Worse Outcome of Sorafenib Therapy Associated With Ascites and Child-Pugh Score in Advanced Hepatocellular Carcinoma

Hwi Young Kim; Joong-Won Park; Jungnam Joo; Hyoseok Kim; Sang Myung Woo; Woo Jin Lee; Chang-Min Kim


J Gastroenterol Hepatol. 2013;28(11):1756-1761. 

In This Article

Abstract and Introduction


Background and Aim The outcomes of sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC) and impaired liver function remain unresolved. Although Child–Pugh (CP) classification is widely used for patient categorization, heterogeneity within a given CP class makes outcomes less predictable. The aim was to investigate the prognostic significance of CP score elements on the outcome of sorafenib in patients with advanced HCC and impaired liver function.

Methods Of 1385 consecutive patients with advanced HCC in our center between January 2007 and December 2010, we reviewed the medical records of 325 patients who received sorafenib monotherapy.

Results Median duration of sorafenib was 2.0 months (range 0.4–24.2) and median follow-up was 4.9 months (range 0.5–43.4). Disease control rates were significantly higher in CP class A (CPA) than in CP class B (CPB) patients. Median overall survival (OS) was 5.8 months. Subgroups with different CP scores showed significantly different OS (months): CPA5, 8.4; CPA6, 5.1; CPB7, 3.5; CPB8–9, 2.6 (P < 0.001). The presence of ascites was a significant prognostic factor in CPB7 patients (hazard ratio 2.262; P = 0.016). OS of CPB7 patients without ascites was similar to that of CPA6 patients (4.6 months) and was significantly longer than that of CPB7 patients with ascites (2.5 months; P = 0.027). OS of CPB7 patients with ascites was similar to that of CPB8–9 patients.

Conclusions CP score was more important than CP class in predicting the outcome of sorafenib therapy in patients with advanced HCC. Among the CP score components, presence of ascites was a significant prognostic factor, especially in CPB7 patients.


Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer death worldwide.[1] Because most patients are diagnosed at an advanced stage of HCC, potentially curative treatments such as surgical resection, transplantation, and local ablation are not an option. Patients with unresectable HCC typically receive palliative treatments such as transarterial chemoembolization, radiotherapy, and systemic therapy or participate in clinical trials.[2] Sorafenib is the first targeted therapeutic agent approved for the systemic treatment of advanced HCC. Approval of sorafenib therapy was based on the results of the SHARP (Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol) trial and the Asia-Pacific Study. These two randomized, double-blind, placebo-controlled phase III trials demonstrated that sorafenib therapy prolonged overall survival (OS) in patients with advanced HCC.[3,4]

Sorafenib therapy has become the standard of care for patients with advanced-stage, or Barcelona Clinic Liver Cancer (BCLC) stage C, HCC and for patients in the control arms of ongoing clinical trials.[5,6] However, the clinical outcomes of sorafenib therapy in patients with impaired liver function remain an unresolved issue. The Child–Pugh (CP) score is the most widely used classification system for patients with liver disease. Patients enrolled in the SHARP trial (284/299, 95%) and the Asia-Pacific Study (146/150, 97%) were almost exclusively CP class A (CPA; adequate liver function).[3,4] Most patients with HCC, especially those in Asia, have underlying chronic liver disease due to viral hepatitis; therefore, HCC prognosis is highly dependent on liver function. Until recently, available data on the effectiveness of sorafenib monotherapy in advanced HCC patients with impaired liver function were limited; therefore, concerns were raised about the validity of extrapolating these findings to patients other than CPA patients. Moreover, heterogeneity among patients within a given CP class or score makes the outcome of sorafenib therapy less predictable in HCC patients.[7] In this study, we evaluated the effect of CP score elements on the clinical outcomes of sorafenib therapy in HCC patients classified by CP class, especially patients in CP class B (CPB).