Deterioration in liver function after liver‐directed therapy for hepatocellular carcinoma measured by cholate clearance

Background Liver-directed therapy (LDT) for hepatocellular carcinoma (HCC) carries a risk of serious liver toxicity, but the risk is not accurately predicted. Our aim is to evaluate the baseline and change in liver function after LDT measured by a potentially more sensitive test than the usual clinical assessment. Methods We conducted a prospective cohort study of patients undergoing LDT for HCC. We evaluated cholate clearance at baseline (T0) and 4-10 weeks after (T1) LDT in 11 patients. Hepatotoxicity was defined as the development of a new complication of cirrhosis or an increase in Child score by ≥2 points. Results Four patients (36.4%) were Child A and the remainder (63.6%) Child B. Patients were BCLC stage A (63.6%) or BCLC stage B (36.4%). LDT modalities were Transarterial Chemoembolisation (TACE) (45.5%) or external beam radiotherapy (EBRT) (54.5%). From T0 to T1, there was a reduction in oral cholate clearance (4.29 [2.43-15.89] mL/kg/min to 3.58 [2.21-15.68] mL/kg/min, P = 0.05) and a trend towards a worsening Disease Severity Index (32.01 [17.11-39.07] vs 33.01 [18.64-40.20], P = 0.06); however, there was no significant change in MELD (12 [9-13] vs 11 [10-12], P = 0.72), or Child score (7 [5-8] vs 7 [6-8], P = 0.15). Hepatotoxicity was observed in 42.9% Child B patients and none of the Child A patients; and in 60.0% patients with a baseline DSI > 35, and none of the patients with DSI < 35. Conclusions The dual cholate clearance assay may better define baseline disease severity and may be more sensitive to change in liver function induced by LDT than traditional measures.