Hepatobiliary Involvement in Systemic Sclerosis and the Cutaneous Subsets: Characteristics and Survival of Patients From the Spanish RESCLE Registry

Semin Arthritis Rheum. 2018 Jun;47(6):849-857. doi: 10.1016/j.semarthrit.2017.10.004. Epub 2017 Oct 6.


Objective: To assess the prevalence and causes of hepatobiliary involvement (HBI) in systemic sclerosis (SSc), to investigate the clinical characteristics and prognosis of SSc patients with HBI (SSc-HBI) and without HBI (SSc-non-HBI), and to compare both groups according to the cutaneous SSc subsets.

Methods: In all, 1572 SSc patients were collected in the RESCLE registry up to January 2015, and all hepatobiliary disturbances were recorded. We investigated the HBI-related characteristics and survival from the entire SSc cohort and according to the following cutaneous subsets: diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc sine scleroderma (ssSSc).

Results: Out of 1572, 118 (7.5%) patients had HBI. Primary biliary cholangitis (PBC) was largely the main cause (n = 67, 4.3%), followed by autoimmune hepatitis (n = 19, 1.2%), and anti-mitochondrial negative PBC (n = 6, 0.4%). Other causes of HBI were as follows: secondary liver diseases (n = 11, 0.7%), SSc-related HBI (n = 7, 0.4%), nodular regenerative hyperplasia (n = 3, 0.2%), liver cirrhosis (n = 3, 0.2%), and HBI of unknown origin (n = 2, 0.1%). In multivariate analysis, HBI was independently associated to lesser risk of dcSSc (5.1% vs. 24.4%), and higher frequency of calcinosis (26% vs. 18%), left ventricular diastolic dysfunction (46% vs. 27%), sicca syndrome (51% vs. 29%), and anti-centromere antibodies (ACA, 73% vs. 44%). According to the cutaneous subsets, HBI was associated (1) in lcSSc, to longer time from SSc onset to diagnosis (10.8 ± 12.5 vs. 7.2 ± 9.3 years), sicca syndrome (54% vs. 33%), and ACA (80% vs. 56%); (2) in ssSSc, to sicca syndrome (44% vs. 19%), and (3) in dcSSc, no associations were found. HBI was the cause of death in 2.3% patients but the cumulative survival according to the presence or absence of HBI showed no differences.

Conclusions: HBI prevalence in SSc is 7.5% and dcSSc is the least involved subset. PBC is the main cause of HBI. Patients with SSc-HBI exhibited specific clinical and immunologic profile. Survival is similar for SSc patients with HBI.

Keywords: Autoimmune hepatitis; Hepatobiliary involvement; Primary biliary cholangitis; SSc sine scleroderma; Survival; Systemic sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cholangitis / etiology*
  • Cholangitis / mortality
  • Female
  • Hepatitis, Autoimmune / etiology*
  • Hepatitis, Autoimmune / mortality
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Registries
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / mortality
  • Sjogren's Syndrome / complications
  • Sjogren's Syndrome / mortality
  • Spain
  • Survival Rate