By Joel Hughes, PhD, MAACVPR

Cardiovascular disease is the leading cause of death for people with chronic liver disease. It’s not liver cancer, liver failure, or other liver-specific causes, as people might expect. Liver disease is a “silent epidemic” affecting up to a third of adults globally, but it is often not recognized by patients or providers.

What Does This Mean for Cardiac Rehabilitation (CR)?

Many of the patients we encounter in secondary prevention of cardiovascular disease already have chronic liver disease. What used to be called “non-alcoholic fatty liver disease” (NAFLD) is now termed “metabolic dysfunction-associated steatotic liver disease” (MASLD), which progresses to metabolic dysfunction-associated steatohepatitis (MASH). MASLD means that the fat content of the liver has exceeded 5%, and MASH means that fat accumulation and inflammation have led to liver damage in the form of fibrosis.

MASH can lead to cirrhosis and/or liver cancer, but the primary cause of death for patients with MASLD and MASH is cardiovascular disease, which accounts for up to 40% of all-cause mortality in these patients. Liver disease and heart disease are interconnected through multiple physiological mechanisms, such as insulin resistance, dyslipidemia, oxidative stress, systemic inflammation, and endothelial dysfunction.¹ Having both cardiovascular disease and liver disease appears to be a “double hit” to the heart. Fortunately, cardiac rehabilitation (CR) is an opportunity for a synergistic intervention.

How Many Patients in CR Have MASLD or MASH?

A study in Japan reported that 48.9% of patients hospitalized for acute coronary syndromes had chronic liver disease.² Also, up to 70% of patients with type 2 diabetes and 90% of obese patients have chronic liver disease. A reasonable guess is “somewhere between half and most,” depending on your patient population. For example, MASLD is more common in men and people of Mexican-American ethnicity.

How Do We Know If a Patient Has MASLD or MASH?

Asking the patient may not help, as only about 1 in 10 patients are aware that they have a liver disease (in contrast to 7 in 10 patients with diabetes). MASLD and MASH are also under-recognized and under-diagnosed by health care providers. Accurately diagnosing liver disease can be complex and beyond the scope of practice of CR staff. A practical approach might be to identify patients with the highest risk of advanced fibrosis.

Focus on Fibrosis

The fibrosis-4 index (FIB-4) is based on age, liver enzymes (ALT, AST), and platelets. It is sometimes built into the electronic medical record, and if the necessary values are already there, the system can calculate it for you (e.g., EPIC has a “.fib4” function that takes available data and calculates the FIB-4). A score of < 1.30 suggests no advanced fibrosis, a score > 2.67 suggests advanced fibrosis, and an intermediate score suggests further evaluation. For patients with a high score, a referral to a hepatologist is warranted.³ 

How Does MASLD/MASH Change CR?

The good news is that the core components of CR target both cardiovascular disease and chronic liver disease.⁴ Lifestyle interventions, including weight loss, resistance training, and exercise, are first-line treatments for liver disease. Smoking cessation, alcohol cessation, and adoption of a Mediterranean-style diet are also essential and addressed in CR. Specific areas of focus for patients with MASLD or MASH could include resistance training to combat sarcopenia and aerobic exercise to reduce hepatic fat accumulation, systemic inflammation, and insulin resistance.

In August 2025, semaglutide became FDA-approved for patients with MASH,^5,6 so eligible patients should be evaluated for pharmacological treatments, and adherence should be optimized. As of now, there are no consensus statements, clinical guidelines, or other well-developed recommendations for how to address MASLD and MASH specifically in the context of CR, so these must be considered preliminary observations.

As awareness of the interconnectedness of heart disease and liver disease continues to emerge, CR professionals can begin discussing how to best manage patients with comorbid heart disease and MASLD/MASH. Already a powerful intervention for secondary prevention of cardiovascular disease, for some, CR may become primary prevention for cirrhosis and liver failure.

Joel Hughes, PhD, MAACVPR, is a professor of psychology at Kent State University and maintains non-employee medical staff privileges at University Hospitals, Portage Medical Center, so he can volunteer at cardiopulmonary rehabilitation. He also sits on AACVPR's Board of Directors.

REFERENCES

1. Sebastiani, G., Raggi, P., & Guaraldi, G. (2025). Integrating the Care of Metabolic Dysfunction-associated Steatotic Liver Disease Into Cardiac Rehabilitation: A Multisystem Approach. The Canadian Journal of Cardiology. https://doi.org/10.1016/j.cjca.2025.06.075

2. Noda T, Kamiya K, Hamazaki N, et al. The Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Association with Physical Function and Prognosis in Patients with Acute Coronary Syndrome. Journal of Clinical Medicine. 2022;11(7). https://doi:10.3390/jcm11071847

3. Khan, M.S., Javaid, S.S., Dinani, A., Wegermann, K., Pandey, A., Bhatt, A.S., Muthiah, M., Van Spall, H.G., Zannad, F., Butler, J. and Volk, M.L., 2025. The Basics of Metabolic Dysfunction–Associated Steatotic Liver Disease for Cardiologists: Pathophysiology, Diagnosis, and Treatment. Journal of the American College of Cardiology, 86(20), pp.1861-1884.

4. Brown TM, Pack QR, Aberegg E, et al. Core Components of Cardiac Rehabilitation Programs: 2024 Update: A Scientific Statement From the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation. 2024;150(18):e328-e347

5. U.S. Food and Drug Administration. Approval letter for Wegovy (semaglutide) injection for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis. NDA 215256/S-024. August 15, 2025. Available  at: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215256Orig1s024ltr.pdf

6. Hughes, J. W., Levin, J. B., Sajatovic, M, & Sclair, S. N. Semaglutide for metabolic dysfunction–associated steatohepatitis (MASH): Estimating eligibility from the 2021–2023 National Health and Nutrition Examination Survey (NHANES). Hepatology Communications 9(12):e0860, December 2025. https://doi:10.1097/HC9.0000000000000860