Precision medicine for autoimmune hepatitis

Chen, Rui Ling; Wang, Qi Xia; Ma, Xiong

doi:10.1111/1751-2980.12786

Cited by 6 publications

(2 citation statements)

References 62 publications

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“…Aberrant autoimmunity is thought to induce an interaction between genetic susceptibility and unknown environmental triggers to cause persistent hepatocyte damage. Precision medicine for AIH, including diagnosis, medicinal therapy, and drug monitoring, is a novel therapeutic pattern distinct from evidence-based medicine that aims to develop a personalized treatment strategy (Bossen et al, 2018; Chen et al, 2019; Fan et al, 2019). However, ∼20% of AIH patients exhibit a poor response to standard treatment with glucocorticoids alone or in combination with azathioprine, and the number of effective second-line therapeutic options for AIH is limited (2015; Cropley and Weltman, 2017; Shen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Methylprednisolone Decreases Mitochondria-Mediated Apoptosis and Autophagy Dysfunction in Hepatocytes of Experimental Autoimmune Hepatitis Model via the Akt/mTOR Signaling

et al. 2019

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Autoimmune hepatitis (AIH) is characterized by massive immune cell-mediated hepatocyte destruction. Glucocorticoids, particularly methylprednisolone (MP), are the most effective treatment for AIH; however, the mechanism underlying the effects of glucocorticoid treatment has not been fully elucidated. The present study explored the effects of MP on damaged hepatocytes in mice with concanavalin A (ConA)−induced experimental autoimmune hepatitis (EAH). C57BL/6 mice were divided into three groups: a normal control group (injected with normal saline), a ConA (20 mg/kg) group, and a ConA + MP (3.12 mg/kg) group. The serum levels of liver enzymes, cytokines, activated T cells, and apoptosis− and autophagy−associated marker proteins were determined 12 h after ConA injection. Human hepatocyte cell line LO2 was used to verify the effects of ConA and MP in vitro. MP treatment significantly decreased inflammatory reactions in the serum and liver tissues and activated the Akt/mTOR signaling pathway to inhibit apoptosis and autophagy in hepatocytes in vivo. Transmission electron microscopy (TEM) revealed fewer autophagosomes in the MP-treated group than in the ConA-treated group. MP treatment obviously suppressed apoptosis and mitochondrial membrane potential (ΔΨm) loss in hepatocytes in vitro. Furthermore, ConA treatment increased the levels of LC3-II, p62/SQSTM1, and Beclin-1, while bafilomycin A1 did not augment the levels of LC3-II. MP treatment decreased the levels of LC3-II, p62/SQSTM1, and Beclin-1 and upregulated the levels of phosphorylated (p)-Akt and p-mTOR. In conclusion, MP ameliorated mitochondria-mediated apoptosis and autophagy dysfunction in ConA-induced hepatocyte injury in vivo and in vitro via the Akt/mTOR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Methylprednisolone Decreases Mitochondria-Mediated Apoptosis and Autophagy Dysfunction in Hepatocytes of Experimental Autoimmune Hepatitis Model via the Akt/mTOR Signaling

et al. 2019

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“…Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cholangitis, and primary sclerosing cholangitis, as well as their overlap syndromes. All of these diseases are associated with various autoantibodies and human leukocyte antigen (HLA) alleles (Chen et al 2019 ; Lee and Ronnekleiv-Kelly 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Presence of autoantibodies in serum does not impact the occurrence of immune checkpoint inhibitor-induced hepatitis in a prospective cohort of cancer patients

Purde

Niederer

Wagner

et al. 2021

J Cancer Res Clin Oncol

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Purpose Immune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients. Methods Data from a prospective biomarker cohort comprising melanoma and non-small cell lung cancer (NSCLC) patients were used to analyze the incidence of ICI-induced hepatitis, putatively associated factors, and outcome. Results 40 patients with melanoma and 91 patients with NSCLC received ICI between July 2016 and May 2019. 11 patients developed ICI-induced hepatitis (8.4%). Prior to treatment, 45.5% of patients in the hepatitis cohort and 43.8% of the control cohort showed elevated titers of autoantibodies commonly associated with autoimmune liver diseases (p = 0.82). We found two nominally significant associations between the occurrence of ICI-induced hepatitis and HLA alleles associated with autoimmune liver diseases among NSCLC patients. Of note, significantly more patients with ICI-induced hepatitis developed additional irAEs in other organs (p = 0.0001). Neither overall nor progression-free survival was affected in the hepatitis group. Conclusion We found nominally significant associations of ICI-induced hepatitis with two HLA alleles. ICI-induced hepatitis showed no correlation with liver-specific autoantibodies, but frequently co-occurred with irAEs affecting other organs. Unlike other irAEs, ICI-induced hepatitis is not associated with a better prognosis.

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Phenotypic Response and Personalized Medicine in Liver Cancer and Transplantation: Approaches to Complex Systems

Zarrinpar

Kim

Boominathan

2020

Advanced Therapeutics

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Rapid improvements in medical technology, big data analysis, and molecular medicine come with promises of revolutionizing medical care. They span the spectrum from diagnostics to genome-based drug selection to multi-biomarker analysis to deciphering large amounts of data. Below, recent developments in personalized and precision medicine are reviewed, focusing specifically on the liver, ranging from fatty liver disease to liver cancer treatment and liver transplantation. Furthermore, current technologies and their advantages and limitations are discussed, in addition to ways in which these disadvantages can be overcome, using phenotypic personalized medicine.

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Precision medicine for autoimmune hepatitis

Cited by 6 publications

References 62 publications

Methylprednisolone Decreases Mitochondria-Mediated Apoptosis and Autophagy Dysfunction in Hepatocytes of Experimental Autoimmune Hepatitis Model via the Akt/mTOR Signaling

Methylprednisolone Decreases Mitochondria-Mediated Apoptosis and Autophagy Dysfunction in Hepatocytes of Experimental Autoimmune Hepatitis Model via the Akt/mTOR Signaling

Presence of autoantibodies in serum does not impact the occurrence of immune checkpoint inhibitor-induced hepatitis in a prospective cohort of cancer patients

Phenotypic Response and Personalized Medicine in Liver Cancer and Transplantation: Approaches to Complex Systems

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