Trending Topics in Gastroenterology | GastroAGI

ISHEN Consensus Standardizes Ammonia Testing in Cirrhosis : J Hepatol | May 2026

Introduction Hepatic Encephalopathy is a major complication of Cirrhosis and is closely linked to ammonia metabolism. Despite ammonia’s central pathogenic role, the clinical value of blood ammonia measurement has remained controversial because of inconsistent sampling methods, laboratory variability and uncertainty regarding interpretation in routine practice. Problem Statement Lack of standardized guidance regarding ammonia measurement has resulted in major variability in clinical practice, limiting its reliable use in diagnosis, prognostication, therapeutic monitoring and research in cirrhosis and hepatic encephalopathy. Summary This International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus represents the first structured international effort to standardize the role of ammonia measurement in cirrhosis care using a formal evidence-based Delphi methodology. The recommendations were developed through a rigorous multinational multidisciplinary consensus process involving expert hepatologists and researchers with specific expertise in hepatic encephalopathy and ammonia metabolism. The panel addressed 25 clinically relevant PICO questions spanning diagnostic utility, prognostication, therapeutic monitoring and technical aspects of ammonia measurement. A major contribution of the document is its emphasis on preanalytical standardization. The consensus highlights that ammonia measurements are highly susceptible to methodological error, including delays in processing, improper sample handling and variability in collection techniques. Standardized acquisition and processing protocols are therefore essential for clinically interpretable results. The panel supports the clinical relevance of ammonia measurement in selected settings rather than indiscriminate routine use. Elevated ammonia levels were recognized as useful in supporting the diagnosis of overt hepatic encephalopathy, particularly when diagnostic uncertainty exists, while acknowledging that ammonia alone cannot definitively establish or exclude the diagnosis. Importantly, the consensus also emphasizes ammonia’s prognostic role. Elevated levels may help identify patients at higher risk of developing overt hepatic encephalopathy and other liver-related complications, supporting incorporation into risk stratification frameworks for both inpatient and outpatient management. The recommendations additionally address therapeutic monitoring. Serial ammonia assessment may provide supportive information regarding response to ammonia-lowering therapies, although clinical evaluation remains the cornerstone of management decisions. A particularly valuable aspect of the document is its balanced interpretation of ammonia biology. The panel acknowledges that hepatic encephalopathy is multifactorial and not solely ammonia-dependent, explaining why some patients with elevated ammonia remain clinically asymptomatic while others develop encephalopathy despite lower concentrations. The consensus also identifies several important research priorities. These include development of reliable point-of-care ammonia testing, validation of ammonia-based predictive models and improved understanding of non-hyperammonemic encephalopathy phenotypes. Clinically, the document may substantially improve harmonization of practice across centers and trials. Standardized ammonia measurement protocols are especially important for multicenter hepatic encephalopathy studies, biomarker development and emerging therapeutic trials targeting ammonia metabolism. The work additionally reinforces the growing movement toward precision phenotyping in cirrhosis. Rather than viewing ammonia as a binary diagnostic marker, the consensus frames ammonia as a dynamic biologic variable integrated within broader clinical, inflammatory and metabolic contexts. From a translational perspective, the document is also highly relevant for drug development. Reliable ammonia measurement frameworks will likely become increasingly important as novel therapies targeting nitrogen metabolism, microbiome modulation and skeletal muscle ammonia handling continue to emerge. Overall, this ISHEN Delphi consensus establishes the first evidence-based international framework for ammonia measurement in cirrhosis. The recommendations provide practical guidance for clinicians, standardize best practices for sampling and interpretation, and reinforce ammonia’s evolving role in diagnosis, risk stratification and management of hepatic encephalopathy.

Impaired VO₂ Recovery Highlights Frailty Physiology in Cirrhosis : Liver Transpl | May 2026

Introduction Frailty and reduced functional capacity are increasingly recognized as major prognostic determinants in patients with Cirrhosis awaiting Liver Transplantation. The Six-Minute Walk Test is widely used to assess exercise tolerance and frailty in cirrhosis, yet the physiologic mechanisms underlying impaired performance remain incompletely characterized. Understanding cardiovascular, metabolic and muscular responses during functional testing may help refine prehabilitation strategies and exercise prescription in transplant candidates. Problem Statement Although patients with cirrhosis demonstrate markedly reduced aerobic capacity, the dynamic physiologic abnormalities during exercise and recovery that contribute to impaired functional performance are poorly understood, particularly among frail and pre-frail transplant candidates. Summary This physiologic study evaluated real-time cardiopulmonary and skeletal muscle responses during six-minute walk testing in frail/pre-frail cirrhotic patients awaiting transplantation compared with age-matched controls. Investigators continuously measured heart rate, oxygen consumption and calf muscle oxygenation before, during and after exercise using portable metabolic monitoring and near-infrared spectroscopy. Patients with cirrhosis demonstrated profound impairment in functional capacity, walking substantially shorter distances than controls during the six-minute walk test. At baseline, cirrhotic participants already exhibited elevated resting heart rates and reduced calf muscle oxygenation, suggesting underlying circulatory and peripheral tissue abnormalities even before exertion began. During exercise, patients with cirrhosis displayed blunted physiologic responses characterized by lower peak heart rate, reduced oxygen consumption and diminished tissue deoxygenation compared with controls. These findings suggest impaired aerobic reserve and reduced skeletal muscle oxygen extraction during exertion, likely reflecting the combined effects of sarcopenia, mitochondrial dysfunction, autonomic dysregulation and cirrhotic cardiomyopathy. One of the most important observations involved delayed recovery kinetics after exercise. Although heart rate and muscle oxygenation recovery were relatively preserved, recovery of oxygen consumption remained significantly prolonged in cirrhotic patients. This delayed VO₂ recovery likely reflects impaired oxidative metabolism and delayed restoration of aerobic homeostasis following exertion. The physiologic pattern observed resembles impaired metabolic flexibility seen in advanced heart failure and severe frailty syndromes. Reduced mitochondrial efficiency, skeletal muscle dysfunction and altered peripheral oxygen utilization may collectively contribute to the slowed recovery phenotype identified in these transplant candidates. Clinically, the findings provide mechanistic support for structured prehabilitation programs in cirrhosis. Importantly, the study suggests that exercise training protocols may need modification in this population, particularly by incorporating longer recovery intervals between exercise bouts because of delayed oxygen consumption normalization. The work also reinforces that frailty in cirrhosis is not simply deconditioning but rather a complex multisystem physiologic disorder involving cardiovascular, muscular and metabolic impairment. Functional limitation appears to arise not only from reduced exercise tolerance itself but also from impaired post-exercise recovery dynamics. These findings may have important implications for transplant assessment and longitudinal frailty monitoring. Recovery physiology — particularly delayed VO₂ normalization — may eventually emerge as a more sensitive marker of physiologic reserve than walk distance alone. Overall, this study demonstrates that frail/pre-frail cirrhotic patients awaiting transplantation exhibit markedly impaired aerobic endurance and delayed metabolic recovery after exercise. The findings strengthen the rationale for individualized prehabilitation strategies and suggest that recovery kinetics may represent an important physiologic target in exercise-based interventions for advanced liver disease.

Wilson Disease Remains a Single-Gene Disorder : JHEP Reports | May 2026

Introduction Wilson disease (WD) is an autosomal recessive copper metabolism disorder caused by pathogenic variants in the ATP7B gene. Although genetic confirmation is increasingly incorporated into diagnostic algorithms, up to 20% of clinically diagnosed patients in historical cohorts remained genetically unresolved despite strong clinical evidence of WD. This multicenter international study evaluated whether modern genomic and functional approaches could clarify the molecular basis of these unresolved cases and determine whether WD truly represents a single-gene disorder. Problem Statement Conventional sequencing strategies, including hotspot analysis and Sanger sequencing, frequently fail to identify all pathogenic ATP7B variants. This diagnostic gap has generated speculation regarding alternative genetic causes, modifier genes or genetically heterogeneous Wilson-like syndromes. Uncertainty in unresolved cases complicates diagnostic confidence, family screening and genetic counselling, particularly when clinical Leipzig scores strongly support WD despite incomplete molecular confirmation. Summary This international multicenter study analyzed 761 clinically confirmed WD patients from tertiary referral centers in Germany, USA, Spain and Denmark. Among the cohort, only 44 patients (5.8%) had zero or one previously identified pathogenic ATP7B variant despite definite clinical WD. A comprehensive five-step diagnostic strategy incorporating whole genome sequencing (WGS), expanded gene panel analysis, long-read sequencing and ATP7B peptide quantification was applied to these unresolved cases. Reanalysis of ATP7B alone resolved 52% of previously unexplained cases. Seven patients were solved through reinterpretation of previously reported variants of uncertain significance, while 16 additional patients were diagnosed after WGS identified previously undetected ATP7B variants, including intronic, structural and complex rearrangements missed by earlier sequencing methodologies. Overall, 11 novel ATP7B variants were identified. Functional ATP7B peptide analysis further confirmed protein dysfunction in additional unresolved patients, increasing the diagnostic confirmation rate to 66% within the genetically unresolved subgroup and to 98% across the entire WD cohort. Importantly, extensive screening of 97 copper metabolism-related genes and more than 4,300 genes associated with hepatic or neurological disorders failed to identify alternative monogenic causes of disease. Even advanced long-read sequencing approaches did not reveal non-ATP7B pathogenic mechanisms. These findings strongly reinforce the concept that WD is fundamentally a single-gene disorder caused by ATP7B dysfunction rather than a genetically heterogeneous syndrome. The study has major clinical implications. It demonstrates that many historically “genetically negative” WD cases reflect limitations of older sequencing technologies or outdated variant classification rather than alternative disease biology. The authors advocate routine re-evaluation of unresolved WD cases using contemporary WGS, comprehensive ATP7B analysis and functional peptide assays before considering alternative diagnoses. This strategy can substantially improve diagnostic certainty, cascade family testing and personalized clinical management in WD.

Tacrolimus Shows Promise in Refractory Paediatric AIH : Frontline Gastroenterol | May 2026

Introduction Autoimmune hepatitis (AIH) in children is typically managed with corticosteroids and azathioprine, achieving remission in most patients. However, a subset of paediatric patients remain refractory to standard therapy or develop significant treatment intolerance, creating a major therapeutic challenge with risk of progressive fibrosis and liver failure. Problem Statement Evidence supporting second-line immunosuppressive therapy in difficult-to-treat paediatric AIH remains limited, particularly regarding long-term efficacy and safety of tacrolimus. Optimal management strategies for children with incomplete response or intolerance to conventional therapy are not well established. Summary This single-centre retrospective study evaluated tacrolimus as rescue immunosuppression in children with refractory or treatment-intolerant autoimmune hepatitis. Most patients received tacrolimus because of inadequate biochemical response to standard therapy, while a smaller proportion required escalation because of medication intolerance. Notably, many children already demonstrated progression of hepatic fibrosis at the time tacrolimus was initiated, underscoring the aggressive nature of difficult-to-control paediatric AIH. Tacrolimus induced complete biochemical remission in approximately two-thirds of patients, with remission often achieved rapidly after treatment initiation. Importantly, even patients who failed to achieve full remission demonstrated significant biochemical improvement, suggesting clinically meaningful disease control despite persistent low-grade activity. The treatment was well tolerated overall, with no major adverse effects or treatment discontinuations observed during follow-up. These findings support tacrolimus as a viable second-line or third-line immunosuppressive strategy in carefully selected paediatric AIH patients managed within specialized hepatology centres. The study also reinforces the importance of early recognition of treatment-refractory disease, as ongoing inflammatory activity may contribute to progressive fibrosis despite conventional therapy. Although limited by retrospective design and small cohort size, the findings add important real-world evidence supporting calcineurin inhibitor–based rescue therapy in paediatric AIH and highlight the need for prospective multicentre studies to better define long-term outcomes, optimal therapeutic timing and predictors of response.

Delisting for Clinical Improvement Emerges as a Practical Marker of Cirrhosis Recompensation : Liver Transpl | April 2026

Introduction The concept of recompensated cirrhosis has gained increasing importance with the advent of effective disease-modifying therapies for chronic liver disease, including antiviral treatment and sustained alcohol abstinence. As more patients experience meaningful clinical recovery, reassessing transplant candidacy and determining when liver transplantation may no longer be necessary have become major clinical challenges. Problem Statement Although recompensation is increasingly recognized as a relevant therapeutic endpoint, standardized real-world markers for durable clinical improvement remain poorly defined. Delisting for clinical improvement (DCI) from the liver transplant waitlist has been proposed as a potential surrogate for recompensation, but the durability of improvement and risk of subsequent clinical deterioration remain uncertain. Summary This large national cohort study demonstrates that delisting for clinical improvement occurs in a meaningful subset of liver transplant waitlist patients and may serve as a practical surrogate marker for recompensated cirrhosis. Rates of DCI varied substantially according to liver disease etiology, with the highest frequencies observed in hepatitis B, alcohol-associated liver disease and autoimmune hepatitis, reflecting the greater reversibility of these conditions under effective therapy or sustained disease control. Importantly, the study shows that true durable recompensation is not fully captured by MELD improvement alone. Patients achieving both MELD reduction and improvement in Child–Turcotte–Pugh class had the lowest risk of relisting, suggesting that combined biochemical and clinical recovery better defines stable recompensation. Notably, many patients delisted for improvement still retained significant underlying liver dysfunction, as fewer than half normalized to Child–Turcotte–Pugh class A. Relisting remained relatively uncommon overall but was frequently driven by hepatocellular carcinoma, emphasizing the continued oncologic vulnerability of cirrhotic patients despite hepatic improvement. Additional predictors of relapse included hypoalbuminemia, male sex and underlying disease etiology. Overall, the study supports a more nuanced and multidimensional approach to defining recompensated cirrhosis and provides important real-world evidence that integrated clinical improvement metrics may help guide safer liver transplant delisting decisions.

Integrating Portal Hypertension and HCC into a Unified Stage-Based Cirrhosis Model : Nat Rev Gastroenterol Hepatol | May 2026

Introduction Cirrhosis and hepatocellular carcinoma (HCC) represent closely interconnected consequences of chronic liver disease, with portal hypertension serving as a central driver of hepatic decompensation and a major determinant of prognosis. Despite this biologic overlap, clinical management frameworks have traditionally approached portal hypertension and HCC as separate entities. Problem Statement Current guidelines frequently fail to integrate cirrhosis stage, clinically significant portal hypertension (CSPH) and HCC stage into a unified prognostic model. This separation may lead to suboptimal treatment selection, inaccurate risk stratification and inadequate personalization of therapy, particularly when determining candidacy for curative interventions such as hepatic resection or transplantation. Summary This review proposes a clinically integrated, stage-based framework that combines cirrhosis severity, portal hypertension status and HCC stage to guide prognostication and therapeutic decision-making. The authors emphasize that CSPH represents a critical biologic and clinical milestone in compensated cirrhosis, strongly influencing risk of decompensation, survival and eligibility for curative HCC therapies. Importantly, the review highlights the transition from invasive hepatic venous pressure gradient measurement toward non-invasive assessment using liver stiffness and platelet-based tools, with emerging evidence suggesting these methods may soon become standard even in patients with HCC. The article further argues that management strategies should differ substantially according to the interaction between cirrhosis stage and tumor burden rather than relying on tumor stage alone. In compensated cirrhosis without CSPH, aggressive curative approaches may remain feasible, whereas decompensated disease substantially limits therapeutic tolerance and prognosis independent of tumor stage. The authors also call for future HCC clinical trials to incorporate cirrhosis stage and portal hypertension stratification into study design and outcome analysis. Overall, this review advances an important conceptual shift toward fully integrated hepatology-oncology care, where liver function, portal hypertension and tumor biology are evaluated simultaneously to optimize individualized management in cirrhosis-associated HCC.

Semaglutide Reduces Heavy Drinking in Alcohol Use Disorder with Obesity | The Lancet

Introduction Alcohol use disorder (AUD) remains a major global health challenge with limited pharmacologic treatment options and persistently high relapse rates. Although behavioural therapies remain foundational, currently approved medications offer modest efficacy, creating a substantial need for more effective therapeutic strategies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in obesity and diabetes, have emerged as promising candidates owing to their effects on reward signalling, appetite regulation and addictive behaviours. Problem Statement Effective pharmacotherapy for AUD remains limited, particularly in patients with coexisting obesity, a phenotype increasingly recognized to share overlapping neurobiological and metabolic pathways with addictive behaviour. While preclinical and early human data have suggested that GLP-1RAs may reduce alcohol consumption, robust randomized evidence in treatment-seeking patients with clinically significant AUD has been lacking. Summary This randomized, placebo-controlled trial demonstrates that once-weekly semaglutide significantly reduces heavy drinking in treatment-seeking patients with moderate-to-severe AUD and comorbid obesity. Over 26 weeks, semaglutide produced greater reductions in heavy drinking days, total alcohol intake, alcohol craving and WHO drinking risk levels compared with placebo, while also improving several objective alcohol-related biomarkers. These benefits were accompanied by substantial reductions in body weight, waist circumference and glycated hemoglobin, supporting a broader metabolic benefit in this high-risk population. The treatment was generally well tolerated, with predominantly mild-to-moderate gastrointestinal adverse effects consistent with the known safety profile of semaglutide. Importantly, this is the first randomized trial to show clinically meaningful reductions in alcohol consumption with semaglutide in treatment-seeking individuals, supporting GLP-1 receptor agonism as a promising therapeutic strategy for AUD. Although larger and more diverse studies are needed before routine clinical adoption, these findings position semaglutide as a potentially important dual-purpose intervention for patients with coexisting alcohol use disorder and obesity.

PPAR Agonists in PBC: Hepatology | April 2026

Introduction Primary biliary cholangitis is a chronic cholestatic liver disease that can progress to cirrhosis and liver failure if inadequately treated. While ursodeoxycholic acid remains the first-line therapy, a significant proportion of patients have incomplete response or intolerance. In this context, peroxisome proliferator–activated receptor agonists have emerged as promising second-line options, targeting metabolic and inflammatory pathways involved in cholestasis. However, comparative efficacy among different PPAR agents remains unclear due to lack of direct head-to-head trials. Problem Statement There is limited comparative evidence to guide the selection of the most effective and safest PPAR agonist as second-line therapy in PBC. Summary This network meta-analysis of eight randomized trials involving over 700 patients demonstrates that all PPAR agonists are superior to placebo in achieving biochemical response and alkaline phosphatase (ALP) normalization, key surrogate markers of disease control in PBC. Among available agents, bezafibrate ranked highest for overall biochemical response, while both bezafibrate and seladelpar showed the best performance for ALP normalization. Interestingly, the magnitude of ALP reduction was consistent regardless of baseline disease severity, suggesting broad applicability across patient subgroups. Total bilirubin outcomes were similar across treatments, and adverse events leading to discontinuation were infrequent, supporting a favorable safety profile. In the absence of direct comparative trials, this study provides valuable indirect evidence to guide clinical decision-making. However, differences in ranking should be interpreted cautiously due to variability in study design and populations. Clinically, PPAR agonists represent an effective and safe second-line strategy in PBC, with bezafibrate and seladelpar emerging as leading options. Future research should focus on long-term outcomes and patient-centered benefits beyond biochemical response.

Extrahepatic Abdominal Surgery in Cirrhosis: EASL Clinical Practice Guidelines

Surgery in patients with cirrhosis is no longer viewed as uniformly prohibited, but it remains high-risk and must be approached in a structured way. The two most important determinants are the severity of liver disease and the type and urgency of surgery. A compensated patient with preserved liver function may tolerate elective surgery reasonably well, whereas a decompensated patient with significant portal hypertension may deteriorate rapidly after even a technically successful operation. For this reason, these guidelines strongly support multidisciplinary assessment involving hepatology, surgery, anaesthesia, radiology, nutrition, and critical care teams. How Surgical Risk Should Be Assessed The guideline makes it clear that risk assessment should not rely on clinical impression alone. A multimodal approach is preferred. The VOCAL-Penn score is currently the most useful modern surgical risk calculator and should be incorporated into practice. Traditional scores such as Child-Turcotte-Pugh and MELD still remain clinically relevant, especially because much of the existing literature still uses them. Portal hypertension is a major issue because it strongly influences postoperative decompensation, bleeding, ascites, renal injury, and death. Non-invasive tests such as transient elastography and platelet count can help identify compensated advanced chronic liver disease and rule in or rule out clinically significant portal hypertension in selected patients. However, when surgical decision-making depends on accurate haemodynamic risk, hepatic venous pressure gradient (HVPG) remains the most informative tool. The guideline emphasizes that risk rises particularly when HVPG is above 16 mmHg and becomes especially concerning at 20 mmHg or more. Risk According to Severity of Liver Disease Patients with Child-Pugh A cirrhosis generally represent the group in whom elective surgery can be considered most safely, especially if portal hypertension is absent or limited and the operation can be performed laparoscopically in an experienced centre. This is the subgroup where the concept of “careful surgery after optimization” best applies. Patients with Child-Pugh B cirrhosis fall into an intermediate but clearly increased risk category. Surgery is not automatically ruled out, but the threshold for proceeding should be higher. These patients require detailed assessment of portal hypertension, nutritional status, frailty, cardiopulmonary reserve, and operative necessity. In some selected patients, especially those with significant portal hypertension, preoperative strategies such as TIPS may be considered. Patients with Child-Pugh C cirrhosis have very high perioperative mortality and morbidity. Elective extrahepatic abdominal surgery should generally be avoided in this group. If surgery is required, it is usually because of an emergency or life-saving indication, and even then, outcomes are poor. The guideline is particularly cautious in patients with acute-on-chronic liver failure (ACLF). Once ACLF grade 2 or 3 is present, emergency surgery may often be futile unless the surgical pathology itself is reversible and the patient has a realistic path to recovery or transplantation. Risk According to the Type of Surgery Not all operations carry the same risk. The guideline supports thinking not just in terms of liver function, but also in terms of surgical stress. Gallbladder surgery can be performed in selected cirrhotic patients, especially those with Child-Pugh A or B disease. Laparoscopic cholecystectomy is preferred over open surgery because it reduces complications and recovery time. In advanced disease, especially Child-Pugh C, non-surgical approaches such as percutaneous or endoscopic gallbladder drainage may be safer. Hernia surgery is very relevant because umbilical and abdominal wall hernias are common in cirrhosis, particularly with ascites. The guideline supports elective repair in experienced centres after careful optimisation, because emergency surgery for incarceration or rupture carries much worse outcomes. In practical terms, elective repair is often safer than waiting for a crisis. Colorectal surgery carries a substantially higher risk, especially because of infection, leakage, and decompensation. Emergency colorectal surgery is particularly dangerous. If surgery must be performed, minimally invasive approaches are preferred when feasible, and surgeons may need to consider diversion rather than primary anastomosis in high-risk patients. Pancreatic surgery is one of the highest-risk operations in cirrhosis. The guideline allows consideration only in carefully selected Child-Pugh A patients without clinically significant portal hypertension, and only for malignancy or premalignant disease. It should be discouraged in Child-Pugh B or C patients, and it should not be done for benign pancreatic disease. Aortic surgery, particularly for abdominal aortic aneurysm, may be considered in Child-Pugh A patients after careful assessment, but is discouraged in Child-Pugh B and C disease. Endovascular repair is preferred over open repair because it reduces physiological stress. Emergency Surgery and the Concept of Futility The guideline recognises that emergency surgery is often where the greatest uncertainty lies. In compensated cirrhosis, decisions may be made broadly in line with general surgical principles. However, in decompensated cirrhosis, especially with organ failures, a realistic discussion about futility becomes necessary. If surgery is unlikely to achieve the intended physiological goal, or if it may only prolong dying without meaningful recovery, proceeding may not be in the patient’s best interest. This is particularly relevant in advanced ACLF, severe sepsis, refractory shock, and profound physiological collapse. Preoperative Optimization The guideline places major emphasis on optimisation before any elective operation. The cause of liver disease should be treated whenever possible. This means strict alcohol abstinence in alcohol-related disease, antiviral therapy in viral cirrhosis, and broader metabolic treatment in MASLD where relevant. Nutritional status should be assessed in all patients. Malnutrition, sarcopenia, and frailty are common in cirrhosis and meaningfully worsen outcomes. The guideline recommends prehabilitation, ideally starting 4 to 6 weeks before surgery, with physical conditioning, dietary intervention, and psychological preparation when possible. Cardiopulmonary evaluation is also essential. A patient with cirrhosis may also have occult cardiac dysfunction, pulmonary hypertension, or hepatopulmonary syndrome. Electrocardiography, echocardiography, and pulse oximetry should be part of routine workup for major surgery. Upper GI endoscopy is recommended in most patients unless clinically significant portal hypertension has already been excluded or appropriate variceal prophylaxis is already in place. Role of TIPS Before Surgery The guideline does not recommend routine preoperative TIPS for all cirrhotic patients with portal hypertension. In Child-Pugh A patients, evidence is not strong enough to support routine use. In selected Child-Pugh B or C patients with significant portal hypertension, however, preparatory TIPS may be considered by expert teams, particularly if the aim is to reduce postoperative ascites and portal hypertension-related complications. This remains an individualized decision rather than a standard rule. Perioperative Bleeding and Coagulation One of the most clinically useful messages from the guideline is that abnormal coagulation tests in cirrhosis should not automatically trigger correction. INR is not a reliable guide to true bleeding risk in these patients, and routine correction with plasma is not recommended. The haemostatic system in cirrhosis is rebalanced, and bleeding often relates more to portal hypertension or procedural injury than to simple clotting factor deficiency. If active bleeding occurs, viscoelastic testing is preferred to guide transfusion. Platelets and fibrinogen may be corrected selectively in high-risk bleeding situations, but prophylactic transfusion based purely on standard laboratory values is discouraged. Fluid Therapy and Haemodynamic Management Fluid overload should be avoided. This is extremely important in cirrhosis because over-resuscitation worsens ascites, oedema, pulmonary congestion, and wound complications. Balanced crystalloids are generally preferred, and hydroxyethyl starch should be avoided because of kidney injury risk. The anaesthetic and critical care teams must maintain tissue perfusion while avoiding venous congestion and portal pressure excess. Anaesthesia and Analgesia Drug handling is altered in cirrhosis, so anaesthetic and analgesic doses must be adjusted according to hepatic function. Propofol is generally safe, and fentanyl is the preferred opioid because it lacks toxic metabolites and is less affected by hepatic dysfunction than longer-acting opioids. NSAIDs should be avoided because of renal risk and bleeding risk. Paracetamol remains safe in reduced doses, usually up to 2–3 grams daily. Benzodiazepines should be avoided in patients with encephalopathy. Regional techniques may reduce systemic drug exposure, but nerve blocks and especially neuraxial techniques should be used cautiously in more advanced cirrhosis because of bleeding risk. Enhanced Recovery and Postoperative Care The guideline supports enhanced recovery after surgery (ERAS) principles in cirrhotic patients. These include structured perioperative nutrition, early mobilisation, careful analgesia, minimisation of unnecessary lines and drains, and early enteral feeding. Although data specific to cirrhosis are limited, the principles are strongly supported. Postoperatively, patients require close monitoring for hepatic encephalopathy, ascites, jaundice, renal dysfunction, infection, and bleeding. The guideline suggests that intensive or high-dependency monitoring may be beneficial after major surgery, especially in high-risk patients, because deterioration can occur rapidly and early intervention matters. Practical Clinical Take-Home For a clinician, the most important way to remember this guideline is simple. A cirrhotic patient should never be judged for surgery based only on the label “cirrhosis.” The real questions are: How severe is the liver disease? Is clinically significant portal hypertension present? Is the surgery elective or emergency? Can it be done minimally invasively? Has the patient been optimised nutritionally and medically? And is the procedure being performed in a centre that truly understands cirrhosis? In broad terms, Child-Pugh A patients may undergo selected elective surgery after proper assessment; Child-Pugh B patients require much greater caution and individualised planning; Child-Pugh C and ACLF patients are usually poor surgical candidates unless surgery is life-saving. Minimally invasive approaches are preferred wherever feasible, portal hypertension must be actively considered, and postoperative monitoring should be more vigilant than in non-cirrhotic patients. If you want, I can next convert this into a one-page clinic table with columns for severity of cirrhosis, type of surgery, and practical recommendations

Psychomotor Speed and Frailty in Advanced Liver Disease: AJG | April 2026

Introduction Minimal hepatic encephalopathy (MHE) and physical frailty are highly prevalent yet often under-recognised complications in patients with advanced chronic liver disease (AdvCLD). While MHE reflects subtle neurocognitive impairment, frailty represents systemic physical vulnerability. Traditionally, complex tools like the Psychometric Hepatic Encephalopathy Score have limited routine clinical assessment of MHE. The simpler Stroop EncephalApp (StE) offers a practical alternative, raising interest in understanding how cognitive dysfunction—particularly psychomotor speed—relates to physical frailty. Problem Statement Despite both MHE and frailty being strong predictors of poor outcomes, their interrelationship remains poorly defined. Specifically, it is unclear whether cognitive impairment assessed by simple tools like StE correlates meaningfully with frailty indices and whether this relationship can be used for risk stratification in clinical practice. Summary In this multicenter study of patients awaiting liver transplantation, MHE was present in 73% and frailty in 18%. Patients with MHE had significantly worse Liver Frailty Index (LFI) scores and were more frequently classified as prefrail or frail. A strong correlation was observed between psychomotor speed—particularly StE off-time—and frailty, with LFI independently predicting MHE (OR 2.41). These findings highlight a critical brain–muscle axis in cirrhosis, where impaired psychomotor speed mirrors physical decline. The study supports the use of simple bedside tools like StE to identify high-risk patients and suggests that integrated cognitive and physical interventions may improve outcomes in advanced liver disease.