Neoplastic disease after liver transplantation: Focus on de novo neoplasms.

De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma (HCC) recurrence have been reported with the use of mTOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs mTOR-inhibitor-free immunosuppression is more efficacious in reducing HCC recurrence.

Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review.

Calcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased risk of post-transplant hepatocellular carcinoma (HCC) recurrence. The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. In the present systematic review, the association between mTORi and HCC recurrence after liver transplantation (LT) was evaluated and compared against that of CNIs-treated patients. In total, 3666 HCC liver transplant recipients from 42 studies met the inclusion criteria. Patients under CNIs developed HCC recurrence significantly more frequently, compared with patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although patients treated with CNIs had a higher proportion of HCC within Milan criteria (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi-treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus had significantly lower recurrence rates of HCC, compared with those on sirolimus or CNIs (4.1% vs. 10.5% vs. 13.8%, respectively, P < 0.05), but everolimus-treated recipients had shorter follow-up period (13 vs. 30 vs. 43.2 months, respectively) and more frequently been transplanted for HCC within Milan criteria (84% vs. 60.5% vs. 74%, respectively, P < 0.05). Our findings favor the use of mTORi instead of CNIs to control HCC recurrence after LT, but comparative studies with longer follow-up are needed for final conclusions.

Whole blood rotation thromboelastometry (ROTEM®) profiles in subjects with non-neoplastic portal vein thrombosis.

The coagulation pattern and the determinants of portal vein thrombosis (PVT), both in patients with and without cirrhosis, are still largely unknown. The aim of this study was to evaluate whole blood thromboelastometry profile, performed by ROTEM®, of both cirrhotic and non-cirrhotic subjects with PVT. Two different groups were considered: i) 14 non-cirrhotic PVT patients, ii) 35 cirrhotic patients with PVT. Controls were sex- and age-matched healthy volunteers and cirrhotic subjects without PVT, respectively. ROTEM® assays (i.e. INTEM, EXTEM, NATEM, and FIBTEM) and traditional coagulative parameters (i.e. platelet count, PT/INR, aPTT, and fibrinogen) were performed on blood samples from each subject. There were no significant differences in ROTEM® profile, as for INTEM, EXTEM, and NATEM assays, and in traditional coagulative parameters, between PVT patients, both with and without cirrhosis, and control groups. Interestingly, Maximum Clot Firmness (MCF) in FIBTEM was significantly higher in non-cirrhotic PVT patients (19 mm) than in healthy volunteers (11 mm, p<0.05). The amplitude of MCF in FIBTEM revealed to be a useful tool to discriminate non-cirrhotic subjects with PVT from those without thrombotic events. Larger prospective studies are needed to evaluate the relevance of the association between the alterations of ROTEM® profiles and PVT in cirrhotic patients.

Who fares worse after liver transplantation? Impact of donor and recipient variables on outcome: data from a prospective study.

BACKGROUND: Numerous donor and recipient risk factors influence survival after liver transplantation (LT). METHODS: The aim of this study was to prospectively evaluate the effect of donor and recipient variables on 12-month patient and graft survival after LT. Five hundred forty-six patients underwent LT in a single center (2000-2010). RESULTS: Bilirubin (P=0.006) and cold ischemia time (P=0.002) were predictive of graft loss at 12 months after LT. Model for End-Stage Liver Disease score ≥25 was associated with a lower 12-month graft survival than Model for End-Stage Liver Disease score <15 (P=0.02). Hepatitis C virus (HCV)-positive patients showed a lower survival than HCV-negative patients 12 months after LT (P=0.04), with serum sodium concentration (P=0.01) predictive for graft survival. Donor age demonstrated a trend of prediction (P=0.05) for HCV-positive patient survival. In hepatocellular carcinoma patients, donor age (P=0.02 and 0.02) and use of partial graft (P=0.01 and 0.02) were predictive of patient and graft survival at 12 months after LT. CONCLUSIONS: Bilirubin and cold ischemia time are crucial for graft outcome post-LT. Survival in HCV-positive patients is lower than in HCV-negative recipients. Donor age and partial graft use are predictive of patient and graft survival in hepatocellular carcinoma patients.

Management of nonneoplastic portal vein thrombosis in the setting of liver transplantation: a systematic review.

BACKGROUND: Nonneoplastic portal vein thrombosis (PVT) is frequent in patients with cirrhosis who undergo liver transplantation (LT); however, data on its impact on outcome and strategies of management are sparse. METHODS: A systematic review of the literature was performed by analyzing studies that report on PVT in LT recipients and were published between January 1986 and January 2012. RESULTS: Of 25,753 liver transplants, 2004 were performed in patients with PVT (7.78%), and approximately half presented complete thrombosis. Thrombectomy/thromboendovenectomy was employed in 75% of patients; other techniques included venous graft interposition and portocaval hemitransposition. Overall, the presence of PVT significantly increased 30-day (10.5%) and 1-year (18.8%) post-LT mortality when compared to patients without PVT (7.7% and 15.4%, respectively). However, only complete PVT accounted for this increased mortality. Rethrombosis occurred in up to 13% of patients with complete PVT and in whom no preventative strategies were used, and was associated with increased morbidity and mortality. CONCLUSIONS: PVT is common in patients with cirrhosis undergoing LT, and it affects survival when it is complete, at least in the short term after transplant. Therefore, screening for this condition is essential, alongside adequate treatment strategies to attempt repermeation of the PV and prevent thrombosis extension.