Incidence and Predictors of an Abnormal Liver Function Test Among 674 Systemic Sclerosis Patients: A Cohort Study

Kookwan Sawadpanich,1 Palinee Promasen,1 Pisaln Mairiang,1 Wattana Sukeepaisarnjareon,1 Apichat Sangchan,1 Tanita Suttichaimongkol,1 Kawin Tangvoraphonkchai,1 Chingching Foocharoen2 1Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; 2Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, ThailandCorrespondence: Chingching Foocharoen, Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand, Tel +66-43-363-746 ; +66-43-363-664, Email fching@kku.ac.thBackground: Abnormal liver function tests (LFTs) can indicate cirrhosis or liver cancer leading to mortality among systemic sclerosis (SSc) patients. No recent studies have investigated the clinical predictors of an abnormal LFT in SSc. We aimed to determine the incidence of abnormal LFT (including from hepatitis and cholestasis) and to identify its clinical predictors in SSc patients.Methods: An historical cohort was conducted on 674 adult SSc patients who attended the Scleroderma Clinic, Khon Kaen University, between January 2012 and November 2019 and who underwent routine screening for LFT. A Cox regression was used to analyze the clinical predictors of abnormal LFT.Results: Four hundred and thirty cases, representing 4190 person-years, had abnormal LFTs (viz, from hepatitis, cholestasis, and cholestatic hepatitis) for an incidence rate of 10.2 per 100 person-years. The respective incidence of hepatitis, cholestasis, and cholestatic hepatitis was 20.5, 12.9, and 20.4 per 100 person-years. The respective median first-time detection of hepatitis, cholestasis, and cholestatic hepatitis was 3.0, 5.9, and 2.8 years, and none had signs or symptoms suggestive of liver disease. According to the Cox regression analysis, the predictors of an abnormal LFT in SSc were elderly onset of SSc (hazard ratio (HR) 1.02), alcoholic drinking (HR 1.74), high modified Rodnan Skin Score (mRSS) (HR 1.03), edematous skin (HR 2.94), Raynaud’s phenomenon (HR 1.39), hyperCKaemia (HR 1.88), and methotrexate use (HR 1.55). In contrast, current sildenafil treatment (HR 0.63) and high serum albumin (HR 0.70) were protective factors.Conclusion: Occult hepatitis, cholestasis, and cholestatic hepatitis can be detected in SSc patients using LFT screening, especially in cases of early disease onset. The long-term outcome is uncertain, and more longitudinal research is required.Keywords: systemic sclerosis, scleroderma, scleroderma and related disorders, hepatitis, cholestasis, cholestatic hepatitis, abnormal liver function test, liver, cohort study