The week in GI, filtered to what is worth knowing.

Outpatient positioning is unchanged from the ACG 2025 UC guideline and the AGA living guideline for moderate-to-severe UC. Confirm UC with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step C. difficile testing. Treat mild-moderate disease with 5-ASA chosen by route and extent: suppository for proctitis, enema for left-sided disease, oral plus rectal for extensive disease. If 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by efficacy tier, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab. Intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab. Lower: adalimumab. Previously TNF-exposed, higher efficacy: tofacitinib, upadacitinib, ustekinumab. Lower: adalimumab, vedolizumab, ozanimod, etrasimod. After anti-TNF primary non-response, switch mechanism rather than cycling within the class. Treat to target (STRIDE-II): endoscopic improvement, Mayo endoscopic subscore 0-1. Begin CRC surveillance 8-10 years after diagnosis for extensive or left-sided disease; isolated proctitis follows average-risk screening. Inpatient care now follows the 2026 AGA Clinical Practice Update (13 best-practice statements). Admit for severe symptoms refractory to outpatient therapy, suspected complications (obstruction, abscess, toxic megacolon) or significant malnutrition, and identify acute severe UC by Truelove-Witts. Give every patient admitted with diarrhea two-step C. difficile testing. Test for CMV, with early endoscopy, if symptoms worsen, the patient is systemically toxic or disease is steroid-refractory. Give routine VTE prophylaxis with LMWH or fondaparinux unless contraindicated, and individualize post-discharge extension. Give IV methylprednisolone 60 mg/day or equivalent; the AGA living guideline says 40-60 mg/day, and higher doses add no benefit. Do not give adjunctive antibiotics without infection. Involve surgery early. Assess response by day 3 (72 h) using stool frequency and CRP (Oxford criteria); do not continue IV steroids beyond about 7 days without response. Rescue steroid non-responders with infliximab (accelerated or intensified dosing in selected patients with high inflammatory burden or protein-losing colopathy), cyclosporine, or a JAK inhibitor at standard or intensified dosing, or with colectomy. Before discharge, the response should be stable and a transition plan should be in place.

Two current US guidelines govern Crohn's disease and should be read together. ACG 2025 (Lichtenstein et al.) remains the reference for diagnosis, mild-to-moderate disease, perianal, postoperative and abscess management. DIAGNOSIS: fecal calprotectin (>50-100 μg/g) separates inflammatory from noninflammatory disease of the colon. Workup is ileocolonoscopy with biopsies, including uninvolved mucosa, plus small-bowel imaging. CTE and MRE are comparable; prefer MRE in patients <35 y and when serial exams are likely. Intestinal ultrasound is an ungraded adjunct. Do routine CRC surveillance in Crohn's colitis. MILD-TO-MODERATE: recommend against oral mesalamine; sulfasalazine only for symptomatic mild colonic CD; ileal-release budesonide 9 mg for induction in ileocecal disease but not for maintenance. MODERATE-TO-SEVERE (AGA Living Guideline, Scott et al., Gastroenterology 2025;169(7):1397-1448, 16 recommendations: 1 strong, 9 conditional, 6 knowledge gaps; updated quarterly, adult outpatients only): RECOMMEND infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab or upadacitinib over no treatment; SUGGEST certolizumab pegol or vedolizumab over no treatment. Advanced-therapy-naive: suggest higher-efficacy agents (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) over lower-efficacy ones (certolizumab pegol, upadacitinib). Prior advanced-therapy (especially anti-TNF) exposure: suggest higher- or intermediate-efficacy agents (adalimumab, risankizumab, guselkumab, upadacitinib; ustekinumab, mirikizumab) over lower-efficacy ones (vedolizumab, certolizumab pegol). Suggest against thiopurine monotherapy for induction; suggest it for maintenance of remission. Suggest SC/IM methotrexate monotherapy; suggest against oral methotrexate. In thiopurine-naive patients starting infliximab, suggest infliximab + thiopurine over infliximab alone. No recommendation on IFX + MTX, adalimumab + immunomodulator, or non-TNF biologic + immunomodulator. After ≥6 months of steroid-free remission on anti-TNF + immunomodulator, suggest withdrawing the immunomodulator and suggest against withdrawing the anti-TNF. SUGGEST upfront advanced therapy over step-up therapy (corticosteroids and/or immunomodulator first). No recommendation on treating to endoscopic vs symptomatic remission. The ACG 2025 moderate-to-severe recommendations (anti-TNF, IFX + thiopurine combination and IL-12/23/IL-23 agents, each strong/moderate; upadacitinib after anti-TNF exposure; steroids for short-term induction only; TPMT/NUDT15 testing before thiopurines) still stand alongside AGA. ACG perianal (infliximab first; drain abscesses and place setons before escalating), postoperative (endoscopy at 6-12 months; anti-TNF strong, vedolizumab conditional in high-risk patients) and intra-abdominal abscess (>2 cm: antibiotics plus drainage, hold immunosuppression) positions are unchanged. THERAPEUTIC ENDOSCOPY (AGA Clinical Practice Update, CGH 2026; details below come from AGA news coverage, not the full text, and are ungraded advice): get cross-sectional imaging before the procedure. Endoscopic balloon dilation is first-line for short strictures (about ≤4-5 cm) with few risk factors (fistula, prestenotic dilation >5 cm, high CRP, prior anti-TNF). Longer or multiple strictures, or ≥3 risk factors, favor surgery.

This standard applies to MASLD: hepatic steatosis on imaging or biopsy, at least one cardiometabolic criterion, no other liver disease, and alcohol below the MetALD range. The AGA 2026 MetALD update sets MetALD at about 140-350 g/week of alcohol in women and 210-420 g/week in men, averaged over at least 3 months. MASLD therefore means under about 140 g/week (women) or 210 g/week (men), and drinking above the MetALD range is ALD. Assess alcohol use in every patient with steatotic liver disease at diagnosis and at least once a year, by interview, a validated questionnaire (e.g., AUDIT-C) and/or biomarkers such as phosphatidylethanol (PEth). Advise every patient with steatotic liver disease to stop drinking. Screen people with type 2 diabetes, people with overweight or obesity plus at least one more metabolic risk factor, and anyone with incidental steatosis or raised aminotransferases. Use FIB-4 first. A score below 1.3 (below 2.0 at age 65 or older) is low risk: the patient stays in primary care and repeats FIB-4 every 1-2 years. A score at or above the cutoff goes to a second-line test: VCTE, or ELF if elastography is not available. VCTE below 8 kPa is low risk. VCTE of 8 kPa or more, or ELF of 9.2 or more, means clinically significant fibrosis is likely and the patient should be referred to hepatology. Read liver stiffness with caution if the patient is actively drinking. Reserve biopsy for discordant or unclear results. Lifestyle change is the base of treatment for everyone: at least 5% weight loss improves steatosis, and 10% or more is usually needed for fibrosis to improve. Pharmacotherapy is recommended for adults with non-cirrhotic MASH and F2-F3 fibrosis (by non-invasive tests or biopsy), alongside structured lifestyle intervention and optimised management of comorbidities. The NIT ranges that stand in for F2-F3 differ by society. AASLD uses VCTE 8-15 kPa, MRE 3.1-4.4 kPa or ELF 9.2-10.5. EASL-EASD-EASO 2026 frames the treatable high-risk group as, for example, VCTE 10-20 kPa, MRE 3.1-5.0 kPa or ELF 9.8-11.3. Two drugs are approved: resmetirom (80 mg oral daily, or 100 mg at body weight of 100 kg or more; AASLD Oct 2024 guidance) and semaglutide 2.4 mg subcutaneously once weekly (FDA accelerated approval Aug 2025, AASLD Nov 2025 guidance; in ESSENCE, MASH resolved without fibrosis worsening in 62.9% vs 34.3% on placebo). EASL-EASD-EASO 2026 says to choose between them by patient preference, risks and cardio-renal-metabolic profile. Semaglutide may be preferred with obesity, type 2 diabetes, established cardiovascular disease or high cardiovascular risk. Resmetirom may be prioritised without obesity, or when the patient is already on or cannot tolerate a GLP-1 receptor agonist. On semaglutide, monitoring includes nutrition and sarcopenia assessment, and fibrosis NITs are used over time to judge response. In MASH cirrhosis, resmetirom and semaglutide appear safe but should not be used as MASH-targeted treatment until liver-related benefit is shown. Pioglitazone or vitamin E remain options under the AASLD 2023 guidance. Neither resmetirom nor semaglutide has been formally studied in MetALD. Manage cardiometabolic risk in every patient whatever the fibrosis stage, including statins for ASCVD and control of glucose and blood pressure. On semaglutide, watch for GI side effects and rare risks (AKI, gallbladder disease, pancreatitis, retinopathy, loss of lean mass). For MetALD, treat moderate or severe alcohol use disorder with medication plus behavioural therapy, correct micronutrient deficiencies (folate, thiamine, vitamin D), and do not offer bariatric or endobariatric procedures. HCC surveillance with ultrasound, with or without AFP, every 6 months is indicated only when cirrhosis is present.

ACG 2025 (GRADE) is still the governing guideline. The ASGE 2026 consensus Part 2 (modified Delphi, 28 statements at ≥80% agreement; not GRADE) adds endoscopic and pediatric detail without contradicting it. DIAGNOSIS: symptoms of esophageal dysfunction plus ≥15 eos/hpf after excluding other causes of esophageal eosinophilia. A PPI trial is not a diagnostic criterion (PPI-REE abandoned). Do the initial diagnostic EGD off PPI, topical steroid and dietary therapy (ACG key concept; ASGE consensus, which gives no washout duration). Initial assessment is a standard EGD, not a less-invasive modality, so that full biopsies and dilation are possible (ASGE). Take ≥6 esophageal biopsies from ≥2 levels in anyone with symptoms or endoscopic findings consistent with EoE, targeting visible lesions. In CHILDREN with suspected EoE, also biopsy the stomach and duodenum (ASGE). Use EREFS at every endoscopy and report a quantified peak eosinophil count (ACG strong/low; ASGE). TREATMENT (ACG): swallowed topical steroids STRONG/moderate; high-dose PPI CONDITIONAL/low; empiric elimination diet CONDITIONAL/low. Choose a single initial therapy by shared decision-making. Fluticasone or budesonide are both reasonable. Adult doses: PPI double the reflux dose (e.g., omeprazole 20 mg BID or 40 mg daily); budesonide 2-4 mg/day (BOS 2 mg BID); fluticasone 1,760 mcg/day divided. Pediatric doses: PPI 2 mg/kg/day; budesonide 1-2 mg/day; fluticasone 110-880 mcg/day. Allergy testing is not used to direct diets. A 1FED/2FED step-up diet with a dietitian is acceptable, with endoscopic and biopsy confirmation after each reintroduced food. Dupilumab is CONDITIONAL for PPI-nonresponsive patients aged ≥12 (moderate) and for ages 1-11 at ≥15 kg (low). Weight-band dosing: 15-<30 kg 200 mg q2w; 30-<40 kg 300 mg q2w; ≥40 kg 300 mg weekly. Recommendations AGAINST: omalizumab, cromolyn, montelukast. No recommendation for cendakimab, benralizumab, lirentelimab, mepolizumab or reslizumab. DILATION: an adjunct to anti-inflammatory therapy for strictures causing dysphagia (ACG conditional/low). Start low and go slow; target ≥16 mm in adults and adolescents over ≥1 session. In children, ASGE supports dilation of symptomatic strictures or a narrow-caliber esophagus regardless of disease activity, using the same start-low/go-slow approach. MAINTENANCE: continue effective therapy (ACG STRONG despite low evidence) at the lowest effective dose. MONITORING: judge response on symptoms, endoscopy and histology together, never symptoms alone. Assess response endoscopically at 8-12 weeks after starting a PPI or topical steroid. For diet, ACG says 8-12 weeks and ASGE says 6-8 weeks. For dupilumab or biologics, assess at 12-24 weeks (ASGE: up to 24 weeks). Allow appropriate washout or timing after any treatment change before the follow-up EGD (ASGE). Take monitoring biopsies from the most severe-appearing lesions (rings, furrows, exudates) (ASGE). Monitoring biopsies may be limited to the esophagus when prior gastric and duodenal biopsies were normal and nothing new suggests other pathology (ASGE). The histologic response threshold of <15 eos/hpf is a 'may consider' target, read alongside endoscopic and symptom findings. Shorten follow-up after complications. Care gaps of ≥2 years are associated with fibrostenosis. PEDIATRIC (ACG): esophagram for children with dysphagia to assess fibrostenotic disease; feeding therapy and dietitian for feeding dysfunction; growth, development and nutrition are treatment goals.

ACG 2025 (GRADE) is still the governing guideline. The ASGE 2026 consensus Part 2 (modified Delphi, 28 statements at ≥80% agreement; not GRADE) adds endoscopic and pediatric detail without contradicting it. DIAGNOSIS: symptoms of esophageal dysfunction plus ≥15 eos/hpf after excluding other causes of esophageal eosinophilia. A PPI trial is not a diagnostic criterion (PPI-REE abandoned). Do the initial diagnostic EGD off PPI, topical steroid and dietary therapy (ACG key concept; ASGE consensus, which gives no washout duration). Initial assessment is a standard EGD, not a less-invasive modality, so that full biopsies and dilation are possible (ASGE). Take ≥6 esophageal biopsies from ≥2 levels in anyone with symptoms or endoscopic findings consistent with EoE, targeting visible lesions. In CHILDREN with suspected EoE, also biopsy the stomach and duodenum (ASGE). Use EREFS at every endoscopy and report a quantified peak eosinophil count (ACG strong/low; ASGE). TREATMENT (ACG): swallowed topical steroids STRONG/moderate; high-dose PPI CONDITIONAL/low; empiric elimination diet CONDITIONAL/low. Choose a single initial therapy by shared decision-making. Fluticasone or budesonide are both reasonable. Adult doses: PPI double the reflux dose (e.g., omeprazole 20 mg BID or 40 mg daily); budesonide 2-4 mg/day (BOS 2 mg BID); fluticasone 1,760 mcg/day divided. Pediatric doses: PPI 2 mg/kg/day; budesonide 1-2 mg/day; fluticasone 110-880 mcg/day. Allergy testing is not used to direct diets. A 1FED/2FED step-up diet with a dietitian is acceptable, with endoscopic and biopsy confirmation after each reintroduced food. Dupilumab is CONDITIONAL for PPI-nonresponsive patients aged ≥12 (moderate) and for ages 1-11 at ≥15 kg (low). Weight-band dosing: 15-<30 kg 200 mg q2w; 30-<40 kg 300 mg q2w; ≥40 kg 300 mg weekly. Recommendations AGAINST: omalizumab, cromolyn, montelukast. No recommendation for cendakimab, benralizumab, lirentelimab, mepolizumab or reslizumab. DILATION: an adjunct to anti-inflammatory therapy for strictures causing dysphagia (ACG conditional/low). Start low and go slow; target ≥16 mm in adults and adolescents over ≥1 session. In children, ASGE supports dilation of symptomatic strictures or a narrow-caliber esophagus regardless of disease activity, using the same start-low/go-slow approach. MAINTENANCE: continue effective therapy (ACG STRONG despite low evidence) at the lowest effective dose. MONITORING: judge response on symptoms, endoscopy and histology together, never symptoms alone. Assess response endoscopically at 8-12 weeks after starting a PPI or topical steroid. For diet, ACG says 8-12 weeks and ASGE says 6-8 weeks. For dupilumab or biologics, assess at 12-24 weeks (ASGE: up to 24 weeks). Allow appropriate washout or timing after any treatment change before the follow-up EGD (ASGE). Take monitoring biopsies from the most severe-appearing lesions (rings, furrows, exudates) (ASGE). Monitoring biopsies may be limited to the esophagus when prior gastric and duodenal biopsies were normal and nothing new suggests other pathology (ASGE). The histologic response threshold of <15 eos/hpf is a 'may consider' target, read alongside endoscopic and symptom findings. Shorten follow-up after complications. Care gaps of ≥2 years are associated with fibrostenosis. PEDIATRIC (ACG): esophagram for children with dysphagia to assess fibrostenotic disease; feeding therapy and dietitian for feeding dysfunction; growth, development and nutrition are treatment goals.

Stage cholangiocarcinoma with multiphasic MRI/MRCP plus CT chest/abdomen/pelvis, obtain tissue via ERCP brush cytology with FISH, cholangioscopy-directed biopsy, or EUS-FNA (avoiding primary perihilar tumor sampling if liver transplant is being considered due to theoretical seeding risk), and manage through a multidisciplinary tumor board with treatment stratified by tumor location: resect (anatomic hepatectomy for intrahepatic, hemihepatectomy with bile duct resection for perihilar, Whipple for distal) with adjuvant capecitabine (category 1, per BILCAP) when resectable. For unresectable or metastatic disease, first-line systemic therapy is gemcitabine plus cisplatin combined with a PD-L1/PD-1 checkpoint inhibitor, either durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966), both listed as category 1 preferred options by NCCN; comprehensive molecular/genomic profiling is recommended for all unresectable/metastatic candidates for systemic therapy to identify actionable targets (e.g., FGFR2 fusions, IDH1 mutations, HER2 amplification) for later-line therapy. Selected unresectable early-stage perihilar tumors may undergo neoadjuvant chemoradiation and liver transplant per the Mayo Clinic protocol at experienced centers, and jaundice or cholangitis is managed with biliary drainage (ERCP preferred over PTC).

Risk-stratify suspected choledocholithiasis (high >50%, intermediate 10-50%, low <10% probability). HIGH-risk criteria, any of which should directly prompt ERCP: (1) CBD stone on ultrasound or cross-sectional imaging; (2) ascending cholangitis; (3) total bilirubin >4 mg/dL AND dilated CBD (>6 mm in adults with gallbladder in situ, >8 mm after cholecystectomy). Gallstone pancreatitis was deliberately REMOVED as a high-risk criterion in the 2019 revision. INTERMEDIATE risk (abnormal liver biochemical tests, age >55 y, or bile-duct dilation on imaging): the panel suggests confirmation with either EUS or MRCP (conditional recommendation, low-quality evidence; choice by patient preference, local expertise, availability), laparoscopic intraoperative cholangiography (IOC) or intraoperative US are equally sanctioned alternatives. LOW risk: cholecystectomy with or without IOC/intraoperative US if indicated for symptomatic cholelithiasis; no ERCP and no mandatory advanced biliary imaging. In gallstone pancreatitis WITHOUT cholangitis or biliary obstruction/choledocholithiasis, the panel recommends AGAINST urgent (<48 h) ERCP (strong recommendation, low-quality evidence). Same-admission cholecystectomy is recommended for patients with MILD gallstone pancreatitis (consensus, PONCHO-based); ERCP with prophylactic sphincterotomy should not be used as an alternative to cholecystectomy unless surgery is absolutely contraindicated (e.g., recurrent pancreatitis in end-stage liver disease). For large bile-duct stones, the panel suggests endoscopic sphincterotomy followed by large-balloon dilation (ES-LBD) rather than sphincterotomy alone (conditional, moderate); for large AND difficult stones, it suggests intraductal therapy (cholangioscopy-guided EHL or laser lithotripsy) or conventional therapy with papillary dilation, chosen by local expertise, cost, and patient/physician preference (conditional, very low). Timing versus cholecystectomy: pre- or postoperative ERCP or laparoscopic bile-duct clearance for patients at high risk or with positive IOC, depending on local surgical and endoscopic expertise (consensus).

Diagnosis: use a positive diagnostic strategy based on Rome IV criteria rather than a strategy of exclusion (strong for cost-effectiveness, high quality; consensus for time-to-therapy), and categorize by IBS subtype (consensus). In patients with IBS and diarrhea symptoms: check celiac serology (strong, moderate) and, in those WITHOUT alarm features, fecal calprotectin (or fecal lactoferrin) plus CRP to rule out IBD (strong; moderate quality for CRP/calprotectin, very low for lactoferrin). Recommend AGAINST routine stool testing for enteric pathogens (conditional, low) and AGAINST routine colonoscopy in patients younger than 45 without warning signs (conditional, low). Anorectal physiology testing only when symptoms suggest a pelvic floor disorder and/or for refractory constipation not responding to standard medical therapy (consensus). Treatment, all subtypes: soluble, not insoluble, fiber (strong, moderate); a LIMITED trial of a low-FODMAP diet (conditional, very low); gut-directed psychotherapies for global symptoms (conditional, very low); TCAs for global symptoms (strong, moderate); peppermint suggested (conditional, low); antispasmodics for abdominal pain (conditional, low); AGAINST probiotics (conditional, very low), AGAINST fecal transplant (strong, very low). IBS-C: chloride channel activators (strong, moderate) and guanylate cyclase activators (strong, high); AGAINST PEG products for global IBS-C symptoms (conditional, low); tegaserod reserved for women younger than 65 with ≤1 cardiovascular risk factor who have not adequately responded to secretagogues (strong/conditional, low). IBS-D: rifaximin (strong, moderate); alosetron only for women with severe IBS-D who have failed conventional therapy (conditional, low); mixed opioid agonists/antagonists, i.e. eluxadoline (conditional, moderate); AGAINST bile acid sequestrants (conditional, very low).