| Abstract: | BACKGROUND AND AIMS: Down-staging is commonly used to select patients with hepatocellular carcinoma (HCC) beyond Milan criteria (MC) for liver transplantation (LT), but outcomes are heterogenous. We aimed to estimate pooled down-staging success rates, HCC recurrence and overall survival (OS), stratified by criteria used for baseline tumor burden. METHODS: We searched Pubmed and EMBASE databases from inception till Aug 2021 for studies reporting down-staging success (reduction of tumor burden to within MC) and outcomes of adult HCC patients. Additionally, we performed a pooled analysis using reconstructed individual participant data to obtain robust estimates for OS. RESULTS: We screened 1,059 articles and included 25 articles involving 3,997 patients. Overall, 55.16% (45.49 - 64.46) underwent successful down-staging, and 31.52% (24.03 - 40.11) received LT (by intention-to-treat analysis [ITT]). Among patients that received LT, 16.01% (11.80 - 21.37) developed HCC recurrence. Comparing studies that utilized the United Network for Organ Sharing Down-staging (UNOS-DS) criteria versus studies beyond UNOS-DS or did not specify criteria, down-staging success (by ITT) was 83.21% versus 45.93%, p<0.001, the proportion that received LT (by ITT) was 48.61% vs 28.60%, p=0.030, and HCC recurrence (among patients who received LT) occurred in 9.06% versus 20.42%, p<0.001. Among studies that used UNOS-DS criteria, ITT 1- and 5- year OS from the initiation of downstaging treatment was 86% and 58% respectively, while 1- and 5-year post-LT OS was 94% and 74% respectively. CONCLUSIONS: Among studies that adhered to UNOS-DS criteria, down-staging was successful in four-fifths of patients, >50% received LT and post-LT outcomes were excellent. These data provide clinical validation for the utilization of UNOS-DS criteria. |
