Deterioration of hepatic function after locoregional therapy (LRT) for hepatocellular carcinoma (HCC) measured by hepatic cholate clearance: A pilot study.

Abstract

468 Background: LRT is used in treating HCC, but is associated with a risk of hepatotoxicity, which is not accurately predicted by traditional measures of liver function. In this pilot study, we evaluated the change in liver function after LRT as measured by a test using dual, oral and IV, cholate clearances (HepQuantSHUNT). Our hypothesis is that LRT would impose a significant reduction in the disease severity index (DSI) measured in the HepQuant SHUNT test, as an indicator of reduced liver function. Methods: We conducted a prospective cohort study of 11 subjects undergoing LRT for HCC. HepQuantSHUNT was performed at baseline (T0) and 4-10 weeks after LRT (T1). Clinical assessment was performed at T0 and T1, and at 12-18 weeks after LRT (T2). Decompensation was defined as either a new complication of cirrhosis or an increase in Child-Pugh (CP) score by ≥2 points. Results: Median age was 61 years, 73% were men, 55% had hepatitis C. Median CP score was 7[5-8], including 36%CP A and 64%CP B. Subjects had a BCLC stage A(64%) or BCLC stage B(36%) HCC. LRT modalities were TACE (45%) or SBRT (55%). From T0 to T1, there was a reduction in oral cholate clearance(422[235-768] vs 339[208-362], p = 0.03) and in IV cholate clearance(210[150-300] vs 191[144-203],p = 0.04) as well as a trend towards a worsening disease severity index (DSI) (32.0[19.5-37.8] vs 33.0[29.7-38.0],p = 0.10); however, there was no significant change in MELD(12[9-13]vs 11[10-12],p = 0.72) or CP score(7[5-8] vs 7[6-8],p = 0.15). 89% of the subjects had a reduction in oral and IV cholate clearance, and 78% had a worsening DSI; while 44% subjects had increase in CP score, and 56% had an increase in MELD. Decompensation was observed in 43% of CP B patients and none of CP A patients; and in 60% patients with a DSI > 35, and none of the patients with DSI < 35. Conclusions: The dual cholate clearance assay HepQuant-SHUNT detects a deterioration in liver function after LRT for HCC more frequently than clinical measures of liver function. DSI 35 might be a cutoff for risk of clinical decompensation after LRT for HCC. Additional research is needed to evaluate the role of the HepQuant SHUNT test in improving the selection of Child B patients for LRT.