Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome: A prospective multi-centre cohort study

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.

Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients

“…However, their role in chronic liver diseases is discussed controversially. In patients with nonalcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), higher IgG levels were associated with increased risks of hepatic decompensation and mortality [18], and serum IgA levels were independent predictors of advanced fibrosis [19,20]. In contrast, Basho and colleagues [21] reported that hypergammaglobulinemia was a rather protective factor in patients with decompensated ACLD, reflecting a more intact ability to sufficiently produce IgG antibodies in the light of systemic inflammation.…”

A Biomarker Panel Based upon AFP, Fucosylated Kininogen and PEG-Precipitated IgG Is Highly Accurate for the Early Detection Hepatocellular Carcinoma in Patients with Cirrhosis in Phase II and Phase III Biomarker Evaluation

“…Alterations in immunoglobulins have been associated with many diseases. Indeed, we and others, have previously identified changes in the level and in the glycosylation on IgG in patients with cirrhosis [ 26 ]. These increases in both protein level and the alterations in glycosylation have proven to be confounders in plate-based assays for the analysis of fucosylated proteins in HCC.…”

Gut–Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome

“…The presence of LPS in the systemic circulation is correlated with the severity of liver damage [ 101 , 102 ]. Patients with biopsy-proven NAFLD/NASH had higher levels of abnormal plasma immunoglobulin G against endotoxins, which were correlated with a greater degree of severity of NASH [ 103 ].…”