Overview of Fatty Liver Disease and Its Impact on Health

Understanding Fatty Liver Disease

Fatty liver disease refers to the accumulation of excess fat in liver cells. Most cases are metabolic in origin, now termed MASLD—metabolic dysfunction–associated steatotic liver disease. This condition is driven by factors such as insulin resistance, weight gain, dyslipidemia, and hypertension. A smaller subset of cases is related to alcohol consumption, with many patients experiencing mixed contributors. The spectrum of fatty liver disease ranges from simple steatosis (fat accumulation) to inflammation and hepatocyte injury, known as steatohepatitis (historically referred to as “NASH,” now MASH). This progression can lead to fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Clinicians face the challenge of identifying patients with fibrosis who require treatment escalation without subjecting everyone to unnecessary testing.

The Importance of Awareness

MASLD is now recognized as the most prevalent liver disease worldwide. It is closely associated with cardiometabolic risks, including type 2 diabetes, sleep apnea, visceral adiposity, and atherogenic dyslipidemia. Cardiovascular events remain the leading cause of death in this population, followed by cancer and liver-related outcomes. Therefore, it is crucial to manage liver health while maintaining a focus on overall risk reduction.

Identifying Those at Risk

The risk of developing fatty liver disease increases with central obesity, diabetes or prediabetes, hypertriglyceridemia, and conditions like PCOS. Sedentary lifestyles also contribute to this risk. Certain medications, such as amiodarone or tamoxifen, can exacerbate the condition. Clues from physical exams and routine lab tests—such as elevated ALT compared to AST, low HDL, and high triglycerides—should prompt a fibrosis risk screening, particularly in individuals with diabetes or a BMI of 30 or higher.

How We Diagnose Fatty Liver Disease

To diagnose fatty liver disease, we start with simple fibrosis scores like FIB-4 or the NAFLD Fibrosis Score. These scores utilize age, AST/ALT levels, and platelet counts. Low scores can rule out advanced fibrosis, allowing for primary care management. Indeterminate or high scores necessitate further evaluation through non-invasive liver stiffness testing. Techniques like vibration-controlled transient elastography (FibroScan®), shear-wave elastography, or MR elastography are effective. For quantifying steatosis, controlled attenuation parameter (CAP) on FibroScan or MRI-PDFF can be utilized. While ultrasound can detect moderate to severe fat accumulation, it often misses milder cases and cannot stage fibrosis. Liver biopsy is now reserved for situations where uncertainty remains or when results could significantly alter management.

Effective Lifestyle Treatments

Weight Loss as a Primary Strategy

Weight reduction is the most effective treatment for fatty liver disease. A realistic target for weight loss is 7–10% of total body weight. Losing 10% or more can lead to regression of steatohepatitis and even fibrosis. Various dietary approaches can help achieve this goal, including Mediterranean-style eating, higher-protein lower-refined-carb plans, or structured calorie reduction. The key is to choose a sustainable plan that fits the individual.

The Role of Exercise

Exercise offers independent benefits, even without weight loss. Aim for 150–300 minutes of moderate aerobic activity or 75–150 minutes of vigorous activity each week, along with two sessions of resistance training. Resistance training improves insulin sensitivity and reduces liver fat, making it an excellent entry point for those who may not enjoy running.

The Benefits of Coffee

Drinking 2–3 cups of coffee daily, whether caffeinated or decaffeinated and with minimal sugar, is consistently associated with a lower risk of fibrosis and fewer liver-related events. This simple addition can be a practical strategy for many patients.

Targeted Nutrition and Supplements

The Role of Vitamin E

Vitamin E, at a dosage of 800 IU/day of natural α-tocopherol, is reasonable for non-diabetic adults with biopsy-proven steatohepatitis who are aware of the associated risks, such as hemorrhagic stroke and potential prostate cancer signals. While it can improve steatohepatitis, the effects on fibrosis remain uncertain. It's important to avoid megadoses or combining it with multiple antioxidant supplements without a clear plan.

Omega-3 Fatty Acids

Omega-3 fatty acids can help lower triglyceride levels but do not specifically treat steatohepatitis. They should be used primarily for lipid control rather than liver health endpoints.

Medications Currently in Use

To address metabolic syndrome, we often start with statins for ASCVD risk, which are safe for those with fatty liver. Controlling blood pressure and managing diabetes with therapies that also reduce hepatic fat is essential. GLP-1 receptor agonists, such as semaglutide, and dual GIP/GLP-1 agents, like tirzepatide, can lead to significant weight loss, improve steatosis, and increase rates of steatohepatitis resolution. While consistent fibrosis improvement is emerging, it is not universal. These medications are foundational for individuals with obesity or diabetes and MASLD. Pioglitazone can improve steatohepatitis and may benefit fibrosis, particularly in those with type 2 diabetes. However, it is important to monitor for weight gain, edema, and fracture risk.

Exploring New and Novel Drugs

The development of new treatments is accelerating. Thyroid hormone receptor-β agonists, such as resmetirom, have shown promise in reducing liver fat and improving fibrosis in many patients with MASH and significant fibrosis. These treatments require careful monitoring of lipid levels and thyroid status. Other emerging therapies include FXR agonists, FGF analogs, and ACC inhibitors, each targeting different aspects of lipid handling and inflammation. Each class of drugs has its own side effects, such as pruritus, LDL changes, or gastrointestinal effects, necessitating careful patient selection and lab follow-up. Combination therapy, which pairs metabolic drivers like GLP-1s with anti-fibrotic agents, is likely to become a reality in the near future.

Monitoring Progress and Referral Guidelines

Regular monitoring is crucial. Reassess ALT/AST levels, lipids, A1C, and weight every 3–6 months during active treatment. For stable patients, repeat non-invasive fibrosis assessments (FIB-4 and elastography) annually or sooner if there are clinical changes. Referral to a hepatologist is warranted if there is suspicion of cirrhosis.

Conclusion: The Path Forward

Fatty liver disease is common, cardiometabolic, and largely modifiable. It is essential to identify patients at risk for fibrosis, promote realistic weight-loss and exercise habits, and consider adding coffee and vitamin E for the right non-diabetic cohort. Utilizing modern metabolic medications, including GLP-1–based therapies, can help improve both liver health and cardiovascular risk. Non-invasive tools like FibroScan make diagnosis and follow-up practical in routine care, and the next wave of anti-fibrotic drugs is on the horizon.

At True North Metabolic, we are dedicated to diagnosing and treating fatty liver disease for patients in Kitchener, Waterloo, Cambridge, and Guelph, Ontario

References

1. American Association for the Study of Liver Diseases (AASLD) Practice Guidance on MASLD/MASH, 2023–2024 updates.

2. European Association for the Study of the Liver (EASL) Clinical Practice Guidelines for MASLD, 2023–2024.

3. NEJM. Semaglutide in NASH: randomized trial showing higher rates of NASH resolution.

4. Meta-analyses on coffee consumption and chronic liver disease outcomes.

5. Pivotal trials of resmetirom (thyroid hormone receptor-β agonist) demonstrating reduction in liver fat and fibrosis endpoints.