HCV-positive kidney transplant patients treated with direct-acting antivirals maintain stable medium-term graft function despite persistent reduction in tacrolimus trough levels

Background/aim: Direct-acting antivirals (DAAs) have improved the treatment of HCV-positive kidney transplant recipients (KTRs). However, their medium-term follow-up effects on graft function are conflicting. This study aimed to analyze how the interplay between DAAs, calcineurin inhibitors (CNI), and HCV eradication impacts 12-month kidney graft function.Methods: This double-center retrospective study with a prospective follow-up enrolled 35 KTRs with HCV treated with DAAs for 12 weeks. We compared three parameters: estimated glomerular filtration rate (eGFRI, 24-h proteinuria, and CNI trough levels at three time points: baseline, end of treatment (EOT), and 12 months later.Results: Kidney allograft function remained stable when comparing baseline and 12-month post-treatment values of eGFR (60.7 versus 57.8 ml/min; p = 0.28) and 24-h proteinuria (0.3 versus 0.2 g/24 h; p = 0.15), while tacrolimus (Tac) trough levels underwent a statistically significant decline 16.9 versus 5.4 ng/ml; p = 0.004). Using an ongoing triple Tac-based maintenance therapy as a conservative measure, a dose escalation of Tac was applied only in seven patients. No variation in CyA and mTOR levels was detected.Conclusion: DAA therapy is safe and effective in HCV-positive KTRs. It also produces a persistent significant reduction in Tac trough levels that does not influence graft function at 12 months

Age-Related Dietary Habits and Blood Biochemical Parameters in Patients with and without Steatosis—MICOL Cohort

Background: Steatosis is now the most common liver disease in the world, present in approximately 25% of the global population. The aim of this study was to study the association between food intake and liver disease and evaluate the differences in blood parameters in age classes and steatosic condition. Methods: The present study included 1483 participants assessed in the fourth recall of the MICOL study. Patients were subdivided by age (65 years) and administered a validated food frequency questionnaire (FFQ) with 28 food groups. Results: The prevalence of steatosis was 55.92% in the adult group and 55.88% in the elderly group. Overall, the results indicated many statistically significant blood parameters and dietary habits. Analysis of food choices with a machine learning algorithm revealed that in the adult group, olive oil, grains, processed meat, and sweets were associated with steatosis, while the elderly group preferred red meat, dairy, seafood, and fruiting vegetables. Furthermore, the latter ate less as compared with the adult group. Conclusions: Many differences were found between the two age groups, both in blood parameters and food intake. The random forest also revealed different foods predicted steatosis in the two groups. Future analysis will be useful to understand the molecular basis of these differences and how different food intake causes steatosis in people of different ages

IL-33 expands suppressive CD11b+ Gr-1int and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival

IL-33 administration is associated with facilitation of Th2 responses and cardioprotective properties in rodent models. However, in heart transplantation, the mechanism by which IL-33, signaling through ST2L (the membrane-bound form of ST2), promotes transplant survival is unclear. We report that IL-33 administration, while facilitating Th2 responses, also increases immunoregulatory myeloid cells and CD4(+) Foxp3(+) regulatory T cells (Tregs) in mice. IL-33 expands functional myeloid-derived suppressor cells, CD11b(+) cells that exhibit intermediate (int) levels of Gr-1 and potent T cell suppressive function. Furthermore, IL-33 administration causes an St2-dependent expansion of suppressive CD4(+) Foxp3(+) Tregs, including an ST2L(+) population. IL-33 monotherapy after fully allogeneic mouse heart transplantation resulted in significant graft prolongation associated with increased Th2-type responses and decreased systemic CD8(+) IFN-gamma(+) cells. Also, despite reducing overall CD3(+) cell infiltration of the graft, IL-33 administration markedly increased intragraft Foxp3(+) cells. Whereas control graft recipients displayed increases in systemic CD11b(+) Gr-1(hi) cells, IL-33-treated recipients exhibited increased CD11b(+) Gr-1(int) cells. Enhanced ST2 expression was observed in the myocardium and endothelium of rejecting allografts, however the therapeutic effect of IL-33 required recipient St2 expression and was dependent on Tregs. These findings reveal a new immunoregulatory property of IL-33. Specifically, in addition to supporting Th2 responses, IL-33 facilitates regulatory cells, particularly functional CD4(+) Foxp3(+) Tregs that underlie IL-33-mediated cardiac allograft survival

Development and validation of a scoring system to predict response to obeticholic acid in primary biliary cholangitis

Background & aims: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. Methods: We used data from the Italian RECAPITULATE (N 441) and the IBER-PBC (N 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS), or also after 6 months of treatment (ORS+). Multivariable Cox's regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (ALP/ULN<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or NORMAL RANGE criteria (NR: normal ALP, ALT and bilirubin) up to 24 months. Results: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were of 0.75, 0.78 and 0.72 for POISE, ALP/ULN<1.67 and NR response, which raised to 0.83, 0.88, 0.81 with ORS+, respectively. The respective performances in validation were of 0.70, 0.72 and 0.71 for ORS, and 0.80, 0.84, 0.78 for ORS+. Results were consistent across groups with mild/severe disease. Conclusions: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC