Liver stiffness measurement predicts clinical outcomes in autoimmune hepatitis

Abstract

Background & aims: Liver stiffness measurement (LSM) has been shown to adequately predict outcomes in patients with liver disease. However, the value of LSM as a predictor of disease progression in autoimmune hepatitis (AIH) remains to be determined. This study aimed to evaluate the role of LSM as a predictor of disease progression and decompensation of cirrhosis in patients with AIH.

Methods: This multicentre cohort study included 439 patients with histologically confirmed AIH and at least one LSM during follow-up. The association between the first LSM performed at least 6 months after treatment initiation (baseline LSM [BLSM]) and cirrhosis development and poor outcomes (decompensation, liver transplantation, and/or liver-related death) was assessed using Cox regression and its discriminating capacity with a receiver-operating characteristic curve.

Results: Most patients were female (n = 301, 70%), with a median age of 52 years. BLSM performed after a median of 2.18 (1.19-4.68) years had a median value of 6 kPa (4.5-8.5). At the time of BLSM, 332 (76%) patients had achieved a biochemical response and 57 (13%) had cirrhosis. During follow-up, eight patients (2%) presented with poor outcomes and 26 (7%) developed cirrhosis. BLSM was higher among patients with poor outcomes (13.5 kPa vs. 6 kPa; p <0.001) and was independently associated with cirrhosis development (hazard ratio 1.300; p <0.001), irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes, with AUCs of 0.859 (95% CI 0.789-0.929) and 0.900 (95% CI 0.847-0.954), respectively.

Conclusion: BLSM could play a significant role in predicting AIH outcomes, potentially identifying a subgroup of patients at a high risk of progressing to cirrhosis and experiencing decompensation.

Impact and implications: The value of liver stiffness measurement as a predictor of outcomes in patients with autoimmune hepatitis (AIH) remains to be determined. In this large multicentre study, liver stiffness measurement was found to be an independent predictive factor of adverse clinical outcomes and cirrhosis development in AIH, irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes in AIH.

Keywords: autoimmune hepatitis; cirrhosis; decompensation; elastography; liver stiffness measurement; outcome.

Graphical abstract

Fig. 1

Study flowchart. AIH, autoimmune hepatitis. BLSM, first liver stiffness measurement 6 months after diagnosis. HCC, hepatocellular carcinoma.

Fig. 2

Association of BLSM with poor clinical outcomes. (A) ROC curve of BLSM for the prediction of poor clinical outcomes. (B) Probability of being free of poor clinical outcomes according to the BLSM. Patients with BLSM greater than 8.5 kPa had a significantly lower probability of being free from poor clinical outcomes, represented by a Kaplan-Meier curve and log-rank test (p <0.001). BLSM, baseline liver stiffness measurement.

Fig. 3

Multivariate Cox regression analysis for cirrhosis development according to BLSM. Two models were performed including statistically significant parameters in the previous univariate analysis. BLSM (Model 1 = HR 1.161; 95% CI 1.07408–1.24425; p <0.001), BLSM <8.5 kPa (Model 2 = HR 0.096; 95% CI 0.033–0.278), mHAI (Model 1 = HR 1.212; 95% CI 1.062-1.382; p = 0.004; Model 2 = HR 1.183; 95% CI 1.041–1.345; p = 0.010), and BR at the time of BLSM (Model 1 = HR 0.267; 95% CI 0.095-0.750; p = 0.012; Model 2 = HR 0.278; 95% CI 0.107–0.723; p = 0.009) were independently associated with the risk of developing cirrhosis during follow-up. BLSM, baseline liver stiffness measurement; HR, hazard ratio; mHAI, modified hepatitis activity index.

Fig. 4

Association of BLSM with cirrhosis. (A) ROC curve of BLSM for the prediction of cirrhosis development. (B) Probability of being free of cirrhosis during follow-up according to BLSM. Patients with BLSM greater than 8.5 kPa had a significantly higher probability of developing cirrhosis during follow-up, represented by a Kaplan-Meier curve and log-rank test (p <0.001). BLSM, baseline liver stiffness measurement.

Fig. 5

Pairwise comparisons using a general linear model between BLSM and last LSM in each group. Groups: cirrhosis at baseline, development of cirrhosis during follow-up, development of poor clinical outcomes, and BR at last follow-up. Dots represent individual LSM values in each group, bars represent median values, and error bars represent the 25^th and 75^th percentiles of the median (IQR). BLSM, baseline liver stiffness measurement; BR, biochemical response; LSM, liver stiffness measurement.