Introduction
Autoimmune hepatitis (AIH) is associated with an increased risk of developing cirrhosis and progressing to hepatic decompensation. While a successful treatment of the underlying aetiology has been shown to enable hepatic recompensation in some aetiologies of cirrhosis, implications of recompensation have not yet been assessed in decompensated cirrhosis due to AIH.
Aims & Methods
In this pilot study, we assessed the incidence and prognostic role of hepatic recompensation in patients with decompensated cirrhosis (F3/F4 histology) due to AIH (simplified AIH score ≥6). Patients were included at first hepatic decompensation, marked by the first occurrence of ascites, variceal bleeding or hepatic encephalopathy (HE). Patients with acute liver failure were excluded due to the indication of the high urgency liver transplantation. In accordance with the Baveno VII criteria, recompensation was defined as (i) resolution of ascites and HE despite cessation of all diuretics and anti-HE therapies, (ii) absence of variceal bleeding and (iii) sustained improvement in hepatic synthetic function (bilirubin, albumin, INR) to Child-Pugh A values. Successful aetiological control in AIH was defined as a complete biochemical response under immunosuppressive therapy, i.e., a normalisation of transaminases and immunoglobulin G.
Results
Twenty-one patients with cirrhosis due to AIH (90.5% female, age: 54.6 [39.8-61.6] years) were included at time of first decompensation (85.7% ascites, 14.3% variceal bleeding) and followed for a median of 80.4 (14.6-133.0) months. The median MELD at decompensation was 15 (11-18). Clinically, decompensation occurred in two scenarios, resulting in two distinct patient subgroups: In the first subgroup (n=10; 47.6%), patients had already been diagnosed with AIH prior to hepatic decompensation and decompensation occurred despite ongoing immunosuppressive treatment (median treatment duration: 128 [70-164] months). Decompensation in this subgroup was primarily the result of an insufficient biochemical response and none of these patients achieved hepatic recompensation. In the second subgroup, which included 11 patients (52.4%), the diagnosis of AIH was first established in the context of index decompensation. Out of these 11 patients, 5 (45.5%) did not receive immunosuppressive treatment until more than 1 month after decompensation. This delay was mainly a consequence of a delayed diagnosis and none of these patients recompensated. In contrast, in the other 6 patients (54.5%), both the diagnosis of AIH and immunosuppressive treatment were established within less than 1 month after decompensation, resulting in hepatic recompensation in 4 patients. Notably, all recompensated patients achieved a 50% decrease in transaminase levels after 4 weeks of treatment. With regard to clinical outcomes, the 4 recompensated patients survived for 62.6, 101.3, 106.3 and 202.3 months, respectively, without the need for liver transplantation. In contrast, 6 of the 17 patients who remained decompensated died (35.3%, all liver-related) after a median of 32.8 (15.1-58.5) months and 4 (23.5%) required liver transplantation (after median 37.5 [15.9-57.1] months).
Conclusion
In AIH patients who first present with decompensated cirrhosis, a timely diagnosis followed by a prompt initiation of immunosuppressive treatment is associated with a higher probability of recompensation and improved survival. In contrast, decompensation despite ongoing immunosuppressive therapy is associated with a poorer prognosis.
Disclosure
MM served as a speaker and/or consultant and/or advisory board member for AbbVie, Collective Acumen, Gilead, and W. L. Gore & Associates and received travel support from AbbVie and Gilead.
MT has received research grants from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and Ultragenyx and travel grants from Abbvie, Falk, Gilead, Intercept and Jannsen. He further has advised for Abbvie, Albireo, BiomX, Boehringer Ingelheim, Falk Pharma GmbH, Genfit, Gilead, Hightide, Intercept, Janssen, MSD, Novartis, Phenex, Pliant, Regulus, Siemens and Shire and has served as speaker for BMS, Falk, Gilead, Intercept, Madrigal and MSD. He is a co-inventor of patents for the medical use of norUDCA (nor-ursodeoxycholic acid/norucholic acid) filed by the Medical Universities of Graz and Vienna.
TR received grant support from AbbVie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; 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 Boehringer-Ingelheim, Gilead and Roche.
