Identification of hepatocyte immune response in Autoimmune Hepatitis from human plasma cfChIP-seq

Autoimmune hepatitis (AIH) is a self-perpetuating inflammatory liver disease with significant morbidity and mortality risks. Patients undergo liver biopsy to confirm diagnosis and affirm subsequent remission. Advances in liquid biopsies show promise to replace tissue biopsy in cancer, however little research has been done in liver disease. Here, we use plasma chromatin immunoprecipitation and sequencing (cfChIP-seq) to analyze cell-free nucleosomes carrying an active histone modification which reports on gene transcription in the dying cells. Comparing plasma samples from pediatric AIH patients to a control group we identify immune-related transcriptional processes activated in hepatocytes of AIH patients. We devise a classifier that based on cfChIP-seq profiles distinguishes AIH from other conditions involving increased liver damage. Our work demonstrates the potential of plasma cfChIP-seq as a non-invasive diagnostic tool for AIH, which could replace the need for liver biopsy, aid accurate diagnoses, and enable further scientific exploration of AIH pathogenesis. ### Competing Interest Statement N.F., J.G., R.S. and I.S. are co-founder and share holders of Senseera LTD ### Funding Statement This work was supported by the European Research Councils AdG Grant cfChIP 101019560 (to N.F.) and Israel Science Foundation IPMP Grant 3751/21 (to N.F and E.G.) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committees of the SZMC of Jerusalem (0269-19-SZMC). Informed consent was obtained from all individuals or their legal guardians before blood sampling. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study will be deposited in public repository. And will be available upon reasonable request.