Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Abstract

Liver disease (LD), defined as ≥ 2-fold elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), was examined in a longitudinal study of systemic lupus erythematosus (SLE) patients. Among 435 patients, 90 (20.7%) had LD with a greater prevalence in males (15/39; 38.5%) than females (75/396; 18.9%; p = 0.01). SLE disease activity index (SLEDAI) was greater in LD patients (7.8 ± 0.7) relative to those without (5.8 ± 0.3; p = 0.0025). Anti-smooth muscle antibodies, anti-DNA antibodies, hypocomplementemia, proteinuria, leucopenia, thrombocytopenia, and anti-phospholipid syndrome were increased in LD. An absence of LD was noted in patients receiving rapamycin relative to azathioprine, cyclosporine A, or cyclophosphamide. An absence of LD was also noted in patients treated with N-acetylcysteine. LFTs were normalized and SLEDAI was diminished with increased prednisone use in 76/90 LD patients over 12.1 ± 2.6 months. Thus, LD is attributed to autoimmunity and disease activity, it responds to prednisone, and it is potentially preventable by rapamycin or N-acetylcysteine treatment.

Keywords: Autoimmunity; Disease activity; Liver disease; Lupus; Treatment.

Fig. 1

LD is associated with increased disease activity in SLE. A) Assessment of disease activity by SLEDAI in 90 patients with LD defined as ≥2-fold elevation of AST or ALT, 126 patients with iLD defined as <2-fold elevation of AST or ALT, and 219 patients with normal LFTs. B) Modified SLEDAI scores in patients with LD, iLD, and normal LFTs after excluding anti-DNA and complement values. Data represent mean ± SEM. p values indicate comparison with two-tailed unpaired t-test.

Fig. 2

Increased production of anti-DNA autoantibodies and hypocomplementemia in lupus patients with LD. A) Correlation of AST but not ALT with anti-DNA. B) Increased anti-DNA production in SLE patients with LD. C) Correlation of C3 with AST and ALT. D) C3 hypocomplementemia in SLE patients with LD. Pearson r values and corresponding two-tailed p values are indicated for correlation dot plots. Data represent mean ± SEM in bar charts; p values indicate comparison with two-tailed unpaired t-test.

Fig. 3

Reduction of SLEDAI with reversal of LD in patients with SLE. A) Correlation of SLEDAI with AST and ALT in lupus patients with LD. Pearson r values and corresponding two-tailed p values are indicated. B) Assessment of disease activity by SLEDAI in LD patients with normalized LFT. C) Modified SLEDAI scores with exclusion of anti-DNA and complement values in patients with LD upon normalization of LFTs. D) Diminished anti-DNA antibody production in LD patients upon normalization of LFTs. Data represent mean ± SEM. p values indicate comparison with two-tailed paired t-test.