COVID-19 and hepatic injury: cellular and molecular mechanisms in diverse liver cells

Table 1 Explore the main causes of liver injuries during COVID-19

Cause of liver injury	The main finding of the study	Ref.
	SARS-CoV-2 directly invades the liver and displays hepatic impairment characterized by liver enzyme abnormalities	Wang et al[84], 2020
SARS-CoV-2 tropism	Intrahepatic SARS-CoV-2 contributes to liver inflammation, endothelium, and bile duct damage	Fiel et al[97], 2021
	SARS-CoV-2 cytopathic effect involved in the rapid progression of acute liver injury to acute liver failure	Melquist et al[98], 2020
Cytokine storm	Elevation of liver enzymes in COVID-19 is mainly related to immune dysregulation caused by cytokine storm and hepatic damage	Li et al[106], 2020
	Systemic inflammation is the fuel for hepatic injury in COVID-19 patients	Effenberger et al[244], 2021
Hypoxic liver injury	Hypoxic hepatitis is not a rare condition in COVID-19 patients admitted to the intensive care unit and is dramatically associated with elevated liver enzymes	Huang et al[117], 2020
	Hepatic artery thrombosis is highly associated with hepatic injury and abdominal pain during COVID-19	Antunes de Brito et al[124],2021
	SARS-CoV-2 induces severe disruption of the intrahepatic blood vessel and also affects the endothelial layer of blood vessels	Sonzogni et al[125], 2020
Endothelial cells and liver injury	Hepatic injury is attributed to platelet-fibrin microthrombi in the hepatic sinusoids along with some portal vein platelet aggregates	Rapkiewicz et al[126], 2020
	SARS-CoV-2 activates IL-6/JAK/STAT pathway consequently, stimulating coagulopathy and hepatic epitheliopathy	McConnell et al[139], 2021

SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019; IL-6: Interleukin-6; JAK: Janus kinases; STAT: Signal transducer and activator of transcription proteins.

Table 2 Summarizing the effect of comorbid hepatic disorders with SARS-CoV-2 infection

Hepatic disorders	Main finding	Ref.
	SARS-CoV-2 comorbidity with HCV shows a high percentage of ferritin, white blood cell count, prothrombin time, lymphocyte count, and hypoglycemia	Cerbu et al[159], 2022
	SARS-CoV-2 and HCV coinfection reported higher levels of IL-6 and IL-17, and TNF-α when compared with HCV and COVID-19 alone	León et al[161], 2022
HCV	The Serum levels of ALT, AST, CRP and ferritin, and calprotectin were significantly elevated in patients with COVID-19 infection than in patients with active HCV and patients with cured HCV infection	Toma et al[160], 2022
	HCV patients with SARS-CoV-2 infection are more likely to be hospitalized with a high possibility of liver fibrosis and mortality	Butt et al[158], 2021
	Individuals with HCV and SARS-CoV-2 co-infection are more vulnerable to developing liver cirrhosis	Afifyet al[245], 2021
	Patients with a history of HBV are anticipated to have a worse outcome with a high probability of ICU admission, and more organ failures	Choe et al[162], 2022
	S SARS-CoV-2 and chronic HBV showed severe monocytopenia, lymphopenia, thrombocytopenia, hypoalbuminemia, and lipid metabolism deficiency in the liver	Zou et al[164], 2021
HBV	Patients with HBV and SARS-CoV-2 coinfection died from severe liver disease and haptic sclerosis	Chen et al[163], 2020
	Patients with HBV who have COVID-19 were more likely to develop devastating illnesses and/or death. Additionally, the elevation of LDH, and D-dimer, with decreased albumin, and albumin/globulin ratio is helpful for early clinical surveillance	Wang et al[165], 2022
	Patients with DM with advanced liver fibrosis infected by SARS-CoV-2 are assumed to have a 10-time risk of mortality when compared with patients without comorbidities	Kim et al[203], 2021
	The high proportion of ICU admission, and the need for mechanical ventilation	Hassnine et al[206], 2022
Liver cirrhosis	Patients with liver cirrhosis and COVID-19 were admitted to the hospital than liver cirrhosis alone	An et al[208], 2021
	Those with cirrhosis alone or cirrhosis with COVID-19 had equal death rates, while patients with COVID-19 alone had a greater mortality rate	Bajaj et al[209], 2021
	HCC predicts a greater mortality rate in individuals with HCC infected by SARS-CoV-2 than COVID-19 alone, especially in patients with obesity, diabetes mellitus, hypertension, and hyperlipidemia, older patients ≥65 years, and Hispanic ethnicity	Kim et al[211], 2021
HCC	HCC and COVID-19 were shown to be more susceptible to have a higher risk of death and admitted to the ICU	Liang et al[212], 2020
	Patients with HCC-COVID-19 coinfection found that about one-third of patients need hospital admission, and two-thirds of patients have an elevation of transaminases. Alkaline phosphatase which independently linked to a high mortality rate, higher C reactive protein levels, and more severe respiratory failure upon admission to the hospital	Leo et al[213], 2022
	LT patients with COVID-19 had a considerably increased risk of hospitalization but not a significantly higher risk of mortality, thrombosis, or need for ICU admission	Mansoor et al[216], 2021
	High alkaline phosphatase levels, and lymphovascular invasion	Shafiq et al[217], 2022
LT	LT cases could be successful in active SARS-CoV-2 patients without developing post-operative COVID-19 symptoms	Mouch et al[214], 2022
	Found that liver transplantation from COVID-19-positive donors to informed recipients who have SARS-CoV-2 immunity may help to increase the donor pool safely	Romagnoli et al[219], 2021
	Successful LT In patients with severe liver failure due to cholestasis with a good graft function and recovering function in the native liver remnant	Rela et al[220], 2022

HCV: Hepatitis C virus; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019; IL-6: Interleukin-6; IL-17: Interleukin-17; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CRP: C-reactive protein; HBV: Hepatitis B virus; ICU: Intensive care unit; HCC: Hepatocellular carcinoma; LT: Liver transplantation.