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Ischemia reperfusion injury (IRI) on postreperfusion biopsies is associated with worse outcomes after liver transplantation, although the influence on biliary complications (BC) remains poorly studied. Therefore, the primary aim of our study was to assess the influence of IRI on the incidence of BC. A secondary aim was to assess the influence of steatosis on biliary complications and determine factors that predictor BC.We report a retrospective cohort study including patients with liver transplantation and postreperfusion injury. Biopsies were classified as relevant and nonrelevant ischemia reperfusion injury for assessment of BC. BC included anastomotic stricture, ischemic cholangiopathy, leaks, and bilomas. Independent predictive factors of biliary complications were assessed using univariate and multivariate analyses.302 patients were included, and 125 patients fulfilled the criteria for relevant IRI (41.4%). Worse IRI was not associated with biliary complications (42.5% vs 40.1%; P = .68), nor was liver graft steatosis associated with BC (40.5% vs 41.5%, P = .95). The median time until biliary complications did not differ between the 2 groups (2 months; interquartile range = 1-15 vs 3 months; interquartile range = 1-12.5; P = .18). Hepatic artery thrombosis (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.4-8.2; P = .004), older donor age (OR = 2.1; 95% CI, 1.1-4.1; P = .024), and prolonged cold ischemia time (OR = 1.9; 95% CI, 1.1-3.2) were independent factors of biliary complications.Severe IRI on the postreperfusion injury does not predict development of biliary complications.

We present an uncommon cause of liver transplant in a patient with a particular personal situation, who suffered loss of follow-up during his antitubercular treatment. He presented a dress syndrome with fulminant liver failure that required a liver transplant. This case demonstrates the importance of close monitoring of liver function during this treatment.

Background Immunosuppressive calcineurin inhibitors have been associated with an increased risk of post-transplant malignancies. The mammalian target of rapamycin inhibitors (mTORi) is an alternative immunosuppressive regimen with an antineoplastic effect. The aim of the study was to determine the long-term survival of mTORi-treated recipients with de novo or recurring tumors after liver transplantation (LT). Methods This retrospective analysis included mTORi-treated LT recipients between March 2013 and March 2019. We analyzed long-term survival and mTORi indications in an oncology setting in patients with de novo and recurrent malignancies after LT. Overall survival (OS) rate was compared from the Spanish Liver Transplant Registry (SLTR) data using the Kaplan-Meier method. High-risk hepatocellular carcinoma (HCC) was defined as microvascular invasion or satellite lesions as described in the liver explant. Results A total of 237 patients underwent LT during the study period; 111 patients underwent mTORi-based immunosuppression (48%, cancer was the main indication): 24.5% high-risk HCC; 24.4% HCC recurrence; 14.3% cholangiocarcinoma; and 36.7% de novo malignancies. The 1- and 5-year OS rates after LT in the mTORi group were 83% and 65%, respectively (SLTR group, 85% and 72.6%, respectively); 30.6% patients received mTORi monotherapy, and 38.7% patients had an early switch to mTORi in the first 3 months after oncologic diagnosis. mTORi monotherapy or oncologic treatment strategies had a nonsignificant association with prognosis. The OS rate was higher when the mTORi switch occurred early, 83% and 67%, respectively. Conclusions mTORi-based immunosuppression may be a preferred option in patients transplanted with tumors. The OS rate was comparable to data from the SLTR. An mTORi early switch improves OS rate.

DRESS syndrome is a multisystem disorder that appears in the context of an adverse drug reaction, characterized by fever, rash and peripheral eosinophilia with involvement of other organs such as the liver. The typical liver involvement is acute toxic hepatitis (DILI), showing improvement and a tendency to resolution when corticotherapy is started. We must not forget this manifestation in the clinical context of a DRESS syndrome.

BACKGROUND: Postreperfusion liver biopsy (PRB) can assess the degree of ischemia/reperfusion injury (IRI) after orthotopic liver transplantation (OLT). The influence of IRI on graft outcomes and overall survival is controversial. AIM: To determine the correlation between the severity of IRI in PRB and overall graft and patient survival and, secondarily, to identify factors on PRB that predict poor graft outcomes. METHODS: This is a retrospective analysis of all patients who underwent OLT using donation after brain death (DBD) with PRB. The severity of IRI in PRB was graded. Predictors of IRI were assessed using univariate and multivariate analysis and the Kaplan–Meier with log rank test for the graft and overall survival, respectively. RESULTS: We included 280 OLTs (64.7%). The histopathological assessment of IRI severity was as follows: no IRI (N = 96, 34.3%), mild IRI (N = 65; 23.2%), moderate IRI (N = 101; 36.1%), and severe IRI (N = 18; 6.4%). The incidence rates of initial good graft function (IGGF), primary nonfunction and early allograft dysfunction (EAD) were 32.5%, 3.9%, and 18.6%, respectively. Severe IRI was associated with a lower incidence of IGGF (OR: 0.34, 95% CI 0.12–0.92; P = 0.03). Patients with severe IRI tended to have a higher incidence of EAD (33.2% vs. 18.6, P = 0.23). The cold ischemia time was an independent predictor of severe IRI on the multivariate analysis. Severe IRI was associated with poor 1- and 5-year overall survival rates (67% and 44%, respectively, compared with 84 and 68% in nonsevere IRI). Patients with severe IRI exhibited worse graft and overall survival. CONCLUSIONS: Cold ischemia time predicts the development of severe IRI. Patients with severe IRI show worse graft and overall survival and a lower incidence of IGGF, suggesting that histopathological findings could be useful for identifying patients at high risk of worse outcomes after OLT.

Background A rare but life-threatening cause of pancytopenia after liver transplantation is hemophagocytic syndrome. We present a 48-year-old woman who underwent liver transplantation and developed a hemophagocytic syndrome secondary to Epstein-Barr virus with a fatal course, despite initial treatment with immunosuppressants. The diagnosis was made based on the bone marrow aspiration, in which macrophages with phagocytic activity were observed, and clinical findings. Due to the very poor outcomes and high mortality, in patients with severe pancytopenia hemophagocytic syndrome should be excluded, and a bone marrow aspiration should be considered.

Background & aims The evidence suggests that most vulnerable subjects to COVID-19 infection suffer from patients with comorbidities or immunosuppression, including liver transplant recipients. Liver graft dysfunction may be a rare complication. Some patients complain about the post-COVID-19 syndrome. The aim of this study was to assess medium- and short-term outcomes in liver transplant patients. Patients and methods A retrospective case series was performed at a tertiary referral center. We screened 845 patients who had liver transplant (LT) in our center. All consecutive LT patients with COVID-19 during the Spanish outbreak from March 2020 to April 2021 were included. Demographics, pre-existing comorbidities, clinical and radiological data of COVID-19 infection, complications, and liver graft function were assessed at diagnosis and 3-month follow-up. Results Overall, 20 LT patients were diagnosed with confirmed COVID-19. We included 16 patients that met the inclusion criteria, 8 nonhospitalized (50%) and 8 (50%) hospitalized patients were analyzed. The median follow-up was 5.33 months (IQR 3.06–8.26). One patient died during the follow-up. All patients presented some grade of respiratory or functional symptoms. Dyspnea and fatigue were the most prevalent symptoms during the 3-month follow-up. No liver graft dysfunction were reported despite of partial immunosuppression withdrawal in four patients (25%). One patient had cardiovascular complications. Conclusions Our results suggest the presence of post-COVID-19 syndrome with mild residual physical and psychological dysfunction in this subgroup of patients at 3 months after COVID-19. However, no cases of loss or liver graft dysfunction were reported.

BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver transplantation and identify predictive risk factors. METHODS This was a retrospective analysis of de-novo-NAFLD at 5-year post-liver transplantation. NAFLD was defined as the radiological evidence of steatosis. Data from transplanted patients between November 2001 and May 2014 were collected. Noninvasive fibrosis scores were calculated. Predictors of de-novo NAFLD and survival were assessed by multivariate analyses and Kaplan-Meier method. RESULTS A total of 252 liver transplantations were evaluated after applying exclusion criteria, (78.6% men) with 54.9 years old (SD ± 9.5). Prevalence of de-novo NAFLD at 5-year post-liver transplantation was 36.1%. Cardiovascular events were presented in 19.88% and 23.08% of non-NAFLD and NAFLD patients, (P = 0.58). On multivariate analysis, male sex (OR, 5.40; P = 0.001), obesity (OR, 3.72; P = 0.017), metabolic syndrome (OR, 4.69; P

Background Cirrhosis as a result of alcohol-related liver disease is one of the most common indications for liver transplantation (LT) in Spain. Patients presenting for LT should be checked for alcohol abuse in clinical interviews and use of laboratory tests to confirm abstinence. The ethyl-glucuronide (EtG) test is very sensitive and can be positive in urine up to 5 days after consumption. Our main objective is to know the rate of alcohol abstinence by using the urine EtG test in patients evaluated for LT and to assess its correlation with the clinical interviews and laboratory test. Methods We conducted a prospective analysis of the results of the EtG in urine of patients evaluated for LT from January 2017 to March 2019 and its correlation with the medical and psychiatric interviews and with the laboratory test. Results We included 160 patients who were referred to LT evaluation. Among all cases, 84.1% were men, with an average age of 57.8 years. Alcohol-related liver disease was the most frequent cause (64.1%). Urine-EtG was positive in 10 patients (6.2%), 9 of them in patients with ALD and 1 in a patient with hepatitis C virus. The alcohol consumption was recognized by 80% of the patients in the clinical interview. Cases with positive EtG had higher levels of analytical parameters than those with a negative test. Conclusions In our series, 6.2% of patients referred for LT evaluation had recently consumed alcohol. The determination of EtG in urine is probably an effective and objective technique in the detection of alcohol consumption to ensure abstinence in the LT candidates.

Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment.Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients.A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (N = 83), risperidone (N = 12), quetiapine (N = 46), and ziprasidone (N = 50). At intake, 180 patients were antipsychotic naïve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score ≥60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score ≥60 and only 16.6 % who had a FLI score30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score ≥60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score ≥ 60, 91.7 %; FLI 60, 55.9 %; p 0.001), increased triglyceride levels (FLI score ≥ 60, 54.2 %; FLI 60, 5.6 %; p 0.001), decreased HDL levels (FLI score ≥ 60, 41.7 %; FLI 60, 17.5 %; p = 0.001), hypertension (FLI score ≥ 60, 19.5 %; FLI 60, 4.5 %; p = 0.002), and waist circumference increase (steatosis 68.8 %; FLI 60, 14.0 %; p 0.001).Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.

Current evidence suggests that gut dysbiosis drives obesity and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Toll-like receptor 2 (TLR2) and TLR6 specifically recognize components of Gram-positive bacteria. Despite the potential implications of TLR2 in NAFLD pathogenesis, the role of TLR6 has not been addressed. Our aim is to study a potential role of TLR6 in obesity-related NAFLD. Forty morbidly obese patients undergoing bariatric surgery were prospectively studied. Cell surface expression of TLR2 and TLR6 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated monocytes were cultured with specific TLR2/TLR6 agonists and intracellular production of cytokines was determined by flow-cytometry. In liver biopsies, the expression of TLR2 and TLR6 was analyzed by immunohistochemistry and cytokine gene expression using RT-qPCR. TLR6 expression in PBMCs from non-alcoholic steatohepatitis (NASH) patients was significantly higher when compared to those from simple steatosis. The production of pro-inflammatory cytokines in response to TLR2/TLR6 stimulation was also significantly higher in patients with lobular inflammation. Hepatocyte expression of TLR6 but not that of TLR2 was increased in NAFLD patients compared to normal liver histology. Deregulated expression and activity of peripheral TLR6 in morbidly obese patients can mirror the liver inflammatory events that are well known drivers of obesity-related NASH pathogenesis. Moreover, TLR6 is also significantly overexpressed in the hepatocytes of NAFLD patients compared to their normal counterparts. Thus, deregulated TLR6 expression may potentiate TLR2-mediated liver inflammation in NAFLD pathogenesis, and also serve as a potential peripheral biomarker of obesity-related NASH.