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Background: Clinical trials have demonstrated the efficacy and safety of ustekinumab in Crohn's disease (CD). However, more data are necessary on the effectiveness of ustekinumab in bio-naïve patients in real-life studies., Objectives: The aim of our study was to evaluate the effectiveness and safety of ustekinumab in patients with CD refractory or intolerant to conventional therapy and without previous exposure to biological drugs., Design: We performed a nationwide, observational, retrospective, multicentre study including patients with CD, in which ustekinumab was used as the first biological drug., Methods: The corticosteroid-free clinical and biological response and remission were analysed at weeks 16, 24, 52 and 72. Clinical remission was defined as Harvey-Bradshaw index ⩽ 4 and biological remission as a faecal calprotectin (FC) <250 mg/g and C-reactive protein (CRP) <5 mg/L. Moreover, the persistence of the treatment and any adverse events were assessed., Results: In all, 84 patients were included in the study, males and females were equally distributed, with a median age of 63 years [interquartile range (IQR): 51-75] and a median disease duration of 6.8 years [IQR: 3.6-17.0]. The majority (86.9%) of patients were treated with ustekinumab as monotherapy, without concomitant immunosuppressive medication. The proportion of patients in corticosteroid-free clinical remission or response at weeks 16, 24, 52 and 72 was 93.3% (56/60), 86.8% (46/53), 82.2% (37/45) and 71.4% (30/42), respectively. CRP returned to normal values in 47.6%, 43.2%, 50% and 52.4% of patients at weeks 16, 24, 52 and 72, respectively. Similarly, FC was normalized in 45.5%, 45.5%, 48.6% and 50% of patients at weeks 16, 24, 52 and 72, respectively. The cumulative probability of remaining on ustekinumab treatment was 84.8% (95% confidence interval: 73.3-91.6) after 72 weeks. Ustekinumab was discontinued in 10 patients (11.9%) within 72 weeks of follow-up. Reasons for discontinuing treatment were lack of response ( n  = 4), adverse events ( n  = 4) and death ( n  = 2). There were no discontinuations because of stable remission., Conclusions: Ustekinumab was effective and safe in Spanish bio-naïve CD patients, showing a quicker and more durable response than obtained in patients with previous biological treatment. In this cohort of bio-naïve patients starting on ustekinumab, the average age was high., Plain Language Summary: Effectiveness and safety of ustekinumab in Crohn's disease patients not previously exposed to other biological therapies Evidence on the use of ustekinumab in biological naïve real-world patients is scarce. Here, we present real-world data evaluating the effectiveness and safety of ustekinumab in 84 bio-naïve patients from 17 Spanish hospitals. We report high rates of both clinical and biological remission. Moreover, after 1 year, 90.4% of patients remained being treated with ustekinumab. The safety profile of ustekinumab in these patient population was favourable. In conclusion, our results show that in patients with CD, ustekinumab could be considered as first-line therapy., Competing Interests: All the authors declare that have received fees for papers, consultancies, research, or other collaborations from the following laboratories: MSD, Abbvie, Pfizer, Takeda, Janssen, Galapagos, Kern Pharma, Amgen, Sandoz., (© The Author(s), 2023.)

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 < 0.001) and de-novo diabetes (OR, 2.79; P = 0.018), were predictive. Significant fibrosis (≥F2) was presented in 58-86%. The mean survival in NAFLD and control group was 166.3 and 173.6 months, respectively (P = 0 0.50)., Conclusion: De-novo NAFLD at fifth-year post-liver transplantation is frequently and associated with cardiovascular comorbidity. Male sex, obesity, de-novo diabetes and metabolic syndrome were factors associated with de-novo NAFLD. A significant proportion of patients had advanced fibrosis. This group trends toward worse patients' survival., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Inc.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)