Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down-staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow-up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06-1.85; I² = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060-2.370; I² = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down-staging therapy versus no downstaging, and this showed a significant increase in 1-year (two studies, RR, 1.11; 95% CI, 1.01-1.23) and 5-year (1 study, RR, 1.17; 95% CI, 1.03-1.32) post-LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. Conclusion: In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (Hepatology 2018;67:381-400).