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De novo malignancy (DNM) is the primary cause of mortality after liver transplantation (LT) for alcohol-related liver disease (ALD). However, data on risk factors for DNM development after LT are limited, specifically in patients with ALD. Therefore, we retrospectively analyzed all patients transplanted for ALD at our center before October 2016. Patients with a post-LT follow-up of <12 months, DNM within 12 months after LT, patients not on tacrolimus in the 1st year post-LT, and unknown smoking habits were excluded. Tacrolimus drug exposure level (TDEL) was calculated by area under the curve of trough levels in the 1st year post-LT. 174 patients received tacrolimus of which 19 (10.9%) patients developed a DNM between 12 and 60 months post-LT. Multivariate cox regression analysis identified TDEL [HR: 1.710 (1.211-2.414); p = 0.002], age [1.158 (1.076-1.246); p < 0.001], number of pack years pre-LT [HR: 1.021 (1.004-1.038); p = 0.014] and active smoking at LT [HR: 3.056 (1.072-8.715); p = 0.037] as independent risk factors for DNM. Tacrolimus dose minimization in the 1st year after LT and smoking cessation before LT might lower DNM risk in patients transplanted for ALD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vanlerberghe, van Malenstein, Sainz-Barriga, Jochmans, Cassiman, Monbaliu, van der Merwe, Pirenne, Nevens and Verbeek.)

Background: Recently, the term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace non-alcoholic fatty liver disease (NAFLD). This concept enables diagnosing liver disease associated with metabolic dysfunction in patients with alcohol-related liver disease (ALD), a main indication for liver transplantation (LTx). We assessed MAFLD prevalence in ALD patients undergoing LTx and its prognostic value on post-LTx outcomes., Methods: We retrospectively analyzed all ALD patients transplanted at our center between 1990 and August 2020. MAFLD was diagnosed based on the presence or history of hepatic steatosis and a BMI > 25 or type II diabetes or ≥ 2 metabolic risk abnormalities at LTx. Overall survival and risk factors for recurrent liver and cardiovascular events were analyzed by Cox regression., Results: Of the 371 included patients transplanted for ALD, 255 (68.7%) had concomitant MAFLD at LTx. Median follow-up post-LTx was 72 months (IQR: 34.50-122). Patients with ALD-MAFLD were older at LTx (p = .001), more often male (p < .001) and more frequently had hepatocellular carcinoma (p < .001). No differences in perioperative mortality and overall survival were found. ALD-MAFLD patients had an increased risk of recurrent hepatic steatosis, irrespective of alcohol relapse, but no superimposed risk of cardiovascular events., Conclusions: The co-presence of MAFLD at LTx for ALD is associated with a distinct patient profile and is an independent risk factor for recurrent hepatic steatosis. The use of MAFLD criteria in ALD patients might increase awareness and treatment of specific hepatic and systemic metabolic abnormalities before and after LTx., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: The increasing rate of liver transplantation (LT) for nonalcoholic fatty liver disease (NAFLD) raises concerns on cardiovascular morbidity and mortality after LT in these patients., Methods: We collected variables regarding the presence of metabolic risk factors, NAFLD recurrence, cardiovascular morbidity, and overall survival at time of listing and after LT of 112 patients with NAFLD and a control group of 120 patients with hepatitis C (HCV)., Results: Metabolic syndrome and cardiovascular morbidity component rates (24.1% vs 12.5%) at the time of LT listing were higher in patients with NAFLD compared with patients with HCV (for all, P < .0390). Median follow-up after LT was 5.6 years in patients with NAFLD vs 13.5 years in patients with HCV (P = .0009). There was no difference in 6-weeks postoperative mortality (1.7% vs 2.5%) (P =1.0000). Metabolic syndrome components after LT were more frequent in patients with NAFLD than in patients with HCV (for all, P < .0008). The incidence of NAFLD 5 years after LT was higher in patients transplanted for NAFLD compared with HCV (43.5% vs 4.2%) (P < .0001). Patients with recurrent NAFLD more often had myocardial infarction compared with those without recurrence (8.3% vs 0%) (P = .0313). Five years after LT, cardiovascular morbidity was more frequent in the NAFLD group than in the HCV group (12.8% vs 9.3%) (P = .0256), whereas no difference in overall survival was observed., Conclusion: LT for NAFLD is associated with satisfactory 5-year outcomes; however, our data underscore the need for close monitoring and aggressive management of cardiovascular risk factors in these patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Donor hepatectomy and liver implantation time reduce long-term graft and patient survival after liver transplantation. It is not known whether these surgical times influence early outcomes after liver transplantation., Methods: This single-center study evaluated the effect of donor hepatectomy and implantation time on the risk of nonanastomotic biliary strictures (NAS) occurring within 1 year and of early allograft dysfunction (EAD) after deceased-donor solitary liver transplantation, adjusting for other donors, recipient, and surgical factors., Results: Of 917 transplants performed between January 2000 and December 2016, 106 (11.56%) developed NAS and 247 (27%) developed EAD. Donor hepatectomy time (median 35 min, IQR: 26-46) was an independent risk factor of NAS [adjusted hazard ratio, 1.19; 95% CI, 1.04-1.35; P = 0.01]. Implantation time (median 80 min, IQR: 69-95) was independently associated with EAD [adjusted odds ratio (OR), 1.15; 95% CI,1.07-1.23; P < 0.0001). The risk of EAD was increased by anastomosis time of both portal vein (adjusted OR, 1.26; 95% CI, 1.12-14.42; P = 0.0001) and hepatic artery (adjusted OR, 1.13; 95% CI, 1.04-1.22; P = 0.005). The magnitude of these effects was similar in donation after circulatory death liver grafts., Conclusions: Donor hepatectomy and implantation time negatively affect short-term outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Since 2005, a New Wilson Index (NWI) ≥11 is used as a predictor of death without transplantation in fulminant Wilson disease (WD). Plasma exchange is advocated as a new treatment modality., Methods: We present a patient with fulminant WD treated with plasma exchange. All published cases applying plasma exchange for fulminant WD were reviewed systematically., Results: A 14-year-old girl presented with hemolysis and fulminant liver failure. She had no encephalopathy; NWI was 14. As a bridge to transplantation plasma exchange was started immediately. Complete remission was achieved with plasma exchange and later chelation therapy with D-penicillamine. She is now at 3-year transplant-free survival. Literature review identified 37 patients presenting with fulminant WD and NWI ≥11 who were treated with plasma exchange. Seventeen of these patients (ie, 46%) recovered without transplantation., Conclusions: Multiple case reports and case series demonstrate transplant free survival after plasma exchange and subsequent chelation therapy, despite a NWI ≥11. Plasma exchange affects the clinical course and is a therapeutic option in children and young adults presenting with fulminant WD.

Little is known about nonsurgical risk factors for hepatic artery thrombosis (HAT) after liver transplantation (LT). We determined risk factors for HAT occurring within 90 days post-LT and analysed the effect of HAT on graft and patient survival. Donor and recipient demographics, surgery-related data and outcome in transplants complicated by thrombosis (HAT+) and their matched controls (HAT-) were compared. Risk factors were assessed by univariate logistic regression. Median (IQR) is given. A total of 25 HAT occurred among 1035 adult LT (1/1997-12/2014) and 50 controls were manually matched. Donor and recipient demographics were similar. Pre-LT trans-catheter arterial chemo-embolization (TACE) was more frequent in HAT+ (HAT+ 20% vs. HAT- 4%, P = 0.037). HAT+ had longer implantation [HAT+ 88 min (76-108) vs. HAT- 77 min (66-93), P = 0.028] and surgery times [HAT+ 6.25 h (5.18-7.47) vs. HAT- 5.25 h (4.33-6.5), P = 0.001]. Early graft dysfunction and sepsis were more frequent in HAT+ and hospitalization longer. TACE had the greatest odds ratio in unadjusted analysis (OR: 6, 95% CI: 1.07-33.53, P = 0.03). All but seven grafts were lost after HAT (HAT+ 72% vs. HAT- 36%, P = 0.003); however, patient survival was unaffected (HAT+ 79.8% vs. HAT- 76%, P = 0.75). LT candidates undergoing TACE are at risk of developing HAT early after transplant., (© 2017 Steunstichting ESOT.)

Liver failure is reported with increasing frequency in patients who underwent bariatric surgery for morbid obesity. In most cases, liver transplantation is the only possible treatment to avoid fatal outcome. Although most cases are observed after older bariatric surgery techniques characterized by high malabsorption rates, we report on a 38-year-old woman who developed liver failure seven months after long-limb gastric bypass., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objectives: The Z allele (Glu342Lys) in α1-antitrypsin (AAT) deficiency is a combined deficiency and dysfunctional allele. Carrying one Z allele induces a risk of a more aggressive evolution in patients with a chronic liver disease. As most of the carriers of Z allele do not have overt liver disease, it is likely that Z allele-containing livers have been used previously for liver transplantation. We analyzed the incidence, epidemiology, and clinical features of AAT accumulation in the hepatocytes after liver transplantation., Methods: Follow-up biopsies of liver transplant recipients were analyzed with periodic acid Schiff staining until 2006 (n=486); from 2006 on (n=303), all biopsies were stained with a specific monoclonal antibody against mutated AATZ protein. Genotyping of both recipient and donor was performed in the case of positive staining., Results: Of 789 liver transplantation patients, six patients (0.8%) showed mutated AATZ accumulation in the transplanted liver. Mutation analysis confirmed the presence of the Z allele in all donor organs including one transplanted organ with the SZ phenotype. There was a clear concordance between the isoelectrical focusing of the recipient AAT after transplantation and the genotype of the donor., Conclusion: Presumed healthy donor organs containing the Z allele were used for transplantation in 0.8% of cases in our series. As the presence of a Z allele is an independent risk factor of aggravation of chronic liver disease, AATZ accumulation in biopsies after liver transplantation should be actively looked for.

Obesity is a frequent complication following liver transplantation and is insufficiently responsive to dietary and life style advice. We studied the safety of orlistat treatment in obese and overweight liver transplant recipients (n = 15) on a stable tacrolimus-based immunosuppressive regimen. For safety reasons, the treatment period was restricted (6 months 120 mg t.i.d., 3 months 120 mg daily). Three patients dropped out, tacrolimus dose was adjusted in six of 12 remaining patients (dose reduction in 4, increase in 2, P = N.S.). All dose adjustments occurred during the 6 months of orlistat 120 mg t.i.d. therapy. No drug intolerance, adverse events or episodes of rejection occurred during the study. Efficacy of orlistat treatment in this population could not be shown, because a formal control population was not included in this safety trial. Moreover, only a significant decrease of waist circumference (P < 0.01 versus start of the study), but not of weight or body mass index, was achieved in the treated group. Orlistat treatment is well tolerated in liver transplant recipients and can be started safely, provided immunosuppressive drug levels and dietary adherence are closely monitored.

Background: We recently showed that human hepatic progenitor cells (HPCs) express muscarinic acetylcholine (Ach) receptor subtype 3 and that – following liver transplantation – HPC numbers are significantly reduced. To further elaborate on this, we examined whether HPC also express receptors for vasoactive intestinal peptide (VIP), which, besides Ach, also is an important parasympathetic neurotransmitter. VIP expressing nerves are known to be present in the liver. Methods: We performed immunohistochemistry for VIP receptor subtypes 1 and 2 (VIPR1 and 2), on sections of normal and diseased human liver ( n=17), and double staining for VIPR2 and known HPC markers. We performed RT-PCR for VIPR1 and 2 on total RNA from purified rat HPC. To document the probability of direct interaction, we also performed double immunostaining for nerve markers and HPC markers on human liver sections. Results: VIPR2 immunostaining was clearly positive in HPC and reactive bile ductules on paraffin-embedded and frozen tissue sections. We could not demonstrate VIPR1 protein expression in the liver, with either of two VIPR1 antibodies tested. The presence of VIPR2 mRNA in HPC was confirmed by RT-PCR. Nerve endings were shown to abut on reactive bile ductules. Conclusion: We show here for the first time that HPC express VIPR2 and receive nerve endings. These features, and the fact that HPC numbers are influenced by the presence or absence of the autonomic innervation of the liver, suggest a direct interaction. [ABSTRACT FROM AUTHOR]