FIB-4 index associated with mortality risk of patients with systemic lupus erythematosus: a large retrospective cohort study
Ziyi Jin 1,   Xuebing Feng 1,   Dandan Wang 1,   Wenyou Pan 2,   Lin Liu 3,   Min Wu 4,   Huaixia Hu 5,   Xiang Ding 6,   Hua Wei 7,   Yaohong Zou 8,   Xian Qian 9,   Meimei Wang 10,   Jian Wu 11,   Juan Tao 12,   Jun Tan 13,   Zhanyun Da 14,   Miaojia Zhang 15,   Jing Li 16,   Lingyun Sun 1
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Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Department of Rheumatology, Huai’an First People’s Hospital, Huai’an, China
Department of Rheumatology, Xuzhou Central Hospital, Xuzhou, China
Department of Rheumatology, the Third Affiliated Hospital of Soochow University, Changzhou, China
Department of Rheumatology, Lianyungang Second People’s Hospital, Lianyungang, China
Department of Rheumatology, Lianyungang First People’s Hospital, Lianyungang, China
Department of Rheumatology, Northern Jiangsu People’s Hospital, Yangzhou, China
Department of Rheumatology, Wuxi People’s Hospital, Wuxi, China
Department of Rheumatology, Jiangsu Province Hospital of TCM, Nanjing, China
Department of Rheumatology, Southeast University Zhongda Hospital, Nanjing, China
Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, China
Department of Rheumatology, Wuxi TCM Hospital, Wuxi, China
Department of Rheumatology, Zhenjiang First People’s Hospital, Zhenjiang, China
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China
Department of Rheumatology, Jiangsu Province Hospital, Nanjing, China
Department of Rheumatology, Affiliated Hospital of Jiangsu University, Jiangsu, China
Submission date: 2020-01-20
Final revision date: 2020-02-17
Acceptance date: 2020-05-19
Online publication date: 2020-11-20
A considerable proportion of patients with systemic lupus ery­thematosus (SLE) have liver enzyme abnormalities. We evaluated whether fibrosis-4 (FIB-4) was associated with increased mortality of SLE patients.

Material and methods:
A multicenter retrospective cohort study was conducted based on medical records of first-admission SLE patients who were hospitalized during 1999–2009 in Jiangsu province. FIB-4 was estimated by age, platelet (PLT) count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and FIB-4. A Cox model and a restricted cubic spline (RCS) model were used to estimate hazard ratio (HR) and 95% confidence interval (95% CI).

During up to 15 years of follow-up, 226 deaths were observed among 2331 SLE patients. Increased overall mortality was associated with abnormal groups of PLT, ALT, AST, and high FIB-4 (≥ 1.92), with adjusted HRs (95% CI) of 1.58 (1.19–2.11), 1.54 (1.14–2.07), 1.58 (1.17–2.12), and 1.88 (1.42–2.50), respectively. Moreover, significant dose-response relationships were found between mortality of SLE and those indexes, and it was nonlinear for PLT (p < 0.001), ALT (p = 0.046) and FIB-4 (p < 0.001), but not AST (p = 0.109). In cause-specific analyses, high FIB-4 index was directly associated with death from liver failure and indirectly associated with other death from infection and neuropsychiatric impairment. We found no significant differences of areas under curves (AUCs) between FIB-4 index and the disease activity index score of SLE.

This is the first report to describe the nonlinear association between FIB-4 index and increased mortality of SLE patients. The FIB-4 index may be used as an independent prognostic indicator for SLE patients.