Liver injury in COVID-19: an insight into pathobiology and roles of risk factors

Abstract

COVID-19 is a complex disease that can lead to fatal respiratory failure with extrapulmonary complications, either as a direct result of viral invasion in multiple organs or secondary to oxygen supply shortage. Liver is susceptible to many viral pathogens, and due to its versatile functions in the body, it is of great interest to determine how hepatocytes may interact with SARS-CoV-2 in COVID-19 patients. Liver injury is a major cause of death, and SARS-CoV-2 is suspected to contribute significantly to hepatopathy. Owing to the lack of knowledge in this field, further research is required to address these ambiguities. Therefore, we aimed to provide a comprehensive insight into host-virus interactions, underlying mechanisms, and associated risk factors by collecting results from epidemiological analyses and relevant laboratory experiments. Backed by an avalanche of recent studies, our findings support that liver injury is a sequela of severe COVID-19, and certain pre-existing liver conditions can also intensify the morbidity of SARS-CoV-2 infection in synergy. Notably, age, sex, lifestyle, dietary habits, coinfection, and particular drug regimens play a decisive role in the final outcome and prognosis as well. Taken together, our goal was to unravel these complexities concerning the development of novel diagnostic, prophylactic, and therapeutic approaches with a focus on prioritizing high-risk groups.

Keywords: SARS-CoV-2; COVID-19; Liver injury; Pathobiology mechanisms; Risk factors.

Fig. 1

An overview of the renin-angiotensin-aldosterone system, including organs, enzymes, functions, interactions, and the ultimate outcome that leads to the modulation of blood pressure in response to situations in which the human body needs to alter the balance of electrolytes and its vascular tone

Fig. 2

A scheme of ACE-2 receptors illustrating a comparison between two states: (1) the free to perform normally and (2) the exploited status by SARS-CoV-2 which results in a variety of complications in patients with COVID-19

Fig. 3

A depiction of various mechanisms that may contribute to the development of SIH in COVID-19 patients. It is noteworthy that, in addition to the direct invasion of SARS-CoV-2 to ACE-2-positive hepatocytes, indirect pathways such as immune-based hepatopathology, cytokine storm, and RAAS disturbance should also be highlighted as potential mechanisms of SIH pathogenesis

Fig. 4

As a multifactorial complication, the development and severity of SIH are considered to be relatively dependent on host-oriented, environmental, and viral risk factors, which can influence the outcome of the disease in COVID-19 patients

Fig. 5

A general flowchart visualizing possible mechanisms and outcomes related to drug hepatotoxicity and their association with the progression of SIH in patients with COVID-19; (1) Drugs may interact with particular receptors and cause a detrimental response or suppress/shut down a crucial function. (2) Drugs can cause different types of hypersensitivity reactions (HSR). (3) Drugs may trigger certain cascade reactions that affect regulatory systems. (4) Drugs might also interfere with transcription and replication processes