MASLD: A Silent, Growing Threat to Liver Health

Did you know that liver health is changing drastically worldwide, according to a landmark

study in The Lancet? The Global Burden of Disease Study 2023 recently shared a wake-up call about a serious liver condition called MASLD that we can no longer afford to overlook (1). The report stated that in 2023, around 1.3 billion people were reported to have Metabolic

Dysfunction-Associated Steatotic Liver Disease (MASLD). This accounts for around 16.1 %

of the world’s total population. Since 1990, the number of MASLD cases has increased by

143%. And it is also estimated that MASLD cases could increase up to 1.8 billion by 2050 (1).

What is MASLD?

The liver is our most vital organ. It performs many important functions, such as filtering blood,

storing iron and energy in the form of glycogen, producing blood-clotting proteins, and

detoxifying drugs. Basically, the liver works throughout life (2).

A healthy liver usually contains fats that are less than 5% of its total weight. When the fat

storage exceeds more than 5%, it leads to a condition called MASLD, without even alcohol

consumption (3). Earlier, MASLD was known as non-alcoholic fatty liver disease (NAFLD). People who are overweight or obese or have additional metabolic conditions, such as high blood pressure, type 2 diabetes, insulin resistance, or high cholesterol, are more likely to have MASLD (4). Nonetheless, a thin individual or a non-diabetic may also be affected by MASLD (5).

How MASLD Progresses: The four stages

MASLD is a silent warning about overall liver health. The liver isn’t damaged yet, but it's

continuously working under pressure. The person may not even know they have the disease,

which may further lead to severe consequences if left unchecked (6).

MASLD is a spectrum of conditions that ranges from mild fat accumulation to serious liver

damage, which includes:

Steatosis (Fatty Liver): It is the initial stage, where the liver gradually begins to store fat.

However, there have not been any serious wounds or scarring yet (7).

MASH (Metabolic dysfunction-associated steatohepatitis): If fat continues to accumulate in

the liver, it progresses to MASH. In this condition, the liver swells and enlarges. MASH was

once known as Non-alcoholic Steatohepatitis (NASH) (8).

Liver fibrosis: As a result of ongoing inflammation, the liver develops scar tissue (6).

Cirrhosis: Heavy scarring permanently damages the liver and increases the risk of liver

failure or liver cancer (hepatocellular carcinoma) (8).

Warning signs of MASLD

Patients with MASLD generally do not have any major symptoms. A few signs or symptoms

that may occur include (9):

• Fatigue

• Sharp or dull pain in the upper abdomen

• Bloating

• Thirst

• Sleep

If MASLD progresses to MASH, the following symptoms could appear (9):

• Abdominal swelling

• Itchiness

• Jaundice

• Easy bleeding and bruising

• Visible spider-like veins just under the skin

• Slurred speech and confusion

• Loss of appetite

In addition to the symptoms listed above, cirrhosis and liver failure, if it happens, may also

cause the following symptoms (9):

• Nausea and vomiting

• Tiredness and weakness

• Diarrhea

• Red or purple patches on the palms of the hands

• Dark urine

• Pale or dark, tarry stools

• Swelling of ankles, legs, and feet

• Changes in the menstrual cycle

• Enlarged breasts in males

• Memory loss

• Difficulty in focusing and confusion

Triggers of MASLD

The causes of MASLD are still under investigation. According to research, certain factors may raise the likelihood of having the disease.

Major metabolic contributors: Metabolic dysfunctions affect how the body processes and

stores fats (4, 10).

• Insulin resistance affects the body’s response to insulin, raises blood sugar levels, and

forces the liver to store excess fat (10).

• Type 2 diabetes is interconnected with MASLD development (4).

• Metabolic syndrome is a collection of medical conditions, often linked to being

overweight or obese. Among the few factors that considerably increase the chances of

liver fat accumulation are high waist circumference, high blood pressure, high

triglycerides, high LDL cholesterol levels, etc (10).

Sedentary Lifestyle:

• Regular consumption of more processed foods that are calorie-rich, especially those

that are high in sugar and fat, promotes weight gain and fat storage in the body (3).

• Prolonged sitting, particularly in desk-based jobs, along with limited physical activity,

further worsens the condition (5).

• Furthermore, smoking, sleep problems, and moderate alcohol use significantly increase

the chance of developing MASLD (5).

Other factors:

Genetics: Certain gene variants, like PNPLA3, TM6SF2, and ApoC-III, may make some

people more likely to retain liver fat regardless of their diet (5).

Hormonal Problems: Certain conditions, like hypothyroidism and polycystic ovarian

syndrome (PCOS), impact the body's metabolism (11).

Detection of MASLD

Due to a lack of any obvious symptoms, the patient is often unaware of having MASLD and is left undiagnosed. It is only during a routine blood test, along with screening for other metabolic diseases, that the condition gets discovered (12, 13).

The doctor uses a variety of techniques to assess the liver condition, such as:

i. Current medical history of the patient (13):

• Diet, physical activity, and lifestyle habits.

• Ongoing medicines.

• Alcohol use.

• Any existing health conditions like high blood pressure, type 2 diabetes, obesity, or

high fat levels, such as triglycerides or cholesterol in the blood.

ii. Blood tests (3):

• Complete blood count (CBC) test to measure the sizes and amounts of the blood cells.

• Lipid profile test to measure blood cholesterol and triglycerides.

• A liver function test measures the level of liver enzymes to check for any liver disease

or damage.

• Sugar tests, like fasting blood sugar (FBS) and A1C, to determine the condition of

sugar in the blood.

• Tests for any chronic viral hepatitis, such as hepatitis B and hepatitis C.

iii. Imaging test (5):

• Ultrasonography

• Computed tomography scan (CT scan)

• Magnetic resonance imaging (MRI)

iv. Liver Biopsy (3):

• It is considered the gold standard test for confirming and assessing the degree of liver

damage.

Treating and managing MASLD

The goal of treatment for MASLD is to prevent the liver condition from getting worse while

managing the other metabolic disorders that drive the liver disease.

Lifestyle change:

• The first line of treatment is adopting a healthy lifestyle with a balanced diet and

regular physical activity(3).

• Losing weight can be very helpful, especially for those who are overweight or obese.

Even a 3-5% loss of body weight can help to reduce liver fat. Furthermore, a 7-10%

weight loss can help to lower the risk of liver inflammation and scarring (14).

• However, rapid weight loss and malnutrition can further worsen the liver disease.

Therefore, it is recommended to follow professional counsel (14).

• Perform 150–200 minutes (about 2.5–3.5 hours) of moderate cardiac exercise per

week, divided into three to five sessions, to maintain your health (3).

• Maintaining a healthy lifestyle will also aid in the management of underlying

metabolic diseases like obesity, high blood pressure, and type 2 diabetes (5).

Proper diet plan

• Restrict the consumption of calorie-rich fats (14) (15).

• A person diagnosed with MASLD should replace trans and saturated fats in the diet

with unsaturated fats, especially omega-3 fatty acids. This will reduce the risk of

getting heart disease (16).

• Consume more foods that have a low glycemic index, such as whole grains,

vegetables, and certain fruits. These foods do not cause a sharp rise in blood sugar and

insulin levels (15).

• Avoid foods and beverages high in simple sugars like fructose, such as soft drinks,

sports drinks, and sweetened tea (14).

• Limiting the amount of daily table sugar consumption (9).

• If MASLD is detected, limit alcohol intake because it may further worsen the liver

condition (9).

Prescription Options

• Currently, only two drugs are recommended under the guidelines of the American

Association for the Study of Liver Diseases (AASLD) and the European Association

for the Study of the Liver (EASL): Vitamin E and Pioglitazone (3).

• Vitamin E acts as an antioxidant. It is primarily recommended for non-diabetic

patients with biopsy-proven MASLD, but not for patients with cirrhosis and diabetes

(5).

• Pioglitazone is a drug that helps to improve insulin sensitivity. Even though it is quite

effective, it still carries the risk of weight gain and loss of bone density (3).

Other medications

To manage underlying metabolic issues, certain medications are usually prescribed, such as

• Metformin, which reduces liver enzyme levels and improves insulin sensitivity (5).

• A GLP-1 receptor agonist called semaglutide (Ozempic) aids in lowering weight,

inflammation, and liver fat (8).

• Resmetirom, a thyroid receptor-β agonist that lowers liver fat and fibrosis (17).

• Efruxifermin is a long-acting FGF21 analog that has the potential to reduce steatosis

and fibrosis (13).

• Lanifibranor, a pan-PPAR agonist that targets inflammation and fibrosis (13).

Bariatric Surgery

• It is only recommended for severely obese patients with MASLD or MASH. In obese

patients, bariatric surgery may help to improve MASH and also reduce liver fibrosis.

Research studies have shown that after the surgery, nearly 73% of obese patients were

able to control their diabetes for up to 2 years (3, 10).

• It is crucial to remember that having MASH does not justify bariatric surgery (3).

When to see a doctor (MASLD)

As MASLD is a silent condition, it is better to consult a doctor, particularly if the individual

has risk factors such as type 2 diabetes, obesity, high cholesterol, and high blood pressure.

If the person experiences persistent fatigue, upper right abdominal pain, or unexplained weight fluctuations, the person must seek immediate medical help. If routine blood tests reveal abnormal liver function, discuss it with a doctor. Early detection can help stop the illness from developing into more severe liver issues.

References

1. Kim S, Oh J, Shin JI, Aalruz H, Abbas N, Abdulmalik AE, et al. Global burden of

metabolic dysfunction-associated steatotic liver disease, 1990–2023, and projections to 2050:

a systematic analysis for the Global Burden of Disease Study 2023. 2026.

2. Ozougwu JCJIJoRiP, Biosciences. Physiology of the liver. 2017;4(8):13-24.

3. Sahu P, Chhabra P, Mehendale AMJC. A comprehensive review on non-alcoholic fatty

liver disease. 2023;15(12).

4. Yoneda M, Kobayashi T, Iwaki M, Nogami A, Saito S, Nakajima AJG, et al.

Nonalcoholic fatty liver disease as a systemic disease and the need for multidisciplinary care.

2023;17(6):843.

5. Ştefan AG, Mitrea A, Clenciu D, Vladu IM, Roşu MM, Protasiewicz-Timofticiuc DC,

et al. MASH in Type 2 Diabetes: Pathophysiology, Diagnosis, and Therapeutic

Management—A Narrative Review. 2026.

6. Huang DQ, Singal AG, Kono Y, Tan DJ, El-Serag HB, Loomba RJCm. Changing

global epidemiology of liver cancer from 2010 to 2019: NASH is the fastest growing cause of

liver cancer. 2022;34(7):969-77. e2.

7. Buzzetti E, Pinzani M, Tsochatzis EAJM. The multiple-hit pathogenesis of non-

alcoholic fatty liver disease (NAFLD). 2016;65(8):1038-48.

8. Xie Z, Li Y, Cheng L, Huang Y, Rao W, Shi H, et al. Potential therapeutic strategies

for MASH: from preclinical to clinical development. 2024;3(5):loae029.

9. Girish V, John S. Metabolic dysfunction-associated steatotic liver disease (MΑSLD).

StatPearls [Internet]: StatPearls Publishing; 2025.

10. Chan W-K, Chuah K-H, Rajaram RB, Lim L-L, Ratnasingam J, Vethakkan SRJJoo, et

al. Metabolic dysfunction-associated steatotic liver disease (MASLD): a state-of-the-art

review. 2023;32(3):197.

11. Arvanitakis K, Chatzikalil E, Kalopitas G, Patoulias D, Popovic DS, Metallidis S, et

al. Metabolic dysfunction-associated steatotic liver disease and polycystic ovary syndrome: a

complex interplay. 2024;13(14):4243.

12. Abd El-Kader SM, El-Den Ashmawy EMSJWjoh. Non-alcoholic fatty liver disease:

The diagnosis and management. 2015;7(6):846.

13. Tincopa MA, Anstee QM, Loomba RJCm. New and emerging treatments for

metabolic dysfunction-associated steatohepatitis. 2024;36(5):912-26.

14. Romero-Gómez M, Zelber-Sagi S, Trenell MJJoh. Treatment of NAFLD with diet,

physical activity and exercise. 2017;67(4):829-46.

15. Janota B, Janion K, Buzek A, Janczewska EJM. Dietary strategies in the prevention of

MASLD: A comprehensive review of dietary patterns against fatty liver. 2025;15(8):528.

16. Barrios MDM, Trujillo KJR, Aguirre JOE, Inga MAM, Díaz SLM, Chirinos

LACJCNOS. Effectiveness of omega-3 supplementation in reducing the degree of steatotic

liver disease associated with metabolic dysfunction in adults. 2025.

17. Karim G, Bansal MBJtiE. Resmetirom: an orally administered, smallmolecule, liver-

directed, β-selective THR agonist for the treatment of non-alcoholic fatty liver disease and

non-alcoholic steatohepatitis. 2023;19(1):60.