Objective: Transient elastography (TE) allows non-invasive evaluation of the severity of liver disease in patients with chronic hepatitis C. This procedure, however, warrants further validation in the setting of liver transplantation (LT), including patients under follow-up for recurrent hepatitis C. Setting: Tertiary referral hospital. Patients: 95 patients (75 males) transplanted for end-stage liver disease due to hepatitis C virus. Interventions: Paired liver biopsy (LB) and TE were carried out 6–156 (median, 35) months after LT. 40 patients with recurrent hepatitis C sequentially evaluated 6–21 months apart. Main outcome measures: Clinical, laboratory and graft histological features influencing TE results. Results: Median TE values were 7.6 kPa in the 90 patients with a successful TE examination, being 5.6 kPa in the 30 patients with Ishak fibrosis score (S) of 0–1, 7.6 kPa in the 38 with S2–3; 16.7 kPa in the 22 with S4–6, (p<0.0001). Areas under the ROC curves were 0.85 (95% CI, 0.76 to 0.92) for S⩾3, 0.90 (95% CI, 0.82 to 0.95) for S⩾4 with 7.9 and 11.9 kPa optimal TE cut-off (81% and 82% sensitivity, 88% and 94% negative predictive value, respectively). Fibrosis, necroinflammatory activity and higher than 200 IU/l gamma-glutamyl transpeptidase levels independently influenced TE results. During post-LT follow-up, TE results changed in parallel with grading (r = 0.63) and staging (r = 0.71), showing 86% sensitivity and 92% specificity in predicting staging increases. Conclusions: TE accurately predicts fibrosis progression in LT patients with recurrent hepatitis C, suggesting that protocol LB might be avoided in patients with improved or stable TE values during follow-up.

Fibrosis is the result of an overly abundant deposition of extracellular matrix (ECM) due to the fact of repetitive tissue injuries and/or dysregulation of the repair process. Fibrogenesis is a pathogenetic phenomenon which is involved in different chronic human diseases, accounting for a high burden of morbidity and mortality. Despite being triggered by different causative factors, fibrogenesis follows common pathways, the knowledge of which is, however, still unsatisfactory. This represents a significant limit for the development of effective antifibrotic drugs. In the present paper, we aimed to review the current evidence regarding the potential role played in fibrogenesis by growth arrest-specific 6 (Gas6) and its receptors Tyro3 protein tyrosine kinase (Tyro3), Axl receptor tyrosine kinase (Axl), and Mer tyrosine kinase protooncogene (MerTK) (TAM). Moreover, we aimed to review data about the pathogenetic role of this system in the development of different human diseases characterized by fibrosis. Finally, we aimed to explore the potential implications of these findings in diagnosis and treatment.

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Our aim was to describe the clinical course of patients with immunosuppressed autoimmune hepatitis (AIH) during coronavirus disease 2019 (COVID‐19) infection in Italy. Our study is a case series of patients with AIH treated with immunosuppression, who tested positive for SARS‐CoV‐2 in March 2020 during the outbreak of COVID‐19. Ten patients from seven different hospitals in Italy were diagnosed with COVID‐19 during the outbreak of SARS‐CoV‐2 in March 2020. Seven subjects were female (70%), and age ranged from 27 to 73 years. Before the onset of SARS‐CoV‐2 infection, all patients were taking immunosuppressive therapy for AIH, and eight of them were on biochemical remission. Two other patients had recent acute onset of their AIH, and consequently started high‐dose steroids, as per induction protocol. All patients had a respiratory syndrome and a positive nasal swab for SARS‐CoV‐2. Five patients developed a computed tomography–confirmed COVID‐19 pneumonia. Six subjects received a combination of antiretroviral and antimalarial drugs. In seven patients, the dosage of immunosuppressive medication was changed. Liver enzymes were repeated during SARS‐CoV‐2 infection in all hospitalized cases; they remained within the normal range in all cases, and improved in the two acute cases treated with high‐dose steroids. The clinical outcome was comparable to the reported cases occurring in non‐immunosuppressed subjects. Conclusion: Patients under immunosuppressive therapy for AIH developing COVID‐19 show a disease course presumptively similar to that reported in the non‐immunosuppressed population. These data might aid in medical decisions when dealing with SARS‐CoV‐2 infection in immunocompromised patients.