Hepatology, in full.

Diagnose MASLD by hepatic steatosis on imaging (or biopsy) plus at least one cardiometabolic criterion and exclusion of competing etiologies (significant alcohol use, other liver disease), then risk-stratify fibrosis using a sequential non-invasive approach: FIB-4 first, followed by a second-line imaging-based test (VCTE, MRE, or ELF) for indeterminate/high-risk FIB-4, with liver biopsy reserved for discordant or unclear cases. Lifestyle modification (≥7-10% weight loss, Mediterranean diet, exercise) remains the foundation for all patients. For adults with MASH and F2-F3 fibrosis identified by non-invasive tests (VCTE 8-15 kPa, MRE 3.1-4.4 kPa, or ELF 9.2-10.5) rather than biopsy, AASLD now gives dedicated, updated practice guidance on both FDA-approved pharmacotherapies: resmetirom (Oct 2024 update) and semaglutide 2.4mg/week subcutaneous (Nov 2025 update, following August 2025 accelerated FDA approval based on ESSENCE trial data: 62.9% vs 34.3% MASH resolution without fibrosis worsening; 36.8% vs 22.4% ≥1-stage fibrosis improvement). Pioglitazone or vitamin E remain options per the 2023 base guidance. Manage cardiometabolic risk with statins for ASCVD reduction plus glycemic and blood-pressure control; for semaglutide specifically, routine hepatic panels are recommended only as clinically indicated (no discontinuations for LFT elevation in ESSENCE), with monitoring for GI adverse effects and rare risks (AKI, gallbladder disease, pancreatitis, thyroid C-cell tumors, retinopathy progression, lean mass loss). HCC surveillance with ultrasound and AFP every 6 months remains indicated only if cirrhosis is present.

Manage portal hypertension without cirrhosis by confirming portal hypertensive features while excluding cirrhosis (liver biopsy is the gold standard), then performing a comprehensive etiology workup (drug history, MPN/thrombophilia/PNH screen, autoimmune, CVID, HIV, schistosomiasis). Treat portal hypertension complications the same as cirrhosis, variceal prophylaxis with NSBB (carvedilol preferred) or EVL, TIPS for refractory or recurrent bleeding, and address the underlying cause by discontinuing offending drugs and treating the specific etiology. For concurrent portal vein thrombosis, anticoagulation decisions should be individualized based on thrombus acuity (recent vs. chronic), bleeding risk, and underlying etiology; liver transplantation is reserved for refractory complications, and HCC surveillance is not routine without cirrhosis.

Treatment of AUD with sustained abstinence is the most effective strategy to prevent progression and improve long-term outcomes at any stage of ALD; ACG recommends brief screening with a tool such as AUDIT-C (strong, high), brief motivational interventions (strong, low), and integrated multidisciplinary care combining behavioral therapy and/or pharmacotherapy (strong, low). AUD pharmacotherapy recommendations are scoped specifically to COMPENSATED ALD and are not co-equal: baclofen is recommended as an option (strong recommendation, moderate evidence); acamprosate or naltrexone are only suggested as options (conditional, very low); gabapentin or topiramate are suggested as options (conditional, very low); disulfiram is suggested AGAINST along any spectrum of ALD (conditional, very low). For severe alcohol withdrawal, benzodiazepines are the treatment of choice but with explicitly cautious use and careful monitoring given their potential to precipitate or exacerbate hepatic encephalopathy (strong, moderate); AWS is managed per CIWA-Ar protocol, differentiating it from HE while acknowledging the two can coexist. For alcohol-associated hepatitis (AH), severity is stratified by MELD: MELD >20 defines severe AH, which carries high short-term mortality and should preferably be managed in hospital; MELD ≤20 defines moderate AH. In severe AH (MELD >20) ACG recommends corticosteroid therapy ONLY if there are no contraindications (strong, moderate); active infection (including untreated HBV infection), uncontrolled diabetes mellitus, gastrointestinal bleeding, and severe renal failure are contraindications to corticosteroid use, though corticosteroids can be started after adequate control or reversal of infection, renal failure, and gastrointestinal bleeding. Prednisolone is preferred over prednisone; both are dosed 40 mg/day for a total of 4 weeks, with IV methylprednisolone 32 mg/day as the alternative for patients unable to take oral medication; there is no evidence supporting rapid vs slow tapering after the 4-week course. Corticosteroid response is assessed by Lille score at day 7 OR day 4 (day-4 shown as accurate as day-7); among non-responders (Lille >0.45) corticosteroids should be discontinued. ACG recommends IV N-acetylcysteine as an adjuvant to corticosteroids in severe AH (strong, moderate), while explicitly noting that other society guidelines have not adopted this recommendation. ACG recommends AGAINST pentoxifylline (strong, moderate) and AGAINST universal prophylactic antibiotics in hospitalized severe AH (strong, moderate); data on G-CSF and microbiome-based therapies are insufficient. Nutrition: target 35 kcal/kg/day with 1.2-1.5 g/kg/day protein; patients consuming <21 kcal/kg/day should receive nutritional support, preferably oral/enteral, oral nutritional supplements first, escalating to enteral nutrition if caloric targets remain unmet (strong, moderate). Thiamine, vitamin B12 and zinc deficiencies are common in AH and should be supplemented. For severe AH unresponsive to medical management with high risk of death, early liver transplantation for highly selected patients should be considered according to regional and institutional protocols (conditional recommendation, low level of evidence); LT selection must not be based solely on an arbitrary duration of sobriety, and should rest on detailed psychosocial evaluation by a social worker and addiction specialist, optionally supported by tools such as SIPAT, HRAR, MAPS, HPSS or SALT. For severe AH with 4 or more organ failures, non-responsive to corticosteroids and ineligible for early LT, palliative care engagement is appropriate.

Diagnose PSC with high-quality MRCP as the reference-standard imaging (avoid ERCP for diagnostic purposes; if MRCP findings are equivocal, repeat MRCP rather than proceeding to ERCP), reserving ERCP for therapeutic intervention, and exclude secondary sclerosing cholangitis/IgG4-related disease. No disease-modifying therapy is proven to alter transplant-free survival, but moderate-dose UDCA (13-23 mg/kg/day) may now be considered and continued in patients not enrolled in or eligible for a clinical trial if it produces a meaningful improvement in alkaline phosphatase (GGT in children) and/or symptoms by 12 months, discontinuing if no response; high-dose UDCA remains contraindicated. Perform annual abdominal MRI/MRCP with or without serum CA19-9 for cholangiocarcinoma/gallbladder-cancer surveillance in adults with large-duct PSC (not recommended under age 18 or in small-duct PSC). Manage gallbladder polyps by size, cholecystectomy for polyps >8 mm, ultrasound surveillance every 6 months for polyps ≤8 mm, rather than referring every polyp. For colorectal surveillance, begin surveillance colonoscopy at the time of PSC-IBD diagnosis (or at age 15 for childhood-onset disease) and repeat at 1-2 year intervals; in PSC without IBD, perform a diagnostic colonoscopy at PSC diagnosis and repeat every 5 years if IBD is not found. Evaluate dominant strictures with brush cytology plus FISH (± cholangioscopy) before/at balloon dilation, repeating ERCP with sampling in 3 months if cytology is suspicious regardless of FISH result. Treat recurrent cholangitis and cholestatic pruritus, maintain bone health, and refer for transplant evaluation for decompensation, intractable pruritus, recurrent bacterial cholangitis, or early-stage CCA per Mayo protocol.

Determine GI surgical clearance based on the specific condition and its activity rather than an automatic sign-off: most stable chronic GI conditions (GERD, IBS, controlled IBD, compensated MASLD, asymptomatic gallstones) may be cleared, while active conditions, cirrhosis, and perioperative drug management require explicit stratification and documentation. For any cirrhotic patient, perform mandatory risk stratification with VOCAL-Penn and Child-Pugh class before clearance; manage variceal prophylaxis per individualized endoscopic and hemodynamic assessment (including NSBB for appropriate candidates) and address rebalanced hemostasis without prophylactic INR correction. Defer elective surgery for active GI bleeding, active IBD flare, recent pancreatitis, or unoptimized anemia, and specify perioperative precautions (stress-dose steroids, biologic hold matrix, GLP-1/SGLT2 holds, aspiration precautions) where indicated.

Scope: this primary document covers portal hypertension and varices in cirrhosis ONLY. Everything else in the current entry (HCC surveillance, transplant referral, nutrition, vaccination, ascites/SBP/HE/HRS/ACLF management) belongs to the separate documents listed as supporting sources and must not be attributed to this guidance. Risk-stratify compensated advanced chronic liver disease (cACLD) with non-invasive tests before defaulting to endoscopy. By vibration-controlled transient elastography, liver stiffness (LSM) under 10 kPa excludes cACLD, 10 to 14.9 kPa is suggestive and warrants further testing, and 15 kPa or above rules cACLD in. Clinically significant portal hypertension (CSPH, i.e. HVPG above 10 mm Hg) is ruled in non-invasively by LSM at or above 25 kPa alone, or LSM 20 to 24.9 kPa with platelets below 150 x 10^9/L, or LSM 15 to 19.9 kPa with platelets below 110 x 10^9/L. Where spleen stiffness measurement is available, values below 21 kPa argue against CSPH and above 50 kPa argue for it. These non-invasive cutoffs are conditional probability thresholds, not universal diagnostic rules, and hold only when their derivation conditions are met. They were established in compensated advanced chronic liver disease of viral (treated or untreated HBV/HCV), alcohol-related, or non-obese (BMI under 30) MASLD etiology, and are not validated for and should not be applied to cholestatic (e.g. PBC, PSC), vascular, or other etiologies, in which different cutoffs apply. They also require a technically reliable liver stiffness measurement by vibration-controlled transient elastography, fasting, at least 10 valid acquisitions, and an IQR/median ratio below 30 percent, and are confounded by factors that raise liver stiffness independently of fibrosis, including ALT flares or acute hepatitis, extrahepatic cholestasis, hepatic congestion (right heart failure), and recent food intake; Baveno VII recommends confirming an LSM-based rule-in on a repeat measurement obtained on a separate day. The spleen stiffness cutoffs apply only to a dedicated 100 Hz spleen module, carry a higher technical failure rate, are machine-dependent, and are not interchangeable with values obtained using the standard 50 Hz liver probe. Where these population or acquisition conditions are not met, the numeric thresholds do not reliably classify CSPH, and HVPG measurement or endoscopy is required rather than a non-invasive determination. Preserve the gray zone: LSM 15 to 25 kPa without a qualifying platelet count is explicitly indeterminate (roughly 40 to 60 percent of cACLD patients) and calls for HVPG and/or endoscopy rather than assumption in either direction. Once CSPH is established, offer a non-selective beta-blocker, carvedilol preferred at 12.5 mg/day, to lower portal pressure and prevent FIRST decompensation, on the strength of PREDESCI. This is a treat-the-pressure strategy rather than a treat-the-varices one: because a patient already on NSBB for CSPH would not have management changed by the finding, screening endoscopy becomes unnecessary for most such patients. Screening EGD is still indicated where elastography is unavailable, technically difficult, or gives discordant results, and for patients who do not meet non-invasive criteria. Standard beta-blocker contraindications (severe asthma, advanced heart block, bradyarrhythmias) continue to apply. For varices needing treatment managed endoscopically, band ligation is repeated every 2 to 4 weeks until obliteration, with surveillance endoscopy at 6 months and annually thereafter. Gastric/cardiofundal varices are treated with cyanoacrylate injection or EUS-guided coil embolization rather than banding, with hepatology involvement. In acute variceal hemorrhage, consider preemptive (early) TIPS within 24 to 72 hours in high-risk patients: Child-Turcotte-Pugh class B with score above 7 and active bleeding at endoscopy despite vasoactive therapy, or CTP class C with score 10 to 13. Keep the document's own qualifier: there is no established universal MELD or CTP cutoff at which TIPS is mandatory, and the decision is case-by-case with hepatology consultation. Statin use in compensated cirrhosis is NOT a recommendation traceable to this document; the current entry's statin sentence needs its own source or removal. Verification note: the Hepatology full text is paywalled (402/403 on direct fetch). Document identity, title, year, volume, pages and authorship were confirmed via Crossref and PubMed metadata; the numeric thresholds above were corroborated from two independent peer-reviewed commentaries on this specific guidance and match the Baveno VII rule-of-five, but were not read verbatim from the primary PDF. A human should confirm the exact guidance-statement wording against the full text before this entry is treated as quotation-grade.

In adults with cirrhosis, acetaminophen 500 mg every 6 h, up to a maximum of 2 g/day, is the preferred first-line analgesic (Statement 30), and systemic NSAIDs should be avoided (Statement 31). Opioids should be avoided when possible for chronic pain; when necessary, opioid use should be approached with caution and with careful discussion with patients and caregivers, and low-dose oxycodone or hydromorphone can be started in select cases on an as-needed basis and titrated to effect, often in consultation with pain-management experts (Statement 32). First-line opioids are low-dose, short-acting agents with extended dosing intervals: oxycodone 2.5 mg PO q6-8h PRN or hydromorphone 1 mg PO q6h PRN (hydromorphone 0.4 mg IV); the initial prescription should be a 7-day supply of a low-dose short-acting opioid with close follow-up, and extended-release formulations should be avoided. Codeine, morphine, and tramadol should generally be avoided; because morphine is relatively contraindicated in advanced cirrhosis, clinicians should first consider hydromorphone or oxycodone. Methadone should only be used in consultation with a specialist. IV fentanyl is a preferred opioid because of its favorable metabolism, but the transdermal fentanyl patch is problematic for outpatient use because its lowest available dose (12 µg/h) may be too high for patients with cirrhosis, and cachexia is a relative contraindication to the patch. When an opioid is started, prophylactic medications should be considered proactively to prevent constipation and hepatic encephalopathy (e.g., lactulose).

Scope: this primary document covers portal hypertension and varices in cirrhosis ONLY. Everything else in the current entry (HCC surveillance, transplant referral, nutrition, vaccination, ascites/SBP/HE/HRS/ACLF management) belongs to the separate documents listed as supporting sources and must not be attributed to this guidance. Risk-stratify compensated advanced chronic liver disease (cACLD) with non-invasive tests before defaulting to endoscopy. By vibration-controlled transient elastography, liver stiffness (LSM) under 10 kPa excludes cACLD, 10 to 14.9 kPa is suggestive and warrants further testing, and 15 kPa or above rules cACLD in. Clinically significant portal hypertension (CSPH, i.e. HVPG above 10 mm Hg) is ruled in non-invasively by LSM at or above 25 kPa alone, or LSM 20 to 24.9 kPa with platelets below 150 x 10^9/L, or LSM 15 to 19.9 kPa with platelets below 110 x 10^9/L. Where spleen stiffness measurement is available, values below 21 kPa argue against CSPH and above 50 kPa argue for it. These non-invasive cutoffs are conditional probability thresholds, not universal diagnostic rules, and hold only when their derivation conditions are met. They were established in compensated advanced chronic liver disease of viral (treated or untreated HBV/HCV), alcohol-related, or non-obese (BMI under 30) MASLD etiology, and are not validated for and should not be applied to cholestatic (e.g. PBC, PSC), vascular, or other etiologies, in which different cutoffs apply. They also require a technically reliable liver stiffness measurement by vibration-controlled transient elastography, fasting, at least 10 valid acquisitions, and an IQR/median ratio below 30 percent, and are confounded by factors that raise liver stiffness independently of fibrosis, including ALT flares or acute hepatitis, extrahepatic cholestasis, hepatic congestion (right heart failure), and recent food intake; Baveno VII recommends confirming an LSM-based rule-in on a repeat measurement obtained on a separate day. The spleen stiffness cutoffs apply only to a dedicated 100 Hz spleen module, carry a higher technical failure rate, are machine-dependent, and are not interchangeable with values obtained using the standard 50 Hz liver probe. Where these population or acquisition conditions are not met, the numeric thresholds do not reliably classify CSPH, and HVPG measurement or endoscopy is required rather than a non-invasive determination. Preserve the gray zone: LSM 15 to 25 kPa without a qualifying platelet count is explicitly indeterminate (roughly 40 to 60 percent of cACLD patients) and calls for HVPG and/or endoscopy rather than assumption in either direction. Once CSPH is established, offer a non-selective beta-blocker, carvedilol preferred at 12.5 mg/day, to lower portal pressure and prevent FIRST decompensation, on the strength of PREDESCI. This is a treat-the-pressure strategy rather than a treat-the-varices one: because a patient already on NSBB for CSPH would not have management changed by the finding, screening endoscopy becomes unnecessary for most such patients. Screening EGD is still indicated where elastography is unavailable, technically difficult, or gives discordant results, and for patients who do not meet non-invasive criteria. Standard beta-blocker contraindications (severe asthma, advanced heart block, bradyarrhythmias) continue to apply. For varices needing treatment managed endoscopically, band ligation is repeated every 2 to 4 weeks until obliteration, with surveillance endoscopy at 6 months and annually thereafter. Gastric/cardiofundal varices are treated with cyanoacrylate injection or EUS-guided coil embolization rather than banding, with hepatology involvement. In acute variceal hemorrhage, consider preemptive (early) TIPS within 24 to 72 hours in high-risk patients: Child-Turcotte-Pugh class B with score above 7 and active bleeding at endoscopy despite vasoactive therapy, or CTP class C with score 10 to 13. Keep the document's own qualifier: there is no established universal MELD or CTP cutoff at which TIPS is mandatory, and the decision is case-by-case with hepatology consultation. Statin use in compensated cirrhosis is NOT a recommendation traceable to this document; the current entry's statin sentence needs its own source or removal. Verification note: the Hepatology full text is paywalled (402/403 on direct fetch). Document identity, title, year, volume, pages and authorship were confirmed via Crossref and PubMed metadata; the numeric thresholds above were corroborated from two independent peer-reviewed commentaries on this specific guidance and match the Baveno VII rule-of-five, but were not read verbatim from the primary PDF. A human should confirm the exact guidance-statement wording against the full text before this entry is treated as quotation-grade.