@article{2286, author = {Sayaka Deguchi and Kaori Kosugi and Rina Hashimoto and Ayaka Sakamoto and Masaki Yamamoto and Rafal P Krol and Peter Gee and Ryosuke Negoro and Takeshi Noda and Takuya Yamamoto and Yu-suke Torisawa and Miki Nagao and Kazuo Takayama}, title = {Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips}, abstract = {SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct and blood vessel. We found that hepatic dysfunctions, but not hepatobiliary diseases, were strongly induced by SARS-CoV-2 infection. Next, we evaluated the therapeutic effects of COVID-19 drugs to inhibit viral replication and recover hepatic dysfunctions, and found that the combination of anti-viral and immunosuppressive drugs (Remdesivir and Baricitinib) is effective to treat hepatic dysfunctions caused by SARS-CoV-2 infection. Finally, we analyzed the sera obtained from COVID-19 patients, and revealed that COVID-19 patients, who were positive for serum viral RNA, are likely to become severe and develop hepatic dysfunctions, as compared with COVID-19 patients who were negative for serum viral RNA. We succeeded in modeling the liver pathophysiology of COVID-19 patients using LoC technology and clinical samples.}, year = {2023}, journal = {PNAS Nexus}, volume = {2}, pages = {pgad029}, month = {2023-03-01}, issn = {2752-6542}, url = {https://doi.org/10.1093/pnasnexus/pgad029}, doi = {10.1093/pnasnexus/pgad029}, }