Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.

Background: Intrahepatic cholangiocarcinoma (iCCA) is a contraindication to liver transplantation (LT) in most centers worldwide. Therefore, only a few such cases have been performed in each individual center and the need for a systematic review and meta-analysis to cumulatively pool these results is apparent. Methods: A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the PRISMA statement (end-of-search date: May 29^th, 2020). Meta-analyses of proportions were conducted to pool the overall survival (OS), recurrence-free survival (RFS), and overall recurrence rates using the random-effects model. Meta-regression was utilized to examine cirrhosis and incidental diagnosis as confounders on OS and RFS. Results: Eighteen studies comprising 355 patients and a registry study of 385 patients were included. The pooled 1-, 3-, and 5-year OS rates were 75% (95%CI: 64%-84%), 56% (95%CI: 46%-67%), and 42% (95%CI: 29%-55%), respectively. The pooled 1-, 3-, and 5-year RFS rates were 70% (95%CI: 63%-75%), 49% (95%CI: 41%-57%), and 38% (95%CI: 27%-50%), respectively. Cirrhosis was positively associated with RFS, while incidental diagnosis was not. Neither cirrhosis nor incidental diagnosis were associated with OS. The pooled overall recurrence rate was 43% (95%CI: 33%-53%) over a mean follow-up of 40.6±37.7 months. Patients with very early (single ≤ 2 cm) iCCA exhibited superior pooled 5-year RFS (67%, 95%CI: 47%-86%) versus advanced iCCA (34%, 95%CI: 23%-46%). Conclusions: Cirrhotics with very early iCCA or carefully selected patients with advanced iCCA after neoadjuvant therapy may benefit from LT under research protocols.

Background: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States, although nonalcoholic steatohepatitis (NASH) is on the rise. Increasingly effective HCV antivirals are available, but their association with diagnosis-specific liver transplantation rates and early graft survival is not known. Methods: The Scientific Registry of Transplant Recipients database records were retrospectively stratified by HCV antiviral era: interferon (2003-2010), protease inhibitors (2011-2013), and direct-acting antivirals (2014 to present). Kaplan-Meier, χ², and multivariable Cox proportional hazards regression models evaluated the effects of antiviral era and etiology of liver disease on transplantation rates and graft survival over 3 years. Results: Liver transplants for HCV decreased (35.3% to 23.6%), whereas those for NASH and alcoholic liver disease increased (5.8% to 16.5% and 15.6% to 24.0%) with each advancing era (all P < 0.05). Early graft survival improved with each advancing era for HCV but not for hepatitis B virus, NASH, or alcoholic liver disease (multivariable model era by diagnosis interaction P < 0.001). Era-specific multivariable models demonstrated that the risk of early graft loss for NASH was 22% lower than for HCV in the interferon era (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96; P = 0.02) but risks associated with these diagnoses did not differ significantly in the protease inhibitor (P = 0.06) or direct-acting antiviral eras (P = 0.08). Conclusions: Increasing effectiveness of HCV antivirals corresponds with decreased rates of liver transplantation for HCV and improved early graft survival. As the rates of liver transplant for NASH continue to increase, focus will be needed on the prevention and effective therapies for this disease.

Background: We aimed to review the indications and outcomes of adults undergoing combined heart-liver transplantation (CHLT) in the US using national registry data.Methods: Adult (≥18 years) CHLT recipients in the United Network for Organ Sharing database were included (09/1987–09/2020; era 1 = 1989–2000, era 2 = 2001–2010, era 3 = 2011–2020). Survival analysis was conducted by means of Kaplan-Meier method, log-rank test, and Cox regression.Results: We identified 369 adults receiving CHLT between 12/1989–08/2020. The number of adult CHLT recipients (R² = 0.75, p < 0.001) and centers performing CHLT (R² = 0.80, p < 0.001) have increased over the study period. The most common cardiac diagnosis in the first two eras was restrictive/infiltrative cardiomyopathy, while the most common in era 3 was congenital heart disease (p = 0.03). The 1-, 3-, and 5-years patient survival was 86.8, 80.1, and 77.9%, respectively. In multivariable analysis, recipient diabetes [adjusted hazard ratio (aHR) = 2.35, 95% CI: 1.23–4.48], CHLT between 1989-2000 compared with 2011–2020 (aHR = 5.00, 95% CI: 1.13–22.26), and sequential-liver first CHLT compared with sequential-heart first CHLT (aHR = 2.44, 95% CI: 1.15–5.18) were associated with increased risk of mortality. Higher left ventricular ejection fraction was associated with decreased risk of mortality (aHR = 0.96, 95% CI: 0.92–0.99).Conclusion: CHLT is being increasingly performed with evolving indications. Excellent outcomes can be achieved with multidisciplinary patient and donor selection and surgical planning.

This study evaluates the clinicopathological characteristics and outcomes of children vs. adults with undifferentiated embryonal sarcoma of the liver (UESL). A retrospective analysis of 82 children (<18 years) and 41 adults (≥18 years) with UESL registered in the National Cancer Database between 2004–2015 was conducted. No between-group differences were observed regarding tumor size, metastasis, surgical treatment, margin status, and radiation. Children received chemotherapy more often than adults (92.7% vs. 65.9%; p < 0.001). Children demonstrated superior overall survival vs. adults (log-rank, p < 0.001) with 5-year rates of 84.4% vs. 48.2%, respectively. In multivariable Cox regression for all patients, adults demonstrated an increased risk of mortality compared to children (p < 0.001), while metastasis was associated with an increased (p = 0.02) and surgical treatment with a decreased (p = 0.001) risk of mortality. In multivariable Cox regression for surgically-treated patients, adulthood (p = 0.004) and margin-positive resection (p = 0.03) were independently associated with an increased risk of mortality. Multimodal treatment including complete surgical resection and chemotherapy results in long-term survival in most children with UESL. However, adults with UESL have poorer long-term survival that may reflect differences in disease biology and an opportunity to further refine currently available treatment schemas.