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Association between positivity of serum autoantibodies and liver disease severity in patients with biopsy-proven NAFLD
Authors:Yu-Jie Zhou  Kenneth I Zheng  Hong-Lei Ma  Gang Li  Xiao-Yan Pan  Pei-Wu Zhu  Giovanni Targher  Christopher D Byrne  Xiao-Dong Wang  Yong-Ping Chen  Xiao-Bo Li  Ming-Hua Zheng
Institution:1. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China;2. NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;3. Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;4. Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;5. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy;6. Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK;7. Institute of Hepatology, Wenzhou Medical University, Wenzhou, China;8. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
Abstract:Background and aimsSome previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD.Methods and resultsA total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77–11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30–7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3–F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype.ConclusionsSerum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.
Keywords:Autoantibodies  Fibrosis  NAFLD  Liver biopsy  NAFLD"}  {"#name":"keyword"  "$":{"id":"kwrd0035"}  "$$":[{"#name":"text"  "_":"nonalcoholic fatty liver disease  AIH"}  {"#name":"keyword"  "$":{"id":"kwrd0045"}  "$$":[{"#name":"text"  "_":"autoimmune hepatitis  NASH-CRN"}  {"#name":"keyword"  "$":{"id":"kwrd0055"}  "$$":[{"#name":"text"  "_":"nonalcoholic steatohepatitis clinical research network  ANA"}  {"#name":"keyword"  "$":{"id":"kwrd0065"}  "$$":[{"#name":"text"  "_":"anti-nuclear antibodies  PNPLA3"}  {"#name":"keyword"  "$":{"id":"kwrd0075"}  "$$":[{"#name":"text"  "_":"patatin like phospholipase domain containing 3  PBC"}  {"#name":"keyword"  "$":{"id":"kwrd0085"}  "$$":[{"#name":"text"  "_":"primary biliary cholangitis  anti-CENP-B"}  {"#name":"keyword"  "$":{"id":"kwrd0095"}  "$$":[{"#name":"text"  "_":"anti-centromere antibody  AHA"}  {"#name":"keyword"  "$":{"id":"kwrd0105"}  "$$":[{"#name":"text"  "_":"anti-histone antibody  AMA"}  {"#name":"keyword"  "$":{"id":"kwrd0115"}  "$$":[{"#name":"text"  "_":"anti-mitochondrial antibody  SLA"}  {"#name":"keyword"  "$":{"id":"kwrd0125"}  "$$":[{"#name":"text"  "_":"soluble liver antigen  ASMA"}  {"#name":"keyword"  "$":{"id":"kwrd0135"}  "$$":[{"#name":"text"  "_":"anti-smooth muscle antibody  LKM"}  {"#name":"keyword"  "$":{"id":"kwrd0145"}  "$$":[{"#name":"text"  "_":"liver-kidney microsomal antibody  LC-1"}  {"#name":"keyword"  "$":{"id":"kwrd0155"}  "$$":[{"#name":"text"  "_":"liver cytosol antibody type 1  ELISA"}  {"#name":"keyword"  "$":{"id":"kwrd0165"}  "$$":[{"#name":"text"  "_":"enzyme-linked immunosorbent assay  HOMA-IR"}  {"#name":"keyword"  "$":{"id":"kwrd0175"}  "$$":[{"#name":"text"  "_":"homoeostasis model assessment of insulin resistance  SNP"}  {"#name":"keyword"  "$":{"id":"kwrd0185"}  "$$":[{"#name":"text"  "_":"single nucleoid polymorphism  MALDI-TOF"}  {"#name":"keyword"  "$":{"id":"kwrd0195"}  "$$":[{"#name":"text"  "_":"Matrix-Assisted Laser Desorption/Ionization-Time of Flight  IFN"}  {"#name":"keyword"  "$":{"id":"kwrd0205"}  "$$":[{"#name":"text"  "_":"interferon  TNF"}  {"#name":"keyword"  "$":{"id":"kwrd0215"}  "$$":[{"#name":"text"  "_":"tumor necrosis factor  IL"}  {"#name":"keyword"  "$":{"id":"kwrd0225"}  "$$":[{"#name":"text"  "_":"interleukin
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