Current Opinion in Gastroenterology最新文献

Purpose of review: This review summarizes the recent developments of one of the most controversial entities in hepatology, variant syndromes of primary biliary cholangitis (PBC) with characteristics of autoimmune hepatitis (AIH).

Recent findings: Recently a consensus process was initiated to find agreement on the terminology, diagnostic criteria and treatment recommendations for patients with PBC-AIH variant syndromes. The concept and terminology of a variant syndrome, with one component of either AIH or PBC dominating over the other, is currently preferred. No single test can establish the diagnosis of a variant syndrome, only a combination of biochemical, serological and/or histological tests can support the diagnosis. If classical PBC is dominating, histology is mandatory for the diagnosis of a PBC-AIH variant syndrome. Treatment of PBC-AIH variants is based on a combination of ursodeoxycholic acid and immunosuppression. Since the prognosis of a PBC-AIH variant syndrome seems to be worse than the prognosis of classical PBC, the diagnosis of PBC-AIH must not be missed.

Summary: The recent consensus process on PBC-AIH variant syndromes does not provide answers to all questions regarding this entity. Rather, it serves as a starting point for future studies to confirm or even challenge the current consensus.

Purpose of review: Autoimmune hepatitis (AIH) presenting with decompensated cirrhosis poses a major therapeutic dilemma for clinicians. Although the prompt initiation of immunosuppression (IS) can reverse disease activity and lead to the clinical resolution of decompensation, avoiding the need for liver transplantation (LT), it may also be futile or even harmful. International guidelines and cohort studies have begun to address this challenge, making it timely to synthesize available evidence and provide practical guidance for clinicians.

Recent findings: Emerging data highlight that the benefit of IS in AIH-related decompensated cirrhosis is closely related to disease activity, as well as to the type and severity of decompensation. In this context, patients with "burn-out" cirrhosis, advanced hepatic encephalopathy and severely elevated prognostic scores have a low probability to benefit from IS and face a greater risk of developing treatment-related complications. Therefore, international guidelines emphasize individualized decision-making, integrating clinical scores and predictors of treatment benefit, as well as timely evaluation for LT.

Summary: This review summarizes the current evidence and evolving recommendations for managing AIH-related decompensated cirrhosis, providing a structured approach to help clinicians identify candidates for IS and balance treatment decisions to optimize outcomes.

Purpose of review: Multiple cystic fibrosis transmembrane conductance regulator (CFTR) modulators are approved for the treatment of cystic fibrosis (CF) and show significant improvement in lung function, BMI, quality of life, and sweat chloride. However, their ability to impact liver disease is unclear. This review highlights the current published literature on CFTR modulators and liver health and briefly reviews considerations for clinical management of hepatobiliary disease in the CFTR modulator era.

Recent findings: Currently, the primary data available on the clinical efficacy of CFTR modulators on CF hepatobiliary involvement (CFHBI) or advanced CF liver disease (aCFLD) is from small to moderate sized single-center studies, although more recently large, multicenter studies are emerging. Studies report opposing changes in aminotransferases, and mixed liver fibrosis index and elastography results. Yet, in total CFTR modulators generally do not worsen liver disease and may improve it in some individuals. Additional clinical management considerations are necessary in those on CFTR modulators who received an organ transplant or during nutritional evaluations.

Summary: To better understand the possible benefit of CFTR modulator therapies on hepatobiliary health, additionally larger, longer-term, multicenter studies with sub-group phenotyping are necessary. Until then, providers should watch for liver-related adverse events, and be cognizant on how CFTR modulators may impact areas of clinical care for individuals with CF.

Purpose of review: Cystic fibrosis liver disease (CFLD) is a significant nonpulmonary complication of cystic fibrosis, affecting approximately 5-10% of patients. It encompasses a spectrum of hepatic abnormalities ranging from mild, transient elevations in liver enzymes to advanced CFLD (aCFLD), which is marked by clinically relevant portal hypertension due to cirrhotic or noncirrhotic liver pathology. This review focuses on aCFLD as the clinically meaningful form of the disease and summarizes recent mechanistic insights into its pathogenesis that may inform the development of targeted therapeutic strategies.

Recent findings: CFLD pathogenesis has been traditionally linked to defective bile secretion. Emerging evidence, however, highlights additional contributors, including cholangiocyte immune dysregulation, gut dysbiosis, and intestinal barrier dysfunction, which together promote hepatic inflammation. Furthermore, recent studies underscore the role of vascular alterations independent of cirrhosis, specifically noncirrhotic portal hypertension, as the main clinical feature in aCFLD. These findings support a multifactorial, multihit model of disease in the pathogenesis of CFLD.

Summary: The complex interplay of these factors suggests that effective treatment for aCFLD may require a multifaceted approach. Advances in understanding the gut-liver axis and vascular contributions provide new therapeutic targets. Future research should focus on validating these findings and evaluating the efficacy of cystic fibrosis transmembrane conductance regulator modulators and microbiome-targeted treatments in altering the course of CFLD.

Purpose of review: This review summarizes recent advances in pancreatic ductal hypertension (PDH), emphasizing its pathophysiological mechanisms, clinical relevance across pancreatic diseases, and progress in noninvasive assessment. The aim is to highlight translational insights that may improve patient selection for intervention and guide long-term management strategies.

Recent findings: Evidence indicates that PDH contributes not only to pain in chronic pancreatitis but also to exocrine insufficiency, diabetes, and complications such as post-ERCP pancreatitis (PEP) and recurrent acute pancreatitis (RAP). Pancreatic stellate cells (PSCs) are central to fibrosis and are directly activated by pressure, reinforcing disease progression. Traditional methods of measuring pancreatic duct pressure rely on invasive manometry, microtransducer catheters, or pancreatic fistulae, all with inherent risks. Recent translational advances, particularly magnetic resonance cholangiopancreatography (MRCP) integrated with computational fluid dynamics modeling, have demonstrated the feasibility of noninvasive pancreatic duct pressure (PDP) estimation with strong concordance to endoscopic retrograde cholangiopancreatography-based manometry and symptom relief.

Summary: These advances emphasize the critical role of accurate pressure assessment in identifying patients with true ductal hypertension who are most likely to benefit from decompression. Noninvasive measurement offers a promising strategy to limit unnecessary interventions and to delineate the direct contribution of ductal pressure to exocrine, endocrine, and related disorders. Validation in larger cohorts and high-risk populations will be essential.

Purpose of review: Traditional approaches to irritable bowel syndrome with diarrhea (IBS-D) relied on extensive exclusionary testing and empiric symptom management. Recent advances in understanding neuroimmune pathophysiology, refined diagnostic algorithms, emergence of novel biomarkers, and clarification of comparative treatment efficacy through systematic reviews necessitate evaluation of whether accumulated evidence warrants substantive changes to contemporary diagnostic and therapeutic practice in IBS-D management.

Recent findings: Diagnostic paradigms have shifted toward symptom-based approaches utilizing judicious testing informed by alarm features, with emerging biomarkers including neutrophil-to-albumin ratio, microRNA-148, and bile acid malabsorption markers showing promise. Therapeutically, tricyclic antidepressants demonstrate robust efficacy as neuromodulators, while selective serotonin reuptake inhibitors show limited benefit. Emerging neuroimmune therapies targeting mast cell activation, including histamine receptor antagonists, represent promising avenues. Low FODMAP and Mediterranean diets demonstrate substantial efficacy, while brain-gut behavioral therapies achieve clinically meaningful improvements in refractory populations through accessible delivery modalities.

Summary: Contemporary evidence supports fundamental practice shifts from exclusionary testing toward targeted investigation of treatable mimics and from empiric management toward mechanism-based multimodal interventions integrating neuromodulators, dietary modifications, and behavioral therapies. Optimal outcomes require individualized treatment selection informed by symptom phenotype and comorbidity profiles, ideally delivered through integrated care models combining gastroenterology, dietetic, and behavioral expertise.

Purpose of review: This review highlights the emerging role of dietary interventions for Crohn's disease (CD).

Recent findings: An overview of clinical data on dietary strategies for management of CD is presented, including exclusive enteral nutrition, the Crohn's disease exclusion diet (CDED) and the Mediterranean diet, among others. The methodological challenges in performing dietary randomized trials are outlined, including the difficulty in blinding, the multiple components inherent to food interventions and the heterogeneous nature of even 'similar' dietary constituents, collectively making it hard to delineate the responsible mechanism for any observed effect. We also review the data on food supplements explored for this CD treatment, such as vitamin D, omega-3 and combination curcumin-QingDai (CurQD). Novel strategies to integrate personalized nutrition with pharmacologic therapy are discussed and may ultimately improve disease control and patients' long term prognosis and quality of life. Dietary interventions as preventive measures in patients at risk of developing CD are particularly appealing, but are still backed only by association studies, thereby mandating further research before they can be strongly endorsed.

Summary: Emerging evidence suggests a range of dietary interventions as potentially effective and safe strategies for management of small bowel CD.

Purpose of review: Immune-mediated diarrhea and colitis (IMDC) is a very common and severe toxicity to immune checkpoint inhibition that has generated a lot of scientific interest. The current guidelines do not capture the most recent literature on this disease entity, and few reviews if any have been published that describe the advances made in our understanding of IMDC. As more and more patients are being treated with immune checkpoint inhibitors (ICIs), it becomes essential to optimize treatment algorithms for ICI-related toxicities, especially IMDC.

Recent findings: In our review, we discuss the findings of recent studies on IMDC epidemiology including incidence and risk factors, evaluation and treatment modalities, and surveillance and long-term outcomes. We note that while much has been learned regarding disease epidemiology and the utility of stool biomarkers over clinical symptoms, there remains a paucity of data where IMDC treatment options and long-term IMDC outcomes and surveillance is concerned.

Summary: Our results highlight the most recent advances in our knowledge of IMDC and allow us to propose a management algorithm that improves on prior guidelines for IMDC by incorporating new study findings.