Trending Topics in Gastroenterology | GastroAGI

Post-Transplant Liver Assessment: Liver Transplantation | April 2026

Introduction Liver transplantation has dramatically improved survival in patients with end-stage liver disease and hepatocellular carcinoma. However, long-term outcomes are often compromised by complications such as graft rejection, recurrent disease, or de novo liver pathology leading to fibrosis and cirrhosis. Traditionally, monitoring relies on invasive methods like liver biopsy, but increasing attention is being given to Non-invasive tests as safer alternatives. Problem Statement The role and optimal application of non-invasive tests in post-transplant liver assessment remain unclear and are not yet standardized in routine clinical practice. Summary This review emphasizes the emerging role of non-invasive tests in monitoring liver graft health after transplantation. NITs—including tools for assessing fibrosis, steatosis, and portal hypertension—have already transformed management in native liver disease, but their translation into the post-transplant setting is still evolving. The authors highlight that NITs can potentially detect early graft dysfunction, reducing the need for repeated biopsies and enabling closer, safer monitoring. However, interpretation in the transplant setting is more complex due to factors such as immunosuppression, vascular changes, and mixed etiologies of graft injury. A key takeaway is the need for contextual interpretation—NIT results should not be used in isolation but integrated with clinical, biochemical, and imaging data. Despite current limitations, NITs offer a promising pathway toward personalized, longitudinal graft surveillance, allowing earlier intervention and improved long-term outcomes. Overall, this review supports a gradual shift from invasive to non-invasive monitoring strategies in post-transplant care, while emphasizing the need for further validation and standardized protocols.

Hepatic Hypoxia in Donation After Circulatory Death (DCD): Liver Transplantation | February 2026

Introduction Donation after circulatory death (DCD) has emerged as an important strategy to expand the donor pool in liver transplantation. However, compared to brain-dead donors, DCD grafts are more vulnerable to hypoxic injury due to unavoidable periods of warm ischemia. A key concept is donor warm ischemic time (dWIT), particularly the functional dWIT, during which hepatic oxygen delivery becomes critically compromised. The liver has remarkable autoregulatory mechanisms—primarily the hepatic arterial buffer response and high oxygen extraction capacity—but these mechanisms fail beyond certain thresholds of hypoperfusion and hypoxia. This results in ischemia-reperfusion injury (IRI), the central driver of graft dysfunction and complications after transplantation. Problem Statement Despite increasing use of DCD grafts, there is poor understanding of the exact physiological thresholds of hepatic hypoxia and the lack of standardized definitions of functional warm ischemia time, leading to variability in graft selection, discard rates, and clinical outcomes. Summary This review provides a mechanistic framework linking hepatic physiology to DCD outcomes. The liver receives dual blood supply—75% from the portal vein and 25% from the hepatic artery—with intrinsic autoregulation maintaining oxygenation even with reduced flow. However, during DCD, progressive hypotension and hypoxemia eventually overwhelm these compensatory mechanisms. Functional dWIT—when oxygen delivery falls below critical thresholds—is the most relevant determinant of graft injury, yet remains inconsistently defined across centers. Hepatic injury primarily occurs during reperfusion rather than ischemia itself. During ischemia, the liver becomes metabolically primed, accumulating inflammatory mediators. Upon reperfusion, a cascade of sterile inflammation occurs involving neutrophils, Kupffer cells, cytokines, and endothelial dysfunction, leading to hepatocyte necrosis and microcirculatory failure. Clinical correlates from hypoxic hepatitis and congestive hepatopathy suggest that both hypoxia and congestion contribute to injury. Additional factors such as donor hemodynamic trajectory, oxygen saturation, cardiac function, and underlying liver quality (steatosis/fibrosis) further influence outcomes. Future directions include better physiological definition of functional dWIT, real-time monitoring of hepatic oxygenation, and use of emerging technologies such as machine perfusion to mitigate ischemia-reperfusion injury. This integrated physiological approach may reduce graft discard and improve outcomes in DCD liver transplantation.

Modified Cavo-Portal Hemi-Transposition in Adult LDLT: Annals of HPB Surgery | February 2026

Introduction Extensive porto-mesenteric thrombosis has traditionally been considered one of the most difficult situations in liver transplantation because adequate portal inflow is essential for graft regeneration and long-term function. In living donor liver transplantation, this challenge becomes even greater because the graft depends heavily on sufficient portal shear stress for recovery and growth. Although alternative inflow options such as reno-portal anastomosis, cavo-portal hemi-transposition, portal vein arterialization, and multivisceral transplantation exist, each has important technical and physiological limitations. Among these, cavo-portal hemi-transposition is well described in pediatric transplantation but remains rarely reported in adults, especially in living donor liver transplantation. Problem Statement In adult living donor liver transplantation, cavo-portal hemi-transposition is technically difficult because the right lobe graft portal vein is not naturally aligned with the inferior vena cava. This can lead to angulation, poor flow, thrombosis, persistent portal hypertension, and inadequate systemic venous drainage, making outcomes less favorable in adults than in pediatric patients. Summary This article describes an important technical modification of cavo-portal hemi-transposition in two adult living donor liver transplant recipients with diffuse porto-mesenteric thrombosis, one of whom also had Budd-Chiari syndrome. The key modification was to use the left renal vein–inferior vena cava junction as the site for inflow and to add a cryopreserved portal vein graft as an interposition conduit. This created a straighter alignment between the graft portal vein and the systemic venous inflow, while avoiding excessive mobilization of the vena cava and preserving collateral venous channels. The authors believe this improves portal inflow, reduces the risk of kinking and thrombosis, and helps maintain adequate inferior vena cava drainage. One patient had good long-term graft function after management of partial portal vein thrombosis with stenting, while the second patient died from fungal sepsis despite a patent reconstruction. Overall, the study suggests that this modified technique is a practical rescue option in highly selected adult living donor liver transplantation cases with diffuse splanchnic venous thrombosis, but it should be performed only in expert high-volume transplant centers.

Selective Splenectomy Guided by Graft-to-Spleen Volume Ratio in LDLT: Liver Transplantation | April 2026

Introduction Early allograft dysfunction (EAD) remains a major challenge after living donor liver transplantation (LDLT), often driven by portal hyperperfusion and small-for-size graft physiology. Splenectomy has been used to modulate portal flow, but its routine use is controversial due to surgical risks. The graft-to-spleen volume ratio (GSVR) has emerged as a potential physiological marker to better select patients who may benefit from splenectomy. Problem Statement There is no clear, objective criterion to guide selective splenectomy in LDLT. Empirical or routine splenectomy may expose patients to unnecessary risks, while omission in high-risk patients may lead to EAD, thrombocytopenia, ascites, and graft dysfunction. A reliable, reproducible strategy is needed to identify patients who truly benefit from splenic modulation. Summary This prospective study validated a GSVR-based selective splenectomy strategy in 141 LDLT recipients. Splenectomy was performed when GSVR ≤0.70 or in high-risk settings (ABO incompatibility, older donor, high portal pressure).

Neuroprotection in ALF: Journal of Hepatology | March 2026

Introduction Neuroprotection remains a central challenge in the management of acute liver failure, where cerebral oedema and intracranial hypertension are major drivers of mortality. Traditionally, invasive intracranial pressure monitoring has been used to guide management, but recent shifts in clinical practice suggest a move away from this approach. This evolving paradigm reflects a deeper understanding of the pathophysiology of brain injury in acute liver failure, where ammonia toxicity, systemic inflammation, and blood–brain barrier dysfunction act synergistically rather than independently. Summary This article highlights a significant transition in neuroprotective strategies in acute liver failure following evidence that declining use of invasive intracranial pressure monitoring has not adversely affected survival outcomes. The focus is shifting from reactive management of intracranial hypertension to proactive prevention of cerebral oedema. Blood ammonia is emphasised as a key early biomarker for identifying high-risk patients, although it is recognised as a downstream marker rather than the primary driver of injury. Increasing attention is being directed toward upstream mechanisms, particularly systemic inflammation and cytokine-mediated neurotoxicity, which may offer future therapeutic targets. The second major shift is toward non-invasive, multimodal neurological monitoring. Emerging tools such as transcranial Doppler, near-infrared spectroscopy, and continuous electroencephalography offer dynamic insights into cerebral perfusion, oxygenation, and neuronal activity, enabling a more comprehensive and individualised assessment of brain function without procedural risk. Finally, the reduction in invasive monitoring introduces a critical clinical challenge: determining irreversible brain injury and transplant eligibility. The author proposes a multimodal framework combining imaging, functional neurophysiology, and biomarkers to guide decision-making. This approach is essential to ensure appropriate use of liver transplantation while avoiding both futile interventions and missed opportunities for timely transplantation.

Post LT Immunosuppressive Strategies for PSC: Journal of Hepatology | March 2026

Introduction Primary sclerosing cholangitis is a unique indication for liver transplantation because long-term outcomes are influenced not only by graft survival, but also by the risks of acute cellular rejection, recurrent PSC, and complications related to associated inflammatory bowel disease. Although survival after transplantation is generally favorable, the ideal post-transplant immunosuppressive strategy remains uncertain. This international survey from the IPSCSG is important because it highlights how little standardization currently exists in the care of PSC patients after liver transplantation. Summary This survey of 31 transplant centers across Europe, the United States, and other regions showed marked heterogeneity in immunosuppressive practice after liver transplantation for PSC. Nearly half of centers reported using a more intensive immunosuppressive approach in PSC than in other transplant recipients, and basiliximab induction was routinely used by a similar proportion. Triple immunosuppression was common early after transplantation, but long-term practice varied substantially. Some centers tapered to tacrolimus monotherapy, most used dual therapy, and about one-quarter maintained triple therapy long term. Corticosteroid use also differed greatly, with most centers stopping prednisolone within the first year, while nearly one-third continued lifelong prednisolone. Importantly, these differences were seen even among high-volume transplant centers, suggesting that experience alone has not led to convergence in practice. Follow-up strategies also varied, including inconsistent use of imaging and protocol liver biopsies. The major message is that post-transplant care in PSC remains highly individualized and not evidence-based. This variation creates an important opportunity for comparative outcome studies to determine whether certain immunosuppressive strategies are associated with lower recurrence, better graft survival, or fewer long-term complications.

Transplant Timing in Perihilar Cholangiocarcinoma: Ann of Surgery, Feb. 2026

This large single-centre analysis evaluated whether earlier liver transplantation improves survival in patients with perihilar cholangiocarcinoma (pCCA) treated with standardised neoadjuvant therapy and transplant protocol. The key question: Does transplanting within 6 months of protocol registration improve outcomes? Study Overview 392 patients in the intention-to-treat cohort 256 underwent liver transplantation Median time to transplant/dropout: ~5.7 months Key Findings Shorter wait times (0–3 months) did NOT improve overall survival. Waiting longer (≥6 months) did not worsen intention-to-treat survival. Importantly, among transplanted patients: Waiting ≥6 months was associated with lower post-transplant mortality. Survival benefit became more pronounced beyond 9 months. Waiting time was not associated with increased residual tumour in the explant. Clinical Interpretation This study challenges the assumption that “earlier is better” for transplant in pCCA. A minimum 6-month waiting period may: Allow biological selection of favourable tumour behaviour Reduce post-transplant mortality Maintain overall survival in the broader cohort Take-Home Message for Hepatobiliary & Transplant Teams Transplantation within 6 months of registration does not enhance survival, and waiting ≥6 months may optimise outcomes without compromising overall patient survival. This reinforces the importance of disciplined protocol adherence and biological selection in pCCA transplant programs.

Managing Multiple Bile Ducts in LDLT- Liver Transplant Feb.26

Multiple bile ducts (MBDs) in living donor liver transplantation (LDLT) remain a major technical challenge, particularly in right lobe grafts. This large retrospective study analysed 1,780 microsurgical biliary reconstructions over 16 years to determine optimal reconstruction strategies and outcomes. Approximately 23% of grafts had multiple bile ducts. Overall, biliary complications were higher in MBD grafts compared with single-duct grafts (14.7% vs 11.2%), driven mainly by increased bile leak rates (6.1% vs 2.1%), while stricture rates were similar. Among adult LDLT recipients with right lobe grafts, 2-to-2 duct-to-duct reconstructions had the highest complication rate (16.6%). In contrast, 2-to-2 duct-to-jejunum anastomoses showed no biliary complications in this cohort. Overall, duct-to-duct reconstruction was associated with significantly higher biliary complications than duct-to-jejunum anastomosis (12.5% vs 2.6%). The study emphasises the importance of individualised surgical planning. Technical refinements—such as biliary stenting, ipsilateral duct alignment, figure-of-8 suturing at junctions, and centralisation techniques for size mismatch—may reduce complications. For transplant surgeons, the key message is that duct-to-jejunum reconstruction should be strongly considered in grafts with multiple bile ducts, particularly in complex 2-to-2 configurations, as it may lower leak risk and improve early biliary outcomes.

The Liver Transplant Comorbidity Index- Hepatology Feb.26

Frailty is a powerful predictor of outcomes after liver transplantation, but it cannot be used alone to determine transplant candidacy because many frail patients still achieve acceptable survival. This multicenter prospective study introduces the Liver Transplant Comorbidity Index (LTCI), a composite tool designed to better identify patients at higher risk of longer-term post–liver transplant mortality by integrating frailty with other key comorbidities. Using data from the Functional Assessment in Liver Transplantation (FrAILT) study across eight transplant centres, the investigators evaluated adults undergoing primary deceased-donor liver transplantation. Frailty was assessed using the Liver Frailty Index, and additional clinical variables were examined to determine their contribution to three-year posttransplant mortality. Through a combination of statistical rigor and clinical pragmatism, the final LTCI incorporated five readily available pretransplant factors: frailty, coronary artery disease, hepatocellular carcinoma, renal dysfunction, and diabetes. The LTCI effectively stratified patients into low-, moderate-, and high-risk groups with progressively worse posttransplant survival. Importantly, the index remained predictive even after accounting for donor-related factors, demonstrating that recipient comorbidity burden meaningfully influences outcomes beyond traditional transplant risk models. Clinically, the LTCI provides a balanced framework for transplant decision-making. Rather than excluding patients based on frailty alone, it contextualises frailty alongside other comorbidities, allowing clinicians to more accurately weigh transplant risks and benefits. This tool may help standardise candidate assessment, support shared decision-making, and promote equitable and evidence-based liver transplant selection.

Gut–liver–muscle axis -Front. Med. 2026

### The Gut–Liver–Muscle Axis: Overview and Key Insights The "gut-liver-muscle axis" is an emerging concept that highlights the interconnected relationship between gut microbiota, liver metabolism, and skeletal muscle health. This axis provides a framework to understand how disruptions in one organ system (e.g., the gut) can lead to systemic effects on the liver and skeletal muscles, particularly in the context of chronic liver diseases. Below is a detailed breakdown of the concept: --- ### 1. **What is the Gut–Liver–Muscle Axis?** The gut-liver-muscle axis is a physiological network that connects the gut, liver, and skeletal muscle through metabolic, immunological, and hormonal pathways. It emphasizes the role of gut microbiota in modulating liver function and skeletal muscle homeostasis, thereby influencing energy metabolism, protein synthesis, and inflammation. --- ### 2. **Role of Gut Microbiota in the Axis** - **Gut Dysbiosis**: Imbalances in gut microbiota, such as reduced microbial diversity, decreased beneficial bacteria, and increased pathogenic bacteria, play a central role in disrupting the gut-liver-muscle axis. - **Intestinal Barrier Dysfunction**: Gut barrier integrity is often weakened in chronic liver diseases, allowing bacterial products (e.g., lipopolysaccharides or LPS) to enter the portal circulation and trigger liver inflammation. - **Microbial Metabolites**: Key products of gut bacteria, such as short-chain fatty acids (SCFAs), bile acids, and amino acid metabolites, influence both liver and muscle metabolism. --- ### 3. **Liver's Role in the Axis** - **Energy Metabolism**: The liver is a critical organ for energy storage and nutrient metabolism. In chronic liver disease, impaired liver function disrupts glucose, lipid, and protein metabolism, contributing to malnutrition and muscle wasting. - **Inflammation**: Persistent liver inflammation due to gut-derived LPS and other microbial products exacerbates metabolic dysfunction and promotes muscle protein breakdown. - **Amino Acid Imbalances**: Liver dysfunction leads to impaired branched-chain amino acid (BCAA) utilization and increased aromatic amino acids (AAAs), which negatively affect muscle protein synthesis. --- ### 4. **Muscle's Role in the Axis** - **Sarcopenia**: Sarcopenia, or the loss of skeletal muscle mass and strength, is a hallmark of malnutrition in chronic liver disease. It is influenced by systemic inflammation, hyperammonemia, and energy metabolic dysfunction. - **Energy Deficits**: Reduced SCFA production and impaired nitrogen metabolism weaken muscle energy supply, contributing to muscle wasting. - **Hyperammonemia**: Elevated blood ammonia levels (common in liver cirrhosis) impair muscle protein synthesis and energy metabolism. --- ### 5. **Key Pathways in the Gut–Liver–Muscle Axis** - **Inflammatory Signaling**: Gut-derived LPS activates liver Kupffer cells, inducing pro-inflammatory cytokines (e.g., TNF-α, IL-6) via NF-κB signaling. These cytokines promote muscle protein degradation and inhibit synthesis. - **Nitrogen Metabolism**: Dysbiosis leads to increased ammonia-producing bacteria, exacerbating hyperammonemia and nitrogen imbalance, which impair muscle function. - **SCFA Production**: SCFAs (e.g., butyrate, acetate, propionate) are crucial for energy metabolism. Reduced SCFA levels due to gut dysbiosis weaken muscle mitochondrial function and glycogen storage. - **Bile Acid Signaling**: Gut microbiota modulate bile acid metabolism, which influences liver lipid metabolism and systemic energy regulation. --- ### 6. **Chronic Liver Diseases and the Gut–Liver–Muscle Axis** Several liver diseases are closely associated with disruptions in the gut-liver-muscle axis: - **Non-Alcoholic Fatty Liver Disease (NAFLD)**: Gut dysbiosis contributes to insulin resistance, lipid metabolism disorders, and sarcopenic obesity in NAFLD. - **Alcoholic Liver Disease (ALD)**: Chronic alcohol consumption disrupts gut microbiota, weakens the gut barrier, and promotes liver inflammation and muscle wasting. - **Liver Cirrhosis**: Advanced cirrhosis is characterized by significant dysbiosis, hyperammonemia, and systemic inflammation, leading to severe sarcopenia. - **Viral Hepatitis and Autoimmune Liver Diseases**: Persistent inflammation and immune dysregulation in these conditions are exacerbated by gut microbiota imbalances. --- ### 7. **Therapeutic Implications of the Gut–Liver–Muscle Axis** Understanding the gut-liver-muscle axis has opened new avenues for therapeutic interventions: - **Probiotics/Prebiotics**: These can restore microbial balance, enhance SCFA production, and improve gut barrier function. - **Faecal Microbiota Transplantation (FMT)**: FMT has shown promise in reducing gut-derived inflammation, improving ammonia metabolism, and restoring gut-liver axis function. - **Nutritional Support**: Supplementing with branched-chain amino acids (BCAAs), dietary fiber, and polyunsaturated fatty acids (PUFAs) can improve muscle protein synthesis and energy metabolism. - **Integrated Approaches**: Combining microbiome-based therapies with nutritional and pharmacological interventions may offer a comprehensive strategy for managing liver disease-related malnutrition and sarcopenia. --- ### 8. **Future Directions** - **Multi-Omics Research**: Advanced tools like metagenomics, metabolomics, and proteomics will help identify specific microbial and metabolic signatures associated with liver disease and sarcopenia. - **Personalized Medicine**: Developing tailored microbiome interventions and nutritional therapies based on individual microbiota profiles. - **Dynamic Modeling**: Using artificial intelligence and computational models to predict disease progression and optimize treatment strategies for the gut-liver-muscle axis. --- ### Conclusion The gut-liver-muscle axis is a critical and interconnected pathway that plays a significant role in the development of malnutrition and sarcopenia in chronic liver diseases. Gut dysbiosis, liver dysfunction, and muscle wasting are interlinked through complex metabolic and inflammatory pathways. By targeting the gut microbiota and its metabolites, novel therapeutic strategies can be developed to improve the nutritional outcomes, muscle health, and overall prognosis of patients with liver diseases.