Prurigo Nodularis Increases Risk of Non-alcoholic Fatty Liver Disease and Liver Cirrhosis: A Global-federated Retrospective Cohort Study

Abstract

Background/aim: Prurigo nodularis (PN) is a chronic inflammatory skin disorder characterized by intense pruritus and nodular lesions. Emerging evidence suggests PN may be associated with systemic conditions, including liver diseases. This study aimed to investigate the relationship between PN and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis/cirrhosis.

Patients and methods: This study was conducted using the TriNetX Research Network. Adults diagnosed with PN between 2005 and 2018 were compared with a propensity score-matched control group without PN. Patients with prior liver disease or neoplasms were excluded. The outcomes of interest were incident NAFLD, liver fibrosis, and cirrhosis, assessed using ICD-10-CM codes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and sensitivity and stratification analyses were conducted to evaluate the robustness of the findings.

Results: Among 28,390 PN patients and matched controls, PN was associated with an elevated risk of NAFLD (HR=1.27, 95% CI=1.17-1.38) and liver fibrosis/cirrhosis (HR=2.01, 95% CI=1.65-2.45) over a 15-year follow-up. Stratified analyses revealed higher risks in males and younger patients (18-64 years). Sensitivity analyses confirmed consistent findings across various definitions, follow-up durations, and active comparators.

Conclusion: PN is associated with an increased risk of NAFLD, liver fibrosis, and cirrhosis. These findings highlight the need for monitoring and proactive management of liver health in PN patients. Further research is warranted to elucidate the mechanisms underlying this association and explore potential therapeutic strategies.

Keywords: Prurigo nodularis; cohort; electronic medical records; epidemiology; liver cirrhosis; non-alcoholic fatty liver disease.

Figure 1

Patient selection process. In the current study, chronic liver diseases include non-alcoholic fatty liver diseases, liver cirrhosis and fibrosis, alcohol related disorders, autoimmune hepatitis and viral hepatitis.

Figure 2

Forest plot of NAFLD risk in prurigo nodularis patients. The crude model represents the analysis without propensity score matching. In Matching model 1, covariates include age at index, sex, race, socioeconomic status and substance abuse status. In Matching model 2, covariates include age at index, sex, race, comorbidity status (including diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease). In sensitivity analyses, Algorithm 1 included patients with more than 2 PN diagnoses in the PN group; Algorithm 2 included in the PN group patients diagnosed with PN with more than 2 visit records and at least one impatient visit; Algorithm 3 included in the PN group patients diagnosed with PN with more than 2 visit records and a record of systemic corticosteroid, pimecrolimus or tacrolimus. Detailed information of sensitivity analysis was presented in Table II. PN, Prurigo nodularis; NAFLD, non-alcoholic fatty liver diseases; PSO, psoriasis; AA, alopecia areata; CI, confidence interval.

Figure 3

Forest plot of liver cirrhosis and fibrosis risk in prurigo nodularis patients. The crude model represents the analysis without propensity score matching. In Matching model 1, covariates include age at index, sex, race, socioeconomic status and substance abuse status. In Matching model 2, covariates include age at index, sex, race, comorbidity status (including diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease). In sensitivity analyses, Algorithm 1 included patients with more than 2 PN diagnoses in the PN group; Algorithm 2 included in the PN group patients diagnosed with PN with more than 2 visit records and at least one impatient visit; Algorithm 3 included in the PN group patients diagnosed with PN with more than 2 visit records and a record of systemic corticosteroid, pimecrolimus or tacrolimus. Detailed information of sensitivity analysis was presented in Table II. PN, Prurigo nodularis; PSO, psoriasis; AA, alopecia areata; CI, confidence interval. Crude model: analysis did not undergo propensity score matching.