Hepatocellular carcinoma in autoimmune hepatitis remains rare

Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitisJournal of HepatologyPreviewAutoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors. Full-Text PDF See Article, pages xxx–xxx See Article, pages xxx–xxx Autoimmune hepatitis (AIH) remains a critical disease associated with high morbidity and mortality. It is important to better define the disease course and associated complicating factors, and this may be difficult for rare events in a rare disease such as AIH. The risk of hepatocellular carcinoma (HCC) in AIH has been assessed in two larger population-based studies[1]Sharma R. Verna E.C. Simon T.G. Soderling J. Hagstrom H. Green P.H.R. et al.Cancer risk in patients with autoimmune hepatitis: a nationwide population-based cohort study with histopathology.Am J Epidemiol. 2022; 191: 298-319Crossref PubMed Scopus (12) Google Scholar,[2]Jensen M.D. Jepsen P. Vilstrup H. Grønbæk L. Increased cancer risk in autoimmune hepatitis: a Danish nationwide cohort study.Am J Gastroenterol. 2022; 117: 129-137Crossref PubMed Scopus (15) Google Scholar – both reporting a low risk of HCC. In view of this, the study by Colapietro and colleagues in this issue of Journal of Hepatology confirms this and provides further information on the risk of HCC and potential risk factor associations in AIH. They investigated the incidence of HCC in a large retrospective multicentre cohort of 1,428 patients with AIH diagnosed, 1980-2020. The authors mainly aimed to define risk factors for HCC and to provide information to guide personalized HCC surveillance in patients with AIH. It is an interesting paper confirming the previously reported low HCC incidence among patients with AIH. The retrospective nature of the study, the amount of missing information and thereby the selection of eligible patients should be considered when interpreting the findings. Similar results from the more recent study period with less missing information were, however, reassuring. In their study, there were 24 incident cases of HCC for an annual risk of 0.09% during the first 10 years after the AIH diagnosis. The risk was expectedly higher among patients with cirrhosis, with a risk of 0.46% per year during the first 10 years, and also higher for patients with obesity, older age, and primary sclerosing cholangitis (PSC). The HCC association for cirrhosis was confirmed in the risk factor analyses with a 3-fold increased risk of HCC at the time of AIH diagnosis. Similar findings applied to obesity, whereas overlap with PSC carried an even higher risk increment, the latter, however, potentially biased by radiologically defined misdiagnoses of HCC. The statistical power of the data did not allow for final conclusions regarding sex, age, alcohol consumption, primary biliary cholangitis (PBC) or other autoimmune diseases as potential risk factors for HCC. Other studies have recognized male sex, older age, AIH relapse, cirrhosis, and alcohol consumption as risk factors for HCC in AIH – still, a low overall absolute risk of HCC has been reported by the vast majority of studies.[3]Tansel A. Katz L.H. El-Serag H.B. Thrift A.P. Parepally M. Shakhatreh M.H. et al.Incidence and determinants of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2017; 15: 1207-12017 e4Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Cirrhosis and HCC were both associated with increased mortality. The annual risk of HCC in this study by Colapietro and colleagues was well below the internationally recommended cut-off of 1.5% for cost-effective HCC screening – this was also the case in patients with cirrhosis who had been subjected to HCC surveillance during follow-up. The authors highlight the importance of obesity, since the risk factor association with HCC seemed similar to that with cirrhosis. They suggest evaluating the appropriateness of HCC screening based on patients' risk factor profile at AIH diagnosis. We urge caution when taking such a suggestion into consideration: We do not believe that the literature, including data from the present study, provides a clear rationale for personalized HCC surveillance in patients with AIH. Even larger prospective studies are probably needed for this matter. One might even argue that the results from the study by Colapietro and colleagues do not support any screening – from a socio-economic point of view. Even more importantly, screening is potentially harmful to the patients, owing to the potential psychological burden or risk of false-positive results.[4]DeFrank J.T. Barclay C. Sheridan S. Brewer N.T. Gilliam M. Moon A.M. et al.The psychological harms of screening: the evidence we have versus the evidence we need.J Gen Intern Med. 2015; 30: 242-248Crossref PubMed Scopus (51) Google Scholar This concern seems crucial in patients with AIH who have been shown to suffer from impaired quality of life and even symptoms of depression and anxiety in numerous studies.[5]Schramm C. Wahl I. Weiler-Normann C. Voigt K. Wiegard C. Glaubke C. et al.Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis.J Hepatol. 2014; 60: 618-624Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar,[6]Snijders R.J. Milkiewicz P. Schramm C. Gevers T.J. Health-related quality of life in autoimmune hepatitis.World J Hepatol. 2021; 13: 1642-1652Crossref PubMed Scopus (6) Google Scholar Nevertheless, effort must continuously be paid to prevent liver disease progression and death in patients with AIH, and this may include prevention of obesity as well as prevention of alcohol over-consumption. AIH is indeed a serious disease, and there is still a need for clinicians and researchers to improve patient management and thereby reduce morbidity and mortality. The data from the present and previous population-based studies is somehow reassuring in that the risk of HCC is extremely low – even in patients with AIH and less favourable risk factor profiles. Importantly, there is still no evidence to recommend HCC surveillance in patients with AIH without cirrhosis, and the rationale for HCC surveillance in patients with AIH and cirrhosis, as currently recommended, may be questioned. Lisbet Grønbæk received funding from the Danish Council for Independent Research. The funding sources were not involved in the preparation of this editorial. The authors who have contributed declare that they have nothing to disclose with respect to this editorial. Please refer to the accompanying ICMJE disclosure forms for further details. Lisbet Grønbæk drafted the manuscript, and all authors revised it for intellectual content and approved the final draft. The following are the supplementary data to this article: Download .pdf (.23 MB) Help with pdf files Multimedia component 1