Chronic Liver Disease (CLD) and NIH Women's Health Research

Signs, Symptoms, and Risk Factors

CLD refers to conditions that cause liver damage or inflammation that persists for 6 or more months and may progress to fibrosis, cirrhosis, liver cancer, liver failure, and death if not effectively managed.^{1 , 2} People with CLD may be asymptomatic.² In more advanced, life-threatening stages of the disease, symptoms may develop, and common signs include abdominal or leg swelling, jaundice, and changes in stool or urine color.^{1 - 3}

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, affecting about 30% of adults.⁴ Along with alcohol-related liver disease, it is a leading contributor to the global burden of CLD.^{1 , 4} Other potential causes of CLD may include chronic viral infections (e.g., viral hepatitis), autoimmune diseases, and inherited disorders (e.g., hereditary hemochromatosis).^{1 , 2} The risk factors for CLD vary depending on the underlying cause of the disease.¹ Common or recurring risk factors that may increase the likelihood of developing some forms of CLD include excessive alcohol use, metabolic disorders (e.g., obesity, type 2 diabetes), and family history of liver disease.^{1 , 2}

Impact on Women's Health

Women face distinct risks and disease patterns of liver disease onset and progression. These are related to differences in biological factors, such as hormones, immune function, and genetics, as well as environmental exposures and health-system factors, including the potential underrecognition or delayed diagnosis of some liver diseases in women and disparities in treatment access.^{4 - 6} Women are more likely than men to develop acute liver failure, autoimmune hepatitis, benign liver lesions, primary biliary cirrhosis, and liver damage caused by harmful substances.^{5 - 7} Biliary atresia, a condition that affects the liver in infants, is slightly more common in female infants.⁸ Women with hepatitis B may experience unique challenges related to birth control, pregnancy-associated risks, and differences in liver metabolism; younger women with hepatitis C tend to have better short-term outcomes, likely due to estrogen's protective effects on the liver, but liver damage may progress more quickly after menopause as estrogen declines later in life.^{5 , 9} Pregnancy in women with CLD requires careful management, as CLD can affect both maternal and fetal health.¹⁰ Optimizing maternal health before and during pregnancy may improve maternal and perinatal outcomes and could help inform strategies to mitigate the intergenerational risks of liver disease in offspring.^{9 , 10} Women also experience higher waitlist mortality for liver transplantation and are less likely than men to undergo a transplant, reflecting system disparities.^{6 , 11}

Diagnosis and Treatment

Diagnosing CLD involves integrating clinical history and performing targeted blood and imaging tests and sometimes a liver biopsy when noninvasive tests cannot conclusively identify the cause of liver damage and assess complications.^{1 , 3} Treatment is highly individualized and depends on the stage of disease progression, presence of complications, and management of the underlying cause.¹ Primary treatment goals are to stop or slow the progression of disease and related complications; in advanced cases, that may include liver transplant.¹

Ongoing Research

Researchers are continuing to investigate the causes, progression, and treatment of CLD, including the two most common forms: MASLD and alcohol-associated liver disease. These conditions are particularly important for women's health because they disproportionately affect women.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is the primary NIH organization for research on liver diseases. NIDDK supports a wide range of research on liver disease, including genetics and genomics, patient-oriented clinical and epidemiological studies, basic and translational research, and investigations into iron metabolism, HIV-related liver complications, and digestive disease research infrastructure. NIDDK also funds Digestive Diseases Research Core Centers, which bring together interdisciplinary teams at institutions across the country to accelerate discovery and provide shared resources, pilot funding, and training opportunities for liver and digestive disease investigators. In addition, NIDDK supports major parent studies—such as the Liver Cirrhosis Network, which follows people who are living with cirrhosis to understand why complications occur and will launch a statin therapy trial to improve patient outcomes—and provides opportunities for ancillary studies that build on these efforts.