To evaluate predictors of mortality and impact of treatment in patients developing recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT). Despite well-described clinicopathologic predictors of posttransplant HCC recurrence, data on prognosis following recurrence are scarce. Multivariate predictors of mortality following HCC recurrence were identified to develop a risk score model to stratify prognostic subgroups among 106 patients developing posttransplant recurrence from 1984 to 2014, including analysis of recurrence treatment modality on survival. Of 857 patients undergoing LT, 106 (12.4%) developed posttransplant HCC recurrence (median 15.8 months following LT) with a median post-recurrence survival of 10.6 months. Patients receiving surgical therapy (n = 25) had a median survival of 27.8 months, significantly superior to patients receiving nonsurgical therapy (10.6 months) and best supportive care (3.7 months, P < 0.001). Multivariate predictors of mortality following recurrence included model for end-stage liver disease at LT >23, time to recurrence, >3 recurrent nodules, maximum recurrence size, bone recurrence, alphafetoprotein at recurrence, donor serum sodium, and pretransplant recipient neutrophil–lymphocyte ratio. A risk score model based on multivariate predictors accurately stratified recurrent HCC patients into prognostic subgroups, with low-risk patients (16 points) groups (C-statistic 0.75, P < 0.001). In the largest single-center report of recurrent HCC following LT, surgical treatment in well-selected patients is associated with significantly improved survival and should be pursued. A risk score model accurately stratifies prognostic subgroups, and may help guide treatment strategies.

Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally-advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in 7 patients and were treated with systemic therapy and resection. The study population had a higher –than-expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally-advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.

Background and Aims: In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O₂) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O₂ device in the first US randomized control trial. Approach and Results: The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O₂ or SCS. HMP-O₂ livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O₂ (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O₂ and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O₂ (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O₂ and SCS was −5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT₇) was lower with HMP-O₂ [median (IQR) 3.4% (2.4–6.5) vs. 4.5% (2.9–9.4), p=0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p=0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O₂ (p=0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4). Conclusions: HMP-O₂ demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT₇ was lower in HMP-O₂, suggesting improved early clinical function. Recipients of HMP-O₂ livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.

We sought to evaluate outcomes and predictors of renal allograft futility (RAF—patient death or need for renal replacement therapy at 3 months) after simultaneous liver-kidney transplantation (SLKT). Model for End-Stage Liver Disease (MELD) prioritization of liver recipients with renal dysfunction has significantly increased utilization of SLKT. Data on renal outcomes after SLKT in the highest MELD recipients are scarce, as are accurate predictors of recovery of native kidney function. Without well-established listing guidelines, SLKT potentially wastes renal allografts in both high-acuity liver recipients at risk for early mortality and recipients who may regain native kidney function. A retrospective single-center multivariate regression analysis was performed for adult patients undergoing SLKT (January 2004 to August 2014) to identify predictors of RAF. Of 331 patients dual-listed for SLKT, 171 (52%) expired awaiting transplant, 145 (44%) underwent SLKT, and 15 (5%) underwent liver transplantation alone. After SLKT, 39% experienced delayed graft function and 20.7% had RAF. Compared with patients without RAF, RAF recipients had greater MELD scores, length of hospitalization, intraoperative base deficit, incidence of female donors, kidney and liver donor risk indices, kidney cold ischemia, and inferior overall survival. Multivariate predictors of RAF included pretransplant dialysis duration, kidney cold ischemia, kidney donor risk index, and recipient hyperlipidemia. With 20% short-term loss of transplanted kidneys after SLKT, our data strongly suggest that renal transplantation should be deferred in liver recipients at high risk for RAF. Consideration for a kidney allocation variance to allow for delayed renal transplantation after liver transplantation may prevent loss of scarce renal allografts.

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.