Hepatology, in full.

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).

Perform a diagnostic paracentesis in all patients with new-onset ascites that is accessible for sampling, and in any patient with cirrhosis and ascites who is emergently admitted to the hospital for any reason, to rule out SBP even in the absence of signs or symptoms of infection (up to one-third of SBP is asymptomatic). Also perform it whenever a patient with ascites develops signs, symptoms, or laboratory abnormalities suggestive of infection, and in patients with tense ascites and AKI to exclude SBP as the cause. LVP/paracentesis is safe even with coagulopathy: elevated prothrombin time (INR >1.5) or thrombocytopenia (platelets <50×10^9/L) is not a contraindication, and routine transfusion of clotting factors or platelets is NOT recommended, with possible exceptions in disseminated intravascular coagulation, or uremia with thrombocytopenia (where desmopressin may be considered, especially with prior bleeding). The initial laboratory investigation of ascitic fluid should include ascitic fluid neutrophil (PMN) count, ascitic fluid total protein, and ascitic fluid albumin plus a simultaneous serum albumin to calculate the serum-ascites albumin gradient (SAAG). Ascitic fluid culture is not part of that routine initial panel but should be obtained whenever SBP is being evaluated (routinely for inpatients and when secondary bacterial peritonitis is suspected); when cultured, inoculate ≥10 mL of fluid into aerobic and anaerobic blood culture bottles at the bedside, before the first dose of antibiotics. Amylase, cytology, glucose, LDH, and mycobacterial (AFB/ADA) or triglyceride testing are not routinely indicated and should be guided by clinical context (e.g., suspected pancreatic, malignant, secondary-bacterial, tuberculous, or chylous ascites). Interpret SAAG to classify the cause: SAAG ≥1.1 g/dL indicates portal hypertension (~97% accuracy), while SAAG <1.1 g/dL points to non-portal-hypertensive (peritoneal) causes such as peritoneal carcinomatosis, tuberculous peritonitis, nephrotic syndrome, or pancreatic/chylous ascites. Within high-SAAG ascites, use ascitic total protein to distinguish the source: total protein <2.5 g/dL suggests cirrhosis (also massive liver metastasis, late Budd-Chiari), whereas total protein ≥2.5 g/dL suggests a postsinusoidal/cardiac source (heart failure, portal vein thrombosis, sinusoidal obstruction syndrome, early Budd-Chiari), directing workup toward right-heart catheterization, hepatic-vein Doppler, and echocardiography. The diagnosis of SBP is established with an ascitic fluid absolute neutrophil (PMN) count >250/mm^3 (with or without a positive culture, and in the absence of a surgically treatable intra-abdominal source of infection). Spontaneous bacterial empyema (SBE) is the analogous spontaneous infection of a pre-existing hepatic hydrothorax, not a parapneumonic effusion, and is established by the same pleural fluid PMN count >250/mm^3, but only after pneumonia and other secondary causes of the effusion have been excluded; despite the term "empyema" it is managed as an infection with antibiotics, and a chest tube should NOT be placed.

Perform HCC surveillance in adults with cirrhosis of any etiology who are able to benefit from HCC treatment, accordingly, do not enroll patients with Child-Turcotte-Pugh class C cirrhosis unless they are candidates for (or listed for) liver transplantation, and do not surveil those with life-limiting comorbidity (life expectancy <1-2 years) that transplantation cannot remedy, and in select non-cirrhotic chronic HBV carriers at elevated risk (e.g., active hepatitis/high viral load, family history of HCC, African/African-American ancestry, Asian men >40 and Asian women >50; AASLD references risk scores such as PAGE-B but stops short of mandating a specific numeric cutoff). Surveillance is abdominal ultrasound PLUS serum AFP at ~6-month (semiannual) intervals, a change from prior AASLD guidance, which had left AFP optional (Strong recommendation). Pursue diagnostic evaluation for an AFP ≥20 ng/mL or for a rising AFP, defined as a doubling of AFP or an increase on two consecutive tests even if the absolute value is <20 ng/mL. Any suspicious ultrasound observation ≥1 cm, or an inadequate/limited ultrasound, should be evaluated with multiphasic contrast-enhanced CT or MRI interpreted with CT/MRI LI-RADS. AASLD 2023 stages confirmed HCC using the BCLC framework and links stage to therapy (curative resection, ablation, or transplantation within Milan criteria for very-early/early disease; TACE and other locoregional therapy for intermediate disease; systemic therapy for advanced disease). Its first-line systemic options for advanced HCC with preserved liver function (Child-Pugh A) are atezolizumab+bevacizumab OR durvalumab+tremelimumab (STRIDE) as preferred, with sorafenib, lenvatinib, or durvalumab monotherapy as alternatives when the preferred combinations are contraindicated. After potentially curative therapy, continue surveillance for recurrence given high recurrence risk (AASLD monitors with cross-sectional contrast-enhanced imaging, not ultrasound, in the early post-treatment period).

The 2026 AASLD/IDSA guideline addresses six PICO questions only; it states explicitly that all other 2018 AASLD recommendations for CHB management remain applicable, and that screening/diagnosis were out of scope. Baseline evaluation and the standard treatment indications (cirrhosis with detectable HBV DNA; HBeAg-positive immune-active with ALT >2x ULN and HBV DNA >20,000 IU/mL; HBeAg-negative immune-active with ALT >2x ULN and HBV DNA >2,000 IU/mL; prophylaxis for reactivation risk during immunosuppression) derive from the 2018 document, not this update, which lists 'treatment of HBeAg-positive and -negative immune active CHB with ALT >2x ULN', treatment of children, treatment of cirrhosis, low-level viremia, virologic breakthrough, and special populations (transplant, acute HBV, HCV/HDV/HIV coinfection) as topics 'well covered in previous AASLD 2018 Guidance and for which recommendations have not changed'. Preferred agents remain entecavir, TDF, or TAF. THE SIX 2026 RECOMMENDATIONS: (1) PMTCT, for pregnant persons with HBV DNA >200,000 IU/mL at any time point during pregnancy, regardless of HBeAg status, AASLD RECOMMENDS initiating TDF or TAF at gestational week 28 (STRONG recommendation, MODERATE certainty, the only strong recommendation in the guideline); TDF has a more extensive safety record in pregnancy than TAF. Implementation qualifiers: initiate immediately if care is first sought after week 28; initiate at week 16 if infant HBIG will be unavailable (with subsequent infant vaccination); consider earlier initiation when amniocentesis is anticipated (transmission risk is increased with HBV DNA >2,000,000 IU/mL) or when preterm labor risk is high; continue TDF/TAF if already on it, switch entecavir or other agents to TDF/TAF; if treatment was solely for perinatal prophylaxis it may be discontinued at delivery, with HBV DNA and ALT monitored every 1-3 months for up to 6 months for withdrawal flare and treatment reinitiated if ALT >=5x ULN; use TDF or TAF in breastfeeding persons requiring treatment. (2) HORIZONTAL TRANSMISSION, for HBsAg-positive viremic persons not meeting disease-specific treatment indications who are in high-risk scenarios for transmission to others, AASLD SUGGESTS a shared decision-making approach regarding antiviral treatment (CONDITIONAL, VERY LOW certainty). Qualifiers the guideline stresses: the decision weighs exposure risk and the vaccine/immunity status of contacts, favoring treatment if contacts are unvaccinated, vaccine-nonresponsive, immunocompromised, or of unknown vaccine status; persons requesting treatment for prevention may be prescribed it since risks may not be disclosed; explicitly, people with CHB must NOT be restricted in daily activities, contact sports, school, or professional training and must NOT be required to take antivirals because of transmission risk in those settings; routine contact, shared meals, and hugging are not transmission routes (avoid sharing toothbrushes/razors); most healthcare workers with CHB are NOT high-risk, but those performing SHEA Category III exposure-prone procedures may require antivirals (SHEA target HBV DNA <1000 IU/mL); neither CDC nor SHEA requires disclosure to patients or staff; anti-stigma framing is part of the recommendation. (3) IMMUNE-TOLERANT PHASE, defined as HBeAg-positive, HBV DNA >10^7 IU/mL, and normal ALT; AASLD SUGGESTS antiviral therapy for those over age 40 years, OR with significant liver inflammation (grade >=2) or fibrosis (>=F2) on biopsy or noninvasive tests (CONDITIONAL, VERY LOW certainty). For persons under age 40 who are interested in starting treatment earlier, AASLD suggests shared decision-making weighing risk factors and the benefits and risks of treatment. Accurate phase identification requires persistently normal ALT on >=2 measurements >=6 months apart, using ULN 35 U/L (males) and 25 U/L (females). (4) INDETERMINATE ('grey zone') PHASE, the HBeAg-negative indeterminate phase is defined as HBsAg-positive, HBeAg-negative persons whose ALT and/or HBV DNA fall outside the thresholds for HBeAg-negative immune-active CHB (ALT >2x ULN and HBV DNA >2,000 IU/mL) and outside those for inactive CHB (HBV DNA <2,000 IU/mL with normal ALT), comprising predominantly two subgroups, (I) normal (<ULN) or mildly elevated (<2x ULN) ALT with HBV DNA >=2,000 IU/mL, or (II) elevated ALT (>ULN) with HBV DNA <2,000 IU/mL, with ALT interpreted against ULN 35 U/L (males) and 25 U/L (females) and phase assigned on >=2 ALT and HBV DNA measurements over a 6-12 month period; in adults who are HBsAg-positive, HBeAg-negative, without cirrhosis and in the indeterminate phase so defined, AASLD SUGGESTS antiviral therapy using a shared decision-making approach assessing risks and benefits, and re-evaluating that decision at each follow-up visit if treatment has not been initiated (CONDITIONAL, VERY LOW certainty). Decision-relevant factors include fibrosis stage, age, and sex, e.g. age >40, male sex, and low-normal platelets (<180 k/mm3) favor treatment. (5) DISCONTINUATION, in adults with CHB who are HBeAg-negative, without cirrhosis, with sustained undetectable HBV DNA on nucleos(t)ide analogue therapy, AASLD SUGGESTS NOT withdrawing NA therapy until HBsAg loss (CONDITIONAL, VERY LOW certainty). If a patient nonetheless has a strong desire to stop, shared decision-making applies and ALL of the following must be met: no history of advanced fibrosis/cirrhosis, hepatic decompensation (variceal bleed, ascites, encephalopathy, hepatorenal syndrome), HCC, or extrahepatic HBV complications; if HBeAg-positive at treatment start, HBeAg seroconversion to anti-HBe-positive for >=1 year with undetectable HBV DNA >=2 years; if HBeAg-negative at start, undetectable HBV DNA >=2 years; no HIV or HDV coinfection; quantitative HBsAg <100 IU/mL; and willingness to adhere to frequent monitoring. After stopping, monitor ALT and HBV DNA every 1-3 months for 6 months, then every 3 months for 6-12 months, then every 3-6 months. Restart antivirals IMMEDIATELY if HBV DNA >=10,000 IU/mL (4 log IU/mL) at any time regardless of ALT, OR ALT >=5x ULN regardless of HBV DNA, OR total bilirubin >2.5 mg/dL. (6) HCC SURVEILLANCE (all CONDITIONAL, VERY LOW certainty; modality/interval per AASLD 2023 HCC Practice Guidance), Rec 6: after HBsAg loss, continue surveillance in those with cirrhosis, family history of HCC, men who lost HBsAg after age 40, and women who lost HBsAg after age 50. Rec 7: in HBV-HDV coinfection, surveil adults independent of cirrhosis status; in children, individualize because HCC risk in that population is unknown. Rec 8: in HBV-HIV coinfection, surveil men >=18 years and women >=40 years. Rec 9: in HBV-HCV coinfection, AASLD recommends treating HCV and suggests HCC surveillance per HBV mono-infection criteria. Where a person has more than one coinfection, the surveillance recommendation should follow the coinfection carrying the highest associated risk. The guideline notes that most of its recommendations rest on low or very low certainty evidence and that shared decision-making, not uniform policy, is the intended mode of application.

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.

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.

AATD-associated liver disease (AATD-LD) is defined by elevation of AST, ALT or GGT, which may be episodic, and/or liver fibrosis >=F2, in adults with AATD, particularly but not exclusively those with the PiZZ genotype. Include a serum alpha-1 antitrypsin level in the diagnostic evaluation of chronic liver disease, and confirm a low level with genotyping. Stage fibrosis with noninvasive elastography (vibration-controlled transient elastography or magnetic resonance elastography) as the preferred method; liver biopsy is not routinely required and is reserved for cases where competing etiologies must be excluded. Follow patients with a tiered longitudinal algorithm of serial noninvasive testing, with timely referral for liver transplantation evaluation. There is no approved AATD-specific therapy for the liver disease: manage cirrhosis and its complications per standard of care, perform HCC surveillance with ultrasound +/- AFP every 6 months once cirrhotic, screen for varices per standard cirrhosis practice, and refer early for transplant evaluation in decompensated disease (ascites, variceal bleeding, or hepatic encephalopathy). Intravenous augmentation therapy is explicitly NOT recommended as treatment for AATD liver disease (Alpha-1 Foundation 2016, Rec 3j, strong recommendation); its role is pulmonary, where it is strongly recommended for FEV1 30-65% predicted, also recommended (weak, low-quality evidence) for FEV1 <30%, a matter for individualized benefit-versus-cost discussion above 65%, and not recommended for the MZ genotype with COPD or for those who continue to smoke. Tobacco exposure prevention and cessation is a strong, high-quality-evidence recommendation. Adult siblings of an affected individual should be offered genetic counseling and testing (strong, moderate quality); parents, children and extended family should also be offered counseling and testing (weak, low quality). For trial design, phase 3 should enroll F2-F4; F1 may suit phase 1-2 safety studies; cirrhotics may be excluded depending on therapeutic class; preserved pulmonary function is not required for trials of DNA/RNA-editing therapies that raise AAT levels; the consensus primary efficacy endpoint is a >=1-stage improvement in fibrosis.

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.

The 2026 AASLD/IDSA guideline addresses six PICO questions only; it states explicitly that all other 2018 AASLD recommendations for CHB management remain applicable, and that screening/diagnosis were out of scope. Baseline evaluation and the standard treatment indications (cirrhosis with detectable HBV DNA; HBeAg-positive immune-active with ALT >2x ULN and HBV DNA >20,000 IU/mL; HBeAg-negative immune-active with ALT >2x ULN and HBV DNA >2,000 IU/mL; prophylaxis for reactivation risk during immunosuppression) derive from the 2018 document, not this update, which lists 'treatment of HBeAg-positive and -negative immune active CHB with ALT >2x ULN', treatment of children, treatment of cirrhosis, low-level viremia, virologic breakthrough, and special populations (transplant, acute HBV, HCV/HDV/HIV coinfection) as topics 'well covered in previous AASLD 2018 Guidance and for which recommendations have not changed'. Preferred agents remain entecavir, TDF, or TAF. THE SIX 2026 RECOMMENDATIONS: (1) PMTCT, for pregnant persons with HBV DNA >200,000 IU/mL at any time point during pregnancy, regardless of HBeAg status, AASLD RECOMMENDS initiating TDF or TAF at gestational week 28 (STRONG recommendation, MODERATE certainty, the only strong recommendation in the guideline); TDF has a more extensive safety record in pregnancy than TAF. Implementation qualifiers: initiate immediately if care is first sought after week 28; initiate at week 16 if infant HBIG will be unavailable (with subsequent infant vaccination); consider earlier initiation when amniocentesis is anticipated (transmission risk is increased with HBV DNA >2,000,000 IU/mL) or when preterm labor risk is high; continue TDF/TAF if already on it, switch entecavir or other agents to TDF/TAF; if treatment was solely for perinatal prophylaxis it may be discontinued at delivery, with HBV DNA and ALT monitored every 1-3 months for up to 6 months for withdrawal flare and treatment reinitiated if ALT >=5x ULN; use TDF or TAF in breastfeeding persons requiring treatment. (2) HORIZONTAL TRANSMISSION, for HBsAg-positive viremic persons not meeting disease-specific treatment indications who are in high-risk scenarios for transmission to others, AASLD SUGGESTS a shared decision-making approach regarding antiviral treatment (CONDITIONAL, VERY LOW certainty). Qualifiers the guideline stresses: the decision weighs exposure risk and the vaccine/immunity status of contacts, favoring treatment if contacts are unvaccinated, vaccine-nonresponsive, immunocompromised, or of unknown vaccine status; persons requesting treatment for prevention may be prescribed it since risks may not be disclosed; explicitly, people with CHB must NOT be restricted in daily activities, contact sports, school, or professional training and must NOT be required to take antivirals because of transmission risk in those settings; routine contact, shared meals, and hugging are not transmission routes (avoid sharing toothbrushes/razors); most healthcare workers with CHB are NOT high-risk, but those performing SHEA Category III exposure-prone procedures may require antivirals (SHEA target HBV DNA <1000 IU/mL); neither CDC nor SHEA requires disclosure to patients or staff; anti-stigma framing is part of the recommendation. (3) IMMUNE-TOLERANT PHASE, defined as HBeAg-positive, HBV DNA >10^7 IU/mL, and normal ALT; AASLD SUGGESTS antiviral therapy for those over age 40 years, OR with significant liver inflammation (grade >=2) or fibrosis (>=F2) on biopsy or noninvasive tests (CONDITIONAL, VERY LOW certainty). For persons under age 40 who are interested in starting treatment earlier, AASLD suggests shared decision-making weighing risk factors and the benefits and risks of treatment. Accurate phase identification requires persistently normal ALT on >=2 measurements >=6 months apart, using ULN 35 U/L (males) and 25 U/L (females). (4) INDETERMINATE ('grey zone') PHASE, the HBeAg-negative indeterminate phase is defined as HBsAg-positive, HBeAg-negative persons whose ALT and/or HBV DNA fall outside the thresholds for HBeAg-negative immune-active CHB (ALT >2x ULN and HBV DNA >2,000 IU/mL) and outside those for inactive CHB (HBV DNA <2,000 IU/mL with normal ALT), comprising predominantly two subgroups, (I) normal (<ULN) or mildly elevated (<2x ULN) ALT with HBV DNA >=2,000 IU/mL, or (II) elevated ALT (>ULN) with HBV DNA <2,000 IU/mL, with ALT interpreted against ULN 35 U/L (males) and 25 U/L (females) and phase assigned on >=2 ALT and HBV DNA measurements over a 6-12 month period; in adults who are HBsAg-positive, HBeAg-negative, without cirrhosis and in the indeterminate phase so defined, AASLD SUGGESTS antiviral therapy using a shared decision-making approach assessing risks and benefits, and re-evaluating that decision at each follow-up visit if treatment has not been initiated (CONDITIONAL, VERY LOW certainty). Decision-relevant factors include fibrosis stage, age, and sex, e.g. age >40, male sex, and low-normal platelets (<180 k/mm3) favor treatment. (5) DISCONTINUATION, in adults with CHB who are HBeAg-negative, without cirrhosis, with sustained undetectable HBV DNA on nucleos(t)ide analogue therapy, AASLD SUGGESTS NOT withdrawing NA therapy until HBsAg loss (CONDITIONAL, VERY LOW certainty). If a patient nonetheless has a strong desire to stop, shared decision-making applies and ALL of the following must be met: no history of advanced fibrosis/cirrhosis, hepatic decompensation (variceal bleed, ascites, encephalopathy, hepatorenal syndrome), HCC, or extrahepatic HBV complications; if HBeAg-positive at treatment start, HBeAg seroconversion to anti-HBe-positive for >=1 year with undetectable HBV DNA >=2 years; if HBeAg-negative at start, undetectable HBV DNA >=2 years; no HIV or HDV coinfection; quantitative HBsAg <100 IU/mL; and willingness to adhere to frequent monitoring. After stopping, monitor ALT and HBV DNA every 1-3 months for 6 months, then every 3 months for 6-12 months, then every 3-6 months. Restart antivirals IMMEDIATELY if HBV DNA >=10,000 IU/mL (4 log IU/mL) at any time regardless of ALT, OR ALT >=5x ULN regardless of HBV DNA, OR total bilirubin >2.5 mg/dL. (6) HCC SURVEILLANCE (all CONDITIONAL, VERY LOW certainty; modality/interval per AASLD 2023 HCC Practice Guidance), Rec 6: after HBsAg loss, continue surveillance in those with cirrhosis, family history of HCC, men who lost HBsAg after age 40, and women who lost HBsAg after age 50. Rec 7: in HBV-HDV coinfection, surveil adults independent of cirrhosis status; in children, individualize because HCC risk in that population is unknown. Rec 8: in HBV-HIV coinfection, surveil men >=18 years and women >=40 years. Rec 9: in HBV-HCV coinfection, AASLD recommends treating HCV and suggests HCC surveillance per HBV mono-infection criteria. Where a person has more than one coinfection, the surveillance recommendation should follow the coinfection carrying the highest associated risk. The guideline notes that most of its recommendations rest on low or very low certainty evidence and that shared decision-making, not uniform policy, is the intended mode of application.

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.