Published online Nov 21, 2021. doi: 10.3748/wjg.v27.i43.7563
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
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.
To determine if autoimmune markers in NASH patients are independently associated with poorer clinical outcomes.
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.
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.
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.