Large study ties sarcoidosis to risk of permanent liver scarring

People with sarcoidosis but no documented liver involvement have a nearly threefold higher risk of developing permanent liver scarring (cirrhosis) than those without the inflammatory disease, according to a large, population-based study from Israel.

The risk was particularly elevated among patients whose sarcoidosis affected multiple organs. Still, the absolute risk of cirrhosis remained low: After statistical adjustment, the estimated cumulative frequency at 20 years was 2.8% among sarcoidosis patients, vs. 1.1% for controls.

The findings support “a risk-stratified spectrum from heightened clinical awareness to closer hepatic [liver] surveillance in selected patients,” the researchers wrote.

The study, “Cirrhosis Risk in Sarcoidosis Without Documented Hepatic Involvement—A Large Nationwide Population-Based Cohort Study,” was published in Liver International.

Sarcoidosis is an inflammatory disease marked by the formation of granulomas, or clusters of immune cells, in body’s tissues, potentially causing permanent damage. It most commonly affects the lungs and lymph nodes (immune structures throughout the body) but can involve many other organs, including the liver.

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When granulomas develop in the liver, the condition is known as hepatic sarcoidosis. Tissue analysis has identified liver granulomas in up to 70% of sarcoidosis patients, yet clinically apparent liver disease is reported in just 4%-11%. Most affected patients have no symptoms or only mild abnormalities on blood tests of liver function.

“This discrepancy is consistent with frequent underrecognition of hepatic sarcoidosis,” the researchers wrote.

In some cases, hepatic sarcoidosis can progress to serious liver disease. Cirrhosis has been reported in 14%-26% of sarcoidosis patients with liver involvement.

“However, population-based estimates of cirrhosis risk among sarcoidosis patients without documented hepatic involvement remain limited,” the researchers wrote.

The team retrospectively analyzed electronic medical records from 5,489 adults with sarcoidosis (mean age, 55.7, 61% women) and 6,016 age- and sex-matched adults without sarcoidosis, who served as controls.

The medical records were provided by Clalit Health Services, Israel’s largest healthcare organization. The researchers said Clalit insures approximately 53% of the national population.

None of the participants had cirrhosis at the study’s start, and none of the patients had documented hepatic sarcoidosis. Participants were followed until cirrhosis, death, departure from the health system, or August 2025.

The researchers’ goal was to determine the long-term risk of cirrhosis among sarcoidosis patients without documented liver involvement, and whether that risk was influenced by the number of organs affected by sarcoidosis and by commonly used immunomodulatory therapies.

Data showed that across more than 142,000 person-years of follow-up, cirrhosis developed in 112 sarcoidosis patients (2%) versus 38 controls (0.6%). Person-years combines the number of people in a study with the duration of follow-up for each person. For example, 100,000 person-years could represent 100,000 people followed for one year.

The rate of new cirrhosis cases per 1,000 person-years was 1.61 in sarcoidosis patients and 0.53 in controls — a roughly threefold difference.

The researchers then used statistical methods to account for factors that could potentially influence cirrhosis risk. These included age, sex, diabetes, obesity, high blood pressure, abnormal lipid (fat) levels, hepatitis (liver inflammation), other liver diseases, and alcohol use disorder. Death was recognized as an event that prevented the possibility of cirrhosis.

After those adjustments, the estimated cumulative frequency of cirrhosis after 20 years was 2.8% among sarcoidosis patients versus 1.1% among controls. This resulted in a nearly three times higher risk of cirrhosis among people with sarcoidosis. Several alternative statistical models produced similar estimates, supporting the robustness of the finding.

Diabetes, obesity, hepatitis B or C, other liver disease, and alcohol use disorder were independently associated with cirrhosis.

Among sarcoidosis patients whose organ involvement was known, 1,057 had disease affecting one organ and 87 had two or more affected organs. In an analysis of 940 patients who were cirrhosis-free five years after sarcoidosis diagnosis, multiorgan disease was significantly associated with a fivefold higher cirrhosis risk relative to single-organ disease after adjusting for age, diabetes, and other liver disease at the study’s start.

The researchers cautioned that their analysis included only 18 cirrhosis events, limiting the precision of the estimate.

None of the several immunomodulatory sarcoidosis treatments, including methotrexate, leflunomide, azathioprine, hydroxychloroquine, anti-TNF therapies, mycophenolate, and cyclophosphamide, was significantly associated with cirrhosis risk.

“Sarcoidosis was independently associated with increased cirrhosis risk despite no hepatic involvement, particularly in multiorgan disease,” the researchers wrote.

Given the overall “low absolute risk” of cirrhosis in sarcoidosis patients, the team wrote, “routine intensified hepatic surveillance cannot be recommended,” but periodic liver tests or noninvasive liver scarring assessment may still be considered in selected patients with greater inflammatory burden.

Future studies that follow patients over time are needed to determine the clinical utility and cost-effectiveness of such risk-based monitoring, they concluded.