Liver enzyme levels are associated with markers of systemic inflammation, disease severity, and metabolic syndrome in patients with hidradenitis suppurativa

In the understanding of hidradenitis suppurativa (HS) as a follicular occlusion disorder with increased systemic inflammatory load, comorbidities across multiple organ systems have been gradually recognized. Recently, metabolic syndrome (MetS) has been linked with HS. The aims of this study were to evaluate liver function in patients with HS, and the potential association between liver enzymes and systemic inflammatory load, disease severity, and presence of MetS.


| INTRODUCTION
In the understanding of hidradenitis suppurativa (HS) as a follicular occlusion disorder with increased systemic inflammatory load, comorbidities across multiple organ systems have been gradually recognized. Recently, metabolic syndrome (MetS) has been linked with HS. 1 The aims of this study were to evaluate liver function in patients with HS, and the potential association between liver enzymes and systemic inflammatory load, disease severity, and presence of MetS. 2,3

| METHODS
A total of 470 outpatients from a university department from January 2016 to May 2020 were included (Table 1). Information on age, sex, smoking, ethnicity, body mass index (BMI), disease duration, and number of boils in the last month was noted. Furthermore, the presence of systemic comorbidities and severity of HS were obtained through clinical examination and confirmed from diagnoses in patient files. All patients with HS referred to the department were eligible to participate in the study, after written consent was obtained.
The prevalence and risk factors of elevated liver enzymes, disease severity, and MetS were explored by descriptive statistics. Cross tabulation was used for chi-square and risk estimation. One-way analysis of variance was used for analyzing the number of MetS criteria, alkaline phosphatase (ALP), and alanine aminotransferase (ALAT) levels between Hurley stages. Association and mean difference (MD) between age and presence of MetS and distribution of continuous variables between sexes were analyzed with independent t test. All tests were considered statistically significant at a P-value of <.05 and 95% confidence interval.

| RESULTS
The hepatic status was investigated by analyzing ALP and ALAT. The median ALP and ALAT levels were 73 U/L (IQR 59-89) and 21 U/L (IQR 16-29), respectively. Unadjusted analysis showed that ALP levels correlated with markers of systemic inflammation in females; C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), leukocytes, neutrophils, and neutrophil-lymphocyte ratio (NLR), whereas among males, ALP levels only correlated significantly with CRP. In males, ALAT levels were negatively correlated with CRP, ESR, leukocytes, neutrophils, and NLR, whereas in females, ALAT levels were positively correlated with CRP and ESR (  F I G U R E 1 Scattergram of body mass index vs disease severity measured by hidradenitis suppurativa score ALP was correlated with hidradenitis suppurativa score (HSS); in females (r = .28, P < .001) and males (r = .24, P = .002), even after adjustment (r = .31, P = .008 and r = .39, P < .001 in females and males, respectively). Only ALP levels correlated with the number of boils in the last month in females (r = .13, P = .024) but not in males (r = .11, P = .162), and for females even after adjustment (r = .30, P = .006).
The prevalence of MetS (defined by the presence of at least three criteria, Table 1

| DISCUSSION
A large percentage of our female patients were obese, which associate with an abnormal cytokine production, 6 and thereby a chronic inflammatory response. Fat accumulation in the liver also stimulates hepatic cytokine production, which may be why we, especially in females, found a strong correlation of ALP with inflammatory bio-

TRANSPARENCY STATEMENT
The corresponding author confirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.