Hypothyroidism and Liver Fibrosis Severity in MASLD

The Relation Between Hypothyroidism and the Severity of Liver Fibrosis in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, characterized by excess fat accumulation in the liver associated with metabolic risk factors such as obesity and type 2 diabetes. Over time, MASLD can progress from simple liver fat accumulation to liver inflammation and fibrosis (scar tissue formation), which is the most critical factor predicting long-term liver health complications.

Thyroid hormones play a key role in controlling hepatic metabolism and lipid handling. An underactive thyroid gland (hypothyroidism), including both overt and mild (subclinical) forms, has been linked to increased fat accumulation and advanced fibrosis in the liver. However, further evidence is needed regarding how thyroid dysfunction relates to liver fibrosis using modern, non-invasive assessment tools in clinical practice.

The primary purpose of this observational case-control study is to evaluate the relationship between hypothyroidism and the severity of liver fibrosis in adult patients with MASLD.

Participants diagnosed with MASLD will be categorized into two groups based on thyroid function: patients with hypothyroidism (cases) and patients with normal thyroid function (controls). All participants will undergo standard clinical assessments, routine fasting laboratory tests, thyroid function tests, abdominal ultrasound, and transient elastography (FibroScan) to measure liver stiffness and fibrosis severity non-invasively. Non-invasive fibrosis scores, including the FIB-4 index and the NAFLD Fibrosis Score (NFS), will also be calculated.

The findings will help determine whether hypothyroidism is independently associated with more severe liver fibrosis in patients with MASLD, potentially guiding screening and management strategies.

Inclusion Criteria:

• Adult patients aged 18 years or older.
• Confirmed diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), defined as hepatic steatosis on abdominal ultrasound along with at least one cardiometabolic risk factor (e.g., overweight/obesity, type 2 diabetes mellitus, or hypertension).
• Thyroid status: Patients with diagnosed primary hypothyroidism (either overt or subclinical hypothyroidism) for the case group, or confirmed normal thyroid function (euthyroid) for the control group.
• Availability of complete clinical and laboratory data necessary to calculate non-invasive fibrosis scores (FIB-4 index and NAFLD Fibrosis Score).
• Willingness to provide written informed consent.

Exclusion Criteria:

• Thyroid-related: Hyperthyroidism, history of thyroidectomy, or radioactive iodine therapy.
• Liver-related: Chronic viral hepatitis (HBV, HCV), autoimmune hepatitis, primary biliary cholangitis, Wilson's disease, hemochromatosis, or other specific chronic liver diseases.
• Decompensated liver cirrhosis or hepatocellular carcinoma (HCC).
• Significant alcohol consumption (to exclude alcohol-related liver disease).
• General/systemic: End-stage renal disease (ESRD) or congestive heart failure.
• Pregnancy or lactation.