De Roza MA, Lamba M, Goh GBB, Lum JHM, Cheah MCC, Ngu JHJ. Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome: A prospective multi-centre cohort study. World J Gastroenterol 2021; 27(43): 7563-7571 [PMID: 34887649 DOI: 10.3748/wjg.v27.i43.7563]
Corresponding Author of This Article
Jing Hieng Jeffrey Ngu, MBChB, FRACP, PhD, Academic Research, Consultant Physician-Scientist, Doctor, Department of Gastroenterology and Hepatology, Christchurch Hospital, Riccarton Avenue, Christchurch 8011, New Zealand. jeffrey.ngu@cdhb.health.nz
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Prospective Study
Open-Access Policy of This Article
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/licenses/by-nc/4.0/
World J Gastroenterol. Nov 21, 2021; 27(43): 7563-7571 Published online Nov 21, 2021. doi: 10.3748/wjg.v27.i43.7563
Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome: A prospective multi-centre cohort study
Marianne Anastasia De Roza, Mehul Lamba, George Boon-Bee Goh, Johnathan Huey-Ming Lum, Mark Chang-Chuen Cheah, Jing Hieng Jeffrey Ngu
Marianne Anastasia De Roza, Johnathan Huey-Ming Lum, Department of Gastroenterology and Hepatology, Sengkang General Hospital, Singhealth, Singapore 544886, Singapore
Mehul Lamba, Jing Hieng Jeffrey Ngu, Department of Gastroenterology and Hepatology, Christchurch Hospital, Christchurch 8011, New Zealand
George Boon-Bee Goh, Mark Chang-Chuen Cheah, Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore
George Boon-Bee Goh, Duke-NUS Medical School, Singapore 169608, Singapore
Author contributions: De Roza MA contributed to study design, data collection and analysis, manuscript writing, critical Review and submission of manuscript; Lamda M contributed to study design, data collection and analysis, manuscript writing and review of manuscript; Goh GBB contributed to study design and critical review of manuscript; Cheah MCC and Lum JHM contributed to data collection; Ngu JHJ contributed to study design, writing and critical review of manuscript; and all authors read and approved the final manuscript.
Institutional review board statement: This study conforms to ethical guidelines and was approved by our institutional review board with waiver of patient consent.
Clinical trial registration statement: This study does not include any intervention and is not a randomized controlled trial.
Informed consent statement: Consent was not obtained as data was anonymized and protected with little to no risk of identification.
Conflict-of-interest statement: All authors declare there are no conflicts of interest. None of the authors received financial support or grants for this study.
Data sharing statement: Statistical code, and dataset is available from the corresponding author at jeffrey.ngu@cdhb.health.nz.
CONSORT 2010 statement: The manuscript was checked according to the CONSORT 2010.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Hieng Jeffrey Ngu, MBChB, FRACP, PhD, Academic Research, Consultant Physician-Scientist, Doctor, Department of Gastroenterology and Hepatology, Christchurch Hospital, Riccarton Avenue, Christchurch 8011, New Zealand. jeffrey.ngu@cdhb.health.nz
Received: April 19, 2021 Peer-review started: April 19, 2021 First decision: June 23, 2021 Revised: July 20, 2021 Accepted: November 2, 2021 Article in press: November 2, 2021 Published online: November 21, 2021 Processing time: 213 Days and 23.6 Hours
Abstract
BACKGROUND
Autoimmune markers including plasma cells (PC), anti-smooth-muscle antibody (ASMA), anti-nuclear antibody (ANA), and raised immunoglobulin G (IgG) are commonly observed in non-alcoholic steatohepatitis (NASH), however their clinical significance is unknown.
AIM
To determine if autoimmune markers in NASH patients are independently associated with poorer clinical outcomes.
METHODS
Consecutive patients with biopsy proven NASH from Christchurch Hospital, New Zealand and Singapore General Hospital (SGH) were included between 2005 to 2016 in a prospective multi-centre cohort study. Patients with other causes of chronic liver disease were excluded. IgG > 14 g/L or globulin fraction > 50%, ANA ≥ 1:40, SMA ≥ 1:40 were considered positive. Multivariate analysis was performed to assess which markers were independently associated with mortality and hepatic decompensation.
RESULTS
Total 261 patients were included of which 201 were from SGH. The median age was 53 and 51.9% were male. Advanced fibrosis was present in 31.4% at diagnosis. PC, ASMA, ANA and raised IgG were observed in 13.1%, 4.9%, 27.8% and 30.1% of patients respectively. After multivariate analysis, elevated IgG [Hazard Ratio (HR) 6.79, 95%CI: 2.93-17.15] and fibrosis stage (HR 1.37, 95%CI: 1.03-1.87) were found to be independently associated with increased risk of liver decompensation. Age (HR 1.06, 95%CI: 1.02-1.10) and elevated IgG (HR 3.79, 95%CI: 1.90-7.68) were independent factors associated with higher mortality risk.
CONCLUSION
Elevated IgG, rather than ANA, ASMA or plasma cells, is independently associated with increased risk of hepatic decompensation and mortality in NASH. It could hence be important for prognostication.
Core Tip: Autoantibodies such as anti-nuclear antibody (ANA) and anti-smooth-muscle antibody (ASMA) can be present in up to 20%-30% of patients with non-alcoholic steatohepatitis (NASH). However, clinical significance is not well studied and there is no published data on the impact of immunoglobulin G (IgG) and plasma cells on hepatic decompensation and mortality outcomes. Our study found that elevated IgG but not ANA, ASMA or plasma cells is associated with higher risk of mortality, including liver related death, as well as increased risk of hepatic decompensation events. Patients with IgG positive NASH should hence be identified early and monitored closely as they are at higher risk of poorer clinical outcomes.
