Letter on ‘Clinical Features of Portal Hypertension and Their Prognostic Implications in Patients With Autoimmune Hepatitis’: Authors' Reply

We thank Drs. Padilla-Lopez, Londoño and Arvaniti for their valuable comments 1 and specifically for addressing potential pitfalls when using liver stiffness measurements (LSM) in patients with autoimmune hepatitis (AIH) for assessing clinically significant portal hypertension (CSPH). In our study 2 including 271 patients with AIH, we found clinical CSPH features in 22.1% at presentation and in up to 38.4% during follow-up. While some CSPH features are regarded as nonspecific (e.g., splenomegaly found in 28% during follow-up), gastroesophageal varices (13.7%) or portosystemic collaterals (14.8%) are considered specific signs of CSPH. While LSM is recommended for identifying compensated advanced chronic liver disease (cACLD) and for CSPH screening in viral and steatotic liver disease, its value for evaluating CSPH in the distinct aetiology of AIH remains largely unknown. LSM in patients with AIH is influenced by the degree of hepatic inflammation 3, that is, AIH activity, and thus LSM may not accurately reflect liver fibrosis, as previously noted by the authors 1. Therefore, the value of LSM for CSPH risk assessment in AIH remains unclear. In our study, n = 14 patients showed LSM > 25 kPa at presentation (i.e., at a timepoint when AIH-related hepatic inflammation may falsy elevate LSM) and among those, n = 6 (42.9%) patients presented features of CSPH. At month 6, N = 3 of those patients declined to an LSM ≤ 25 kPa; and those with LSM remaining at > 25 kPa showed CSPH features in 45.5% (this sub-analysis included only patients with paired measurements). We are happy to provide the suggested breakdown of CSPH features according to different strata of LSM ( 25 kPa) and of platelet count (PLT > 150 vs. PLT 110–150 vs. PLT 150 G/L) vs. (ii) grey zone vs. (iii) CSPH rule-in (LSM > 25 kPa) 5 (Figure 1). Overall, our post hoc analysis suggests a clinical value of using LSM and PLT for assessing CSPH risk in patients with AIH. Notably, we have previously found similar results on the value of LSM and PLT in patients with PBC 6 or Wilson's Disease 7. Since AIH may also exert presinusoidal effects on portal pressure, especially in PBC-variant syndromes, we recommend including spleen stiffness measurements (SSM) in the non-invasive assessment when CSPH is suspected 8. A high SSM-to-LSM ratio has been shown to indicate presinusoidal CSPH in some etiologies, in which CSPH risk is not captured by (low) LSM 9. We thank the authors for their important comments and agree that future AIH studies should incorporate non-invasive CSPH testing as an additional risk-stratification tool. The authors' declarations of personal and financial interests are unchanged from those in the original article 2. Lukas Burghart: validation, conceptualization, writing – original draft, formal analysis, data curation, writing – review and editing. Thomas Reiberger: writing – original draft, conceptualization, supervision, writing – review and editing. Albert Friedrich Stättermayer: writing – review and editing, conceptualization, methodology, supervision, validation. The authors have nothing to report. L.B. received grant support from Gilead, travel support from Gilead, Ipsen and Eli Lilly, and speaker honoraria from Gilead and Ipsen. T.R. received grant support from AbbVie, Boehringer-Ingelheim, Gilead, Gore, Intercept, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant and Siemens; speaking honoraria from AbbVie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from AbbVie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from AbbVie, Boehringer-Ingelheim, Gilead and Roche. A.F.S. consults for, advises and/or is on the speakers' bureau for Abacus Medicine, Ideogen, Boehringer Ingelheim, Gilead and MSD. This article is linked to Burghart et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70349 and https://doi.org/10.1111/apt.70437. The data that support the findings of this study are available from the corresponding author upon reasonable request.