Cirrhosis Risk in Sarcoidosis Without Documented Hepatic Involvement—A Large Nationwide Population‐Based Cohort Study

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BACKGROUND & AIMS: Given the likely underestimation of hepatic sarcoidosis, the aims were to evaluate long-term cirrhosis risk in patients with sarcoidosis without documented hepatic involvement at baseline and to assess the impact of multi-organ disease and immunomodulatory therapies on cirrhosis risk. METHODS: A retrospective cohort study using the Clalit Health Services database in Israel included adults with sarcoidosis without documented hepatic involvement or prevalent cirrhosis and age- and sex-matched controls. The primary outcome was incident cirrhosis, analysed with inverse-probability-of-treatment-weighted (IPTW) Fine-Gray modelling with death as a competing risk. Secondary analyses evaluated multi-organ involvement using landmark methods and immunomodulatory therapies as time-varying exposures. RESULTS: Among 5489 sarcoidosis patients and 6016 controls (142 002 person-years), cirrhosis occurred in 112 (2.0%) and 38 (0.6%), respectively (incidence rate 1.61 vs. 0.53 per 1000 person-years; rate ratio 3.05). In the primary IPTW-weighted Fine-Gray analysis, sarcoidosis was associated with incident cirrhosis (subdistribution hazard ratio [sHR] 2.84, 95% confidence interval [CI] 1.97-4.11, p < 0.001); the weighted 20-year cumulative incidence was 2.8% versus 1.1%. The association was consistent across IPTW-weighted cause-specific, covariate-adjusted and follow-up-truncated analyses (hazard ratio [HR]/sHR range 2.71-2.84). Among patients with confirmed organ involvement, 1057 had single-organ and 87 had multi-organ disease. In the 5-year landmark analysis (n = 940; 18 events), multi-organ involvement was associated with cirrhosis in the parsimonious model (HR 5.33, 95% CI 1.90-15.00, p = 0.002). No immunomodulatory therapy was significantly associated with cirrhosis. CONCLUSIONS: Sarcoidosis was independently associated with increased cirrhosis risk despite no hepatic involvement, particularly in multiorgan disease. This supports a risk-stratified spectrum from heightened clinical awareness to closer hepatic surveillance in selected patients.

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