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Background: Since November 2020, Italy was the first country to carry out a protocol and use liver from COVID‐19 donors. We aimed to evaluate the medium‐term outcome of patients who underwent liver transplant (LT) with those grafts. Methods: We consecutively enrolled 283 patients who underwent first LT from November 2020 to December 2022 in our Center (follow‐up 468 days). Twenty‐five of 283 (8.8%, study population) received a graft from donors with previous (4%) or active (96%) SARS‐CoV‐2 infection, and 258/283 (91.2%, control group) received a graft from COVID‐19‐negative donors. SARS‐CoV‐2‐RNA was tested on graft tissue of COVID‐19 donors and their recipients underwent weekly evaluation of SARS‐CoV‐2‐RNA in nasal swabs for the first month after LT. Results: One‐year and 2‐year patient survival was 88.5% and 88.5% in study group versus 94.5% and 93.5% in control group, respectively (p =.531). In study population there was no evidence of donor‐recipient virus transmission, but three (12%) patients (vs. 7 [2.7%] of control group, p =.048) developed hepatic artery thrombosis (HAT): they were SARS‐CoV‐2‐RNA negative at LT and 1/3 grafts tested SARS‐CoV‐2‐RNA positive on liver tissue. COVID‐19 donor was independently associated with HAT (odds ratio (OR) = 4.85, 95% confidence interval (CI) 1.10–19.15; p =.037). By comparing study population with control group, acute rejection and biliary complication rates were not significantly different (16% vs. 8.1%, p =.26; 16% vs. 16.3% p =.99, respectively). Conclusions: Our 1‐year results of transplant strategy including liver grafts from COVID‐19 donors were favorable. HAT was the only complication with significantly higher rate in patients transplanted with COVID‐19 donors compared with control group. [ABSTRACT FROM AUTHOR]

Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor for patients with homozygous familial hypercholesterolaemia. Due to its mechanism of action, potential hepatic effects of lomitapide are of clinical interest. This study aimed to determine the long‐term hepatic safety of lomitapide. Methods: Data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (median 5.1 years; serum total bilirubin, transaminases, cytokeratin‐18 [CK‐18] and enhanced liver fibrosis [ELF] score, fat‐soluble vitamins and essential fatty acids), 8‐year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) and real‐world evidence from a cohort of patients treated with lomitapide in Italy (hepatic elastography, and FIB‐4 score for hepatic fibrosis). Results: In the phase 3 trial and the LOWER registry, any asymptomatic excursions in liver transaminase levels were not associated with elevations in bilirubin, and no Hy's law cases were detected in up to 8 years follow‐up. There were no clinically relevant increases among hepatic biomarkers CK‐18, CK‐18 fragments or ELF score and fat‐soluble vitamins and essential fatty acids remained above normal levels. In 34 patients treated in Italy with lomita pide for more than 9 years, elevations in hepatic fat were mild‐to‐moderate; hepatic stiffness remained normal, and the mean FIB‐4 score remained below the fibrosis threshold value of 2.67. Conclusions: These data indicate that the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow‐up. Phase 3 trial: NCT00730236; extension phase: NCT00943306; LOWER: NCT02135705. [ABSTRACT FROM AUTHOR]

Objectives: Liver diseases have become a leading cause of death among people with AIDS (PWA). This study aimed to investigate whether PWA experienced excess mortality related to liver diseases as compared to the general population (non‐PWA), using a multiple cause of death (MCoD; i.e. all conditions reported on death certificates) approach. Methods: A population‐based, nationwide, retrospective cohort study was conducted among Italian people, aged 15–74 years, who had been diagnosed with AIDS since 2006. Date of death and MCoD data were retrieved, up to December 2015, by individual record linkage with national mortality data. Sex‐ and age‐standardized mortality ratios (SMRs), with 95% confidence intervals (CIs), were estimated by dividing the observed number of deaths related to a specific condition among PWA to the expected number, based on non‐PWA mortality rates. Results: Among 7912 PWA (34 184 person‐years), 2076 deaths occurred. The number of death certificates reporting liver diseases among MCoDs was 583 (28.1%), including 382 (18.4%) reporting viral hepatitis, 370 (17.8%) reporting nonviral liver diseases, and 41 (2.0%) reporting liver cancers. The corresponding SMRs were 40.4 (95% CI 37.2–43.8) for all liver diseases, 131.1 (95% CI 118.3–145.0) for viral hepatitis, 29.9 (95% CI 27.0–33.1) for nonviral liver diseases, and 11.2 (95% CI 8.1–15.3) for liver cancers. Particularly elevated SMRs emerged among PWA aged 15–49 years and those infected by injecting drug use. Conclusions: The high excess liver‐related mortality observed among PWA warrants preventive actions to limit the burden of viral hepatitis coinfections, alcohol abuse, and metabolic disorders, especially among younger PWA and injecting drug users. [ABSTRACT FROM AUTHOR]

Summary: Background: The Glu167Lys (E167K) transmembrane 6 superfamily member 2 (TM6SF2) variant has been associated with liver steatosis, high alanine transaminase (ALT) levels and reduced plasma levels of liver‐derived triglyceride‐rich lipoproteins. Objectives: The objectives of this study were to investigate in a group of obese children the association among the 167K allele of TM6SF2 gene and ALT, cholesterol and triglycerides levels, and hepatic steatosis, and to evaluate the potential interaction between this variant and the I148M patatin like phospholipase 3 gene (PNPLA3) polymorphism on liver enzymes. Methods: We genotyped 1010 obese children for TM6SF2 E167K and PNPLA3 I148M polymorphisms. Anthropometrical and biochemical data were collected. Ultrasound imaging of the liver was performed. Results: The 167K allele showed an association with steatosis (P < 0.0001), higher ALT levels (P < 0.001) and lower total cholesterol (P < 0.00001), low‐density lipoprotein cholesterol (P < 0.0001), triglycerides (P = 0.02) and non‐high‐density lipoprotein cholesterol levels (P < 0.000001). The subjects homozygous for the PNPLA3 148M allele carrying the rare variant of TM6SF2 showed an odds ratio of 12.2 (confidence interval 3.8–39.6, P = 0.000001) to present hypertransaminasaemia compared with the remaining patients. Conclusion: Although the TMS6SF2 E167K variant predisposes the obese children to non‐alcoholic fatty liver disease, there is an association between this variant and lower levels of cardiovascular risk factors. Overall, the data suggest differential effects of TMS6SF2 E167K variant on liver and heart health. [ABSTRACT FROM AUTHOR]