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

Diagnose active infection with HCV antibody testing with reflex HCV RNA PCR (Rating I, A); one-time opt-out anti-HCV testing is recommended for all adults ≥18 years and with each pregnancy (I, B), with annual testing for people who inject drugs, men with HIV who have unprotected sex with men, and MSM on PrEP (IIa, C). Treatment is recommended for all persons with acute or chronic HCV infection EXCEPT those with a short life expectancy that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy. Stage fibrosis noninvasively (FIB-4; biopsy not required). The simplified treatment algorithm applies only to treatment-naive adults and EXCLUDES prior HCV treatment, HBsAg positivity, current pregnancy, known or suspected HCC, prior liver transplantation, and any current or prior episode of decompensated cirrhosis; excluded patients are managed by the genotype/population-specific sections, not the simplified pathway. Treatment-naive WITHOUT cirrhosis (FIB-4 ≤3.25 and no other evidence of cirrhosis): glecaprevir 300 mg/pibrentasvir 120 mg once daily with food × 8 weeks, OR sofosbuvir 400 mg/velpatasvir 100 mg once daily × 12 weeks, both pangenotypic and equally recommended; pretreatment CBC, hepatic function panel, eGFR, quantitative HCV RNA, HIV, HBsAg, pregnancy test within 6 months, plus medication reconciliation for drug-drug interactions. Treatment-naive WITH compensated cirrhosis (Child-Pugh A): glecaprevir/pibrentasvir × 8 weeks for genotypes 1-6, OR sofosbuvir/velpatasvir × 12 weeks for genotypes 1, 2, 4, 5, and 6 only, in genotype 3 with compensated cirrhosis, baseline NS5A resistance testing is required before sofosbuvir/velpatasvir and the presence of Y93H changes the regimen; pretreatment labs within 3 months plus CTP score and liver ultrasound within 6 months. On treatment, no routine laboratory monitoring is required except counseling diabetic patients about hypoglycemia and monitoring INR in patients on warfarin. Decompensated cirrhosis (CTP class B or C, or any prior decompensation): refer to a practitioner with expertise, ideally at a liver transplant center; ALL protease-inhibitor-containing regimens (glecaprevir, grazoprevir, voxilaprevir) are contraindicated. Ribavirin-eligible, treatment-naive: sofosbuvir/velpatasvir + weight-based ribavirin × 12 weeks (all genotypes), or ledipasvir/sofosbuvir + ribavirin × 12 weeks for genotypes 1, 4, 5, 6; ribavirin-ineligible: sofosbuvir/velpatasvir (or ledipasvir/sofosbuvir for GT 1, 4, 5, 6) × 24 weeks without ribavirin; prior sofosbuvir-based or NS5A inhibitor-based treatment failure: sofosbuvir/velpatasvir + weight-based ribavirin × 24 weeks. In CTP class C, start ribavirin at 600 mg/day and increase as tolerated toward weight-based dosing. Cure is defined by quantitative HCV RNA undetectable ≥12 weeks after completing therapy (SVR12), checked with a hepatic function panel; patients without cirrhosis who achieve SVR need no further liver-related follow-up, while patients with cirrhosis continue HCC ultrasound surveillance every 6 months and variceal screening per AASLD guidelines after SVR. Repeat annual HCV RNA testing in anyone with ongoing exposure risk.

Confirm ACTIVE infection before treating using a urea breath test, fecal (stool) antigen test, or endoscopic biopsy-based test (histology or rapid urease); do NOT use serology. Testing and treatment are a SINGLE decision, do NOT test unless you intend to treat, and, conversely, offer eradication to EVERY patient found to have confirmed active infection regardless of why they were tested ('if you test, you treat'); confirmed active infection is itself the indication to treat, not one of the conditions below. The following are indications to TEST for H. pylori (and to treat whenever the test is positive): active or prior peptic ulcer disease, gastric MALT lymphoma, atrophic gastritis / gastric intestinal metaplasia and other gastric premalignant conditions, uninvestigated dyspepsia in patients under 60 without alarm features (test-and-treat), functional dyspepsia, long-term NSAID or aspirin use, unexplained iron-deficiency anemia, immune (idiopathic) thrombocytopenic purpura, resected early gastric cancer or gastric adenomas, first-degree relatives of gastric-cancer patients, and adult household members of an infected person (test non-serologically). First-line in treatment-naive patients: the PREFERRED regimen (strong recommendation, moderate quality of evidence) is optimized bismuth quadruple therapy (BQT) for 14 days = standard-dose PPI twice daily + bismuth subcitrate or subsalicylate four times daily + tetracycline 500 mg four times daily + metronidazole 500 mg three or four times daily; 'optimized' means the full 14 days, using tetracycline (do NOT substitute doxycycline) and adequate metronidazole (at least 1.5 g/day). Optimized BQT is preferred even with penicillin allergy; avoid tetracycline in women of childbearing potential and avoid bismuth subsalicylate in salicylate allergy. CONDITIONAL alternatives (low/moderate QOE, require no penicillin allergy) are rifabutin triple therapy (omeprazole 10 mg / amoxicillin 250 mg / rifabutin 12.5 mg, i.e. Talicia, 4 capsules three times daily for 14 days) and vonoprazan-amoxicillin DUAL therapy (vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily for 14 days). Vonoprazan-clarithromycin TRIPLE therapy (vonoprazan 20 mg twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days) should be used ONLY when the strain is clarithromycin-susceptible. AVOID any empiric clarithromycin-containing (including PPI-clarithromycin triple) or levofloxacin-containing regimen unless susceptibility is documented (clarithromycin resistance ~22-31%, levofloxacin ~38%); prefer esomeprazole or rabeprazole, or a PCAB, over omeprazole/lansoprazole/pantoprazole in known rapid or ultrarapid CYP2C19 metabolizers. Test of cure is required for ALL treated patients: confirm eradication with a urea breath test, fecal antigen test, or biopsy-based test performed at least 4 weeks after finishing antibiotics and after holding PPIs/PCABs for at least 2 weeks (an H2-receptor antagonist may be used in the interim).

Surveillance practice is now defined by the AGA 2025 surveillance guideline (Wani et al., Gastroenterology 2025;169:1184-1231; endorsed by the Canadian Association of Gastroenterology). Its 8 GRADE recommendations are: (1) endoscopic surveillance for nondysplastic BE rather than none (conditional, low certainty); (2) NO endoscopic surveillance for columnar-lined esophagus <1 cm, even with intestinal metaplasia, when there is no neoplasia (conditional); (3) high-definition white-light endoscopy PLUS chromoendoscopy over white light alone (STRONG); (4) no recommendation for or against wide-area transepithelial sampling (WATS-3D) as an adjunct to structured biopsy; (5) no recommendation on p53 IHC and (6) no recommendation on TissueCypher as adjuncts to histopathology in NDBE, indefinite for dysplasia (IND), or LGD; (7) daily PPI over no PPI to prevent neoplastic progression (conditional); (8) PPI over antireflux surgery to prevent progression to HGD/EAC (conditional). Implementation statements require a high-quality exam, a structured (Seattle-type) biopsy protocol, confirmation of any BE-related dysplasia by an expert GI pathologist, intervals tailored to segment length and dysplasia grade, and shared decision-making. Surveillance should stop when a patient could not tolerate endoscopic therapy, surgery, or oncologic treatment for EAC, at any age. The AGA 2025 interval table could not be read directly (full text paywalled). Until it is, the intervals below are the ACG 2022 intervals, which remain consistent with AGA's segment-length framing: NDBE <3 cm every 5 years; NDBE >=3 cm every 3 years; IND, after a second-pathologist read, optimize to twice-daily PPI, repeat EGD within 6 months, then annually if IND persists; confirmed LGD on surveillance, EGD at 6 and 12 months, then annually. Diagnosis (IM plus >=1 cm columnar mucosa, no biopsy of a normal or <1 cm irregular Z line, >=8 biopsies), endoscopic eradication therapy (EET over esophagectomy for HGD/T1a (strong); EET suggested for confirmed LGD with surveillance an acceptable alternative; resect visible lesions before RFA; sm1 low-risk T1b may be considered for EET) and post-EET intervals (baseline LGD: 1 year, 3 years, then every 2 years; baseline HGD/T1a: 3, 6, 12 months, then annually) are still governed by ACG 2022. The AGA surveillance guideline does not address them, and AGA has said a separate screening guideline will follow in 2026.

Evaluate suspected pancreatic adenocarcinoma with a dedicated pancreatic-protocol (multiphasic, contrast-enhanced) CT of the abdomen as the preferred imaging for diagnosis and staging (MRI/MRCP is an acceptable alternative); PET/CT may be added after, never as a substitute for, protocol CT/MRI in higher-risk situations. Obtain tissue confirmation, preferably by EUS-guided FNA/FNB with core biopsy where feasible; biopsy is generally required before neoadjuvant or palliative therapy, whereas patients with clearly resectable disease may proceed to surgery without preoperative biopsy. Measure baseline CA 19-9 (interpret after biliary decompression / with normal bilirubin; it can be falsely low in Lewis-antigen-negative patients and falsely elevated with cholestasis). Offer GERMLINE testing for inherited susceptibility to EVERY patient with confirmed pancreatic adenocarcinoma regardless of family history, using a comprehensive multi-gene panel; separately, for patients with locally advanced or metastatic disease who are candidates for anti-cancer therapy, obtain TUMOR/SOMATIC molecular profiling (broad NGS; RNA-based assays improve fusion detection; cell-free/liquid biopsy if tissue is insufficient). Assign resectability, resectable, borderline resectable, locally advanced (unresectable), or metastatic, by multidisciplinary review, ideally at a high-volume center. RESECTABLE disease: upfront resection (pancreaticoduodenectomy for head/uncinate; distal pancreatectomy ± splenectomy for body/tail) followed by adjuvant therapy, or neoadjuvant therapy in selected high-risk patients; preferred adjuvant regimen is modified FOLFIRINOX in patients able to tolerate it, ideally begun within 12 weeks of surgery, for a total of ~6 months of perioperative systemic therapy. BORDERLINE RESECTABLE and LOCALLY ADVANCED disease: neoadjuvant systemic therapy, with or without subsequent chemoradiation/RT, then restaging and reassessment for resection. METASTATIC disease by performance status: good PS (ECOG 0-1, adequate organ function), first-line FOLFIRINOX/modified FOLFIRINOX, NALIRIFOX, or gemcitabine + nab-paclitaxel, with clinical trial preferred; after ~4-6 months without progression, transition to a maintenance strategy (including olaparib for germline BRCA1/2 carriers who have NOT progressed on first-line platinum-based therapy), a clinical trial, or a treatment break; intermediate PS (ECOG 2), clinical trial preferred, otherwise less-intensive first-line therapy (preferred gemcitabine + nab-paclitaxel [category 1], or single-agent gemcitabine or capecitabine, or FOLFOX/FOLFIRI/CapeOx), since the intensive triplets (FOLFIRINOX/modified FOLFIRINOX and NALIRIFOX) are limited to ECOG 0-1 and are generally not appropriate at ECOG 2, with the same maintenance-versus-progression reassessment applied after ~4-6 months without progression; poor PS (ECOG 3-4), palliative/best supportive care, with single-agent chemotherapy or a biomarker-directed agent only if clinically appropriate. Treat by molecular target wherever an actionable alteration is present, across lines: pembrolizumab (or dostarlimab) for MSI-H/dMMR and pembrolizumab for TMB-H, olaparib for germline BRCA1/2 (maintenance after platinum), larotrectinib/entrectinib for NTRK fusions, selpercatinib for RET fusions, dabrafenib + trametinib for BRAF V600E, erdafitinib for FGFR2 alterations, fam-trastuzumab deruxtecan for HER2-positive disease, zenocutuzumab for NRG1 fusion-positive disease, and (in recent NCCN versions) KRAS G12C inhibitors (adagrasib/sotorasib), several of these after prior systemic therapy. Integrate supportive care throughout: relieve obstructive jaundice with an endoscopic self-expanding metal stent in non-operative or neoadjuvant pathways, but do NOT perform routine preoperative biliary drainage before planned upfront resection; treat exocrine insufficiency with pancreatic enzyme replacement titrated to symptoms (common starting dose ~40,000-50,000 units of lipase with main meals, roughly half with snacks, increased as needed); manage refractory pain with celiac plexus neurolysis or palliative RT; relieve gastric outlet obstruction with surgical or EUS-guided gastrojejunostomy (or enteral stenting); and provide VTE prophylaxis, nutritional support, and early palliative care.

Two current US documents now apply: ASCRS 2024 (GRADE-graded clinical practice guideline) and the AGA 2026 Clinical Practice Update (expert review, 11 best practice advice statements, no GRADE strength; Qureshi, Hoang, Frye, Rao; Clin Gastroenterol Hepatol, online April 29, 2026). Diagnosis: take a disease-specific history and exam. AGA advises anoscopy, whenever possible, for every new patient with suspected hemorrhoids before any treatment, to confirm the diagnosis and exclude other pathology including cancer. Do not automatically attribute rectal bleeding to hemorrhoids. Complete colonic evaluation is for select patients: no obvious anorectal bleeding source, associated abdominal symptoms or change in bowel habit, persistent hematochezia after successful treatment, or due for CRC screening. Grade internal hemorrhoids I-IV by prolapse. First line is diet and behavior: fiber (AGA cites 20-30 g/day) plus fluid, avoid straining, and limit toilet time (AGA cites about 3 minutes). Sitz baths have little evidence. Topical anesthetics, corticosteroids and vasoactive agents may give short-term relief on weak evidence; AGA limits topical corticosteroids to 2 weeks or less because of skin atrophy. ASCRS adds that oral phlebotonics help bleeding, pruritus and discharge but not pain. Office procedures come before surgery for grade I-III disease (ASCRS: grade I-II and select grade III refractory to conservative care). Rubber band ligation is the most effective office procedure (AGA: 66-94% success, more durable for prolapse and recurrent bleeding; about 2% complications). Infrared coagulation is comparable in the short term and preferred in anticoagulated patients, patients with coagulopathy or cirrhosis, and pregnant patients. Counsel every procedural patient on the rare risk of pelvic sepsis and its warning signs. Refer grade III disease refractory to office procedures, grade IV disease, and symptomatic combined internal/external disease for excisional hemorrhoidectomy, the definitive treatment. Doppler-guided artery ligation is an option (less pain, more recurrence). Stapled hemorrhoidopexy is not routinely first line (higher recurrence, unique serious complications). Special populations (AGA): in active Crohn's disease or UC, defer hemorrhoid treatment until remission; in pregnancy, treat conservatively and defer procedures until after delivery unless necessary; in cirrhosis, distinguish hemorrhoids from rectal varices. Acutely thrombosed external hemorrhoids: the two societies differ. ASCRS 2024 says select patients may benefit from early surgical excision, which beats incision/evacuation for recurrence. AGA 2026 says these are best treated surgically by incision and drainage, which relieves symptoms faster than nonoperative care (a secondary summary places this within 72 hours).

Perform a diagnostic paracentesis as soon as possible in any patient with new-onset ascites that can be sampled. Also perform one in any patient with cirrhosis and ascites who is admitted to hospital. AASLD 2021 says this applies to emergent admission for any reason. AGA 2025 BPA 2 names admission for ascites- or encephalopathy-related symptoms. The tap rules out SBP even without signs of infection, because up to one-third of SBP is asymptomatic. Repeat it whenever signs, symptoms or labs suggest infection, and in tense ascites with AKI. Paracentesis is safe with coagulopathy: INR >1.5 or platelets <50×10^9/L is not a contraindication, and routine FFP or platelet transfusion is not recommended. Possible exceptions are DIC, and uremia with thrombocytopenia, where desmopressin may be considered. Initial fluid testing: neutrophil (PMN) count, total protein, and ascitic albumin with a same-day serum albumin to calculate the SAAG. AGA 2025 adds Gram stain and culture to the initial panel for new-onset ascites and hospitalized patients. AASLD 2021 treats culture as part of the SBP workup rather than the routine panel. Either way, inoculate ≥10 mL into aerobic and anaerobic blood-culture bottles at the bedside before antibiotics. Amylase, cytology, glucose, LDH, AFB/ADA and triglycerides are ordered only for a clinical reason. SAAG ≥1.1 g/dL means portal hypertension (~97% accuracy). SAAG <1.1 g/dL points to a non-portal-hypertensive cause: carcinomatosis, TB peritonitis, nephrotic syndrome, pancreatic or chylous ascites. Within high-SAAG ascites, total protein <2.5 g/dL suggests cirrhosis (also massive liver metastases or late Budd-Chiari). Total protein ≥2.5 g/dL suggests a cardiac or postsinusoidal cause (heart failure, portal vein thrombosis, SOS, early Budd-Chiari), so work up with echocardiography, hepatic-vein Doppler or right-heart catheterization. SBP is diagnosed by ascitic PMN >250/mm^3, with or without a positive culture, once a surgically treatable source has been excluded. SBE is diagnosed by pleural fluid PMN >250/mm^3 in a hepatic hydrothorax after pneumonia and other secondary causes are excluded. It is treated with antibiotics and no chest tube.

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.