02078nas a2200289   4500000000100000008004100001260001500042100001900057700001700076700001900093700001900112700002000131700001700151700001400168700001900182700001700201700002000218700002100238700001500259700001900274245008900293856004600382300001200428490000600440520132800446022001401774       2023                            d  c2023-03-011 aSayaka Deguchi1 aKaori Kosugi1 aRina Hashimoto1 aAyaka Sakamoto1 aMasaki Yamamoto1 aRafal P Krol1 aPeter Gee1 aRyosuke Negoro1 aTakeshi Noda1 aTakuya Yamamoto1 aYu-suke Torisawa1 aMiki Nagao1 aKazuo Takayama00aElucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips  uhttps://doi.org/10.1093/pnasnexus/pgad029  apgad0290 v23 aSARS-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.  a2752-6542