Author information

¹Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. Electronic address: sternlouisa@gmail.com.

²Department of Internal Medicine and Gastroenterology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

³Department of Internal Medicine and Gastroenterology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

⁴Bioinformatics Core, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

⁵Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, 125, rue de Stalingrad, 93000 Bobigny, France.

⁶Department Gastroenterology and Hepatology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, the Netherlands; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

⁷Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei Blvd. 98, HU-4026 Debrecen, Hungary; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

⁸Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy.

⁹Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece; Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.

¹⁰Division of Gastroenterology & Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

¹¹Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

¹²First Department of Medicine, University Hospital Schleswig-Holstein, Ratzeburger Allee 160, 23538 Lübeck, Germany.

¹³Department of Gastroenterology, Hepatology, and Endocrinology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.

¹⁴Department of Gastroenterology and Hepatology, University Hospital Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.

¹⁵Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Block B, 2nd floor, Banacha 1A, 02-097 Warsaw; European Reference Network on Hepatological Diseases (ERN RARE-LIVER); Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.

¹⁶Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.

¹⁷Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy and Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Via A. Manzoni 56, 20089 Rozzano, Italy; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

¹⁸Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece; European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

Abstract

Introduction and objectives: Autoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC). and data on the efficacy and tolerability of anti-tumour therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease.

Materials and methods: 107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included. 65 received TACE and 28 received TKI therapy. 43 (66%) were female (median age 73 years) with HCC tumour stage BCLC A (34%), B (46%), C (9%) or D (11%). For each treatment type, propensity score matching was used to match AILD to non-AILD-HCC on a 1:1 basis, yielding in a final cohort of 130 TACE and 56 TKI patients for comparative analyses of median overall survival (mOS) and treatment tolerability.

Results: HCC-AILD patients showed comparable mOS to controls for both TACE (19.5 vs 22.1 months, p=0.9) and TKI (15.4 vs 15.1 months, p=0.5). Adverse events were less frequent in AILD-HCC patients than controls (33% vs 62%, p=0.003). For TKIs, there were no significant differences in adverse events (73% vs. 86%, p=0.2) or interruption rates (44% vs. 36%, p=0.7).

Conclusions: In summary, this study demonstrates comparable mOS for AILD-HCC patients undergoing local and systemic treatments, with better tolerability than HCC of other causes. TKIs remain important therapeutic options for AILD-HCC patients, particularly given their exclusion from recent immunotherapy trials.