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. 2025 Apr;45(4):e70074.
doi: 10.1111/liv.70074.

Increased IgG Levels at Diagnosis Are Associated With Worse Prognosis of Patients With Primary Biliary Cholangitis

Eirini I Rigopoulou  1   2 , Vassiliki Lygoura  1   2 , Stella Gabeta  1   2 , Nikolaos Gatselis  1   2 , George Giannoulis  1 , George N Dalekos  1   2
Affiliations

Increased IgG Levels at Diagnosis Are Associated With Worse Prognosis of Patients With Primary Biliary Cholangitis

Eirini I Rigopoulou et al. Liver Int. 2025 Apr.

Abstract

Background and aim: A proportion of patients with primary biliary cholangitis (PBC) have increased IgG (I-IgG) levels at baseline, though not fulfilling the criteria of autoimmune hepatitis/PBC variant. Our aim was to evaluate whether I-IgG has prognostic significance in non-cirrhotic PBC patients.

Methods: Retrospective analysis of prospectively collected data from 675 PBC patients (592 non-cirrhotic) with available IgG levels at first evaluation was performed.

Results: Among non-cirrhotic patients, 97 with I-IgG were more frequently females (p < 0.05), having a higher frequency of concurrent autoimmune diseases (p = 0.01) and a higher frequency of PBC-specific ANA (p < 0.001), sp100 (p < 0.001) and gp210 (p = 0.029) compared to 495 with normal IgG (N-IgG). Patients with I-IgG were older (p < 0.001) and had lower albumin (p < 0.001) and higher AST (p < 0.001), ALT (p = 0.005), ALP (p = 0.006), γGT (p = 0.038) and IgM (p < 0.001) compared to those with N-IgG. I-IgG patients had a higher probability of cirrhosis development (Breslow p < 0.001; log-rank p = 0.05) and liver-related death (Breslow p = 0.034; log-rank p < 0.05) compared to N-IgG patients. IgG > 1.5xULN was the highest risk factor for cirrhosis development (HR = 9.507, 95% CI: 1.221-74.038, p = 0.032) and liver-related death (HR = 27.140, 95% CI: 3.111-236.783; p = 0.003); IgG normalisation after 1 year of UDCA treatment had a favourable effect on disease outcome. Ν-IgG was associated with a higher probability of liver stiffness regression (p = 0.025).

Conclusions: This long-term study demonstrates that I-IgG levels characterise a subgroup of non-cirrhotic PBC patients with faster disease progression and increased probability of liver-related death. Normalisation of IgG levels during UDCA treatment seems to improve prognosis and therefore, these patients could benefit from stricter follow-up and earlier add-on second-line treatments.

Keywords: IgG; autoimmune hepatitis; outcome; primary biliary cholangitis.

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References

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