Liver diseases—MASLD, HCC, viral hepatitis, cirrhosis—pose major global health challenges. Traditional diagnostics (biopsy, imaging, lab tests) suffer from sampling error, inter-observer variability, and limited sensitivity, delaying early detection and optimal treatment selection. Artificial Intelligence-AI (ML-Machine Learning / DL-Deep Learning) offers pattern recognition and predictive modeling that can revolutionize hepatology. We conducted a narrative scoping review (Jan 2020–Aug 2026) drawing on primary studies identified via PubMed, Scopus, and Google Scholar, together with existing peer-reviewed systematic reviews and meta-analyses that have already pooled quantitative performance data for specific AI-in-hepatology applications. Pooled deep-learning models for hepatocellular carcinoma detection on medical imaging achieve sensitivity of 89% (95% CI 87–91) and AUC of 0.95 (95% CI 0.93–0.97) across 30 pooled studies. AI-assisted detection of hepatic steatosis pools to sensitivity of 91% (95% CI 84–95) and AUC of 0.97. Pooled AUC for advanced liver fibrosis is 0.92 and for cirrhosis 0.85 (19 studies). In liver transplantation, ML models consistently outperformed legacy scoring systems (MELD, BAR, SOFT, DRI) in the studies reviewed; the strongest available pooled comparative evidence (9 studies, 18,771 transplants) reports an AUROC of 0.82 for the best model versus the BAR score, notably lower than best-case single-study claims elsewhere in the literature. AI-driven systems show genuine, meta-analytically supported promise for liver disease diagnostics and transplant prognostication, but heterogeneity in study design and validation practice currently limits direct comparison across algorithms. Priorities include standardized external validation, explainable AI, and prospective clinical trials.
Inborn errors of bile acid metabolism are rare causes of infantile cholestasis. They involve inherited deficiencies in enzymes responsible for catalyzing key reactions in the synthesis of primary bile acids.Bile acid synthesis defect (BASD) type 2 is a rare congenital autosomal recessive disease due to mutation in Aldo-keto reductase family 1 member D1 (AKR1D1) gene. If not diagnosed early and treated with bile acid replacement therapy, it can result in rapid progression to liver failure in infancy.There are only 2 published reported cases of BASD type 2 patients who underwent liver transplantation due to progressive chronic liver disease with decompensation.To our knowledge, this appears to be the first published report of an 8-month-old boy with BASD type 2, presenting as acute-on-chronic liver failure requiring emergency living donor liver transplantation. In this report we emphasize that emergency living donor liver transplantation is lifesaving as well as a disease curative option in carefully selected cases.
Background Combined heart–liver transplantation (CHLT) is an effective treatment for hereditary transthyretin amyloidosis (hATTR) with progressive cardiac involvement. The Phe53Leu variant, a rare TTR mutation, is frequently associated with early and severe cardiac involvement and may warrant consideration for CHLT. Case presentation A case of a 53-year-old male patient, presented with NYHA II heart failure and peripheral polyneuropathy. Cardiac MRI and 99mTc-MDP bone scintigraphy revealed extensive myocardial amyloid infiltration, and the diagnosis was confirmed by Congo red staining of a labial salivary gland biopsy and TTR gene sequencing (c.157T>C, p.Phe53Leu). CHLT was performed using a modified en-bloc technique that avoided division of the diaphragm, and the amyloidosis liver was used for domino transplantation in a patient with hepatocellular carcinoma. Total operative time was 8 hours, aortic cross-clamp time was 62 minutes and cardiac cold ischemia time was 75 minutes. The recipient was extubated at 17 hours without respiratory complications, and was discharged on postoperative day 29. Conclusion The uneventful perioperative course supports the feasibility of CHLT with the modified en-bloc technique in a centre with combined cardiac and hepatobiliary transplant expertise. To our best knowledge, this is the first reported CHLT for Phe53Leu hATTR performed in Vietnam and in Asia.
Immune monitoring after liver transplantation is expanding rapidly, but the clinical significance of an abnormal result often remains uncertain, particularly in recipients with stable graft function. Donor-specific antibody testing, donor-derived cell-free DNA, histology, and emerging molecular assays measure different aspects of alloimmune activity or graft injury, and none should be interpreted independently of the clinical context. We propose an indication-first approach that shifts immune monitoring from post hoc interpretation of abnormal results toward prospective test selection, in which the clinical question, anticipated management consequence, competing causes of graft injury, longitudinal testing strategy, and next diagnostic step are defined before testing is ordered. This framework distinguishes targeted diagnostic testing from routine surveillance and research-based monitoring, while emphasizing concordance among biomarkers, liver-test trends, imaging, histology, adherence, and other potential causes of injury. Abnormal biomarkers should not, in isolation, prompt treatment or intensification of immunosuppression; the response should be proportional to the strength and consistency of the available evidence. Prospective evaluation is needed to determine whether an indication-first strategy reduces low-value testing and unnecessary downstream interventions while preserving timely recognition of clinically consequential alloimmune injury. As immune-monitoring technologies become increasingly sensitive, their value will depend not simply on what they can detect, but on whether each test is connected to a defined clinical decision.
Alcohol-related liver disease (ARLD) is the leading indication for liver transplantation (LT) in the United States, yet access remains shaped by demographic, socioeconomic, and geographic factors. This study evaluates patient- and county-level factors associated with LT among patients with ARLD in Maryland. We conducted a retrospective analysis of statewide inpatient records from the Maryland Health Services Cost Review Commission (2013-2020) and mortality data from CDC WONDER. Patients with ARLD and LT recipients were identified using diagnosis and procedure codes. Adjusted odds ratios (aORs) for LT were estimated using hierarchical multivariable logistic regression incorporating patient demographics, county-level social vulnerability index (SVI) tertile, and travel distance to transplant centers. Among 28,053 patients with ARLD, 663 (2.4%) received LT. Black patients (aOR=0.43, 95% CI: 0.31-0.58) and Medicaid recipients (aOR=0.44, 95% CI: 0.35-0.56) had significantly lower odds of LT. Compared with patients aged 55-64 years, those aged 65-74 (aOR=0.56, 95% CI: 0.39-0.79) and 75 years or older (aOR=0.06, 95% CI: 0.015-0.25) were less likely to receive LT. County-level SVI tertile and travel distance were not independently associated with LT. Age, race, and insurance status were the characteristics most strongly associated with LT for ARLD in Maryland. Because transplantation was the only observable endpoint, and because clinical severity, transplant eligibility, and listing activity were not captured, these results cannot establish that non-clinical factors drive access, nor identify where along the transplant pipeline disparities arise. Future work should link administrative, registry, and referral data to determine where differences in transplant access emerge.
Intra-operative ultrasound (IOUS) is now a time-tested modality used in liver resections. This gives valuable surgical anatomy of hepatic artery, portal vein and space-occupying lesions of liver lobes which helps in completion of resections. But no information about biliary ductal anatomy is gained while performing conventional IOUS. We conceptualize that if we inject intrabiliary SonoVue a contrast used in contrast enhanced ultrasound (CEUS) and perform the IOUS we not only get vascular but also real time biliary anatomy and its relation to the segment(s) planned for resection. This will help better plan resection keeping biliary anatomy in view. This can mitigate biliary complications to a larger extent. We share our experience of intrabiliary CEUS during two cases of right anterior and right posterior sectianectomy. The intraoperative images obtained were corelating to MRCP and can be repeatedly reproduced in real-time intra operatively.
Recurrent bacteremia complicates the management of patients with decompensated cirrhosis awaiting liver transplantation (LT). We report a 37-year-old man with hepatitis B virus–related decompensated cirrhosis (Child–Pugh C, MELD 27) on the LT waiting list who had two episodes of Staphylococcus argenteus bacteremia. The first episode (October 2025) was managed as presumed uncomplicated bacteremia on clinical grounds: rapid defervescence, no vegetation on transthoracic echocardiography, absence of prosthetic material, and negative follow-up blood cultures on day 5. New but vague and poorly localised lumbar pain was noted; no contemporaneous lumbar MRI was obtained. Vancomycin was given for 14 days. Approximately four weeks after discharge the patient was readmitted (December 2025) with high fever and worsening lumbar pain; blood cultures again grew S. argenteus. Lumbar MRI demonstrated paraspinal soft-tissue oedema extending L1–S3, new compared with a pre-bacteremia baseline MRI from July 2025. Cefazolin was administered for 21 days guided by repeat susceptibility testing; the patient was discharged after documented blood-culture negativity. He remained active on the deceased-donor waiting list without a predefined infection-free interval; LT was performed on 27 March 2026 when a suitable organ became available. At more than four months after LT, the patient remained clinically well without recurrent bacteremia or other infectious complication. This case underscores that new musculoskeletal symptoms during bacteremia — even when vague — should prompt consideration of targeted imaging, and that recurrent bacteremia, once adequately controlled, need not preclude timely transplantation.
Introduction: Abdominal compartment syndrome (ACS) is an uncommon but potentially life-threatening complication after liver transplantation that may lead to graft hypoperfusion and multiorgan dysfunction. Prompt recognition and timely intervention are essential to prevent irreversible graft injury.Case presentation: We report the case of a 36-year-old woman who underwent liver retransplantation and developed abdominal distension, oliguria, and progressive hemodynamic deterioration within the first postoperative day. Doppler ultrasound demonstrated complete absence of portal venous flow without evidence of portal thrombosis or technical vascular complications. Intravesical pressure measurement revealed intra-abdominal hypertension (20mmHg), supporting the diagnosis of ACS-associated portal hypoperfusion. Decompressive laparotomy was performed, resulting in immediate restoration of portal flow and clinical improvement.Conclusion: ACS should be considered a potentially reversible cause of low portal flow in the immediate postoperative period after liver transplantation. Doppler ultrasound may be used as an extra tool to diagnose complications when ACS occurs post liver transplant.
Amanita phalloides poisoning is an uncommon cause of acute liver failure, although it is associated with high mortality in the absence of urgent liver transplantation. We report the case of a 53-year-old man who developed fulminant amatoxin-induced acute liver failure complicated by refractory shock, severe hyperlactatemia, and acute kidney injury requiring continuous renal replacement therapy and therapeutic plasma exchange. Despite rapid progression of coagulopathy and multiorgan failure, the patient remained free of hepatic encephalopathy throughout the pre-transplant period. Progressive clinical deterioration and fulfillment of specific prognostic criteria led to urgent liver transplantation. After a prolonged and complex ICU stay, the patient achieved graft recovery and survived to hospital discharge. This case highlights that the absence of encephalopathy does not exclude a fulminant course in Amanita phalloides poisoning and underscores the importance of early multiorgan support and timely transplant evaluation.
Prolonged preservation time is a major risk factor for graft dysfunction in liver transplantation, particularly when extended criteria donor (ECD) grafts are used. Hypothermic oxygenated machine perfusion (HOPE) has emerged as a promising preservation strategy for marginal grafts by improving mitochondrial function and limiting ischemia-reperfusion injury. We report 3 cases of liver transplantation performed using ECD grafts that had been declined by other transplant centers and arrived at our institution after prolonged static cold storage (SCS). In all cases, grafts underwent end-ischemic ex vivo HOPE before implantation. SCS time was 14, 13, and 11 hours, respectively, whereas HOPE time was 3, 6, and 5 hours, resulting in total preservation times of 17, 19, and 16 hours. All grafts were successfully transplanted, with satisfactory early graft recovery and no early allograft dysfunction or primary non-function. The recipients were discharged 15, 14, and 17 days after transplantation, respectively. At a median follow-up of 6 years, all recipients were alive with functioning grafts and without biliary complications, infectious complications, or HCC recurrence. These cases suggest that ex vivo HOPE may represent a useful post-conditioning strategy for selected ECD liver grafts exposed to prolonged preservation in challenging logistical settings.
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome associated with high mortality. We report a case of secondary HLH associated with herpes simplex virus type 2 (HSV-2) viremia in a 21-year-old postpartum woman who developed acute liver failure. The patient presented with fever, cytopenias, and extreme hyperferritinemia (>30,000 ng/mL). Bone marrow examination demonstrated prominent hemophagocytosis. Despite treatment with dexamethasone, intravenous immunoglobulin (IVIG), and acyclovir, she developed fulminant hepatic failure with severe coagulopathy and encephalopathy, requiring urgent liver transplantation. Postoperatively, she developed refractory shock due to polymicrobial sepsis and died. The explanted liver showed massive hemorrhagic necrosis. This case highlights the diagnostic challenges of HLH presenting as acute liver failure in the postpartum period, emphasizes the importance of early recognition of HSV infection, and illustrates the substantial risks associated with liver transplantation during active hyperinflammation.
Extended criteria donor (ECD) livers are increasingly used to mitigate organ shortage, yet they carry a higher risk of post-transplant complications. Normothermic machine perfusion (NMP) enables functional assessment, but current viability criteria cannot always distinguish transplantable from non-transplantable grafts. Here, we identify proteomic signatures and propose underlying mechanisms that determine ECD liver suitability during NMP. Using label-free shotgun proteomics, we analysed 72 perfusate samples collected during hypothermic oxygenated perfusion, controlled rewarming, and NMP of 24 human ECD livers. Non-transplanted grafts were consistently enriched in oxidative stress–related proteins, associated with disrupted glutathione metabolism and severe ischemia–reperfusion injury. In contrast, transplanted livers maintained balanced antioxidant responses and progressively upregulated functional and regenerative pathways. Oxidative stress proteins distinguished transplantable from non-transplantable grafts within 60 minutes of NMP (AUC≥0.94), while prolonged perfusion supported recovery in moderate livers. These findings propose a mechanistic basis for graft viability and demonstrate how oxidative stress and regeneration markers can refine organ assessment during machine perfusion.
During liver and combined liver-kidney transplantation, rapid and massive shifts in potassium levels can lead to serious complications, including malignant arrhythmias, severe myocardial depression, and catecholamine-refractory cardiogenic shock. In selected high-risk cases, extracorporeal life support with veno-arterial ECMO (VA-ECMO) combined with continuous renal replacement therapy (CRRT) is proposed as a preventive measure. A 5-year-old patient with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis underwent combined liver–kidney transplantation. Initial serum potassium was 6.2 mmol/L due to a previous infective peritoneal dialysis. During pre-anhepatic phase, despite optimal medical therapy, serum potassium reached 7.87 mmol/L. CRRT was instituted and potassium levels did not normalized, leading to a cardiac collapse, secondary to hyperkalemia socentral VA-ECMO was established to provide cardiac support, after a failed peripheral cannulation attempt due to deterioration of myocardial function leading to hemodynamic collapse refractory to inotropes. Although Custodiol (HTK) was used as the preservation solution, a new potassium peak was reached associated with ST segment elevations, ventricular arrhythmias, and global myocardial depression. During the remainder of the procedure, VA-ECMO therapy and CRRT were used to restore hemodynamic stability and potassium levels before intensive care unit (ICU) transport. ECMO was weaned postoperatively, and the patient was discharged with satisfactory graft function. Although the use of ECMO in liver transplantation is uncommon, early application allowed treatment of potentially life-threatening hyperkalemia with CRRT and preventing hemodynamic collapse.
Background Cold ischemia time (CIT) represents a pivotal, potentially modifiable determinant of ischemia–reperfusion injury (IRI) and early allograft dysfunction. Its influence is particularly pronounced in extended-criteria and older donor livers, yet the mechanistic links have not been examined in an age- and CIT-focused integrative manner. Objective To integrate clinical and experimental evidence to clarify how prolonged CIT amplifies IRI in the aged liver, to delineate convergent and interacting molecular pathways, and to summarize therapeutically actionable strategies with translational potential. Review Scope and Search Strategy To ensure transparency in this narrative review, a structured literature search was conducted across PubMed/MEDLINE and Web of Science from database inception to March 2026 for English-language publications. The search strategy utilized Boolean combinations of MeSH terms and keywords: (1) "liver transplantation", "hepatic transplantation", or "liver graft"; (2) "aging", "aged donor", "elderly donor", or "extended criteria donor" intersected with "cold ischemia time", "CIT", "ischemia-reperfusion injury", or "IRI"; and (3) "ferroptosis", "mitochondrial dysfunction", "endoplasmic reticulum stress", "ERS", "UPR", "machine perfusion", "HOPE", or "NMP". Inclusion and Exclusion Criteria Peer-reviewed original research was eligible if it investigated: (i) hepatic IRI in the context of donor aging or prolonged CIT; (ii) convergent ferroptosis, mitochondrial collapse, or ERS-UPR axes; or (iii) post-transplant outcomes (EAD, biliary complications, graft survival). Non-English papers, case reports (n < 5), conference abstracts, and pediatric-only studies or models were excluded. Data Integration Retrieved evidence was categorized into two complementary streams within this narrative framework: preclinical studies (in vitro and in vivo models) mapped molecular cross-talk and organelle interactions, while clinical registries and cohorts defined operational risk thresholds, collectively aligning molecular vulnerability with clinical risk stratification. The literature identification and screening process is summarized in a PRISMA-style flow diagram (Supplementary Fig. S1). Results Longer CIT is linked to higher early allograft dysfunction and worse short-term outcomes, with larger effects in older and other extended-criteria grafts. Prolonged CIT promotes lipid peroxidation and iron dysregulation with impaired antioxidant defenses (Nrf2–SLC7A11–GSH–GPX4), disrupts mitochondrial energetics and quality control with excess ROS and mitophagy imbalance, and sustains maladaptive ERS–UPR signaling. These pathways amplify each other, driving cell death, microcirculatory failure, and sterile inflammation. HOPE/NMP and solution optimization may reduce injury, whereas drugs and exosome adjuncts need translational validation. Conclusion Advanced donor age and prolonged CIT may interact as a mechanistic working hypothesis, aggravating IRI through an interconnected network involving ferroptosis, mitochondrial dysfunction, and maladaptive ERS–UPR signaling. The proposed age × CIT framework should be interpreted as a center-adapted risk-alert heuristic rather than a validated prediction, allocation, or graft-discard rule.
Right lobe grafts typically have a single hepatic artery, although arterial variations are not uncommon. We encountered a rare and complex hepatic arterial anatomy during procurement of a modified right lobe graft (MRLG), in which the right hepatic artery (RHA) arose from the proximal common hepatic artery (CHA) and bifurcated into the right anterior hepatic artery (RAHA) and right posterior hepatic artery (RPHA). The left hepatic artery (LHA) originated from the RAHA, while the middle hepatic artery (MHA) arose from the distal CHA. Preserving the LHA would have resulted in short (7–10 mm) and small-calibre (1 mm) arterial stumps of both the RAHA and RPHA, potentially compromising arterial reconstruction. Following completion of parenchymal transection and right hepatic duct division, the main portal vein and LHA were temporarily clamped. No ischaemic demarcation developed in the remnant liver, indicating adequate intrahepatic collateral arterial communication between the MHA and LHA. The LHA was therefore divided, and satisfactory pulsatile back-bleeding confirmed preserved arterial inflow to the remnant liver. This strategy provided the MRLG with a single RHA stump measuring 3 mm in diameter and 2.5 cm in length, facilitating a technically favourable arterial reconstruction. Both donor and recipient had uneventful postoperative recoveries. In selected LDLT donors with complex arterial anatomy, division of the LHA may be considered only when preoperative imaging demonstrates robust intrahepatic arterial communications with the MHA, intraoperative assessment confirms adequate remnant liver perfusion, and a contingency plan for arterial reconstruction is available.
Wilson disease is a genetic disorder of copper metabolism that is associated with a variety of clinical manifestations with hepatic and neuropsychiatric being the most relevant. Involvement of other organs is not uncommon and is attributed to copper accumulation and toxicity. Endocrine disorders have been sporadically reported including cases of hypoparathyroidism, hypopituitarism, gonadal abnormalities and metabolic bone disease. Several reports of hypoparathyroidism in children and young adults with hepatic and neurologic WD highlight the overlap between symptoms of hypoparathyroidism and neurologic symptoms of WD. Hypocalcemia in this context might be refractory to conventional supplementation requiring concomitant chelation therapy. Pituitary disorders can manifest as panhypopituitarism, hypothyroidism, secondary adrenal insufficiency or gonadal abnormalities. Pituitary MRI usually fails to show copper deposition, but these disorders may improve with chelation therapy. Menstrual cycle disorders, infertility and spontaneous abortions are more common in untreated or poorly controlled WD and may improve or resolve with chelation therapy. Hypogonadism can be the effect of cirrhosis in patients with hepatic WD. Metabolic bone disease also occurs largely in the context of cirrhosis. Recognizing such disorders might be challenging, as their clinical presentation may overlap with that of WD.
