Purpose of review Living donor liver transplantation (LDLT) increasingly depends on biologically related donors, particularly in Asia and the Middle East, where deceased donation remains limited. This review evaluates genetic risks in living donors and proposes a system-based approach to donor selection. Recent findings Heterozygous carriers exhibit variable functional capacity determined by enzyme thresholds and epigenetic mechanisms such as X-chromosome lyonization. In ornithine transcarbamylase deficiency (OTCD), maternal donors may have insufficient enzymatic activity, resulting in donor risk and incomplete metabolic correction. Conversely, certain autosomal recessive disorders permit safe use of heterozygous donors within defined functional limits. In regions with high consanguinity, especially in parts of the Middle East, hereditary liver diseases are more prevalent, increasing the likelihood that potential donors share pathogenic variants. Additionally, reports of acute liver failure following gene therapy in Duchenne muscular dystrophy (DMD) highlight systemic vulnerability in genetically affected individuals. Summary Donor evaluation must extend beyond anatomical suitability to include disease-specific genetic risk assessment. A system-based, globally informed framework integrating genomics, functional assessment, and multidisciplinary oversight is essential to ensure donor safety and optimize outcomes.
PURPOSE OF REVIEW:The indications for liver transplantation have continued to evolve and now extend beyond elective transplantation for decompensated cirrhosis and emergency liver transplantation for acute liver failure (ALF), to patients who present with acute-on-chronic liver failure (ACLF), including those with severe alcoholic hepatitis. This review focuses on the pretransplant critical care aspects of ALF patients and on recent developments, as the ACLF syndrome was defined and early transplantation for alcohol-related hepatitis has entered practice in some countries. RECENT FINDINGS:ACLF severity, graded by the number of failing organs, predicts both waiting list and posttransplant mortality. The UK has introduced a national prioritization tier for selected critically ill patients with ACLF. High-volume plasma exchange improves transplant-free survival in ALF, with ongoing trials in ACLF. Artificial liver support and G-CSF have not shown survival benefit in randomized trials. Continuous renal replacement therapy lowers ammonia and is associated with reduced mortality in ALF. Early transplantation for steroid-nonresponsive severe alcohol-related hepatitis produces survival comparable to standard transplantation and is now delivered through structured programmes in some countries. SUMMARY:Pretransplant critical care focuses on extrahepatic organ support and maintaining transplant candidacy. Prognostic scores identify risk but do not by themselves determine futility, which is dynamic and selection-dependent.
PURPOSE OF REVIEW:Vascularized composite allotransplantation (VCA) restores form and function after disfiguring tissue loss with the required need for lifelong immunosuppression for a non-life-saving indication, creating a distinct risk-benefit ratio compared to other solid organ transplants. This review summarizes recent advances in VCA immunosuppression, with emphasis on strategies that reduce drug-related toxicity while preserving graft function. RECENT FINDINGS:Long-term cohort data continue to document substantial nephrotoxic, metabolic, infectious, and oncologic morbidity from tacrolimus-based triple therapy, with measurable decline in renal function within the first posttransplant year and tacrolimus exposure as the strongest correlate. Costimulation blockade has produced preclinical and early clinical efficacy, particularly belatacept combined with antithymocyte globulin induction to avoid the need for long-term use of calcineurin inhibitors. Next-generation anti-CD40 agents are positioned to overcome the thromboembolic toxicity that limited earlier anti-CD154 antibodies. Regulatory T-cell therapy and chimerism-based tolerance remain promising and investigational. SUMMARY:Tacrolimus-based triple therapy remains the clinical standard, with its concomitant nephrotoxicity requiring kidney transplantation after face and hand transplantation in some cases. Costimulation blockade-based, calcineurin inhibitor-sparing protocols represent an advanced path toward safer VCA immunosuppression.
PURPOSE OF REVIEW:Recent work has linked gut dysbiosis, an imbalance of commensal and pathogenic bacteria, to complications in kidney transplant recipients. The purpose of this review is to evaluate the gut microbiota's relationship to important complications in kidney transplantation. RECENT FINDINGS:In both allogeneic hematopoietic stem cell transplant and solid organ transplant recipients, gut dysbiosis has been linked to an increased risk of infections and higher mortality rates. In kidney transplant recipients, elevated intestinal uropathogen abundance is associated with development of urinary tract infection, and an imbalance between commensal and pathogenic bacteria has been linked to posttransplant diarrhea. SUMMARY:Gut dysbiosis with elevated abundance of pathogenic bacteria and decreased abundance of commensal bacteria is associated with urinary tract infections and posttransplant diarrhea in kidney transplantation.
PURPOSE OF REVIEW:The purpose of this review is to discuss common pain phenotypes in transplantation, summarize known gut microbiome features associated with chronic pain, and to map known gut microbiome features in transplantation with diagnosis-independent pain features. RECENT FINDINGS:Persistent pain is common across solid organ and hematopoietic stem cell transplantation, arises from diverse mechanisms, and often extends well beyond the perioperative period. Growing evidence supports the gut microbiome as a biologically plausible modulator of chronic pain across disease states, including transplantation. Alterations in microbial diversity, microbial metabolites, intestinal barrier integrity, and neuroimmune signaling have been linked to pain amplification and central sensitization across multiple chronic pain conditions. In transplant populations, exposure to immunosuppressive therapies, antibiotics, metabolic comorbidities, and other transplant-related stressors creates a unique environment for sustained microbiome disruption that may contribute to persistent symptom burden. SUMMARY:Collectively, these data highlight the importance to systematically assess and manage pain as a core transplant outcome rather than a secondary concern, and to highlight the potential role of the gut microbiome as a risk screening tool or a therapeutic target for pain interventions. Although mechanistic and observational data support biologic plausibility, transplant-specific microbiome-pain evidence remains preliminary and warrants longitudinal investigation.
