Pathogenetic Mechanisms of Liver-Associated Injuries, Management, and Current Challenges in COVID-19 Patients.

The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.

SARS-COV-2/COVID-19: scenario, epidemiology, adaptive mutations, and environmental factors.

The coronavirus pandemic of 2019 has already exerted an enormous impact. For over a year, the worldwide pandemic has ravaged the whole globe, with approximately 250 million verified human infection cases and a mortality rate surpassing 4 million. While the genetic makeup of the related pathogen (SARS-CoV-2) was identified, many unknown facets remain a mystery, comprising the virus's origin and evolutionary trend. There were many rumors that SARS-CoV-2 was human-borne and its evolution was predicted many years ago, but scientific investigation proved them wrong and concluded that bats might be the origin of SARS-CoV-2 and pangolins act as intermediary species to transmit the virus from bats to humans. Airborne droplets were found to be the leading cause of human-to-human transmission of this virus, but later studies showed that contaminated surfaces and other environmental factors are also involved in its transmission. The evolution of different SARS-CoV-2 variants worsens the condition and has become a challenge to overcome this pandemic. The emergence of COVID-19 is still a mystery, and scientists are unable to explain the exact origin of SARS-CoV-2. This review sheds light on the possible origin of SARS-CoV-2, its transmission, and the key factors that worsen the situation.