Therapies for Patients with Hepatocellular Carcinoma Awaiting for Liver Transplantation: a Systematic Review and Meta-analysis.Kulik L, Heimbach JK, Zaiem F, Almasri J, Prokop LJ, Wang Z, Murad MH, Mohammed K. Hepatology. 2017 Aug 31. [Epub ahead of print]

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation are often treated while on the waiting list with loco-regional therapy (LRT) which is aimed at either preventing progression of HCC or reducing themeasurable 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 liver transplant waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting liver transplantation and treated with bridging or down-staging therapies before liver transplantation. Therapies included trans-catheter arterial chemoembolization (TACE), trans-arterial radio-embolization (TARE), ablation or radiotherapy. We included both comparative and non-comparative studies. There were no randomized controlled trials identified. RESULTS: For adults with T1 HCC and waiting for liver transplantation there were only 2 non-randomized 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 month in T1 HCC patients underwent loco-regional therapy was 5.3%, while in the other series of T1 HCC patients who did not receive loco-regional therapy, dropout rate at median follow up of 2.4 years and progression rate to T2 HCC was 30% and 88% respectively. For adults with T2 HCC awaiting liver transplantation, transplant with any bridging therapy showed a non-significant reduction in the risk of waitlist dropout due to progression (RR 0.32 (95% CI 0.06 - 1.85, I2 = 0%) and waitlist dropout from all causes (RR 0.38 (95% CI 0.060 - 2.370, I2=85.7%), compared to no therapy based on 3 comparative studies. The quality of evidence is very low due to high risk of bias, imprecision and inconsistency. There were 5 comparative studies which reported on post-transplant survival rates and 10 comparative studies which reported on post-transplant recurrence and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who got LRT, there were 3 studies available reporting on transplant with any down-staging therapy versus no down-staging and this showed significant increase in 1year (2 studies (51, 52)(RR 1.11 (95% CI 1.01-1.23) and 5 year (1 study (52) (RR 1.17 (95% CI 1.03-1.32)post-LT survival rates for the 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 liver transplantation, the use of LRT is associated with a non-significant trend toward improved waitlist and post-transplant outcomes, though there is a high risk of selection bias in the available evidence.

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