Trending Topics in Gastroenterology | GastroAGI

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.

Oral Health Matters in Cirrhosis: JHEP Reports/ March 2026

Introduction: Cirrhosis is increasingly recognised as a multisystem disease influenced by inflammation, microbiome alterations, and extrahepatic factors. Poor oral health, particularly periodontitis, contributes to systemic inflammation and bacterial translocation through the oral–gut–liver axis. However, whether improving oral hygiene through structured dental prophylactic services can modify the natural history of cirrhosis has remained largely unexplored in large real-world cohorts. Problem Statement and Summary: This large Veterans cohort study demonstrates that regular dental prophylaxis (≥1 visit/year) is independently associated with significantly lower rates of cirrhosis decompensation, including ascites and hepatic encephalopathy, as well as reduced hepatocellular carcinoma incidence and hospitalisations over 2 years. Importantly, this protective effect was specific to dental care and not merely a marker of healthcare engagement, as colonoscopy screening did not show similar benefits. The findings highlight a novel, modifiable and under-recognised factor in cirrhosis management. Clinical Implication: Routine dental care should be integrated into standard cirrhosis management, shifting focus toward holistic care and reinforcing the importance of the oral–liver axis in disease progression.

Recompensation in Decompensated Cirrhosis: CGH/ April 2026

Introduction: Decompensated cirrhosis has traditionally been considered an irreversible stage of liver disease, associated with poor survival and frequent complications such as ascites, variceal bleeding, and hepatic encephalopathy. However, emerging evidence challenges this paradigm, suggesting that effective etiological treatment can lead to “recompensation,” defined as resolution of decompensating events with sustained improvement in liver function. This evolving concept represents a fundamental shift in cirrhosis management, moving from palliation toward potential disease modification. Summary: This systematic review and meta-analysis involving over 9000 patients demonstrates that recompensation occurs in approximately one-third of patients with decompensated cirrhosis, particularly in viral etiologies such as hepatitis B. Importantly, recompensation is associated with significantly lower risks of hepatocellular carcinoma and mortality, highlighting its prognostic and clinical relevance. Despite these promising findings, heterogeneity across studies and limited high-quality evidence indicate that predictors, durability, and mechanisms of recompensation remain incompletely understood. Clinical Implication: Recompensation should be recognised as an achievable and meaningful therapeutic endpoint, emphasising early etiological treatment, aggressive disease modification, and a dynamic approach to cirrhosis care rather than a static irreversible model.

Baclofen vs Acamprosate in Alcohol-Associated Cirrhosis: Alimentary Pharmacology & Therapeutics | March 2026

Introduction Management of alcohol use disorder in patients with cirrhosis remains a clinical challenge, where drug safety is as critical as efficacy. Acamprosate is generally preferred due to renal clearance, while baclofen has been considered safe even in advanced liver disease. However, comparative real-world safety data between these two commonly used agents in compensated alcohol-associated cirrhosis have been limited. Problem Statement Despite guideline endorsement of both baclofen and acamprosate, uncertainty persists regarding their relative hepatic safety. Clinicians often face a dilemma in choosing therapy, particularly in patients at risk of decompensation, where even small differences in adverse outcomes can significantly impact prognosis. Summary This large, multicenter, real-world cohort study using a target trial emulation framework compared baclofen and acamprosate in compensated alcohol-associated cirrhosis. After robust propensity matching, baclofen was associated with a higher incidence of major adverse liver outcomes at one year compared to acamprosate (34.3% vs 27.4%). Notably, the increased risk was primarily driven by a higher incidence of hepatic encephalopathy, while other decompensation events and mortality did not differ significantly. The risk appeared more pronounced in older patients. These findings suggest that while baclofen remains an option, acamprosate may be the safer first-line agent in compensated cirrhosis, particularly in patients at risk for encephalopathy. This study provides important real-world evidence to guide individualised therapeutic decision-making in this vulnerable population.

Early Portopulmonary Hypertension in Cirrhosis: Journal of Hepatology | February 2026

Introduction Portopulmonary hypertension represents a complex cardiopulmonary complication of cirrhosis that significantly impacts prognosis and transplant eligibility. Recent data from the PORTO-DETECT cohort have suggested that even early-stage portopulmonary hypertension, defined using updated hemodynamic criteria, is associated with increased mortality. This has generated considerable interest, particularly regarding whether early disease represents a true biological risk state or simply reflects differences in treatment exposure and detection. Problem Statement The key clinical uncertainty is whether early portopulmonary hypertension independently predicts mortality or whether observed outcomes are confounded by treatment bias, patient selection, and methodological limitations inherent to observational studies. Additionally, it remains unclear whether early detection should alter management, given the lack of evidence supporting early therapeutic intervention and the challenges in implementing invasive screening strategies such as right-heart catheterisation. Summary The association between early portopulmonary hypertension and increased mortality compared to patients with normal hemodynamics, independent of liver disease severity and portal hypertension. Importantly, no patients were on pulmonary vasodilator therapy at baseline, minimising treatment-related confounding in the early disease group. The authors acknowledge that treatment imbalance and observational design limit causal inference but argue that these factors do not fully explain the observed mortality signal. They emphasise that early portopulmonary hypertension should currently be viewed as a prognostic marker rather than an indication for immediate treatment. The findings support closer surveillance and risk stratification rather than therapeutic escalation. Future prospective studies and dedicated trials are needed to determine whether early intervention can improve outcomes and to define optimal screening strategies in patients with cirrhosis.

Post-Banding Ulcer Bleeding After EBL: Alimentary Pharmacology & Therapeutics | March 2026

Introduction Endoscopic band ligation (EBL) remains the standard of care for managing esophageal varices, both in acute variceal bleeding and for prophylaxis. However, post-banding ulcer bleeding (PBUB) is an important and often under-recognized complication, associated with significant morbidity and mortality. Identifying patients at higher risk for PBUB is clinically relevant, particularly in acute settings where outcomes are already compromised. Problem Statement Despite increasing recognition of PBUB, risk stratification remains inconsistent in clinical practice. Recent data have suggested that urgent EBL and renal dysfunction may increase PBUB risk, but real-world validation across larger cohorts is limited, and standardized definitions are lacking. Summary In this large real-world analysis of 920 EBL procedures, PBUB occurred in 3.4% overall, with a significantly higher incidence following urgent EBL compared to elective procedures (7.5% vs 1.4%). Urgent EBL emerged as a strong independent predictor of PBUB, reinforcing the vulnerability of patients undergoing intervention during acute bleeding episodes. Additionally, renal dysfunction was identified as a key risk factor, with patients having serum creatinine ≥1.5 mg/dL demonstrating markedly higher bleeding rates and independent risk. These findings are consistent with prior literature and highlight a simple, clinically applicable framework combining urgency of EBL and renal function to identify high-risk patients. This approach may help guide closer monitoring and preventive strategies in routine practice.

Ammonia Measurement in Cirrhosis: Journal of Hepatology| March 2026

Introduction Ammonia has long been recognized as a central neurotoxin in the pathogenesis of hepatic encephalopathy, but its clinical use in cirrhosis has remained inconsistent because of major variability in sampling, processing, reporting, and interpretation. This international ISHEN Delphi consensus is important because it is the first structured, evidence-based effort to define when ammonia should be measured, how it should be measured, and how clinicians should interpret it in both outpatient and inpatient cirrhosis care. The document moves the field beyond the old debate of whether ammonia is useful at all and instead places ammonia within a practical clinical framework. Summary The consensus makes a strong methodological point that ammonia is only clinically useful when measured properly. It recommends a minimum 4-hour fasting period, venous sampling for routine practice, transport on ice, centrifugation within 15 minutes, and measurement within 2 hours. It also advises that ammonia should be reported both as an absolute value and as a multiple of the upper limit of normal to improve comparability across laboratories. In the outpatient setting, ammonia is positioned as a useful biomarker for risk stratification, especially for predicting overt hepatic encephalopathy, liver-related decompensation, and death, with a level greater than 1.4 times the upper limit of normal emerging as an important prognostic threshold. In patients undergoing elective TIPS, pre-procedure ammonia may help predict post-TIPS encephalopathy. In the inpatient setting, ammonia is not considered a standalone diagnostic test for overt hepatic encephalopathy, but a normal value should prompt clinicians to question the diagnosis and search for alternative causes of altered mental status. The consensus also emphasizes that serial ammonia measurement has value during treatment, because falling ammonia levels are associated with better neurological recovery and improved survival, whereas persistent or rising ammonia suggests poor response and worse prognosis. Conclusion The major clinical message of this ISHEN consensus is that ammonia should no longer be dismissed as an unreliable biomarker, but neither should it be used in isolation. When measured under standardized conditions and interpreted within the full clinical context, ammonia provides meaningful diagnostic, prognostic, and therapeutic information in cirrhosis. This document is likely to influence day-to-day hepatology practice, future trial design, and global harmonization of care in hepatic encephalopathy.

A-TANGO for ACLF: Journal of Hepatology | February 2026

Introduction Acute-on-chronic liver failure (ACLF) is a severe syndrome characterized by acute decompensation of cirrhosis, multiorgan failure, and high short-term mortality. The current EASL-CLIF criteria have been widely used for diagnosis and prognostication, but they have important limitations, particularly in accurately defining organ failure thresholds and stratifying risk within severe disease categories. With emerging therapies and increasing emphasis on clinical trials in ACLF, there is a growing need for more precise and reproducible scoring systems. This study introduces the A-TANGO organ failure score, developed using large global cohorts to improve diagnosis, risk stratification, and applicability in clinical trials. Summary The A-TANGO score was derived from nearly 4,000 patients across Europe and Latin America and validated in large independent cohorts from India and China, making it one of the most robust global ACLF datasets to date. The score refines organ dysfunction thresholds and introduces a more granular classification, including a new ACLF grade 4 to better capture patients with extremely high mortality risk. Compared with the traditional CLIF-C OF score, A-TANGO identifies a greater number of organ failures and increases ACLF diagnosis rates, thereby improving patient classification. Importantly, despite identifying more patients with ACLF, the score maintains strong predictive accuracy for short-term mortality. The study also introduces two additional prognostic models incorporating inflammatory markers, which further enhance risk prediction. Overall, A-TANGO provides a more sensitive and clinically relevant framework for identifying high-risk patients, guiding management decisions, and defining endpoints in ACLF clinical trials. Conclusion The A-TANGO organ failure score represents a significant advancement in the field of ACLF by improving diagnostic precision without compromising prognostic performance. Its validation across diverse global populations supports its potential as a new standard for both clinical practice and research. By enabling better identification of high-risk patients and providing more reliable endpoints, A-TANGO is likely to play a key role in the development and evaluation of future therapies in ACLF.