Hepatology, in full.

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.

Kyoto 2024 (IAP) is still the core algorithm for IPMN, and nothing in it has changed. MD-, mixed- and BD-IPMN all go through one HRS/WF algorithm. MDCT, MRI/MRCP and EUS are treated as equivalent for diagnosis, with tumor markers and HbA1c added. Since 2024, EUS imaging and EUS-FNA cytology count toward HRS/WF when EUS is done. High-risk stigmata are: obstructive jaundice with a head cyst; an enhancing mural nodule >=5 mm or a solid component; MPD >=10 mm; or suspicious/positive cytology. Worrisome features are: pancreatitis; CA19-9 >37 U/mL; new-onset or worsening diabetes within 1 year; cyst >=30 mm; enhancing mural nodule <5 mm; thickened or enhancing cyst wall; MPD 5-9 mm; abrupt change in duct caliber with distal atrophy; lymphadenopathy; or growth >=2.5 mm/year. HRS should prompt consideration of resection, weighed against fitness and life expectancy; it does not mean automatic surgery. WF should prompt EUS and multidisciplinary review. EUS-FNA is used only when its result would change management. Surveillance of non-resected BD-IPMN depends on size: <20 mm at 6 months, then every 18 months; 20 to <30 mm every 6 months twice, then every 12 months; >=30 mm every 6 months. Under Kyoto, surveillance may stop for cysts <20 mm with no change and no WF after 5 years, and should stop if the patient is unfit for surgery or life expectancy is <10 years. Continued surveillance remains an option because the risk of a separate pancreatic cancer keeps accumulating. NEW in 2026: an AGA Clinical Practice Update (Das, Serper, Vege; expert opinion, not formally graded) adds stopping rules by age and comorbidity for any pancreatic cystic lesion. (1) At any age, patients with significant comorbidity (age-adjusted Charlson index >=3-5) and an incidental, especially low-risk, cyst should be counseled against routine surveillance. (2) Over 65, cysts <=15 mm stable for 5 years with no WF/HRS should be considered for stopping after shared decision-making. 'Stable' means growth under 3 mm/year and under 6 mm over 2 years. (3) Over 75, cysts <30 mm stable for 5 years with no WF/HRS call for a discussion of whether surveillance is worth continuing, and it may stop if the patient accepts the small residual risk. (4) If comorbidity develops that rules out surgery, stopping should be discussed, even when WF/HRS were found earlier, provided there is no evidence of HGD or cancer. (5) After resection with no HGD or cancer, the remnant follows the same rules, counting surveillance time before surgery, and stopping is discussed after 5 years of stability. (6) After resection with HGD, MRI/MRCP every 6 months for 2 years and then yearly while the patient can still have a completion pancreatectomy. If invasive cancer was found, the remnant follows oncology guidelines. In both cases, stopping is discussed with oncology after 5 years of remnant stability with no WF/HRS. The resect-all-MCNs rule and the familial/germline (CAPS) screening pathway come from other guidelines, not from either of these documents.

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.

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.

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.

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.

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.

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.

Budd-Chiari syndrome (primary hepatic venous outflow obstruction): initiate therapeutic anticoagulation as soon as possible after diagnosis and continue it indefinitely unless contraindicated (strong recommendation), LMWH initially, transitioned to a vitamin K antagonist targeting INR 2-3; DOACs such as apixaban are increasingly used but rest on more limited evidence, so use them cautiously in advanced liver disease. Concurrently identify and treat the underlying cause after a comprehensive thrombophilia/myeloproliferative-neoplasm workup (including JAK2 V617F). Manage the outflow obstruction with a response-guided stepwise strategy, escalating only in patients who do not respond to medical therapy: percutaneous angioplasty/stenting for short-segment venous stenosis, then TIPS for non-correctable outflow obstruction with persistent portal hypertension or clinical deterioration, and liver transplantation for a fulminant presentation or failure of/contraindication to TIPS. Sinusoidal obstruction syndrome, treated with defibrotide, e.g. after HSCT, and acute mesenteric venous thrombosis, a surgical emergency when bowel ischemia is present, are distinct disorders with their own management pathways and are not steps in this Budd-Chiari algorithm.

Perform HCC surveillance with abdominal ultrasound PLUS serum AFP every ~6 months (semiannual, not annual) in adults with cirrhosis of any etiology who could benefit from HCC treatment: Child-Turcotte-Pugh A or B, and CTP C only if a liver-transplant candidate or listed. Do not surveil patients whose life expectancy is <1-2 years from comorbidity that neither transplantation nor HCC therapy can remedy, and weigh the physical, psychological and financial harms of surveillance case by case. Also surveil selected non-cirrhotic chronic HBV carriers: Asian men >40 and women >50 from endemic regions, people of African origin at younger ages, family history of HCC, or high viral load/active hepatitis. AGA 2026 endorses PAGE-B (intermediate/high risk at ≥10) and REAL-B to stratify these patients. Patients with HCV cirrhosis stay in surveillance after SVR. Patients without cirrhosis from other causes are NOT surveilled because incidence is too low (≤F3 fibrosis, MASLD without cirrhosis, HCV cured before cirrhosis), though fibrosis staging uncertainty warrants individual discussion. CT/MRI are not routine surveillance tools. Abbreviated MRI, GALAD and other blood biomarkers are investigational and should not replace ultrasound+AFP. Multicancer blood detection tests should not be used. Recall per AASLD 2023: AFP ≥20 ng/mL or a rising AFP (doubling, or a rise on two consecutive tests even below 20), any ultrasound observation ≥1 cm, or an inadequate ultrasound triggers multiphasic contrast CT or MRI read with LI-RADS. Treatment per AASLD 2023 is BCLC-linked: resection, ablation or transplant within Milan criteria for very-early/early disease, TACE and other locoregional therapy for intermediate disease, systemic therapy for advanced disease. Preferred first-line systemic therapy in Child-Pugh A is atezolizumab+bevacizumab or durvalumab+tremelimumab (STRIDE); sorafenib, lenvatinib or durvalumab monotherapy are the alternatives. BEACON-HCC (AASLD/HCC-LIVE, Hepatology 2026) is a Delphi consensus framework for treatment allocation that complements BCLC; it does not replace it. Under BEACON-HCC, macrovascular invasion does not automatically mean systemic therapy, and EBRT/SBRT and TARE are primary options. Continue post-treatment surveillance with contrast-enhanced cross-sectional imaging early after curative therapy.

Initiate the DILI evaluation only for clinically significant liver injury, serum AST or ALT > 5× ULN, or ALP > 2× ULN (or the pretreatment baseline if that value is abnormal) on two separate occasions; total serum bilirubin > 2.5 mg/dL with an elevated AST, ALT or ALP; or INR > 1.5 with an elevated AST, ALT or ALP, not for any minor liver-test abnormality (GS 13). In a patient with new liver test abnormalities after drug, herbal or dietary supplement (HDS) exposure, take a detailed medication and HDS history including intravenous agents such as monoclonal antibodies; most hepatotoxic drugs cause injury within the first 6 months, though some agents have longer latency and hypersensitivity reactions may appear within 24-72 hours (GS 14). Treat DILI as a diagnosis of exclusion: test for hepatitis A IgM, HBsAg, anti-HBc IgM and HCV RNA, obtain autoantibodies (ANA, anti-smooth muscle) and serum immunoglobulins, add antimitochondrial antibody in cholestatic presentations, test anti-HEV IgM in selected cases, and image the biliary tree, usually with abdominal ultrasound (GS 16). Categorize the case by R value at presentation, R = (ALT/ULN)/(ALP/ULN) (GS 15). Liver biopsy is NOT required for diagnosis but may help in severe or protracted cases, when there is diagnostic uncertainty, or when biochemistries/symptoms fail to improve after dechallenge (GS 19-20). For causality, note that the guidance does not endorse a single instrument: it describes three commonly used methods each with strengths and limitations (GS 24), observes that DILIN semiquantitative expert opinion is frequently used in practice and research but requires specialized expertise that limits generalizability (GS 26), and that updated RUCAM has better instructions but retains age, alcohol and pregnancy as risk factors of unclear value (GS 27). Management: discontinuation of the suspect drug plus supportive care, antiemetics, antipruritics, hydration, is the mainstay (GS 39). A short course of intravenous N-acetylcysteine may benefit hospitalized ADULT patients with DILI-related acute liver failure, but NAC is NOT recommended for children (GS 40); in acetaminophen overdose with established liver injury, continue NAC infusion at 6.25 mg/kg/h until ALT is falling and INR < 2. Corticosteroids for 1-3 months may benefit selected patients, severe hypersensitivity features, DRESS, immune checkpoint inhibitor injury with ALT > 5× ULN, or autoimmune-like features on biopsy, but optimal dose and duration are unknown for lack of controlled trials; typical dosing is prednisone 40-60 mg/day, or methylprednisolone-equivalent 1 mg/kg/day for checkpoint inhibitor cases (GS 41). Ursodeoxycholic acid is not established therapy but is presumably safe, and may be used at 10-15 mg/kg/day in divided doses for severe pruritus (GS 42). Because spontaneous survival in idiosyncratic DILI-related acute liver failure is only about 25%, transfer such patients EARLY to a liver transplant center (GS 36); roughly 10% of registry patients suffer ALF, transplant or death within 6 months (GS 35), with higher bilirubin and INR, lower albumin, severe necrosis or fibrosis on biopsy, comorbidity burden, and pre-existing liver disease marking increased risk (GS 38). Rechallenge with the suspect drug should generally be avoided UNLESS the anticipated benefit is high for a severe or life-threatening condition, e.g. isoniazid rechallenge causes recurrent injury in only 10% but should be attempted only in active, drug-resistant TB (GS 44). Follow liver tests to resolution: DILI persisting beyond 6-12 months (chronic DILI) occurs in 10%-20% of patients (GS 37).

In adults with AIH, first-line induction is predniso(lo)ne of AT LEAST 0.5 mg/kg/day, potentially up to 1 mg/kg/day in more severe and advanced disease, in combination with EITHER azathioprine OR mycophenolate mofetil (LoE 2, strong recommendation; 82% agreement). Azathioprine is added only when bilirubin is <6 mg/dL and ideally 2 weeks after corticosteroid start (to avoid confusing non-response with azathioprine toxicity), at an initial dose of 50 mg/day titrated to a final dose of 1-2 mg/kg/day according to toxicity and response; azathioprine must never be used alone as induction; before starting azathioprine, thiopurine methyltransferase (TPMT) activity should ideally be tested to exclude COMPLETE (absent) TPMT activity, in which azathioprine is CONTRAINDICATED because of the risk of severe, potentially life-threatening myelosuppression, whereas in PARTIAL (intermediate/heterozygous) TPMT deficiency it may be used only with caution and dose reduction; azathioprine should likewise be given cautiously in pregnancy, cytopenias or malignancy, and should be AVOIDED in acute severe AIH and decompensated cirrhosis. Mycophenolate mofetil is dosed 1.5-2 g/day (0.75-1.0 g twice daily) and is positioned by EASL as an alternative first-line option to azathioprine; the CAMARO RCT found MMF superior to azathioprine in treatment-naive patients (CBR at 6 months 72.2% vs 32.3%, p=0.004) with fewer severe adverse events (0% vs 12.9%) and less withdrawal (5.1% vs 25.8%). MMF is teratogenic and counselling of both female and male patients is recommended (LoE 2, strong); it must be withdrawn at least 3 months before conception, and first presentations during pregnancy are treated with standard regimens EXCLUDING MMF. Induction therapy and corticosteroid tapering should be individualised according to CBR status (LoE 4, strong). Budesonide is NOT recommended as part of first-line treatment for AIH and is CONTRAINDICATED in patients with cirrhosis (LoE 2, strong; 82%), but it retains a defined second-line role: switching to budesonide may be suggested because of corticosteroid side effects in patients WITHOUT cirrhosis who are predniso(lo)ne-dependent (LoE 3, WEAK recommendation; 91%). Maintenance after CBR should consist of azathioprine or MMF as monotherapy OR in combination with low-dose corticosteroids (predniso(lo)ne ≤5 mg/day), with the dose adapted to sustain stable CBR (LoE 2, strong); low-dose predniso(lo)ne monotherapy can be suggested ONLY in patients with mild disease who achieved CBR and are intolerant to both azathioprine and MMF (LoE 3, weak). Most patients require long-term, often lifelong immunosuppression, and a trial of stopping is appropriate only in carefully selected patients whose low-dose monotherapy has maintained stable CBR for at least 2 years. For ACUTE SEVERE AIH the guideline stratifies by liver failure: in acute severe AIH WITHOUT ALF or ACLF, an early treatment trial with predniso(lo)ne 0.5-1 mg/kg/day (or intravenous methylprednisolone at equivalent dose) is recommended, and failure to improve after 3-7 days of treatment initiation should trigger REFERRAL TO A LIVER TRANSPLANT CENTRE (LoE 3, strong; 91%); in acute severe AIH WITH ALF or ACLF, direct evaluation (discussion with a transplant centre) for liver transplantation is recommended, because data on the role of corticosteroids in these patients is very limited and outcomes are poor (LoE 3, strong; 97%), and if corticosteroids are given, strict surveillance for infection and close monitoring of efficacy is recommended.