. Because of these co-existing underlying liver diseases, the functional reserve of the liver, in addition to tumor status, is a major prognostic factor in patients with HCC. The Child-Turcotte-Pugh (CTP) classification system has been the most widely accepted prognostic model for evaluating functional hepatic reserve. The CTP classification is based on three objective variables (total bilirubin, albumin, and prothrombin time [PT]) and two subjective variables (ascites and encephalopathy). CTP class has been confirmed as a valuable surrogate marker for survival in many independent cohorts of patients with liver disease.[2, 3] However, the inclusion of ascites and encephalopathy allows for inter-observer variation, which has led clinicians to question the reproducibility of the CTP score. Thus, the need for a more accurate prognostic model has prompted the search for more objective markers of liver function in HCC.[4, 5]
We validated the predictive value of the IGF-CTP classification system for assessing survival in HCC patients from a CHB endemic area. The C-index of the IGF-CTP classification was higher than that of the original CTP classification, but this difference was not significant. The proportion of patients who had a difference in risk stratification between the two classifications was not enough (14.0%) to establish statistical significance. Lower serum IGF-1 levels were significantly associated with more advanced HCC. These findings suggest that the IGF-CTP classification system has a tendency to predict survival more accurately than the CTP system by reflecting underlying HCC status.
Although its improvement was not statistically significant compared to the original CTP classification, the IGF-CTP classification system demonstrated better discriminatory function for predicting survival of patients with HCC in a CHB endemic area. The IGF-CTP classification also considerably improved the accuracy of survival prediction in previous validation studies. Therefore, using the IGF-CTP classification instead of the CTP classification in clinical practice can help physicians properly classify patients regardless of the etiology of HCC.