Usefulness of Clinical and Laboratory Criteria for Diagnosing Autoimmune Liver Disease among Patients with Systemic Lupus Erythematosus: An Observational Study

Abstract

Abnormal liver function tests are frequently observed during follow-up of patients with systemic lupus erythematosus (SLE) but data on co-existence with autoimmune liver diseases (AILD) are scarce. This retrospective study aimed to describe the prevalence of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) among well-characterized subjects with SLE. We also evaluated whether the presence of autoantibodies to complement protein 1q (C1q) and/or ribosomal P protein (anti-ribP) are, directly or inversely, associated with AIH, as proposed in some reports. The number of screened patients was 287 (86% females), and all cases were included in a regional Swedish cohort. Each subject of the study population met the 1982 American College of Rheumatology classification criteria and/or the Fries’ diagnostic principle. By applying the simplified diagnostic AIH criteria combined with persistent transaminasemia, 40 (13.9%) cases reached at least “probable AIH”. However, merely 8 of these had been diagnosed with AIH (overall AIH prevalence 2.8%). Neither anti-C1q nor anti-ribP associated significantly with AIH. By applying the recent PBC guidelines, 6 (2.1%) cases were found, but only 3 of them had actually been diagnosed with PBC and one additional subject was not identified by the guidelines (overall PBC prevalence 1.4%). Compared to prevalence data from the general Swedish population, both AIH and PBC were highly overrepresented in our study population. The sensitivity of the diagnostic AIH criteria was impeccable but the specificity was less impressive, mainly due to positive ANA and hypergammaglobulinemia. Based on our findings, among subjects with SLE, the AIH criteria are less useful and liver biopsy combined with detection of other AILD-associated autoantibodies should be performed.

Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study

“…Notably, although AILD like AIH and PBC are considered rare, their coexistence with SLE in patients presenting with liver enzyme abnormalities is relatively common [61]. The overlap rates of SLE with AIH and PBC were 1.6-15% and 2.2-7.5%, respectively [62,63]. Current MR results support a genetically predicted causal relationship between SLE and PBC.…”

Patients with treated autoimmune hepatitis and persistent suppression of plasmacytoid dendritic cells: A different point of view

“…In addition, we did not perform functional assays, like cytokine, granzyme, and perforin analyses, which could have provided us with important insights about the activity of CD4 and CD8 T cells. Finally, a previous study has shown that Systemic Lupus Erythematosus (SLE) and AIH can reach 14% of similarity in their pathogenesis, 30 an overlap that has been described in pediatric patients. 32 It is speculated that DNA and RNA release by apoptotic cells in patients with SLE are potent stimuli to pDCs, via TLR-7 and -9 activation and high IFN-I production.…”

“…29 Even Treg cells present in the inflamed hepatic tissue, which apparently have normal activity, may be involved in the AIH pathogenesis due to characteristics of the hepatic milieu, such as deficiency of IL-2, an essential cytokine for Treg function. 30 In the context of treated AIH, normal peripheral Treg cell rates could be a consequence of the immunosuppressive therapy, which, among other mechanisms, decreases the activity of selfreactive T and B cells and boost the activity of Treg cells. 31 Our study has a number of limitations, including its cross-sectional design and a small sample size.…”

Autoimmune liver diseases in systemic rheumatic diseases

“…By genome-wide studies, both diseases have been reported to share the IRF5-TNPO3 gene-spanning haplotype loci[ 65 ]. The prevalence of PBC in SLE patients with liver dysfunction ranges from 2.2% to 7.5%, usually lower than that of AIH[ 39 , 53 - 55 , 57 ]. In a review of SLE overlapping with PBC, 69% were diagnosed first by PBC, 24% had coexisting SS, and 2 deaths were due to PBC-related hepatic failure[ 66 ].…”