Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: a scoping review protocol

Objective:; This scoping review aims at systematically mapping reported prognostic factors for spontaneous immunosuppression (IS) free allograft tolerance (operational tolerance, OT) in non-viral hepatitis and non-autoimmune disease liver transplant (LT) recipients who are undergoing immunosuppression withdrawal (ISW). The results may inform the subsequent conduct of a systematic review with a more specific review question.; Background:; LT is currently the most effective treatment for end-stage liver diseases. Whereas the short-term outcomes after LT have dramatically improved over the last decades, the long-term outcomes remain unsatisfactory, mainly because of side effects of lifelong IS, such as infections, cardiovascular diseases, malignancies, and nephrotoxicity. ISW studies have shown that OT can be achieved by a subset of LT recipients and recent research has identified biomarkers of OT in these patients. However, an evidence-based selection algorithm for patients that can predictably benefit from ISW is not available to date. The planned review will, therefore, map existing knowledge on prognostic clinical parameters and biomarkers for OT.; Inclusion criteria:; We will consider studies that record any clinical parameter or biomarker before the initiation of ISW in paediatric or adult non-viral hepatitis and non-autoimmune disease LT recipients and analyse their possible association with ISW outcomes (OT or non-tolerance). Studies addressing the effectiveness of OT-inducing treatments will be excluded.; Methods:; Embase, MEDLINE, and Cochrane Library will be searched for relevant articles or conference abstracts. Full-texts of selected abstracts will be independently screened for inclusion by two reviewers. References and citing articles of included records will be screened for additional relevant records. Clinical trial registries will be searched for ongoing studies, and their investigators contacted for the sharing of unpublished data. Data from included records will be independently extracted by two reviewers using a prespecified data extraction table and presented in both tabular and narrative form

The inhibition of complement system in formal and emerging indications: results from parallel one-stage pairwise and network meta-analyses of clinical trials and real-life data studies

Producción CientíficaThis manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common “off-label” (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs

Vaccin contre le zona: quelles recommandations en 2014?

Zostavax, a live attenuated vaccine against shingles (herpes zoster) has been available in Switzerland since 2008. In a population aged 60 and over, evidence suggests the vaccine effectively reduces the incidence of shingles and some of its corresponding complications. More importantly, in terms of public health, vaccination appears to reduce the burden of illness and be pharmaco-economically viable. Despite being part of the vaccination programmes in the United States and several European countries, the vaccine is not yet part of the Swiss vaccination programme. Should Switzerland follow suit by incorporating Zostavax into their vaccination policy

Immune-Mediated Liver Disease in the Transplanted Liver

Liver transplantation has evolved as the treatment of choice for many patients with end-stage liver disease. Currently, survival posttransplant is excellent, with 10-year survival exceeding 65%. Causes of graft failure include recurrent disease, in particular autoimmune disease, alcoholic liver disease, and NAFLD. Immune-mediated injury is also a cause for graft failure, but this cause has proved to be less common nowadays. With the actual range of potent immunosuppressive agents and a greater use of a tailored approach, rejection is seen less frequently. Rejection may take the form of T-cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), and plasma cell-rich hepatitis. On the opposite end of the spectrum, operational tolerance develops in a small proportion of liver transplant recipients. Finally, as indicated earlier, some autoimmune diseases can recur in the allograft

[Hepatopulmonary syndrome and portopulmonary hypertension].

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are two frequent pulmonary complications of liver disease. Portal hypertension is a key element in the pathogenesis of both disorders, which are however distinct in terms of pathogenesis, diagnosis and treatment. HPS corresponds to an abnormal arterial oxygenation in relation with the development of intrapulmonary vascular dilatations. POPH is a pulmonary arterial hypertension in the setting of portal hypertension and elevated pulmonary vascular resistance. As both diseases are associated with an increased risk of morbidity and mortality, it is important to screen and evaluate the severity of these two disorders particularly in liver transplant candidates