COVID-19 associated liver injury: A general review with special consideration of pregnancy and obstetric outcomes

Abstract

Liver injury is an increasingly recognized extra-pulmonary manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Coronavirus disease 2019 (COVID-19) associated liver injury (COVALI) is a clinical syndrome encompassing all patients with biochemical liver injury identified in the setting of SARS-CoV-2 infection. Despite profound clinical implications, its pathophysiology is poorly understood. Unfortunately, most information on COVALI is derived from the general population and may not be applicable to individuals under-represented in research, including pregnant individuals. This manuscript reviews: Clinical features of COVALI, leading theories of COVALI, and existing literature on COVALI during pregnancy, a topic not widely explored in the literature. Ultimately, we synthesized data from the general and perinatal populations that demonstrates COVALI to be a hepatocellular transaminitis that is likely induced by systemic inflammation and that is strongly associated with disease severity and poorer clinical outcome, and offered perspective on approaching transaminitis in the potentially COVID-19 positive patient in the obstetric setting.

Keywords: COVID-19 liver injury; Perinatal liver disease; Pregnancy; Special populations; Systemic inflammation.

Figure 1

Mechanisms of COVID-19-associated liver injury: Inter-organ crosstalk. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells via interaction of its spike protein with the receptor angiotensin converting enzyme 2 in the presence of TMPRSS2 in many tissues. Proposed mechanisms for SARS-CoV-2-mediaded liver injury include: (1) Direct viral cytopathic effect; (2) IL-6 trans-signaling in liver sinusoidal endothelial cells which leads to endotheliopathy; (3) cytokine storm-induced damage; and (4) hypoxemic injury. There is also a lung-gut crosstalk which promotes an increased inflammatory state as well as dysbiosis which increases intestinal permeability, thus facilitating viral entry. Furthermore, direct viral injury to the vascular endothelium leads to increased cytokine release, enhanced reactive oxygen species production and thrombo-embolic events involving both micro and macro circulation. In a similar fashion, pre-eclampsia spectrum syndromes cause inflammation and endotheliopathy that pre-disposes to liver injury and can be synergistic coronavirus disease 2019 (COVID-19) and COVID-19 associated liver injury. Original figure was created with BioRender.com.