Which condition causes fibrosis: fibroids, Non-Alcoholic Fatty Liver Disease (NAFLD), fibrocystic breast changes, or keloid formation?

NAFLD Causes Fibrosis

Among the conditions listed, Non-Alcoholic Fatty Liver Disease (NAFLD) is the condition that causes true pathologic fibrosis with significant clinical consequences including progression to cirrhosis, hepatocellular carcinoma, and liver-related mortality. 1

Understanding NAFLD and Fibrosis Development

NAFLD encompasses a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis, with fibrosis being the central pathologic feature that determines prognosis. 1

Key pathologic progression:

• Steatohepatitis (NASH) is the driver for fibrosis development - more than half of type 2 diabetes patients with NAFLD have NASH, which leads to progressive liver fibrosis 1
• Fibrosis stages progress from F0 (no fibrosis) through F1 (mild), F2 (moderate/significant), F3 (severe/advanced), to F4 (cirrhosis) 1
• 12-20% of people with type 2 diabetes have clinically significant fibrosis (≥F2) 1

Clinical Significance and Mortality Impact

Fibrosis severity is the strongest predictor of mortality in NAFLD patients. 2, 3

Major complications driven by fibrosis progression include:

• Hepatocellular carcinoma - NASH is now the third most common cause of HCC in the United States 2
• Liver transplantation - NASH is the second most common indication for liver transplant 2
• Cardiovascular disease - the most common cause of death in NAFLD patients 2
• Chronic kidney disease - particularly when liver fibrosis is present 1
• Extrahepatic cancer and overall increased mortality 1

Why the Other Conditions Don't Cause True Fibrosis

Important distinction: The other conditions listed contain "fibro-" in their names but do not cause progressive pathologic fibrosis:

• Fibroids (uterine leiomyomas) - benign smooth muscle tumors, not fibrotic tissue
• Fibrocystic breast changes - benign breast tissue changes with cysts and stromal proliferation, not true fibrosis
• Keloid formation - excessive scar tissue formation after injury, representing abnormal wound healing rather than organ fibrosis with systemic consequences

Screening and Risk Stratification

The American Diabetes Association recommends screening all adults with type 2 diabetes or prediabetes for NAFLD-related fibrosis using the FIB-4 index, even with normal liver enzymes. 1

Algorithmic approach to fibrosis assessment:

• First-line: Calculate FIB-4 index (age, ALT, AST, platelets) for initial screening 1
• Second-line: If FIB-4 is indeterminate or high, proceed to liver stiffness measurement with transient elastography or enhanced liver fibrosis blood biomarker 1
• Third-line: Refer to gastroenterology/hepatology for patients at high risk for significant fibrosis 1

Critical pitfall: Screening based solely on elevated aminotransferases >40 units/L would miss most individuals with clinically significant fibrosis, as many NAFLD patients have normal liver enzymes 1

Metabolic Risk Factors

NAFLD-associated fibrosis is strongly linked to metabolic syndrome components:

• Type 2 diabetes present in 60-75% of NAFLD patients 2
• Obesity present in high percentage of NASH patients 2
• Dyslipidemia present in approximately 50% 2
• Metabolic syndrome present in approximately 50% 2

Fibrosis progression occurs in 25-37% of patients over 3-5 years, making interval monitoring essential. 1 The EASL-ALEH guidelines recommend follow-up assessment for fibrosis progression at 3-year intervals in NAFLD patients. 1