Management of Metabolic Dysfunction‑Associated Steatotic Hepatopathy (MASH)

Diagnostic and Risk‑Stratification Approach

• In high‑risk adults (type 2 diabetes, obesity, abnormal liver enzymes, or imaging evidence of steatosis), apply a stepwise non‑invasive algorithm: start with the FIB‑4 score, then confirm with transient elastography; fibrosis stage ≥ F2 identifies patients at risk for liver‑related outcomes and determines eligibility for therapy. 1

Lifestyle Foundations for All Patients

Weight‑Loss Targets

• Achieving a 7–10 % body‑weight reduction leads to MASH resolution and fibrosis regression; a 5 % loss is sufficient to reduce hepatic steatosis. 2

Dietary Pattern

• Adopt a Mediterranean diet emphasizing vegetables, fruits, low‑fat dairy, nuts, olive oil, legumes, and unprocessed fish or poultry while minimizing processed meat, ultra‑processed foods, and sugar‑sweetened beverages. 2

Physical Activity

• Prescribe ≥150 min/week of moderate‑intensity or ≥75 min/week of vigorous‑intensity aerobic activity. 2

Alcohol Use

• Advise patients to avoid alcohol, especially those with advanced fibrosis or cirrhosis. 2

Pharmacologic Management – Non‑Cirrhotic Disease

MASH‑Targeted Therapy

• Resmetirom is the first FDA‑conditionally approved agent (March 2024) for adults with non‑cirrhotic MASH and fibrosis stage F2/F3; phase III data demonstrate superior histologic resolution of steatohepatitis and fibrosis with an acceptable safety profile. Treatment should be used only where locally approved and according to the label. 1, 3

Dual‑Benefit Therapies for Comorbidities

• GLP‑1 receptor agonists (semaglutide, liraglutide, dulaglutide) and the GLP‑1/GIP co‑agonist tirzepatide are preferred first‑line agents in non‑cirrhotic MASH, providing glycemic control plus hepatic benefit; semaglutide has received FDA conditional approval for MASH with moderate‑to‑advanced fibrosis. 4, 5
• SGLT2 inhibitors (empagliflozin, dapagliflozin) are alternative options; trials show moderate reductions in liver fat content and serum ALT. 4
• Metformin should be continued in patients with compensated cirrhosis (if eGFR > 30 mL/min) because discontinuation may increase mortality; however, metformin alone does not improve MASH histology. 4, 5
• For obesity, incretin‑based agents (GLP‑1 agonists, tirzepatide) are favored for their combined metabolic and hepatic effects. Non‑incretin weight‑loss drugs (orlistat, phentermine‑topiramate, naltrexone‑bupropion) are not recommended due to inconclusive efficacy data. 4, 5

Pharmacologic Management – Cirrhotic Disease

• No MASH‑targeted pharmacotherapy is currently recommended for patients with cirrhosis. 1, 3
• In compensated cirrhosis, metformin may be used if eGFR > 30 mL/min; it is contraindicated in decompensated disease. 5
• Insulin is the preferred glucose‑lowering agent in decompensated cirrhosis when other options are unsuitable. 4, 5
• GLP‑1 agonists and SGLT2 inhibitors can be used cautiously in compensated cirrhosis with close monitoring. 5

Surgical and Endoscopic Options

• Bariatric surgery is indicated for non‑cirrhotic MASLD patients with BMI > 40 kg/m² or BMI > 35 kg/m² plus comorbidities; it yields durable liver improvement, diabetes remission, and better cardiometabolic risk profiles. 4, 5
• In compensated cirrhosis, bariatric surgery may be considered after multidisciplinary assessment for portal hypertension. 4, 5
• Metabolic/bariatric endoscopic procedures are not recommended pending further validation. 4, 5

Nutrition and Lifestyle in Cirrhosis

• Provide a high‑protein diet (1.2–1.5 g/kg body weight/day) with total calories ≥ 35 kcal/kg/day.
• Offer a late‑evening snack to reduce overnight fasting and preserve muscle mass in sarcopenic or decompensated patients.
• In compensated cirrhosis with obesity, a moderate weight‑loss plan emphasizing protein intake and physical activity is acceptable to avoid sarcopenia. 2, 5

Surveillance, Monitoring, and Follow‑Up

• Conduct regular surveillance for portal hypertension and hepatocellular carcinoma in cirrhotic patients.
• Provide nutritional counseling to prevent sarcopenia.
• Evaluate for liver transplantation in decompensated cirrhosis or when HCC develops. 1, 3, 5
• Use non‑invasive fibrosis tests (e.g., repeat FIB‑4, elastography) to monitor disease progression; recognize their limited ability to assess treatment response. Liver biopsy may be reserved for select cases where precise histologic information is required. 2

Multidisciplinary Care

• Implement a multidisciplinary team (hepatology, endocrinology, nutrition, cardiology, surgery) to address the intertwined liver disease, diabetes, obesity, and cardiovascular risk, thereby improving both hepatic and extra‑hepatic outcomes. 2

Common Pitfalls to Avoid

• Do not impose aggressive caloric restriction in patients with sarcopenia or decompensated cirrhosis, as it worsens muscle loss.
• Do not prescribe metformin in decompensated cirrhosis or when eGFR < 30 mL/min due to lactic‑acidosis risk. 5
• Do not withhold statins solely because of liver disease; they remain safe and cardioprotective.
• Do not discontinue metformin in compensated cirrhosis with type 2 diabetes, as this may increase mortality. 4

Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Diagnostic Approach

• The European Association for the Study of the Liver recommends case-finding strategies using non-invasive tests in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis 6, 7
• A stepwise approach using blood-based scores (such as FIB-4) followed by imaging techniques (such as transient elastography) is recommended to assess for advanced fibrosis 6, 7
• Liver biopsy is not suited for routine monitoring due to its invasiveness but may be used in individual cases to assess disease progression or treatment response 8, 9

Non-Pharmacological Management

• The American Gastroenterological Association recommends dietary and behavioral therapy to aim for sustained weight reduction of 7-10% to improve liver inflammation in adults with MASLD and overweight/obesity 8
• A Mediterranean dietary pattern is strongly recommended, characterized by limited consumption of ultra-processed foods rich in sugars and saturated fats, avoidance of sugar-sweetened beverages, and increased intake of fruits, vegetables, whole grains, legumes, nuts, and olive oil 8
• The American Heart Association recommends physical activity tailored to individual preference and ability, with a target of at least 150 minutes/week of moderate-intensity activity or 75 minutes/week of vigorous-intensity physical activity 8, 9
• Coffee consumption has been associated with improvements in liver damage and reduced liver-related clinical outcomes in observational studies 8, 9

Pharmacological Management

• The European Association for the Study of the Liver recommends consideration of treatment with resmetirom for adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) 8, 6
• Resmetirom has demonstrated histological efficacy on steatohepatitis and fibrosis in a large phase III trial with an acceptable safety profile 8, 6
• The American Diabetes Association recommends consideration of incretin-based therapies (e.g., semaglutide, tirzepatide) for patients with comorbid type 2 diabetes or obesity, as they may have beneficial effects on MASLD 6

Special Considerations

• The American Gastroenterological Association recommends bariatric surgery as an option for individuals with MASLD and obesity who don't respond to lifestyle interventions 6
• A multidisciplinary approach is strongly recommended given the connections between MASLD and cardiometabolic comorbidities 8
• Management of MASH-related cirrhosis includes nutritional counseling, surveillance for portal hypertension and hepatocellular carcinoma, and consideration of liver transplantation in decompensated cirrhosis 6, 7

Monitoring

• Non-invasive tests may be repeatedly used to assess fibrosis progression in a tailored fashion but provide limited information about treatment response 9
• Regular follow-up is necessary to assess liver function, fibrosis progression, and treatment response 10
• Hepatocellular carcinoma surveillance is indicated for patients with MASH-related cirrhosis 10

Evidence‑Based Management of MASLD

Non‑Pharmacologic Interventions

• A 5 % reduction in body weight reduces hepatic steatosis in adults with MASLD. 11, 12
• Sustained weight loss of 7–10 % improves liver inflammation and resolves steatohepatitis in patients with MASLD. 11, 12
• Weight loss exceeding 10 % leads to improvement in liver fibrosis in MASLD. 11, 12
• Adopting a Mediterranean dietary pattern—emphasizing vegetables, fruits, low‑fat dairy, nuts, olive oil, legumes, and unprocessed fish or poultry—is recommended for MASLD management. 11, 12
• Complete elimination of sugar‑sweetened beverages is advised for patients with MASLD. 11, 12
• Minimizing intake of ultra‑processed foods that are high in sugars and saturated fats is recommended for MASLD. 11, 12
• Prescribe ≥150 minutes/week of moderate‑intensity or ≥75 minutes/week of vigorous‑intensity aerobic activity for individuals with MASLD. 11, 12

Monitoring and Surveillance

• Use the FIB‑4 score and transient elastography to stage fibrosis; a fibrosis stage ≥ F2 identifies patients at higher risk for liver‑related outcomes and determines eligibility for therapy. 11, 12
• A relative reduction in MRI‑PDFF >30 % and an ALT decrease >17 U/L are associated with histologic resolution of steatohepatitis in MASLD. 11, 12
• Liver biopsy is not suitable for routine monitoring and should be reserved for select cases where precise histologic information is essential. 11, 12

Multidisciplinary Care

• Implementation of a multidisciplinary team (hepatology, endocrinology, nutrition, cardiology, surgery) improves both hepatic and extra‑hepatic outcomes in patients with MASLD. 11, 12

Safety and Contra‑Indications

• Nutraceuticals should not be used in MASLD because evidence of effectiveness is insufficient. 12

Evidence Gaps and Limitations

• No mortality benefit has been demonstrated for treatment‑induced histologic improvements in MASLD; long‑term outcome data are lacking. 11, 12
• Improving diet quality shows strong histologic benefit but limited evidence for translating into clinical liver‑related outcomes. 11, 12
• Physical activity confers well‑documented cardiometabolic benefits, yet its impact on histologic and clinical liver outcomes is less robust. 11, 12

Resmetirom Use in Non‑Cirrhotic MASH: Eligibility, Diagnostic Confirmation, Adjunctive Therapy, Lifestyle, and Safety

Eligibility Criteria

• The U.S. Food and Drug Administration (FDA) approves resmetirom only for adults with non‑cirrhotic NASH/MASH who have moderate to advanced fibrosis (stage F2‑F3) and active steatohepatitis, to be used together with diet and exercise; it is contraindicated in decompensated cirrhosis (stage F4). 13

Required Diagnostic Confirmation

• When non‑invasive tests are discordant (e.g., FibroScan F2 vs. ultrasound that cannot exclude cirrhosis), liver biopsy remains the gold‑standard for definitive fibrosis staging, especially in class III obesity. 14
• Magnetic resonance elastography (MRE) provides reliable fibrosis assessment and is less affected by severe obesity than FibroScan. 15
• Proprietary blood‑based scores (e.g., Enhanced Liver Fibrosis score, FibroTest) can be used as supplementary tools to refine fibrosis staging. 15
• Ultrasound alone cannot rule out cirrhosis, representing a critical barrier to initiating resmetirom in patients with uncertain imaging findings. 15

Adjunctive Pharmacologic Therapy

• Continuing tirzepatide (a GLP‑1/GIP dual agonist) is recommended while awaiting definitive fibrosis staging, as it offers hepatic benefits beyond glycemic control and weight loss. 16
• In the MAESTRO‑NASH trial, tirzepatide was present in ~14 % of participants and did not alter resmetirom’s tolerability or efficacy. 16
• If resmetirom is eventually started, maintaining tirzepatide therapy is advised for patients with residual active MASH and confirmed F2‑F3 fibrosis. 16

Lifestyle Recommendations (to support MASH resolution)

• Aim for 7–10 % total body‑weight loss to promote MASH resolution and potential fibrosis regression. 15
• Adopt a Mediterranean dietary pattern rich in vegetables, fruits, olive oil, nuts, legumes, and fish while avoiding sugar‑sweetened beverages and ultra‑processed foods. 15
• Perform ≥150 minutes per week of moderate‑intensity aerobic activity. 15

Safety Monitoring if Resmetirom Is Initiated

• Liver enzymes should be measured at 12 weeks after starting resmetirom to detect drug‑induced liver injury; transient ALT/AST rises are possible, especially with concurrent statin use. 17
• Gallbladder complications (cholelithiasis, acute cholecystitis, obstructive pancreatitis) occur more frequently with resmetirom; patients should be educated to report abdominal pain, nausea, vomiting, or fever. 17

Statin Dose Adjustments During Resmetirom Therapy

• When using rosuvastatin or simvastatin, limit the dose to ≤ 20 mg per day. 17
• When using pravastatin or atorvastatin, limit the dose to ≤ 40 mg per day. 17

MASLD Definition, Diagnosis, and Management Updates (2024)

Definition and Nomenclature

• MASLD replaces NAFLD and requires hepatic steatosis plus at least one cardiometabolic risk factor (obesity, type 2 diabetes, hypertension, dyslipidemia, or impaired glucose metabolism) — a shift from a diagnosis of exclusion to inclusion [18][19]
• The term MASH (metabolic dysfunction‑associated steatohepatitis) supersedes NASH as the histologic label for steatohepatitis in the context of metabolic dysfunction 18

Case Finding and Risk Stratification

• High‑risk groups (adults with type 2 diabetes, obesity BMI > 30 kg/m², metabolic syndrome, or persistently elevated liver enzymes) should be screened proactively rather than waiting for incidental findings 19
• At diagnosis, clinicians must assess for all cardiometabolic comorbidities (dyslipidemia, hypertension, chronic kidney disease, sleep apnea, polycystic ovary syndrome) to inform staging and management 19
• The 2024 guidelines mandate systematic case‑finding in these populations, contrasting with the opportunistic approach of the 2016 NAFLD recommendations 19

Pharmacologic Therapy

• Resmetirom received FDA approval (March 2024) as the first disease‑modifying agent specifically for non‑cirrhotic MASH with moderate‑to‑advanced fibrosis (stage F2/F3). Phase III trials showed superior histologic resolution of steatohepatitis and regression of fibrosis with an acceptable safety profile 18
• No MASH‑targeted pharmacotherapy is recommended for patients with cirrhosis (stage F4); treatment focuses on managing complications and comorbidities 18

Surveillance and Monitoring

• Hepatocellular carcinoma (HCC) surveillance:
  
  • Mandatory ultrasound ± AFP every 6 months for cirrhotic MASLD (stage F4) 19
  • Consider surveillance for advanced fibrosis (stage F3) based on individual risk assessment 19
  • Not recommended for fibrosis stages F0–F2 19
• In obese patients with cirrhosis, combine AFP with ultrasound due to reduced sonographic sensitivity; employ MRI when ultrasound visualization remains inadequate 19
• Portal hypertension monitoring: regular endoscopic or imaging assessment for varices and decompensation in cirrhotic patients 18
• Fibrosis progression monitoring: repeat FIB‑4 and elastography annually for patients with stage F2/F3 and every 2–3 years for stages F0/F1 19; note that non‑invasive tests primarily track fibrosis progression and have limited ability to gauge treatment response 19

Multidisciplinary Care and Systemic Implications

• MASLD is linked to higher rates of cardiovascular events, chronic kidney disease, and extra‑hepatic malignancies; a coordinated team (hepatology, endocrinology, nutrition, cardiology, surgery) is essential for comprehensive management 18
• Extra‑hepatic cancer screening should be encouraged in patients with obesity and type 2 diabetes, reflecting their elevated risk profile 19

Comparative Summary of 2016 vs. 2024 Guidelines

Management of Metabolic‑Associated Steatotic Liver Disease (MASH) with Fibrosis F2–F3

1. Risk Stratification and Diagnostic Confirmation

• Use a stepwise non‑invasive algorithm to confirm fibrosis ≥ F2: first calculate the FIB‑4 score; if elevated, perform transient elastography – a liver stiffness ≥ 10 kPa indicates at least stage F2. 20
• Exclude decompensated cirrhosis (F4) before starting MASH‑targeted drugs: resmetirom is contraindicated in decompensated cirrhosis, and no disease‑specific agents are recommended for cirrhotic patients. 20

2. Lifestyle Modification (Foundation for All Patients)

2.1 Weight‑Loss Targets

• Aim for a total body‑weight reduction of 7 %–10 % to achieve MASH resolution and fibrosis regression; even a 5 % loss improves hepatic steatosis. 21
• Create a daily caloric deficit of 500–1,000 kcal to promote gradual loss (< 1 kg/week) and avoid rapid weight loss that may aggravate liver injury or sarcopenia. 21

2.2 Dietary Pattern

• Adopt a Mediterranean dietary pattern rich in vegetables, fruits, whole grains, legumes, nuts, fish/white meat, and olive oil as the main fat source. 20

2.3 Physical Activity

• Prescribe ≥ 150 min/week of moderate‑intensity or ≥ 75 min/week of vigorous‑intensity aerobic exercise, which reduces steatosis and improves liver enzymes even without substantial weight loss. 20

3. MASH‑Targeted Pharmacotherapy (Non‑Cirrhotic F2–F3)

• Resmetirom is the first FDA‑approved agent (March 2024) for adults with non‑cirrhotic MASH and fibrosis F2–F3; phase III trials demonstrated superior histologic steatohepatitis resolution and fibrosis regression with an acceptable safety profile. 20 – Evidence level: Phase III randomized controlled trials
• Resmetirom should be used only where locally approved and is contraindicated in decompensated cirrhosis (F4). 20

4. Management of Metabolic Comorbidities

4.1 Type 2 Diabetes & Obesity

• GLP‑1 receptor agonists (e.g., semaglutide, liraglutide, dulaglutide) or the GLP‑1/GIP co‑agonist tirzepatide are preferred first‑line agents in non‑cirrhotic MASH, providing glycaemic control, weight loss, and hepatic benefit. 20 – Evidence level: Consensus/clinical guideline
• Semaglutide has received FDA conditional approval for MASH with fibrosis F2–F3; in randomized trials, 0.4 mg daily achieved MASH resolution without fibrosis worsening in 59 % of patients versus 17 % with placebo. 20 – Evidence level: Randomized controlled trial
• SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) are viable alternatives; trials show moderate reductions in liver fat content and serum ALT. 20 – Evidence level: Controlled clinical studies
• Continue metformin in patients with compensated cirrhosis (eGFR > 30 mL/min); discontinuation may increase mortality, although metformin alone does not improve histology. 20 – Evidence level: Observational cohort
• Non‑incretin weight‑loss agents (orlistat, phentermine‑topiramate, naltrexone‑bupropion) are not recommended due to insufficient efficacy data in MASH. 20

4.2 Dyslipidaemia

• Statins are safe, effective, and strongly recommended for all MASH patients with dyslipidaemia; meta‑analyses show a 37 % reduction in hepatocellular carcinoma risk. 20 – Evidence level: Meta‑analysis
• Do not withhold statins solely because of liver disease; they remain cardioprotective and do not worsen hepatic outcomes. 20

5. Bariatric Surgery

• Offer bariatric surgery (Roux‑en‑Y gastric bypass or sleeve gastrectomy) to patients with BMI ≥ 40 kg/m² or BMI ≥ 35 kg/m² with metabolic comorbidities who have failed lifestyle and pharmacologic measures. 21 – Evidence level: Guideline recommendation
• In the BRAVES trial, 55 % of surgically treated patients achieved histologic MASH resolution without fibrosis worsening at 1 year versus 15 % with lifestyle alone; fibrosis improvement by ≥ 1 stage occurred in 37–39 % after surgery versus 23 % with lifestyle alone. 21 – Evidence level: Randomized controlled trial
• Bariatric surgery may be considered in compensated cirrhosis after multidisciplinary assessment of portal hypertension and surgical risk. 20

6. Special Considerations for Cirrhotic Patients (F4)

• No MASH‑specific pharmacotherapy is recommended for cirrhotic patients; management focuses on metabolic optimization, nutritional support, HCC surveillance, and transplant evaluation when indicated. 20
• Provide a high‑protein diet (1.2–1.5 g/kg body weight/day) with total calories ≥ 35 kcal/kg/day and a late‑evening snack to preserve muscle mass in sarcopenic or decompensated patients. 21 – Evidence level: Expert consensus
• In compensated cirrhosis with obesity, a moderate weight‑loss plan that emphasizes adequate protein intake and physical activity is acceptable to avoid sarcopenia. 21

7. Common Pitfalls & Safety Alerts

• Avoid metformin in decompensated cirrhosis or when eGFR < 30 mL/min due to risk of lactic acidosis. 20
• Do not discontinue metformin in compensated cirrhosis with type 2 diabetes, as withdrawal may increase mortality. 20
• Resmetirom must not be used in cirrhotic patients (F4). 20
• Do not rely on ultrasound alone to exclude cirrhosis; employ FIB‑4, elastography, or magnetic resonance elastography for accurate staging. 20

Evidence‑Based Management of Metabolic Dysfunction‑Associated Steatotic Liver Disease (MASLD)

1. Pathogenic‑Driver Stratification Is Not Clinically Actionable

• The 2024 European Association for the Study of the Liver (EASL)–European Association for the Study of Diabetes (EASD)–European Association for the Study of Obesity (EASO) guidelines state that understanding individual susceptibility and developing pathophysiology‑targeted drugs remains a research gap, confirming that precision‑medicine approaches for MASLD are not yet available. 22

2. Universal Foundational Therapy (All Drivers)

2.1 Weight‑Loss Targets

• Achieving a 7–10 % total body‑weight reduction resolves steatohepatitis and promotes fibrosis regression; even a 5 % loss markedly reduces hepatic steatosis. (High‑quality evidence from multiple cohort studies.) 23, 24

2.2 Dietary Pattern

• Recommend a Mediterranean diet rich in vegetables, fruits, olive oil, nuts, legumes, and unprocessed fish/poultry while avoiding sugar‑sweetened beverages and ultra‑processed foods. (Guideline‑based recommendation.) 23, 24

2.3 Physical Activity

• Prescribe ≥150 min/week of moderate‑intensity or ≥75 min/week of vigorous‑intensity aerobic exercise. (Supported by randomized lifestyle trials.) 23, 24

2.4 Alcohol

• Advise complete alcohol avoidance, especially in patients with advanced fibrosis or cirrhosis. (Consensus safety recommendation.) 23

3. Pharmacologic Therapy for Non‑Cirrhotic MASH (Fibrosis ≥ F2)

3.1 Disease‑Modifying Agent

• Resmetirom is the first FDA‑approved disease‑modifying therapy for non‑cirrhotic MASH with fibrosis stage F2–F3; phase III randomized trials demonstrated superior histologic resolution of steatohepatitis and significant fibrosis regression with an acceptable safety profile. (Level A evidence.) 24, 25

• Contraindication: Resmetirom must not be used in decompensated cirrhosis (F4); no other MASH‑targeted drugs are recommended for cirrhotic patients. (Regulatory labeling.) 24, 25

3.2 Management of Metabolic Comorbidities

• GLP‑1 receptor agonists (e.g., semaglutide, liraglutide, dulaglutide) and the GLP‑1/GIP co‑agonist tirzepatide are first‑line for patients with co‑existing type 2 diabetes or obesity. Semaglutide has FDA conditional approval for MASH with F2–F3 fibrosis, achieving disease resolution without fibrosis worsening in 59 % of treated patients versus 17 % with placebo (phase III trial). (Level A evidence.) 26

• SGLT2 inhibitors (empagliflozin, dapagliflozin) provide modest reductions in liver fat content and serum ALT levels. (Evidence from controlled trials.) 26

• Pioglitazone improves adipose‑tissue function and liver histology via insulin‑sensitizing mechanisms, but it is not recommended as a MASH‑targeted therapy because robust phase III efficacy data are lacking and it causes modest weight gain (≈2–5 kg). (Conditional recommendation.) 24, 26

4. Bariatric Surgery

• Offer bariatric surgery (Roux‑en‑Y gastric bypass or sleeve gastrectomy) to patients with BMI ≥ 40 kg/m² or BMI ≥ 35 kg/m² with metabolic comorbidities who have failed lifestyle and pharmacologic measures; surgery yields durable liver improvement, diabetes remission, and reduced cardiometabolic risk. (Evidence from prospective cohort studies.) 25, 26

• In compensated cirrhosis, bariatric surgery may be considered after a multidisciplinary assessment of portal hypertension and surgical risk. (Expert consensus.) 25, 26

5. Management in Cirrhosis (All Drivers)

• No MASH‑targeted pharmacotherapy is recommended for cirrhotic patients; care focuses on metabolic optimization, adequate nutrition, hepatocellular carcinoma surveillance, and transplant evaluation. (Guideline recommendation.) 24, 25

• Provide a high‑protein diet (1.2–1.5 g protein/kg body weight/day) with total calories ≥ 35 kcal/kg/day and a late‑evening snack to preserve muscle mass in sarcopenic or decompensated individuals. (Nutrition guideline.) 25, 26

• For compensated cirrhosis with obesity, a moderate weight‑loss plan that maintains adequate protein intake and physical activity is acceptable to avoid sarcopenia. (Consensus recommendation.) 25, 26

6. Monitoring and Multidisciplinary Care

• Use FIB‑4 score and transient elastography to stage fibrosis; fibrosis ≥ F2 identifies patients at higher risk of liver‑related outcomes and determines eligibility for resmetirom. (Validated non‑invasive tools.) 23

• Repeat non‑invasive fibrosis assessments annually for patients with F2/F3 disease and every 2–3 years for those with F0/F1; recognize that these tests have limited capacity to gauge treatment response. (Monitoring guideline.) 23

• Implement a multidisciplinary team (hepatology, endocrinology, nutrition, cardiology, surgery) to address the intertwined liver disease, diabetes, obesity, and cardiovascular risk. (Best‑practice recommendation.) 23