Hepatology, in full.

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.

For acute variceal hemorrhage in cirrhosis, resuscitate conservatively with a restrictive RBC transfusion strategy targeting hemoglobin 7-8 g/dL, start a vasoactive agent as soon as bleeding is suspected and before endoscopy (terlipressin, somatostatin, or octreotide; octreotide is the agent available for this indication in US practice) and continue it 2-5 days, and give empiric IV ceftriaxone 1 g every 24 hours in patients with advanced cirrhosis. Perform upper endoscopy within 12 hours of presentation once resuscitated, or as soon as safely possible if the patient is unstable, with band ligation for esophageal varices and for GOV1 (which is treated as an esophageal varix); cardiofundal varices (GOV2 and IGV1) are treated with cyanoacrylate injection, with EUS-guided coil placement with or without cyanoacrylate increasingly used as first-line where expertise exists, and TIPS or BRTO as alternatives or salvage. PPIs started empirically should be stopped immediately after endoscopy unless there is a separate strict indication. Evaluate every patient at presentation for pre-emptive (early) TIPS with a PTFE-covered stent, placed within 72 hours and ideally within 24 hours, in high-risk patients defined as Child-Pugh class C with score under 14 (that is, 10-13) or Child-Pugh class B with score above 7 who have active bleeding at initial endoscopy despite vasoactive drugs; the decision is individualized and multidisciplinary, weighing age, frailty, comorbidity, heart failure, HCC, portal vein thrombosis, and transplant candidacy. For uncontrolled bleeding, a self-expanding covered esophageal metal stent is as effective as balloon tamponade and is the safer option; both are a bridge to definitive therapy (PTFE-covered TIPS) and neither is definitive therapy. Balloon tamponade must NOT be left in place for more than 24 hours, 24 hours is the ceiling, not a range: Baveno VI states it "should only be used in refractory oesophageal bleeding, as a temporary bridge (for a maximum of 24 h) with intensive care monitoring and considering intubation, until definitive treatment can be instituted", because severe esophageal injury/necrosis, perforation and aspiration rise sharply beyond that point. The 72-hour figure in this standard belongs to the pre-emptive TIPS window and must not be read as a permissible tamponade duration. Secondary prophylaxis is mandatory in all survivors and is combination therapy: a nonselective beta-blocker, either a traditional NSBB (propranolol or nadolol) or carvedilol, which Baveno VII endorses as an equivalent rather than clearly superior option in this specific indication, plus serial EVL every 2 to 8 weeks until variceal eradication, with surveillance endoscopy thereafter. TIPS is the treatment of choice for patients who rebleed despite NSBB plus EVL.

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.

Refer patients with decompensated cirrhosis (including those with MELD-Na <15 or MELD 3.0 <15 if they have clinically significant portal hypertension, recurrent ascites, hepatic encephalopathy, or variceal bleeding), acute liver failure meeting King's College Criteria/UNOS Status 1A, or HCC within Milan/UCSF criteria for comprehensive multidisciplinary liver transplant evaluation, with MELD 3.0 driving UNOS waitlist allocation and MELD exception scoring for HCC/HPS/FAP. Optimize modifiable risk factors before listing (alcohol abstinence, HCV DAA treatment, vaccinations, DM/obesity/OSA and dental clearance) and use bridging/downstaging locoregional therapy for HCC while awaiting transplant. After transplant, maintain lifelong immunosuppression with tacrolimus plus mycophenolate ± tapered steroids alongside infection prophylaxis and recurrent-disease surveillance.

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.