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BackgroundIt has been postulated that short wait time before liver transplant (LT) for hepatocellular carcinoma (HCC) results in the inclusion of tumors with aggressive biology, but prolonged wait time could result in a shift to more aggressive tumor behavior. We therefore test the hypothesis that a wait time "sweet spot" exists with a lower risk for HCC recurrence compared with the other 2 extremes.MethodsThis multicenter study included 911 patients from 3 LT centers with short, medium, and long wait times (median of 4, 7, and 13 months, respectively) who received Model for End Stage Liver Disease exception listing for HCC from 2002 to 2012.ResultsWait time, defined as time from initial HCC diagnosis to LT, was less than 6 months in 32.4%, 6 to 18 months in 53.7%, and greater than 18 months in 13.9%. Waitlist dropout was observed in 18.4% at a median of 11.3 months. Probability of HCC recurrence at 1 and 5 years were 6.4% and 15.5% with wait time of less than 6 or greater than 18 months (n = 343) versus 4.5% and 9.8% with wait time of 6 to 18 months (n = 397), respectively (P = 0.049). When only pre-LT factors were considered, wait time of less than 6 or greater than 18 months (HR, 1.6; P = 0.043) and AFP greater than 400 at HCC diagnosis (HR, 3.0; P < 0.001) predicted HCC recurrence in multivariable analysis.ConclusionsThis large multicenter study provides evidence of an association between very short (18 months) wait times and an increased risk for HCC recurrence post-LT. The so-called sweet spot of 6 to 18 months should be the target to minimize HCC recurrence.

ImportanceSeveral factors are associated with increased hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence.ObjectiveWe aimed to develop and validate a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for patients with HCC meeting Milan criteria by imaging.Design, setting, and participantsPredictors of recurrence were tested in a development cohort of 721 patients who underwent LT between 2002 and 2012 at 3 academic transplant centers (University of California-San Francisco; Mayo Clinic, Rochester; and Mayo Clinic, Jacksonville) to create the RETREAT score. This was subsequently validated in a cohort of 341 patients also meeting Milan criteria by imaging who underwent LT at the University of Toronto transplant center using the C concordance statistic and net reclassification index.Main outcomes and measuresCharacteristics associated with post-LT HCC recurrence.ResultsA total of 1061 patients participated in the study; 77.8% (825) were men, and the median (IQR) age was 58.2 (53.3-63.9) years in the development cohort and 56.4 (51.7-61.0) years in the validation cohort (P

Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) can modify the risk of hepatocellular cancer (HCC) in patients with diabetes mellitus (DM). We performed a systematic review and meta-analyses of studies evaluating the effect of metformin, thiazolidinediones (TZDs), sulfonylureas, and/or insulin on the risk of HCC. We conducted a systematic search of Medline, EMBASE, and Web of Science up to August 2012. Studies were included if they (1) evaluated and clearly defined exposure to metformin, TZDs, sulfonylureas, and/or insulin, (2) reported HCC outcomes in patients with DM, and (3) reported relative risks or odds ratio (OR) or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were estimated using the random-effects model. Ten studies reporting 22,650 cases of HCC in 334,307 patients with type 2 DM were included in the analysis. Meta-analysis of observational studies showed a 50% reduction in HCC incidence with metformin use (n=8 studies; OR 0.50, 95% CI 0.34-0.73), 62% and 161% increase in HCC incidence with sulfonylurea (n=8 studies; OR 1.62, 95% CI 1.16-2.24) or insulin use (n=7; OR 2.61, 95% CI 1.46-4.65), respectively. TZDs did not modify the risk of HCC (n=4; OR 0.54, 95% CI 0.28-1.02). There was considerable heterogeneity across studies, which was partly explained by study setting, location, and whether the studies adjusted for the concomitant use of other ADMs. Post-hoc analysis of randomized controlled trials did not reveal any significant association between ADM use and risk of HCC. ADMs may modify the risk of HCC in patients with DM, especially in the Western population. However, the effect of each individual agent should be interpreted with caution owing to inherent cancer-modifying effect of the comparator group. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Several studies have shown that statins could have chemopreventive effects on HCC. We performed a systematic review and meta-analysis of studies that evaluated the effects of statins on the risk of HCC. Methods: We conducted a systematic search of MEDLINE, Embase, and Web of Science through May 2012 and manually reviewed the literature. Studies were included if they evaluated and clearly defined exposure to statins, reported the incidence of HCC, and reported relative risks or odds ratios (ORs) or provided data for their estimation. Ten studies reporting 4298 cases of HCC in 1,459,417 patients were analyzed. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random effects model. Statistical heterogeneity was assessed with the Cochran''s Q statistic and I2 statistic. Results: Statin users were less likely to develop HCC than statin nonusers (adjusted OR, 0.63; 95% CI, 0.52–0.76), although the results were heterogeneous (P = .01, I2 = 59%). This heterogeneity could be accounted for by study location (Asian population [n = 4]: adjusted OR, 0.52; 95% CI, 0.42–0.64; Western population [n = 6]: adjusted OR, 0.67; 95% CI, 0.53–0.85) and design (observational studies [n = 7]: adjusted OR, 0.60; 95% CI, 0.49–0.73; clinical trials [n = 3]: adjusted OR, 0.95; 95% CI, 0.62–1.45). Conclusions: Based on meta-analysis, statin use is associated with a reduced risk of HCC, most strongly in Asian but also in Western populations. Randomized clinical trials in populations at high risk for HCC (especially in Asian populations with hepatitis B) are warranted. [Copyright &y& Elsevier]