No abstract

Since February 21 2020, when the Italian National Institute of Health (Istituto Superiore di Sanità–ISS) reported the first autochthonous case of infection, a dedicated surveillance system for SARS‐CoV‐2‐positive (COVID+) cases has been created in Italy. These data were cross‐referenced with those inside the Information Transplant System in order to assess the cumulative incidence (CI) and the outcome of SARS‐COV‐2 infection in solid organ transplant recipients (SOTRs) who are assumed to be most at risk. We compared our results with those of COVID+ nontransplanted patients (Non‐SOTRs) with follow‐up through September 30, 2020. The CI of SARS‐CoV‐2 infection in SOTRs was 1.02%, higher than in COVID+ Non‐SOTRs (0.4%, p < .05) with a greater risk in the Lombardy region (2.89%). The CI by type of organ transplant was higher for heart (CI 1.57%, incidence rate ratio [IRR] 1.36) and lower for liver (CI 0.63%, IRR 0.54). The 60‐day CI of mortality was 30.6%, twice as much that of COVID+ Non‐SOTRs (15.4%) with a 60‐day gender and age adjusted odds ratio (adjusted‐OR) of 3.83 for COVID+ SOTRs (95% confidence interval [3.03–4.85]). The lowest 60‐day adjusted‐OR was observed in liver SOTRs (OR 0.46, 95% confidence interval [0.25–0.86]). More detailed studies on disease management and evolution will be necessary in these patients at greater risk of COVID‐19.

Background. SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection. Methods.A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002 to March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID + subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56 304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n = 265, COVID + ) or absence (n = 56 039, COVID -) of SARS-CoV-2 infection. Results. The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/ transplanted patients (OR = 4.2; 95% CI, 3.7-4.7; P < 0.0001). HLA-DRB1*08 was more frequent in COVID + (9.7% and 5.2%: OR = 1.9, 95% CI, 1.2-3.1; P = 0.003; P c = 0.036). In COVID + patients, HLA-DRB1*08 was correlated to mortality (6.9% in living versus 17.5% in deceased: OR = 2.9, 95% CI, 1.15-7.21; P = 0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Finally, blood group A was more frequent in COVID + (45.5%) than COVIDpatients (39.0%; OR = 1.3; 95% CI, 1.02-1.66; P = 0.03). Conclusions. Although preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies.

COVID‐19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS‐CoV‐2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS‐CoV‐2‐RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS‐CoV‐2 infection were allowed to be considered for urgent‐need transplant candidates with active/resolved COVID‐19. We present the results of the first 10 LTs with active COVID‐19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post‐LT. None of the other eight recipients was found to be SARS‐CoV‐2 positive during follow‐up. IgG against SARS‐CoV‐2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID‐19. In addition, testing for SARS‐CoV‐2 RNA on donors’ liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID‐19 in informed candidates with SARS‐CoV‐2 immunity, might contribute to safely increase the donor pool.

Angelico and Trapani contributed equally for first authorship.

NAFLD/NASH is a sex‐dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex‐specific personalized therapies.

No abstract

Autoimmune liver diseases (AILDs) include autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. The etiologies of AILD are not well understood but appear to involve a combination of genetic and environmental factors. AILDs commonly affect young individuals and are characterized by a highly variable clinical course. These diseases significantly influence quality of life and can progress toward liver decompensation or the onset of hepatocellular or cholangiocarcinoma; a significant number of patients eventually progress to end-stage liver disease, requiring liver transplantation. In this review, we focus on the sex characteristics and peculiarities of AILD patients and highlight the relevance of a sex-specific analysis in future studies. Understanding the sex differences underlying AILD immune dysregulation may be critical for developing more effective treatments.