Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis.

BACKGROUND & AIMS: The goal of treatment for autoimmune hepatitis is to achieve a complete biochemical response, defined as normalization of transaminases and immunoglobulin G (IgG) levels. Recent data suggest that IgG normalization does not significantly affect survival. We evaluated the impact of persistently elevated IgG levels (IgGe) and IgG flares (IgGf) on fibrosis progression and cirrhosis development.

METHODS: This retrospective multicenter cohort study included 493 patients with autoimmune hepatitis and persistently normal transaminase levels during follow-up. The inverse probability of treatment weighting (IPTW) propensity score method was used to balance the cohorts.

RESULTS: Three hundred forty-nine (70.8%) patients had persistently normal IgG (IgGn) levels, 89 (18.1%) had IgGe, and 55 (11.1%) had IgGf during follow-up. After a median follow-up of 6.2 years (IQR 4.1-10.1 years) with normal transaminase levels, median liver stiffness measurement (LSM) values remained stable, with no significant differences between groups. During the follow-up, 24 patients developed cirrhosis. Predictive factors for cirrhosis were age (hazard ratio [HR] 1.10, p <0.001), albumin (HR 0.20, p <0.001), IgG (HR 1.00, p = 0.001), and platelet count (HR 0.99, p = 0.001) at diagnosis; LSM (HR 1.30, p <0.001) at transaminase normalization; and transaminase normalization at 6 months (HR 0.24, p = 0.025). In the multivariate analysis, only LSM was independently associated with a higher risk of developing cirrhosis. After IPTW application, elevated IgG (IgGe or IgGf) did not affect fibrosis progression (p = 0.275) or cirrhosis development (p = 0.211).

CONCLUSIONS: Persistent or temporary serum IgG elevation in patients with normal transaminase levels did not significantly affect autoimmune hepatitis disease progression, thus challenging the current definition of complete biochemical response.

IMPACT AND IMPLICATIONS: The body of evidence showing a lesser impact of immunoglobulin G (IgG)values on outcomes in patients with autoimmune hepatitis (AIH) is growing. However, there is still a lack of robust information on the long-term outcomes, especially in patients who achieve persistent transaminase normalization. Persistently elevated IgG or IgG flares in patients with persistently normal transaminases do not seem to affect outcomes in patients with AIH. These results challenge the current definition of complete biochemical response in patients with AIH. Transaminase level normalization appeared to be the best treatment endpoint.