Trending Topics in Gastroenterology | GastroAGI

POCUS-Guided AKI Management in Cirrhosis: Hepatology | July 2026

Introduction: Acute kidney injury (AKI) is a frequent and life-threatening complication of cirrhosis, with management often complicated by inaccurate assessment of intravascular volume and the presence of cirrhotic cardiomyopathy (CCM). This prospective study evaluated whether point-of-care ultrasound (POCUS)–guided volume management improves AKI outcomes and examined the prognostic impact of CCM on renal recovery, need for renal replacement therapy (RRT), and survival. Why was this study needed? . Volume assessment in cirrhosis is often unreliable using clinical examination alone. . Inappropriate fluid management can worsen AKI or precipitate volume overload. . The impact of cirrhotic cardiomyopathy on AKI recovery and long-term outcomes remains poorly defined. . POCUS offers real-time bedside assessment of cardiac function and volume status but lacks robust prospective outcome data. Results: Among 372 ICU patients with cirrhosis and AKI, nearly 80% were initially hypovolemic. Serial POCUS-guided assessment enabled individualized fluid management, with pre-renal AKI identified in 62% of patients, while HRS-AKI accounted for 16%. Cirrhotic cardiomyopathy was present in 35% overall but was markedly more common in HRS-AKI (75%). Higher baseline mean arterial pressure and cardiac index independently predicted AKI reversal within 7 days. Only 14% required renal replacement therapy, while pulmonary edema occurred in fewer than 5% despite active volume resuscitation. Importantly, CCM emerged as a strong independent predictor of both 90-day and 1-year mortality, and lower cardiac index and impaired diastolic function (reduced septal e′ velocity) independently predicted the need for RRT. Clinical Impact: This study supports incorporating POCUS into routine bedside management of cirrhotic patients with AKI to optimize volume resuscitation while minimizing fluid-related complications. Assessment for CCM should become part of AKI evaluation, as underlying cardiac dysfunction identifies patients at high risk for persistent renal failure, dialysis requirement, and death. Early recognition may facilitate more individualized hemodynamic management and prognostic stratification. Bottom Line: POCUS-guided volume management improves individualized treatment of AKI in cirrhosis, while cirrhotic cardiomyopathy is a major predictor of renal non-recovery, dialysis requirement, and short- and long-term mortality.

A Novel Pro-Resolving Target (Annexin A1) for ACLF: Hepatology | May 2026

Introduction: Acute-on-chronic liver failure (ACLF) is characterized by overwhelming systemic inflammation and immune dysregulation, leading to high short-term mortality. This study used advanced single-cell and spatial transcriptomic technologies to define the immune landscape of ACLF and identify new therapeutic targets for resolving liver inflammation. Why was this study needed? • ACLF remains associated with extremely high mortality and limited effective therapies. • The immune mechanisms driving persistent liver inflammation are incompletely understood. • Identifying pathways that promote resolution of inflammation may offer new therapeutic strategies. • High-resolution immune profiling can uncover novel cellular interactions in ACLF. • Targeted immunomodulation is urgently needed to improve patient outcomes. Results: • ACLF demonstrated a unique inflammatory immune signature, characterized by expansion of inflammatory neutrophils and monocytes, loss of resident Kupffer cells, and profound dysfunction of innate and adaptive immunity. • The Annexin A1 (ANXA1)–FPR1 signaling pathway emerged as a key endogenous mechanism limiting excessive inflammation, with ANXA1 levels correlating with disease severity. • Treatment with the ANXA1-derived peptide (Ac2-26) significantly reduced liver inflammation, improved liver function, and shifted macrophages from a pro-inflammatory (M1) to a pro-resolving (M2) phenotype in preclinical models. Clinical Impact: This study provides one of the most comprehensive immune maps of ACLF to date and identifies Annexin A1 as a promising pro-resolving therapeutic target. Rather than broadly suppressing immunity, therapies enhancing inflammation resolution may represent a new treatment paradigm for ACLF. Bottom Line: ACLF is driven by profound immune dysregulation rather than inflammation alone. Enhancing the ANXA1–FPR1 pathway promotes resolution of liver inflammation and represents a promising next-generation therapeutic strategy for acute-on-chronic liver failure.

Distal Esophageal Varices in Fontan Circulation: Hepatology | May 2026

Introduction: Adults with Fontan-type circulation are increasingly recognized to develop Fontan-associated liver disease and portal hypertension. This prospective study explored the prevalence, anatomical distribution, and hemodynamic characteristics of esophageal varices (EV), with particular emphasis on distal versus proximal varices. Why was this study needed? • Fontan-associated liver disease is becoming a major long-term complication in adult survivors. • The mechanisms underlying esophageal varices in Fontan circulation remain poorly understood. • The clinical significance of proximal versus distal varices has not been clearly defined. • Better risk stratification is needed to optimize surveillance and management. • The relationship between portal hypertension, hepatic fibrosis, and Fontan hemodynamics requires clarification. Results: • Esophageal varices were present in over one-third of adults with Fontan circulation, with distal varices being the most common subtype. • Distal esophageal varices identified a unique high-risk phenotype, characterized by elevated Fontan pressures, portal hypertension, severe hepatic fibrosis, and a hyperdynamic circulatory state. • Despite advanced liver disease, variceal bleeding was uncommon, suggesting that variceal location may provide greater prognostic value than bleeding risk alone. Clinical Impact: This study demonstrates that distal esophageal varices are not simply an endoscopic finding but a marker of advanced Fontan-associated liver disease and severe hemodynamic impairment. Their presence should prompt comprehensive evaluation for portal hypertension and hepatic fibrosis, potentially improving long-term surveillance and multidisciplinary management. Bottom Line: Distal esophageal varices define a distinct hemodynamic and hepatic phenotype in patients with Fontan circulation. They serve as an important marker of advanced Fontan-associated liver disease, portal hypertension, and severe fibrosis, warranting closer clinical monitoring.

Annexin A1-A Novel Pro-Resolving Target for ACLF: Hepatology | May 2026

Introduction: Acute-on-chronic liver failure (ACLF) is characterized by overwhelming systemic inflammation and immune dysregulation, leading to high short-term mortality. This study used advanced single-cell and spatial transcriptomic technologies to define the immune landscape of ACLF and identify new therapeutic targets for resolving liver inflammation. Why was this study needed? • ACLF remains associated with extremely high mortality and limited effective therapies. • The immune mechanisms driving persistent liver inflammation are incompletely understood. • Identifying pathways that promote resolution of inflammation may offer new therapeutic strategies. • High-resolution immune profiling can uncover novel cellular interactions in ACLF. • Targeted immunomodulation is urgently needed to improve patient outcomes. Results: • ACLF demonstrated a unique inflammatory immune signature, characterized by expansion of inflammatory neutrophils and monocytes, loss of resident Kupffer cells, and profound dysfunction of innate and adaptive immunity. • The Annexin A1 (ANXA1)–FPR1 signaling pathway emerged as a key endogenous mechanism limiting excessive inflammation, with ANXA1 levels correlating with disease severity. • Treatment with the ANXA1-derived peptide (Ac2-26) significantly reduced liver inflammation, improved liver function, and shifted macrophages from a pro-inflammatory (M1) to a pro-resolving (M2) phenotype in preclinical models. Clinical Impact: This study provides one of the most comprehensive immune maps of ACLF to date and identifies Annexin A1 as a promising pro-resolving therapeutic target. Rather than broadly suppressing immunity, therapies enhancing inflammation resolution may represent a new treatment paradigm for ACLF. Bottom Line: ACLF is driven by profound immune dysregulation rather than inflammation alone. Enhancing the ANXA1–FPR1 pathway promotes resolution of liver inflammation and represents a promising next-generation therapeutic strategy for acute-on-chronic liver failure.

Simvastatin Improves Survival After Variceal Bleeding in Cirrhosis: AJG | July 2026

Introduction: Despite advances in the management of portal hypertension, mortality after variceal bleeding remains high in patients with cirrhosis. Experimental and clinical studies suggest that statins may improve portal hypertension and hepatic vascular function. This randomized trial evaluated whether adding simvastatin to standard therapy improves long-term outcomes after variceal bleeding. Why was this study needed? • Mortality remains high after acute variceal bleeding despite standard therapy. • Evidence supporting statin use in decompensated cirrhosis is limited. • Statins may improve portal hypertension and hepatic microcirculation beyond lipid lowering. • Their long-term safety in cirrhosis remains uncertain. • Randomized data evaluating survival benefit are lacking. Results: • Adding simvastatin to standard therapy significantly reduced all-cause mortality over 24 months compared with standard care alone. • Simvastatin also reduced the development of new or refractory ascites and spontaneous bacterial peritonitis, while rates of rebleeding, hepatic encephalopathy, and acute-on-chronic liver failure were similar between groups. • Serious adverse events were not increased, supporting the safety of low-dose simvastatin in appropriately selected patients with cirrhosis. Clinical Impact: This study provides important evidence that simvastatin may offer disease-modifying benefits in cirrhosis, extending beyond cholesterol reduction. When added to carvedilol and endoscopic band ligation, simvastatin improved survival without compromising safety, suggesting a potential role in secondary prophylaxis after variceal bleeding. Bottom Line: Low-dose simvastatin improved long-term survival after variceal bleeding in patients with cirrhosis while reducing ascites-related complications without increasing serious adverse events. Larger multicenter trials are warranted before routine incorporation into clinical practice.

Pre-Emptive CRRT Improves Outcomes in ALF with Cerebral Oedema: AP&T | June 2026

Introduction: Acute liver failure (ALF) complicated by cerebral oedema carries a high risk of early mortality, primarily due to hyperammonemia and intracranial hypertension. The optimal timing of continuous renal replacement therapy (CRRT) in these critically ill patients has remained uncertain. Why was this study needed?: Conventional CRRT is often initiated only after significant metabolic deterioration. Whether earlier (pre-emptive) initiation of CRRT, combined with plasma exchange, could improve survival and neurological outcomes had not been established. What did the study show?: This randomised controlled pilot trial compared pre-emptive CRRT plus plasma exchange with standard CRRT initiation in patients with ALF and cerebral oedema. Early CRRT significantly reduced 7-day mortality, accelerated ammonia clearance, improved markers of cerebral oedema, enhanced hemodynamic stability and SOFA scores, and reduced systemic inflammation. Importantly, each hour of delay in CRRT initiation was associated with worse clinical outcomes. Clinical Impact: These findings support a proactive strategy of initiating CRRT early rather than waiting for clinical deterioration. Early ammonia control and reduction of cerebral oedema may provide a crucial bridge to native liver recovery or liver transplantation while improving short-term survival. Take-Home Message: In patients with acute liver failure and cerebral oedema, pre-emptive initiation of CRRT combined with plasma exchange appears to improve early survival and organ function. Early intervention, rather than delayed rescue therapy, may become an important principle in the critical care management of ALF.

Inpatient Management of Hepatic Encephalopathy : Hepatology | June 2026

Introduction: Hepatic encephalopathy (HE) is a major cause of hospitalization in patients with advanced liver disease and is associated with significant morbidity, mortality, and healthcare utilization. The management of HE extends beyond ammonia reduction and requires a comprehensive strategy addressing precipitating factors, nutritional support, organ dysfunction, and disease-specific complications. Importantly, the approach varies according to the underlying clinical context, including decompensated cirrhosis, acute-on-chronic liver failure (ACLF), and acute liver failure (ALF). Problem Statement: Patients admitted with overt HE often present with multiple concurrent complications that contribute to neurological deterioration. Failure to identify reversible precipitants or recognize syndrome-specific management requirements can adversely affect outcomes. In particular, HE associated with ACLF and ALF presents unique challenges due to multiorgan failure, cerebral edema, and the potential need for emergency liver transplantation. Summary: This review provides a comprehensive overview of the inpatient management of HE across different clinical scenarios. In patients with decompensated cirrhosis, management begins with exclusion of alternative causes of altered mental status, followed by prompt identification and correction of precipitating factors such as infection, gastrointestinal bleeding, electrolyte disturbances, constipation, and renal dysfunction. Nutritional optimization and pharmacological therapies aimed at reducing ammonia production remain central components of care. In ACLF, HE often occurs in conjunction with other organ failures and frequently necessitates intensive care management. Treatment focuses on aggressive management of precipitating events, organ support, and consideration of emergency liver transplantation in carefully selected candidates. The review highlights that ALF represents a distinct clinical entity in which rapidly rising ammonia levels may lead to cerebral edema and intracranial hypertension. Consequently, management includes specialized neuroprotective strategies, close neurological monitoring, osmotic therapy for intracranial pressure control, and extracorporeal ammonia-lowering approaches such as continuous renal replacement therapy and therapeutic plasma exchange. Across all etiologies, patients with grade 3–4 HE require intensive care monitoring because of the high risk of airway compromise and aspiration. The review reinforces the importance of individualized, syndrome-specific management pathways to optimize outcomes in hospitalized patients with HE.

A Practical Diagnostic Framework for Hepatic Encephalopathy : Hepatology | June 2026

Introduction: Hepatic encephalopathy (HE) is one of the most common and debilitating neuropsychiatric complications of liver disease and portal-systemic shunting. It can present with a broad spectrum of manifestations, ranging from subtle cognitive impairment to profound coma, significantly affecting quality of life, healthcare utilization, and survival. Although ammonia plays a central role in its pathogenesis, growing evidence supports a multifactorial process involving gut-derived inflammation, infection, and neuroinflammatory pathways. Problem Statement: Diagnosing HE remains challenging because there is no single definitive diagnostic test. Patients with cirrhosis and portal hypertension are also susceptible to numerous alternative causes of altered mental status, many of which are potentially reversible and require urgent treatment. Consequently, HE remains a diagnosis of exclusion, demanding a structured and systematic clinical approach to avoid misdiagnosis and delayed management. Summary: This review provides a practical framework for the diagnosis of HE in both acute and outpatient settings. The authors emphasize that accurate diagnosis begins with confirmation of the underlying liver disease or portal-systemic shunting capable of causing HE. Clinical characterization is then essential, recognizing the diverse cognitive, behavioral, neurological, and consciousness-related manifestations that may occur. The review highlights the importance of actively searching for precipitating factors, including infection, gastrointestinal bleeding, constipation, dehydration, electrolyte disturbances, renal dysfunction, and medication-related triggers, as correction of these factors often leads to clinical improvement. Equally important is the systematic exclusion of alternative neurological, metabolic, infectious, psychiatric, and toxicological causes of altered mental status. The authors propose a practical four-step diagnostic approach: defining the underlying disease, characterizing the clinical syndrome, identifying precipitants and risk factors, and excluding competing diagnoses. For patients with subtle cognitive dysfunction, the review also discusses the role of neuropsychological and neurophysiological testing in the diagnosis of covert HE. This structured approach provides clinicians with a clinically relevant roadmap for diagnosing HE, ensuring timely recognition while minimizing the risk of overlooking other potentially treatable conditions.

No Safe Protective Level of Alcohol Identified : JSAD | Jun 2026

Introduction: The belief that low or moderate alcohol consumption may confer cardiovascular or overall health benefits has influenced public health messaging for decades. However, emerging evidence has increasingly challenged this concept, particularly as improved analytical methods have addressed biases present in earlier observational studies. Given alcohol’s established association with liver disease, gastrointestinal cancers, cardiovascular disorders, and injury-related harm, a more comprehensive assessment of its lifetime health impact is needed. Problem Statement: Current alcohol consumption guidelines in several countries continue to permit moderate drinking based partly on the assumption that low levels of alcohol may offer health benefits. However, uncertainty remains regarding whether any level of alcohol consumption provides a net protective effect when both mortality and morbidity risks are considered across an individual’s lifetime. Summary: The Alcohol Intake and Health Study provides a comprehensive evaluation of the lifetime health risks associated with alcohol consumption in the United States. Using national exposure, mortality, and morbidity data, the investigators found no evidence of a net protective health effect at low levels of alcohol intake. Instead, alcohol consumption was associated with progressively increasing risks of death and disease beginning at relatively modest levels of use. Importantly, risks were not confined to heavy drinking but extended into ranges commonly perceived as moderate consumption. The study also demonstrated that drinking patterns matter; consuming multiple drinks on a single occasion further amplified risks of cancer, cardiovascular disease, and injury. These findings challenge the longstanding perception that moderate alcohol intake may be beneficial and support a shift toward more conservative alcohol recommendations. From a gastroenterology and hepatology perspective, the results are particularly relevant given alcohol’s central role in liver disease, gastrointestinal malignancies, and pancreatitis. The authors conclude that public health guidance should emphasize risk reduction rather than potential benefits and support limiting alcohol intake to no more than one drink per day for adults who choose to consume alcohol. Overall, the study strengthens the growing body of evidence that lower alcohol consumption is associated with better long-term health outcomes.

CKD Worsens Outcomes in Cirrhosis Worldwide : Gut | June 2026

Introduction: Chronic kidney disease (CKD) is increasingly recognized as a major comorbidity in patients with cirrhosis. The growing global burden of metabolic syndrome, obesity, and diabetes has contributed to a rising prevalence of both liver and kidney disease. In patients with cirrhosis, impaired renal function can complicate management, increase susceptibility to acute kidney injury (AKI), and adversely affect survival. However, data describing the global burden and clinical impact of CKD in cirrhosis have been limited. Problem Statement: Although CKD is known to influence outcomes in advanced liver disease, its prevalence across different regions of the world and its contribution to complications and mortality in hospitalized patients with cirrhosis remain incompletely understood. Identifying the burden of CKD and its clinical consequences is essential for improving risk stratification and patient management. Summary: This large international study from the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium evaluated more than 7,000 hospitalized patients with cirrhosis across 127 centers worldwide. The investigators found that nearly one in five patients had underlying CKD, highlighting the substantial global burden of renal dysfunction in cirrhosis. The prevalence was highest in high-income countries, reflecting the greater burden of metabolic syndrome and related risk factors in these regions. Patients with CKD presented with more advanced and complicated liver disease, including a higher frequency of ascites and other manifestations of decompensation. Importantly, they were significantly more likely to develop AKI during hospitalization, emphasizing the vulnerability of this population to further renal deterioration. CKD was also associated with substantially worse short-term outcomes, including increased in-hospital and post-discharge mortality. These findings establish CKD as a major determinant of prognosis in cirrhosis and reinforce the need for early identification and proactive management of renal dysfunction. Optimizing ascites control, addressing metabolic risk factors, and implementing strategies to prevent kidney injury may play a critical role in improving outcomes for patients with cirrhosis worldwide.