Introduction Response to immunosuppressive treatment in AIH is often monitored by measurement of serum immunoglobulin G (IgG) as well as ALT. It is commonly assumed that serum IgG level correlates with histological activity (or Ishak necroinflammatory score: NIS) on liver biopsy, the historical “gold standard”. However, only one group (Luth et al 2008; J of Clin 42(8):926–930.) have examined this relationship, finding that normalisation of both serum ALT and IgG reliably predicted a NIS of <6 but not a NIS of <4 (corresponding to minimal hepatitis, seen in less than half of the patients presumed to be in remission). Here, we aimed to reassess how well serum IgG correlated with NIS in treated patients with AIH undergoing follow-up biopsy for confirmation of disease remission.
Methods We assessed 31 follow-up biopsies, performed to confirm histological remission in 28 patients with AIH (International Group criteria; Alvarez J Hepatol 1999; 31:929) on immunosuppressive treatment and an accompanying serum IgG (measured within 6 weeks of biopsy).
Results For 29 of the 31 follow-up biopsies, accompanying serum IgG was in the normal range (≤16 gm/L). However, only 13 of these 31 biopsies showed NIS <4 (minimal hepatitis). On ROC analysis, area under the curve (AUC) for IgG in predicting a NIS of ≥4 (n = 31) was 0.596 (p = 0.368). Sensitivity and specificity of IgG (cut off >16 grm/L) in predicting a NIS of ≥4 was 5.5% and 57% respectively. Corresponding positive (PPV) and negative (NPV) predictive values were only 50% and 59% respectively. AUC for change in IgG (∆IgG: baseline values minus values accompanying follow up biopsy; n = 29) in predicting NIS >4 was 0.551 (p = 0.642).
Defining histological remission instead as minimal or mild hepatitis- NIS <6 (as Luth’s group did because they found that such patients did not develop fibrosis progression), there were still 4/29 (14%) patients with normal serum IgG who were not in histological remission. On ROC analysis, AUC for IgG in prediction of NIS >6 on follow-up biopsy (n = 31) was 0.62 (p = 0.39). PPV and NPV for serum IgG (cut off >16 grm/L) in predicting of NIS ≥6) was 50% and 86% respectively. AUC for ∆IgG in prediction of NIS ≥6 was 0.608 (p = 0.453).
Conclusion Normalisation of serum IgG values in patients with AIH following treatment is not predicative of histological remission. At present, this requires a liver biopsy.
Disclosure of Interest None Declared.