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W J H World Journal of
Hepatology
Submit a Manuscript: https://www.f6publishing.com World J Hepatol 2019 April 27; 11(4): 391-401
DOI: 10.4254/wjh.v11.i4.391 ISSN 1948-5182 (online)
ORIGINAL ARTICLE
Observational Study
Nonalcoholic fatty liver disease prevalence in an Italian cohort of
patients with hidradenitis suppurativa: A multi-center retrospective
analysis
Giovanni Damiani, Sebastiano Leone, Kristen Fajgenbaum, Nicola L Bragazzi, Alessia Pacifico,
Rosalynn RZ Conic, Paolo DM Pigatto, Carlo Maiorana, Pierpaolo Poli, Emilio Berti, Maria C Pace,
Piergiorgio Malagoli, Vincenzo Bettoli, Marco Fiore
ORCID number: Giovanni Damiani
(0000-0002-2390-6505); Sebastiano
Leone (0000-0001-7852-4101);
Kirsten Fajgenbaum
(0000-0002-6667-8653); Nicola L
Bragazzi (0000-0001-8409-868X);
Alessia Pacifico
(0000-0003-0348-0620); Ruzica RZ
Conic (0000-0002-9209-2883); Paolo
DM Pigatto (0000-0001-6599-9538);
Carlo Maiorana
(0000-0001-8748-9483); Pierpaolo
Poli (0000-0003-3739-1490); Emilio
Berti (0000-0001-6753-4910); Maria
C Pace (0000-0002-9352-4780);
Piergiorgio Malagodi
(0000-0002-6181-6922); Vincenzo
Bettoli (0000-0002-2760-4600);
Marco Fiore (0000-0001-7263-0229).
Author contributions: Damiani G,
Maiorana C, Berti E, Poli P and
Bettoli V designed the aim of the
study; Damiani G, Pigatto PDM,
Poli P and Pacifico A collected
data; Damiani G, Fajgenbaum K,
Bragazzi NL and Conic RRZ
analyzed data; Conic RRZ and
Pace MC prepared tables; Damiani
G, Pacifico A and Fiore M wrote
the manuscript; Fiore M
supervised the manuscript; Leone
S contributed to the hidradenitis
suppurativa antibiotic treatment
discussion; all the authors
approved the final version of the
manuscript.
Institutional review board
statement: This study was
approved by the Milan Area 2
Ethics Committee (Milan, Italy).
Giovanni Damiani, Rosalynn RZ Conic, Department of Dermatology, Case Western Reserve
University, Cleveland, OH 44195, United States
Giovanni Damiani, Young Dermatologists Italian Network (YDIN), Centro Studi GISED,
Bergamo 24100, Italy
Giovanni Damiani, Paolo DM Pigatto, Clinical Dermatology, IRCCS Galeazzi Orthopaedic
Institute, Milan 20100, Italy
Giovanni Damiani, Paolo DM Pigatto, Department of Biomedical, Surgical and Dental Sciences,
University of Milan, Milan 20161, Italy
Sebastiano Leone, Division of Infectious Diseases, “San Giuseppe Moscati” Hospital, Avellino
83100, Italy
Kristen Fajgenbaum, University of North Carolina School of Medicine, Chapel Hill, NC 27516,
United States
Nicola L Bragazzi, School of Public Health, Department of Health Sciences (DISSAL),
University of Genoa, Gevova 16132, Italy
Alessia Pacifico, San Gallicano Dermatological Institute, IRCCS, Rome 00144, Italy
Carlo Maiorana, Pierpaolo Poli, Center for Jawbone Atrophies Policlinico Hospital, University
of Milan School of Dentistry, Milan 20123, Italy
Emilio Berti, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università
degli Studi di Milano, Unità Operativa di Dermatologia, IRCCS Fondazione Ca’ Granda,
Ospedale Maggiore Policlinico, Milan 20122, Italy
Maria C Pace, Marco Fiore, Department of Women, Child and General and Specialized Surgery,
University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
Piergiorgio Malagoli, Dermatology Unit, Azienda Ospedaliera San Donato Milanese, Milan
20097, Italy
Vincenzo Bettoli, Department of Clinical and Experimental Dermatology, O.C. of Dermatology,
Azienda Ospedaliero-Universitaria di Ferrara, Ferrara 44121, Italy
Corresponding author: Marco Fiore, MD, Doctor, Department of Women, Child and General
and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2,
WJH https://www.wjgnet.com
April 27, 2019 Volume 11 Issue 4
391
Informed consent statement:
Informed consent was obtained
from all HS patients after a careful
explanation of the nature of the
disease and possible complications.
Conflict-of-interest statement: All
authors declare no conflict of
interest.
Data sharing statement: No
additional data are available.
Open-Access: This article is an
open-access article which was
selected by an in-house editor and
fully peer-reviewed by external
reviewers. It is distributed in
accordance with the Creative
Commons Attribution Non
Commercial (CC BY-NC 4.0)
license, which permits others to
distribute, remix, adapt, build
upon this work non-commercially,
and license their derivative works
on different terms, provided the
original work is properly cited and
the use is non-commercial. See:
http://creativecommons.org/licen
ses/by-nc/4.0/
Manuscript source: Invited
manuscript
Received: January 2, 2019
Peer-review started: January 4,
2019
First decision: January 23, 2019
Revised: February 25, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: April 27, 2019
P-Reviewer: Hernanda PY, Luo GH
S-Editor: Cui LJ
L-Editor: A
E-Editor: Zhang YL
Naples 80138, Italy. marco.fiore@hotmail.it
Telephone: +39-81-5665180
Fax: +39-81-455426
Abstract
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) includes two distinct conditions, with
different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and
non-alcoholic steatohepatitis (NASH). Furthermore, NASH is the more
aggressive necro-inflammatory form, which may accumulate fibrosis and result
in End stage liver disease (ESLD). NAFLD is also linked to systemic
inflammatory conditions such as psoriasis. NAFLD is currently the most common
cause of ESLD in Western countries, becoming a serious public health concern.
Hidradenitis suppurativa (HS) is a systemic inflammatory/autoinflammatory
disease of the terminal follicular epithelium of the apocrine gland with a
prevalence of 0.05% to 4.10%. Due to its systemic inflammatory behavior several
comorbidities were recently associated, however liver ones were scarcely
assessed.
AIM
To evaluate the prevalence and characteristics of NASH/NAFL in HS patients.
METHODS
This retrospective study is a sub-analysis of a larger study carried out in 4 Italian
dermatological centers. In this cohort, there were 83 patients: 51 patients with HS
only, 20 patients with HS/NAFL and 12 with HS/NASH.
RESULTS
Inflammatory comorbidities were present in 3.9% of HS only patients, 25% of
HS/NAFL patients and 58.3% of HS/NASH patients (P < 0.001). Similarly, mean
Autoinflammatory Disease Damage Index (ADDI) was significantly higher
among patients with HS/NASH (5.3 ± 2.2, P < 0.001) compared to patients with
HS/NAFL or HS only (2.8 ± 1.6 and 2.6 ± 1.4 respectively). Furthermore, ADDI
correlates with IHS4 in HS, HS/NAFL and HS/NASH. Diabetic patients have
higher Hurley score than not diabetic ones. Ultrasound examination was
significantly different in the three groups.
CONCLUSION
HS patients displayed a high prevalence of NASH/NAFLD and ultrasound
examination should be particularly addressed to patients that display high ADDI
scores.
Key words: Non-alcoholic steatohepatitis; Non-alcoholic fatty liver; Nonalcoholic fatty
liver disease; End stage liver disease; Hidradenitis suppurativa
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Core tip: Nonalcoholic fatty liver disease (NAFLD), in its two variants non-alcoholic
fatty liver and non-alcoholic steatohepatitis, is often linked to systemic inflammatory
conditions, such as psoriasis. Remarkably, hidradenitis suppurativa (HS) is a new
affirming systemic inflammatory disorder of the follicular epithelium of skin apocrine
glands with a prevalence in normal population ranging from 0.05% to 4.10%.
Furthermore, HS patients display a significant comorbidities burden (e.g., cardiovascular
risk, metabolic syndrome, diabetes, and spondyloarthritis) but the association with
NAFLD was not previously investigated. This is the first study which evaluated NAFLD
prevalence and its characteristics in HS patients.
Citation: Damiani G, Leone S, Fajgenbaum K, Bragazzi NL, Pacifico A, Conic RR, Pigatto
PD, Maiorana C, Poli P, Berti E, Pace MC, Malagoli P, Bettoli V, Fiore M. Nonalcoholic
fatty liver disease prevalence in an Italian cohort of patients with hidradenitis suppurativa: A
multi-center retrospective analysis. World J Hepatol 2019; 11(4): 391-401
URL: https://www.wjgnet.com/1948-5182/full/v11/i4/391.htm
WJH https://www.wjgnet.com
April 27, 2019 Volume 11 Issue 4
Damiani G et al. NAFLD prevalence in HS
392
DOI: https://dx.doi.org/10.4254/wjh.v11.i4.391
INTRODUCTION
Nonalcoholic fatty liver disease (NAFLD) includes two distinct entities, with different
histologic clues and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic
steatohepatitis (NASH), the more aggressive necro-inflammatory form, which may
accumulate fibrosis and result in End stage liver disease (ESLD) and its complications,
including hepatocellular carcinoma (HCC)[1].
Nowadays, NAFLD represents the main cause of chronic liver disease in Europe
and North America, where is found in 17%-30% of the population, worldwide the
prevalence is 2%-4% of the population becoming a serious public health concern[2].
Evidences suggest that NAFLD is the hepatic sign of metabolic syndrome; therefore,
is linked not only with an increase of liver-related mortality, but also of the overall
mortality. Noninvasive techniques, such as biological tests and elastography can be
used for the evaluation of NAFLD patients. Today, liver biopsy (diagnostic gold
standard) should be recommended in selected cases.
Patients with NAFLD would benefit from their lifestyle changes by progressive
weight loss through exercise and low sugar and fat intake. Pharmacotherapy should
be reserved for patients with significant fibrosis. Unfortunately, there are no Food and
Drug Administration (FDA) approved therapies[3].
Hidradenitis suppurativa (HS) is a systemic, chronic, inflammatory/autoinflam-
matory disease with a relapsing remitting behavior and a deep impact on patient's
quality of life. Despite its elusive pathogenesis, clinical manifestations are clear and
space from painful nodules to fistula, mainly involving areas rich in apocrine gland-
bearing, such as armpits, inguinal and anogenital regions (Dessau definition)[4-6]. HS is
an affirming systemic inflammatory disease and this idea was sustained by the recent
acquisitions in the pathogenesis[7], epidemiology[8] and therapy[9]. Until recently, it was
considered to be a rare disease with a prevalence cited as approximately 1%[10].
Actually, the prevalence of HS seems to be greater varying from 0.05% to 4.10%; this
variability is intrinsically affected by study type, being lower in retrospectively
designed studies and the higher in prospective or self-reported ones[11].
European guidelines for the management of HS have been published[12]: No therapy
is actually able to guaranty a high rate of complete disease remission. As for patients
with NAFLD also patients with HS would benefit from their lifestyle changes by
losing weight. Furthermore, topical and systemic antibiotics, injected corticosteroids,
or biologics and other systemic treatments may be used. Oral antibiotics may be used
to help prevent new lesions. Moderate stages may be treated with oral antibiotics, oral
retinoids such as isotretinoin, hormonal therapy, and/or surgery[11,12]. For moderate to
severe disease, target therapy directed against TNF-alpha proteins which are involved
in the inflammation process are used: adalimumab has been approved by the FDA as
orphan product for HS treatment. Adalimumab, a TNF blocker, is actually the only
biologic drug approved in Italy for HS patients and notable in October 2018 it
received an extension also for children over 12 years old[13]. Due to the increased body
of comorbidities currently associated with HS[14,15], the liver metabolic comorbidities
were neglected.
NAFLD is considered a multisystem pathology increasing the risk of diabetes
mellitus, cardiovascular and chronic renal disorders, diseases with an increased
incidence in HS patients[16].
Over the last decade, it has been growing the evidence that NAFLD is associated
with psoriasis, another systemic chronic inflammatory disease[17-19]. Despite the high
incidence of NAFLD and the current evidence that HS is not an uncommon disease,
there are currently no studies in the literature investigating the association between
NAFLD and chronic skin diseases other than psoriasis.
MATERIALS AND METHODS
Study population
This retrospective study is a sub-analysis of a larger one carried out in the Department
of Dermatology of Ospedale Maggiore Policlinico at the beginning and after extended
to other 3 primary dermatological Italian centers, namely San Donato Hospital, San
Gallicano Hospital and Galeazzi Hospital. The study started in January 2018 and
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ended in December 2018. Patients were recruited by filling the recently proposed
visual-aided questionnaire for the self- assessment of HS[20]. The positive patients were
after assessed in a dedicated HS-Lab. The diagnosis of HS was performed by two
independent board-certified dermatologists following the Dessau criteria[21]. The
inclusion criteria comprehended HS diagnosis, Alcohol Use Disorders Identification
Test (AUDIT) < 8[22], last 3 complete blood count (CBC) available with transaminases.
The exclusion criteria comprehended AUDIT score > 7, pre-existent hepatic cirrhosis,
viral hepatitis (B, C and E) and recent drug-related hepatitis (< 5 years), congenital
hepatic malformations, hepatic or cholangitic autoimmune conditions.
All patients underwent a hepatologic visit and ultrasonographic (US) evaluation of
the liver. Patients with raised liver enzymes underwent liver biopsy to evaluate the
presence of NAFLD according the European Association for the Study of the Liver
(EASL), European Association for the Study of Diabetes (EASD) and European
Association for the Study of Obesity (EASO) Clinical Practice Guidelines for the
management of NAFLD[23]. Patients were also screened for diabetes, a predisposing
factor for NASH and NAFLD. Diabetes diagnosis was performed following these
criteria: a random blood sugar level of equal or greater than 200 mg/dL or 11.1
mmol/L or fasting blood sugar test of 126 mg/dL (7 mmol/L) or higher on two
separate tests or oral sugar test of equal of higher than 200 mg/dL (11.1 mmol/L)
after two hours.
Outcomes of the study
During dermatological assessment, besides demographics, drug-history and
comorbidities, were collected HS clinical phenotypes[24], static score as Hurley[25],
dynamic score as international HS 4 (iHS4)[26], the Autoinflammatory Disease Damage
Index (ADDI)[27,28] and Dermatology Life Quality Index (DLQI)[29].
Statistical analysis
Variables were described as number and/or percentages. All variables were
preliminarily assessed with Shapiro-Wilk test to establish the parametric behavior.
The Wilcoxon-Mann-Whitney test was employed to deal with quantitative variables,
whilst Fisher’s exact test was applied with qualitative variables comparison. A P value
< 0.05 was considered significant. The analysis was performed with the statistical
software SPSS ver. 20.0 (Armonk, NY: IBM Corp.).
RESULTS
Demographics and clinical characteristics were summarized in Table 1. Interestingly
from the pool of 86 patients that had a positive visual-aided questionnaire for the self-
assessment of HS, after clinical assessment we enrolled 83 HS patients with the above
HS clinical phenotypes: 54 regular type, 6 frictional type, 10 scarring folliculitis type, 5
conglobata type, 5 syndromic type, 3 ectopic type.
In this cohort, there were 51 patients with HS only, 20 patients with HS and NAFL
(HS/NAFL) and 12 with HS and NASH (HS/NASH)(Table 1). The groups were
predominantly composed by females, in fact males were 33.3% of HS only, 43.8%
HS/NAFLD, 41.7% HS/NAFL and 45% HS/NASH patients being female and did not
display significant difference (P = 0.62, P = 0.52, P = 84). The average age between
groups was similar (HS only 43 ± 8.9; HS/NAFLD 41.3 ± 9.0; HS/NAFL 40.6 ± 10.3;
HS/NASH 41.6 ± 7.4, P = 0.56). Patients also had similar Body Mass Index (BMI) with
HS only having an average BMI of 28.3 ± 2.5 kg/m2, HS/NAFLD patients being 27.6 ±
1.9 kg/m2 (P = 0.38), HS/NAFL 27.6 ± 1.7 kg/m2 (P = 0.22) and HS/NASH having
27.6 ± 2.7 kg/m2 (P = 0.38). Diabetes was present in 24% of HS only patients, 30% of
HS/NAFL and 25% of HS/NASH patients. Inflammatory comorbidities (Table 1)
were present in 3.9% of HS only patients, 37.5% of HS/NAFLD, 25% of HS/NAFL
patients and 58.3% of HS/NASH patients with a statistically different prevalence (P <
0.001). Specifically, in HS only patients one had acne conglobata and 1 patient had
lichen sclerosus; while in HS/NAFL there was one patient with Crohn’s disease, 1
with Pyoderma gangrenosum, Acne, and Hidradenitis Suppurativa (PASH), 1 with
psoriasis, 1 with spondyloarthritis and 1 with uveitis. Finally, of the HS/NASH
patients, 1 had Crohn’s disease, 4 had PASH, 1 had psoriasis and 1 had
spondyloarthritis.
The average IHS4 score among HS/NASH patients (12.7 ± 3.6, P = 0.03) was the
highest, while it was similar among those with HS only and HS/NAFL patients (9.6 ±
3.6 and 9.4 ± 3.9 respectively, P = 0.86). Likewise, mean ADDI was significantly higher
among HS/NASH patients (5.3 ± 2.2, P < 0.001) compared to HS only and HS/NAFL
patients (2.8 ± 1.6 and 2.6 ± 1.4 respectively) (Table 1). There were no significant
differences in Hurley score, however 83% of HS/NASH patients had a Hurley score
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Table 1 Characteristics of 83 patients with hidradenitis suppurative, Nonalcoholic fatty liver and Nonalcoholic steatohepatitis and
intercalsses charactersitics
HS only NAFLD P value NASH P value NAFL P value
n51 32 12 20
Age, mean(SD) 43.04 (8.9) 41.32 (9.0) 0.564 41.58 (7.4) 0.602 40.55 (10.3) 0.315
Age cat (%) 0.646 0.463 0.629
< 30 3 (5.9) 4 (12.5) 1 (8.3) 3 (15.0)
30-39 16 (31.4) 8 (25.0) 2 (16.7) 6 (30)
40-49 18 (35.3) 14 (43.8) 7 (58.3) 7 (35.0)
> 50 14 (27.5) 6 (18.8) 2 (16.7) 4 (20.0)
Male, n (%) 17 (33.3) 14 (43.8) 0.623 5 (41.7) 0.835 9 (45.0) 0.52
Diabetes, n (%) 12 (23.5) 9 (28.1) 0.853 3 (25.0) 0.764 6 (30.0) 0.794
BMI, mean(SD) 28.31 (2.5) 27.56 (1.9) 0.381 27.58 (2.7) 0.376 27.55 (1.7) 0.218
bmi_cat (%) 0.559 0.515 0.384
Normal Weight 4 (7.8) 4 (12.5) 2 (16.7) 2 (10.0)
Overweight 38 (74.5) 26 (81.3) 9 (75.0) 17 (85.0)
Obese 9 (17.6) 2 (6.3) 1 (8.3) 1 (5.0)
IHS4, mean(SD) 9.57 (3.6) 11.32 (2.8) 0.025 12.67 (3.6) 0.009 9.40 (3.9). 0.861
IHS4 cat (%) 0.028 0.007 0.97
Mild 5 (9.8) 3 (9.4) 1 (8.3) 2 (10.0)
Moderate 24 (47.1) 10 (31.3) 0 (0) 10 (50.0)
Severe 22 (43.1) 19 (59.4) 11 (91.7) 8 (40)
Hurley (%) 0.494 0.197 0.785
1 5 (9.8) 3 (9.4) 1 (8.3) 2 (10.0)
2 24 (47.1) 6 (18.8) 1 (8.3) 5 (25.0)
3 22 (43.1) 23 (71.9) 10 (83.3) 13 (65.0)
Elevated_liver_enzymes, n (%) 19 (37.3) 9 (28.1) 0.617 4 (33.3) 0.998 5 (25.0) 0.482
ADDI_score, mean(SD) 2.55 (1.4) 3.72 (1.8) < 0.001 5.33 (2.2) < 0.001 2.75 (1.6) 0.603
Inflammatory comorbidities, n (%) 2 (3.9) 12 (37.5) < 0.001 7 (58.3) < 0.001 5 (25.0) 0.025
In detail (%) 0.001 < 0.001 0.047
Acne conglobata 1 (2.0) 0 (0) 0 (0) 0 (0)
Crohn disease 0 (0) 2 (6.3) 1 (8.3) 1 (5.0)
Lichen sclerosus 1 (2.0) 0 (0) 0 (0) 0 (0)
PASH 0 (0) 5 (15.6) 4 (33.3) 1 (5.0)
Psoriasis 0 (0) 2 (6.3) 1 (8.3) 1 (5.0)
Spondyloarthritis 0 (0) 2 (6.3) 1 (8.3) 1 (5.0)
Uveitis 0 (0) 1 (3.1) 0 (0) 1 (5.0)
Positive ultrasound, n (%) 11 (21.6) 32 (100.0) < 0.001 12 (100.0) < 0.001 20 (100.0) < 0.001
NASH 0 (0) 12 (37.5) < 0.001 12 (100.0) 0 (0)
NAFL 0 (0) 20 (62.5) < 0.001 0 (0) 20 (100.0)
ADDI: Autoinflammatory disease damage index; BMI: Body mass index; HS: Hidradenitis suppurativa; IHS4: International Hidradenitis Suppurativa
Severity Scoring System, NASH: NonAlcoholic SteatoHepatitis, NAFL: NonAlcoholic Fatty Liver, PASH: Pyoderma gangrenosum, Acne, and hidradenitis
suppurativa; SD: Standard deviation. Normal weight: 18.5–24.9 kg/m2, Overweight: 25–29.9 kg/m2 Obese: >29. 9 kg/m2.
of 3, whereas only 65% of HS/NAFL and 57% of HS only patients had a Hurley score
of 3 (P = 0.49). Presence of elevated liver enzymes was similar among the three groups
(HS only 37.3%; HS/NAFL 25%; HS/NASH 33.3%, P = 0.62). Finally, ultrasound
revealed a bright liver in 22% of HS only patients and all HS/NAFL and HS/NASH
patients (P < 0.001).
HS only and HS/NAFL patients displayed a significant difference in inflammatory
comorbidities (P = 0.025) and positivity of ultrasound (P < 0.001) (Table 1).
HS/NASH compared with patients with HS only displayed a significant difference
in IHS4 (P = 0.009), ADDI (P < 0.001), inflammatory comorbidities rate (P < 0.001) and
ultrasound positivity (P < 0.001) (Table 1).
HS patients with and without diabetes had a significant difference only in Hurley
stage (P = 0.022) (Table 2).
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Table 2 Differences among hidradenitis suppurativa patients with and without diabetes
Non diabetes Diabetes P value
n62 21
Age, mean(SD) 42.44 (9.4) 41.62 (8.2) 0.722
Age cat (%) 0.203
< 30 4 ( 6.5) 3 (14.3)
> 50 17 (27.4) 3 (14.3)
30-39 20 (32.3) 4 (19.0)
40-49 21 (33.9) 11 (52.4)
Male, n (%) 21 (33.9) 10 ( 47.6) 0.387
Diabetes, n (%) 0 ( 0.0) 21 (100.0) <0.001
BMI, mean(SD) 28.10 (2.6) 27.81 (1.4) 0.636
bmi_cat (%) 0.161
Normal Weight 8 (12.9) 0 ( 0.0)
Obese 9 (14.5) 2 ( 9.5)
Overweight 45 (72.6) 19 ( 90.5)
IHS4, mean(SD) 10.37 (3.6) 8.81 (4.1) 0.101
IHS4 cat, n (%) 0.051
Mild 4 ( 6.5) 4 ( 19.0)
Moderate 23 (37.1) 11 ( 52.4)
Severe 35 (56.5) 6 ( 28.6)
Hurley, n (%) 0.022
1 4 ( 6.5) 4 ( 19.0)
2 14 (22.6) 9 ( 42.9)
3 44 (71.0) 8 ( 38.1)
Elevated_liver_enzymes, n (%) 21 (33.9) 7 ( 33.3) 1
ADDI_score, mean(SD) 3.13 (1.8) 2.62 (2.0) 0.275
Inflammatory comorbidities, n (%) 9 (14.5) 5 ( 23.8) 0.518
In.detail, n (%) 0.563
53 (85.5) 16 ( 76.2)
Acne conglobata 1 ( 1.6) 0 ( 0.0)
Crohn 1 ( 1.6) 1 ( 4.8)
Lichen sclerosus 0 ( 0.0) 1 ( 4.8)
PASH 4 ( 6.5) 1 ( 4.8)
Psoriasis 1 ( 1.6) 1 ( 4.8)
Spondyloarthritis 1 ( 1.6) 1 ( 4.8)
Uveitis 1 ( 1.6) 0 ( 0.0)
Positive_ultrasound, n (%) 31 (50.0) 12 ( 57.1) 0.754
NASH, n (%) 9 (14.5) 3 ( 14.3) 1
NAFL, n (%) 14 (22.6) 6 ( 28.6) 0.795
Disease, n (%) 0.853
HS only 39 (62.9) 12 ( 57.1)
NAFL 14 (22.6) 6 ( 28.6)
NASH 9 (14.5) 3 ( 14.3)
ADDI: Autoinflammatory Disease Damage Index; BMI: Body mass index; HS: Hidradenitis suppurativa;
IHS4: International Hidradenitis Suppurativa Severity Scoring System; NASH: Non-alcoholic steatohepatitis;
NAFL: Nonalcoholic fatty liver; PASH: Pyoderma gangrenosum, Acne, and hidradenitis suppurativa; SD:
Standard deviation. Normal weight: 18.5–24.9 kg/m2; Overweight: 25-29.9 kg/m2; Obese: > 29.9 kg/m2.
Age had a significant moderately positive correlation with ADDI among HS/NAFL
patients (r = 0.57, P = 0.05). Next, BMI and ADDI were moderately negatively
correlated in HS patients with inflammatory comorbidities (R2 = 0.43, Figure 1).
BMI and ADDI were weakly negatively correlated in patients with HS only (r = -
0.25, P = 0.05) and in those who had HS and diabetes (r = -0.46, P = 0.04). Correlation
between BMI and IHS4, age and IHS4, BMI and ADDI, among the three groups was
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Figure 1
Figure 1 Correlation between body mass index and Autoinflammatory Disease Damage Index among patients with hidradenitis suppurative (HS) only, or
HS with other inflammatory comorbidity.
not significant. In addition, correlation between BMI and IHS4, age and IHS4, age and
ADDI based on presence of other inflammatory comorbidity was not significant.
Finally, BMI and IHS4, age and IHS4, age and ADDI based on diabetes status was not
significant.
Hurley score and categorical IHS4 score had good overlap in Hurley 1 and 2 scores,
with 8 Hurley 1 patients also having mild IHS4 categorical score, 22 (96%) Hurley 2
patients having a moderate IHS4 categorical score, and 1 (4%) Hurley 2 patient having
a severe IHS4 categorical score. However, among 52 patients with Hurley score 3, 12
(23%) were considered moderate IHS4, and 40 (77%) were considered severe (P <
0.001). Average ADDI score among Hurley 1 patients was 0.75 ± 1.2, 1.9 ± 1.4 among
Hurley 2 patients and 3.8 ± 1.6 among Hurley 3 patients (P < 0.001).
There was a moderate correlation between IHS4 and ADDI scores among all 3
groups [R2 = 0.48 (P < 0.001) for HS only; R2 = 0.51(P < 0.001), for HS/NAFL; R2 = 0.57
(P < 0.001), for HS/NASH, Figure 2].
DISCUSSION
In our cohort of HS patients, for the first time, was described a 38,5% NAFLD
prevalence: 24% of NAFL and 14,5% of NASH. Likewise, in psoriasis, HS patients
with NAFLD displayed the higher severity scores, namely IHS4 and ADDI. These
findings, together with pathogenetic[7], epidemiologic[8] and therapeutic[9] evidences,
further confirm the recent idea that HS is a systemic inflammatory disease. NAFLD is
the main entity to cause ESLD in Europe and North America, this is easy to predict
that it will become the most frequent liver transplantation indication by 2030[16].
Although the weight of the disease is so overwhelming, there are no really effective
drugs in treatment[3]. Therefore, it is essential to investigate all co-morbidities that can
worsen the prognosis, among these in our study emerges the role of HS, whose
treatment is a controversial issue[30-32]. Microbiological data show that HS is associated
with polymicrobial flora, including anaerobic microorganisms[33,34]. On this point,
Guet-Revillet et al[33], in a French prospective microbiological study on 102 HS lesions
from 82 patients, found that Staphylococcus lugdunensis was cultured in 58% of HS
lesions and anaerobic microorganisms, including actinomycetes, were observed in
24% of abscesses or nodules and in 87% of chronic lesions. More recently, in a
prospective metagenomic study, the same Author, using high-throughput
sequencing, confirmed the high prevalence of polymicrobial anaerobic flora in HS[35].
Overall, topical or oral antibiotics (monotherapy or combination therapy) is
commonly suggested for the management of HS flares[12,36]. The most common
antibiotic regimens used for the treatment of HS included topical clindamycin, oral
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Figure 2
Figure 2 Correlation between international hidradenitis suppurativa severity scoring system and autoinflammatory Disease Damage Index among patients
with hidradenitis suppurative only, or non-alcoholic staetohepatitis or non-alcoholic fatty liver.
tetracyclines, oral clindamycin-rifampicin combination and parenteral ertapenem
followed by oral rifampicin-moxifloxacin-metronidazole combination[12,37]. No data are
available for the antibiotic management of HS with the newer drugs, including
dalbavancin, daptomycin and tigecycline[38-40]. Moreover, there are insufficient data to
support intravenous antibiotics[41-43]. A major concern of the antibiotic use in HS is the
increasing of antimicrobial resistance[44,45]. Finally, a clinical monitoring and a dose
adjustment in patients with liver disease can be required[46,47] in view of the fact that
NAFLD remains the main source of ESLD in Western countries[1]. It is clear, with these
premises, that the available therapeutic armamentarium for the treatment of both
diseases is very inadequate. Of our findings, the most obvious appears the US finding
of bright liver in 22% of HS only and all HS/NAFL or HS/NASH patients (P < 0.001).
However liver biopsy (histology) remains the gold standard in the diagnosis of
NAFLD, as recently suggested in a meta-analysis that compared US and histology
quantifying diagnostic sensitivity to 84.8% (79.5-88.9), specificity to 93.6% (87.2-97.0),
positive likelihood ratio to 13.3 (6.4-27.6) and negative likelihood ratio to 0.16 (0.12-
0.22)[48].
Interestingly the newly proposed ADDI score displayed a clinically meaning in
addressing ultrasound examination in patients with NASH. PASH syndrome patients
all displayed NAFLD and this confirm that higher levels of inflammations trigger the
development of liver disease. Adipose tissue is not inert but metabolically active and
release pro-inflammatory cytokines, furthermore the metabolic syndrome is a
recognized comorbidity of both NASH and HS. Thus, the finding is that ADDI
correlates with BMI in patients with inflammatory comorbidities. To further enforce
its clinical capability, ADDI and IHS4, the dynamic severity index, correlated in the
examined groups. Therefore ADDI, a composite index derived from the global
examination of monogenic autoinflammatory diseases and applied to HS[27], is related
to the dynamic index that monitor HS skin inflammation. This assumption empowers
the thesis that HS should be considered an autoinflammatory polygenic disease and
treated by physicians as a systemic condition. From this point of view, is it really
correct talk about comorbidities or it is more proper define them as different
manifestations of a common spectrum of disease, namely HS as a systemic disease. As
for psoriasis, the real goal for the newly introduced biological therapy will be to act on
both cutaneous and systemic manifestation of HS.
In conclusion high prevalence of NAFLD was found in HS patients and an US
screening to exclude liver abnormalities should be performed especially in HS
patients with active disease and inflammatory comorbidities.
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ARTICLE HIGHLIGHTS
Research background
Nonalcoholic fatty liver disease (NAFLD), in its two variants non-alcoholic fatty liver (NAFL)
and non-alcoholic steatohepatitis (NASH), is the main cause of End stage liver disease (ESLD)
and its complications, including hepatocellular carcinoma (HCC) in North America and Europe.
Due to its impact on morbility and mortality, the identification of population with high risk of
NAFLD is mandatory and in literature some systemic inflammatory diseases are described to be
linked with NAFLD. Hidradenitis suppurativa (HS) is a new affirming systemic inflammatory
disorder of the follicular epithelium of skin apocrine glands with a prevalence in normal
population ranging from 0.05% to 4.10%. No data are present in literature towards the
prevalence of NAFLD in HS.
Research motivation
The estimation of NAFLD in HS patients may lead to an early and optimized treatment.
Research objectives
This study aimed first to evaluate the overall prevalence of NAFLD and specifically of NAFL
and NASH. Secondary aims were the clinical characterization of these patients. Depict a profile
of HS patients with NAFLD will be crucial in optimizing clinical and therapeutic management.
Research methods
This retrospective multicenter carried out 4 primary dermatological Italian centers started in
January 2018 and ended in December 2018. Patients were recruited by filling the recently
proposed visual-aided questionnaire for the self- assessment of HS and after underwent a
dermatologic visit that evaluate HS with static (Hurley score) and dynamic indexes (ADDI:
Autoinflammatory Disease Damage Index, IHS4: International Hidradenitis Suppurativa
Severity Scoring System). Transaminases were assessed and all patients underwent liver
sonography (US). NASH suspected cases were biopsied.
Research results
We included 83 HS patients, in detail 51 patients with HS only and 32 with NAFLD (20 with
NAFL, 12 NASH). Inflammatory comorbidities were present in 3.9% of HS only patients, 37.5%
of HS/NAFLD, 25% of HS/NAFL patients and 58.3% of HS/NASH patients (P < 0.001). The
average IHS4 score among HS/NASH patients (12.7 ± 3.6, P = 0.03) was the highest, while it was
similar among those with HS only and HS/NAFL patients (9.6 ± 3.6 and 9.4 ± 3.9 respectively, P
= 0.86). Likewise, mean ADDI was significantly higher among HS/NASH patients (5.3 ± 2.2, P <
0.001) compared to HS only and HS/NAFL patients (2.8 ± 1.6 and 2.6 ± 1.4 respectively). While
no significant differences were found in Hurley score. There was a significant positive
correlation between IHS4 and ADDI scores among all 3 groups (r = 0.7, P < 0.001 for HS only; r =
0.71, P = 0.0004 for HS/NAFL; r = 0.76, P = 0.004 for HS/NASH). Finally, BMI and ADDI were
weakly negatively correlated in patients with HS only (r = -0.25, P = 0.05) and in those who had
HS and diabetes (r = -0.46, P = 0.04).
Research conclusions
HS patients have a high prevalence of NAFLD. In particular clinicians should sonographically
assess HS patients with more active disease (high IHS4 score) and with other inflammatory
comorbidities (high ADDI).
Research perspectives
The present study highlighted the association between HS and NAFLD. However other issues
remain still open to future investigations. In particular related issues,that should be addressed to
optimize patient management are the prevalence of NAFLD HS-related in different ethnicity and
the impact of systemic therapies on NAFLD development in HS patients.
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