Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis

Abstract

Background & aims: Liver fibrosis regression but also progression may occur in patients with autoimmune hepatitis (AIH) under treatment. There is a need for non-invasive surrogate markers for fibrosis development in AIH to better guide immunosuppressive treatment. The aims of the study were to assess the impact of complete biochemical remission defined as normalisation of aminotransferases and IgG on histological activity and fibrosis development, and the value of repeat transient elastography (TE) measurement for monitoring disease progression in AIH.

Methods: A total of 131 liver biopsies from 60 patients with AIH and more than 900 TE from 125 patients with AIH, 130 with primary biliary cholangitis (PBC) and 100 with primary sclerosing cholangitis (PSC), were evaluated. Time intervals between TE were at least 12 months. Patients with AIH were treated for at least six months at first TE.

Results: In contrast to PBC and PSC, a decrease of liver stiffness (LS) was observed in the whole group of patients with AIH (-6.2%/year; 95% CI -12.6% to -0.2%; p = 0.04). The largest decrease of LS was observed in patients with severe fibrosis at baseline (F4: -11.7%/year; 95% CI -19% to -3.5%; p = 0.006). Complete biochemical remission was strongly linked to regression of LS ("remission": -7.5%/year vs. "no remission": +1.7%/year, p <0.001). Similarly, complete biochemical remission predicted low histological disease activity and was the only independent predictor for histological fibrosis regression (relative risk3.66; 95% CI1.54-10.2; p = 0.001). Patients with F3/F4-fibrosis, who remained in biochemical remission showed a considerable decrease of fibrosis stage (3.7 ± 0.5 to 1.8 ± 1.7; p = 0.007) on histological follow-up.

Conclusions: This study demonstrates that complete biochemical remission is a reliable predictor of a good prognosis in AIH and leads to fibrosis regression that can be monitored by TE.

Lay summary: Autoimmune hepatitis is an inflammatory disease of the liver, which often progresses to cirrhosis if left untreated or in the case of insufficient treatment response. Current guidelines have defined biochemical remission (normalisation of biochemical markers for liver inflammation) as a major goal in the treatment of AIH. However, data on the prognostic relevance of this definition are scarce. Herein, we demonstrate that the current definition of biochemical remission is a reliable surrogate for low disease activity on histological assessment and for a beneficial long-term disease course. In addition, we establish transient elastography, a non-invasive ultrasound-based method of measuring scarring of liver tissue, as a reliable tool to monitor disease course in AIH.

Keywords: Autoimmune hepatitis; Biochemical remission; Fibroscan; Fibrosis regression; IgG; Liver stiffness; Transient elastography.