← Return To Pre-Transplant Guide

NAFLD / MASLD & Liver Transplantation

From Fatty Liver to Cirrhosis, Cancer & Transplant

Nonalcoholic fatty liver disease (NAFLD) is now re-named metabolic dysfunction–associated steatotic liver disease (MASLD) and is the most common chronic liver disease in the world, affecting roughly one third of adults. [1] [2]

  • MASLD is driven by obesity, type 2 diabetes, insulin resistance and metabolic syndrome, and it can progress to steatohepatitis (MASH/NASH), advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). [3] [4]
  • NAFLD/MASLD is now one of the fastest-growing indications for liver transplantation in the United States and Europe. [5] [6]
  • Lifestyle changes that achieve 7–10% or more weight loss can improve steatohepatitis and even fibrosis in many patients. [7] [8]
  • New medications such as resmetirom (Rezdiffra) have now been approved by the U.S. FDA for MASH with moderate–advanced fibrosis, alongside ongoing research on GLP-1 agonists. [9] [10]
Language Matters

From NAFLD / NASH to MASLD / MASH

Patients may see both older and newer names for “fatty liver disease.” The biology is the same, but terminology has been updated to reduce stigma and emphasize metabolic risk factors.

Old Terms (Still in Use in Many Articles)

  • NAFLD – nonalcoholic fatty liver disease: ≥5% steatosis in the absence of other causes, especially significant alcohol use. [11]
  • NASH – nonalcoholic steatohepatitis: fatty liver with inflammation, ballooning injury and variable fibrosis.
  • These terms appear in many historic trials and guidelines and will still be encountered in PubMed searches.

New Terms (MASLD / MASH)

  • In 2023, an international consensus renamed NAFLD to metabolic dysfunction–associated steatotic liver disease (MASLD) and NASH to metabolic dysfunction–associated steatohepatitis (MASH). [2]
  • MASLD emphasizes that most affected patients have obesity, diabetes, dyslipidemia or metabolic syndrome. [1] [2]
  • Major societies (AASLD, EASL, etc.) have adopted the new terminology, but many transplant registries and older data sets still use NAFLD/NASH. [12]
Key point: NAFLD ≈ MASLD and NASH ≈ MASH in most clinical contexts. Transplant literature may use either set of terms during this transition period.
How Common?

Prevalence and Risk Factors

Global and Regional Burden

  • MASLD/NAFLD affects an estimated 25–38% of adults worldwide, with the highest prevalence in North America and the Middle East. [3] [13]
  • AASLD notes that MASLD is now the most common chronic liver disease worldwide. [1]
  • Recent analyses estimate that ≈5% of adults may have MASH (the more severe, inflammatory form). [14]

Major Risk Factors

  • Obesity, especially central (abdominal) obesity. [15]
  • Type 2 diabetes, insulin resistance, dyslipidemia and hypertension. [16]
  • Metabolic syndrome (≥3 of: high waist circumference, elevated blood pressure, high triglycerides, low HDL, elevated fasting glucose).
  • Sedentary lifestyle and diets high in refined carbohydrates and sugary beverages.
Disease Course

Natural History, Cirrhosis and Liver Cancer

Many people with MASLD have stable, early-stage disease. A subset progress to steatohepatitis, advanced fibrosis, cirrhosis and hepatocellular carcinoma – the complications that drive the need for liver transplantation.

Progression Over Time

  • Longitudinal studies show that fibrosis stage is the strongest predictor of outcomes in NAFLD, with higher stages linked to liver-related events and mortality. [4]
  • Patients with NAFLD-related cirrhosis have a substantial risk of HCC, with cumulative incidences around 2–13% across cohorts. [17] [18]
  • HCC can occur even in non-cirrhotic NAFLD, although cirrhosis remains the dominant risk state. [19]

Transplant-Relevant Complications

  • Decompensated cirrhosis from MASLD – ascites, encephalopathy, variceal bleeding, hepatorenal syndrome – is a common pathway to transplant referral.
  • NAFLD/MASLD-related HCC is increasingly recognized as an indication for liver transplantation, often in patients with multiple metabolic comorbidities. [20] [21]
  • Modeling studies suggest that without better prevention and treatment, MASLD will drive continued growth in HCC incidence, transplant need and liver-related deaths. [22]
Clinical takeaway: not every patient with MASLD will progress, but those with advanced fibrosis (F3–F4) or MASH are at highest risk for cirrhosis, HCC and consideration for liver transplantation.
Finding & Grading Disease

Diagnosis, Non-Invasive Tests and Biopsy

Initial Evaluation

  • MASLD is typically suspected when there is unexplained steatosis on imaging (ultrasound, CT, MRI, CAP on FibroScan) or persistently elevated aminotransferases in a patient with metabolic risk factors. [11]
  • Alternative causes of liver disease (viral hepatitis, significant alcohol use, autoimmune liver disease, hemochromatosis, Wilson disease, etc.) must be excluded.
  • A detailed metabolic assessment (BMI, waist circumference, blood pressure, fasting glucose/HbA1c, lipids) is essential.

Non-Invasive Fibrosis Assessment

  • Guidelines recommend using simple scores such as FIB-4 or NAFLD Fibrosis Score as a first step to stratify fibrosis risk. [23]
  • Patients with indeterminate/high scores should undergo vibration-controlled transient elastography (FibroScan) or other elastography-based imaging. [11]
  • Liver biopsy is reserved for selected patients when non-invasive tests are inconclusive or when precise staging will change management (e.g., clinical trial eligibility, transplant timing).
Changing the Trajectory

Treatment Options: Lifestyle, Medications and Surgery

Lifestyle intervention remains the foundation of MASLD treatment, but there is now convincing evidence that substantial weight loss and selected medications can improve steatohepatitis and fibrosis.

Lifestyle & Weight Loss

  • Randomized trials show that weight loss ≥7–10% through diet and exercise can improve NASH histology; ≥10% weight loss is strongly associated with NASH resolution and fibrosis regression. [7] [8]
  • Observational data confirm that weight loss is strongly associated with improvements in histologic activity, fibrosis and non-invasive tests. [24]
  • Mediterranean-style eating patterns, calorie reduction and regular moderate–vigorous physical activity are core components of MASLD management. [16]

Pharmacologic & Surgical Therapies

  • GLP-1 receptor agonists (e.g., semaglutide) produce clinically meaningful weight loss and have shown improvements in NASH activity in phase 2 trials. [25]
  • Semaglutide in patients with NASH and compensated cirrhosis improved metabolic parameters, though primary histologic endpoints were not met; ongoing trials and regulatory submissions focus on MASH with fibrosis. [26]
  • Resmetirom (Rezdiffra), a thyroid hormone receptor-β agonist, was shown in the MAESTRO-NASH phase 3 trial to increase both NASH resolution and fibrosis improvement versus placebo. [10]
  • In March 2024, the U.S. FDA approved resmetirom for adults with noncirrhotic NASH/MASH and moderate–advanced fibrosis (F2–F3), to be used with diet and exercise – the first approved drug for this disease. [9] [27]
  • For selected patients with severe obesity, bariatric–metabolic surgery can lead to marked improvements in NASH and fibrosis and reduced long-term liver-related events. [28]
Transplant relevance: effective treatment of MASLD before cirrhosis may prevent or delay the need for liver transplantation. After transplant, controlling metabolic risk factors is essential to reduce recurrence in the graft.
End-Stage Disease

NAFLD / MASLD as an Indication for Liver Transplantation

Rising Need for Transplant

  • NAFLD/MASLD is currently the fastest-growing indication for liver transplantation in many regions. [5] [6]
  • MASLD and MASH are projected to become – or have already become – leading indications for liver transplant in the United States. [14] [29]
  • NASH is now a major indication not only for isolated liver transplant but also for combined liver–kidney transplantation. [30]

Special Considerations in MASLD Candidates

  • Patients with MASLD often have multiple comorbidities (obesity, diabetes, coronary artery disease, chronic kidney disease) that affect transplant candidacy and perioperative risk. [5]
  • Careful cardiovascular, renal and metabolic evaluation is mandatory, and aggressive risk-factor optimization is needed before listing and after transplant.
  • Recurrence of MASLD in the graft is common if underlying metabolic drivers remain uncontrolled, but improved lifestyle and medical therapy may mitigate this over time. [5]
Partnership

What Patients and Families Can Do

For Patients With MASLD / NAFLD

  • Ask your hepatologist or primary-care clinician whether you have evidence of fibrosis or cirrhosis and whether additional testing (e.g., FibroScan, MRI, or biopsy) is needed.
  • Work with your care team on a structured weight-management plan that is realistic for you – even 5–7% weight loss can help, and ≥10% may change the course of disease.
  • Ensure optimal management of diabetes, blood pressure, cholesterol and sleep apnea, which significantly impact liver and cardiovascular outcomes.
  • If transplant is being discussed, ask specifically how your metabolic comorbidities influence candidacy and what steps you can take now to lower risk.

For Families and Caregivers

  • Support healthy food choices at home, regular physical activity and adherence to medications and appointments.
  • Encourage your loved one to follow up on recommended testing (imaging, FibroScan, labs) and to ask questions about fibrosis stage and transplant risk.
  • Recognize that MASLD is a medical disease – not a moral failing – and that lifestyle change is hard; positive, non-judgmental support works better than guilt or criticism.
  • If transplant becomes necessary, consider attending education sessions with the team so that you understand the journey, expectations and how you can help.
Educational Disclaimer

This page is for educational purposes only and does not provide personal medical advice, diagnosis or treatment. MASLD/NAFLD, MASH/NASH and transplant decisions are complex and must be individualized by clinicians who know your full medical history.

Always discuss test results, treatment options, lifestyle changes and transplant eligibility with your hepatologist, transplant team and primary-care clinicians. Never start, stop or change medications – including weight-loss or diabetes drugs – without professional guidance.

Evidence & Further Reading

Selected References

All citations above link directly to peer-reviewed articles or reputable professional sources.

  1. [1] American Association for the Study of Liver Diseases (AASLD). New MASLD Nomenclature – MASLD as the Most Common Chronic Liver Disease Worldwide.
  2. [2] Rinella ME, et al. From NAFLD to MASLD: Updated Naming and Diagnosis of Steatotic Liver Disease. J Hepatol. 2023.
  3. [3] Younossi ZM, et al. Global Epidemiology of Nonalcoholic Fatty Liver Disease. Hepatology. 2023.
  4. [4] Lindenmeyer CC, et al. The Natural History of Nonalcoholic Fatty Liver Disease. Curr Hepatol Rep. 2018.
  5. [5] Battistella S, et al. Liver Transplantation for Non-Alcoholic Fatty Liver Disease. World J Gastroenterol. 2022.
  6. [6] Terrault NA, et al. Liver Transplantation 2023: Status Report, Current and Future Challenges. Clin Gastroenterol Hepatol. 2023.
  7. [7] Promrat K, et al. Randomized Controlled Trial Testing the Effects of Weight Loss on Nonalcoholic Steatohepatitis. Hepatology. 2010.
  8. [8] Vilar-Gomez E, et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of NASH and Fibrosis. Gastroenterology. 2015.
  9. [9] U.S. Food and Drug Administration (FDA). FDA Approves First Treatment for Patients With Liver Scarring Due to Fatty Liver Disease (Rezdiffra – Resmetirom). 2024.
  10. [10] Harrison SA, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH With Liver Fibrosis. N Engl J Med. 2024.
  11. [11] Rinella ME, et al. AASLD Practice Guidance on the Clinical Assessment and Management of Nonalcoholic Fatty Liver Disease. Hepatology. 2023.
  12. [12] Allen AM, et al. Nonalcoholic Fatty Liver Disease Gets Renamed as Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastroenterology. 2024.
  13. [13] Younossi ZM, et al. Epidemiology of Metabolic Dysfunction-Associated Steatotic Liver Disease. Clin Mol Hepatol. 2024.
  14. [14] Le P, et al. Burden of Metabolic Dysfunction–Associated Steatotic Liver Disease in the US. JAMA Netw Open. 2025.
  15. [15] Wikipedia contributors. Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) – Overview and Risk Factors. Updated 2025.
  16. [16] Khakoo N. AASLD 2023 Practice Guidelines on NAFLD – Slide Summary (Non-Invasive Testing, FIB-4, Elastography). 2023.
  17. [17] Issa D, et al. Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma. Hepatobiliary Surg Nutr. 2017.
  18. [18] Orci LA, et al. Incidence of Hepatocellular Carcinoma in Patients With NAFLD-Related Cirrhosis. Clin Gastroenterol Hepatol. 2022.
  19. [19] Shah PA, et al. NAFLD-Related Hepatocellular Carcinoma: The Growing Challenge. Hepatology. 2023.
  20. [20] Petrelli F, et al. Hepatocellular Carcinoma in Patients With NAFLD: A Systematic Review and Meta-Analysis. Clin Res Hepatol Gastroenterol. 2022.
  21. [21] Parente A, et al. Liver Transplant for Hepatocellular Carcinoma in Metabolic-Associated Fatty Liver Disease. Dig Liver Dis. 2025.
  22. [22] Wong VWS, et al. Changing Epidemiology, Global Trends and Implications for NAFLD. J Hepatol. 2023.
  23. [23] Koutoukidis DA, et al. Association of Weight Changes With Changes in NAFLD Activity and Fibrosis. Clin Gastroenterol Hepatol. 2022.
  24. [24] Newsome PN, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in NASH. N Engl J Med. 2021.
  25. [25] Loomba R, et al. Semaglutide 2.4 mg Once Weekly in Patients With NASH and Compensated Cirrhosis. Lancet Gastroenterol Hepatol. 2023.
  26. [26] Younossi ZM, et al. Evolution of Liver Transplantation in the Metabolic Liver Disease Era. Hepatology. 2024.
← Return To Pre-Transplant Guide
© Dr. Michael Baruch | LiverTransplantGuide.com – This educational page may be printed and shared with patients and trainees with attribution.