Research Article: Validation of a Modified Child-Turcotte-Pugh Classification System Utilizing Insulin-Like Growth Factor-1 for Patients with Hepatocellular Carcinoma in an HBV Endemic Area

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.

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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.[1] 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.




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