L Coletti

Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function.

We present the 12‐month results of a prospective trial of conversion from calcineurin inhibitors (CNI) to everolimus (EVL) in maintenance liver transplant (LT) recipients. Forty (M:F = 28:12; 54.9 ± 11 years) patients were enrolled at a mean interval of 45.5 ± 31.2 months from transplantation. Conversion was with EVL at a dosage of 0.75 mg b.i.d., withdrawal of antimetabolites, and a 50%‐per‐week reduction of CNI to a complete stop within 4 weeks. The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI, death, and graft loss. Indication to conversion was deteriorating renal function in 36 (90%). At 12 months, patient‐ and graft survival were 100% and the success rate was 75% (30/40). Ten patients (25%) were failures: four (10%) for acute rejection; three hepatitis C virus‐RNA positive patients (7.5%) for hypertransaminasemia; one (2.5%) for acute cholangitis; and two (5%) due to persistent pruritus and oral ulcers. In patients on EVL monotherapy, at 12 months the mean change of calculated creatinine clearance (cCrCl) was 4.03 ± 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl (P < 0.0001). Conversion from CNI to EVL is feasible in 75% of the cases and associated with improvement in renal function for patients with higher baseline cCrCl.

Use of Octogenarian Donors for Liver Transplantation: A Survival Analysis

Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long‐term results, especially for hepatitis C virus (HCV)‐positive recipients. This was a retrospective, single‐center review of primary, ABO‐compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60–69 years; 70–79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60–69 years; 233 (27.7%) with donors 70–79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60–69 years; 87.6% and 75.1% for grafts 70–79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5‐year graft survival was lower for HCV‐positive versus HCV‐negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.

Risk analysis of ischemic‐type biliary lesions after liver transplant using octogenarian donors

The use of octogenarian donors to increase the donor pool in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk of ischemic‐type biliary lesions (ITBL). The aim of this study was to investigate retrospectively the role of a number of different pre‐LT risk factors for ITBL in a selected population of recipients of octogenarian donor grafts. Between January 2003 and December 2013, 123 patients underwent transplantation at our institution with deceased donor grafts from donors of age ≥80 years. Patients were divided into 2 groups based on the presence of ITBL in the posttransplant course. Exclusion criteria were retransplantations, presence of vascular complications, and no availability of procurement liver biopsy. A total of 88 primary LTs were included, 73 (83.0%) with no posttransplant ITBLs and 15 (17.0%) with ITBLs. The median follow‐up after LT was 2.1 years (range, 0.7‐5.4 years). At multivariate analysis, donor hemodynamic instability (hazard ratio [HR], 7.6; P = 0.005), donor diabetes mellitus (HR, 9.5; P = 0.009), and donor age–Model for End‐Stage Liver Disease (HR, 1.0; P = 0.04) were risk factors for ITBL. Transplantation of liver grafts from donors of age ≥80 years is associated with a higher risk for ITBL. However, favorable results can be achieved with accurate donor selection. Donor hemodynamic instability, a donor history of diabetes mellitus, and allocation to higher Model for End‐Stage Liver Disease score recipient all increase the risk of ITBL and are associated with worse graft survival when octogenarian donors are used. Liver Transplantation 22 588‐598 2016 AASLD.

Treatment of antibody‐mediated rejection with high‐dose immunoglobulins in ABO‐incompatible liver transplant recipient

ABO‐incompatible liver transplantation (LT) entails high risk of antibody‐mediated rejection (AMR) and poor graft survival. Different treatment modalities have been reported, but none with use of a 2‐week course of high‐dose polyclonal i.v. immunoglobulins (IVIg) associated with plasmapheresis without the use of steroid pulses or monoclonal antibody. A 60‐year‐old male patient with blood‐group O, Caucasian, underwent urgent LT for acute liver failure after hepatectomy for HCV‐related hepatocellular carcinoma. He was grafted with a 66‐year‐old, blood‐group A, HCV‐positive liver graft. Pretransplant conditioning consisted of plasmapheresis and immunosuppression was triple with tacrolimus (TAC), steroids, and mycophenolate mofetil with anti‐IL2‐R monoclonal antibodies, plasmapheresis if hemagglutinin level >1:8, and extracorporeal photopheresis. After reduction of liver function tests to baseline, the patient presented a tenfold increase in alanine aminotransferases (ALT) levels 7 days post‐transplantation. AMR was confirmed on histology. Treatment consisted of IVIg (1.5 g/Kg/daily for the first 7 days, and 1 g/Kg/daily from day 8 to 14) with a 14‐day course of plasmapheresis. No side effect was observed and daily blood IgG levels ranged between 24.4 and 36.4 g/l. At the end of the scheduled course ALT returned to baseline. A control liver biopsy 55 days after LT showed no rejection and replacement of necrosis with fibrous strands. This case may support the role of high‐dose IVIg for treatment and/or prophylaxis of severe AMR.

Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related portal hypertension after liver transplantation.

Ghinolfi D, De Simone P, Catalano G, Petruccelli S, Coletti L, Carrai P, Marti J, Tincani G, Cicorelli A, Cioni R, Filipponi F. Transjugular intrahepatic portosystemic shunt for hepatitis C virus‐related portal hypertension after liver transplantation.

Quality assurance, efficiency indicators and cost‐utility of the evaluation workup for liver transplantation

We report the results of a retrospective review of the outpatient pretransplantation workup for United Network for Organ Sharing (UNOS) 3 patients adopted at a liver transplantation (LT) center and illustrate the efficiency indicators used for quality evaluation and cost‐analysis. A single‐center, pre‐LT evaluation workup was performed on an outpatient basis at a cost per patient evaluation of 2,770 Euros (€). Objective measures were: the number of patients admitted to and excluded from each phase of the algorithm; the rate of patients admitted to pre‐LT evaluation out of the total of referred patients (the referral efficiency rate); the rate of waitlisted patients out of those admitted to pre‐LT evaluation (the evaluation efficiency rate); the rate of waitlisted patients out of those referred for LT (the process efficiency rate); and the cost per waitlisted patient, as the ratio of the cost per patient evaluation to the evaluation efficiency rate. From January 1, 1996, to October 1, 2004, 1,837 patients were referred for LT on an outpatient basis. Based on preemptive evaluation of the available clinical data, 412 patients (22.4%) were excluded from pre‐LT evaluation and 1,425 (77.6%) were admitted to preliminary consultation. Among these, 603 (42.3%) were excluded from and 822 (57.7%) were admitted to pre‐LT evaluation with a referral efficiency rate of 44.7% (822 of 1,837). Out of the patients evaluated for LT, 484 were waitlisted with a cost‐utility and evaluation efficiency rate of 58.8% each (484 of 822). Of the 1,837 patients originally addressed for LT 484 were waitlisted, yielding a process efficiency rate of 26.3% (484 of 1,837) and a cost per waitlisted patient of €4,710.8. In conclusion, the 3 indicators allowed monitoring of the efficiency of the pre‐LT evaluation algorithm. The current process efficiency rate at our center is low (26.3%), but avoiding early referrals we might increase it to 31.6%, with a 12% net saving on costs per waitlisted patient (from €4,710.8 to €4,165.4). (Liver Transpl 2005;11:1080–1085.)

Safety and feasibility of electrochemotherapy in patients with unresectable colorectal liver metastases: A pilot study

BACKGROUND AND OBJECTIVES Electrochemotherapy is a novel ablation technique combining chemotherapeutic agents with reversible cell membrane electroporation. Previous experiences have shown its efficacy for cutaneous tumors. Its application for deep-seated malignancies is under investigation. We performed a prospective, pilot study to evaluate the feasibility, safety, and efficacy of intraoperative electrochemotherapy for otherwise unresectable colorectal liver metastases. METHODS Electrochemotherapy with bleomycin was combined with open liver resection and performed with linear or hexagonal needle electrodes according to an individualized pretreatment plan. The primary endpoints were: feasibility, as ratio of completed to planned treatments; safety, and efficacy, as per response assessed at 30 days with MRI and according to RECIST. The secondary endpoint was overall and progression-free survival at month 6. RESULTS A total of 9 colorectal liver metastases were treated in 5 patients with 20 electrode applications. No intraoperative complications were observed. At day 30, complete response was 55.5% and stable disease 45.5%. All (5) patients reached a 6 months overall survival, and 4 out of 5 patients had 6 months progression free survival. CONCLUSIONS Electrochemotherapy is a feasible and safe adjunct to open surgery for treatment of unresectable colorectal liver metastases. Larger studies and longer follow-ups are favored to better define its role in the treatment of secondary liver malignancies.

Everolimus-based immunosuppression in a case of ABO-incompatible liver transplantation with calcineurin inhibitor-related posterior occipital syndrome.

Dear Sirs, Owing to its high immunological risk, ABO-incompatible liver transplantation (LT) is usually performed with triple or quadruple calcineurin inhibitor (CNI)-based immunosuppression and association with nondrug immunological treatment modalities, such as plasmapheresis or splenectomy [1,2]. The use of preoperative rituximab has been recently reported in small series of living-related liver transplants too [3]. However, management of CNI-related complications may be challenging for the transplant physician due to the increased risk of graft rejection in case of CNI minimization or withdrawal. We report here an

Frequency and characteristics of diabetes in 300 pre-liver transplant patients.

the risk for future type 2 diabetes: results from the Botnia study. Diabetes Care 2009;32:281e6. [3] Priya M, Anjana RM, Chiwanga FS, Gokulakrishnan K, Deepa M, Mohan V. 1-hour venous plasma glucose and incident prediabetes and diabetes in Asian Indians. Diabetes Technol Ther 2013;15:497e502. [4] Alyass A, Almgren P, Akerlund M, Dushoff J, Isomaa B, Nilsson P, et al. Modelling of OGTT curve identifies 1 h plasma glucose level as a strong predictor of incident type 2 diabetes: results from two prospective cohorts. Diabetologia 2015;58:87e97. [5] Fiorentino TV, Marini MA, Andreozzi F, Arturi F, Succurro E, Perticone M, et al. One-hour post-load hyperglycemia is a stronger predictor of type 2 diabetes than impaired fasting glucose. J Clin Endocrinol Metab 2015;100:3744e51.

Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here, a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy, the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2, CK8, CK18, CEA (polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3, CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors (GISTs). The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here, we report the clinicopathological features of our case, along with a review of the few cases present in the literature.