Since its outbreak in Wuhan, China in December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for causing coronavirus disease 2019 (COVID-19) led to a public health crisis resulting in millions of deaths. [1] Although most well-known for causing pulmonary injury, COVID-19 has commonly been implicated in systemic pathology. [2,3] Systemic disease is not unexpected, as the SARS-CoV-2 virus shares many similarities to other prior coronaviruses responsible for large epidemics, such as SARS-CoV (outbreak in 2002–2003). [2,4] Like SAR-CoV, SARS-CoV-2 has been recurrently associated with abnormalities of gastrointestinal and hepatobiliary tracts, with up to 50 % of patients with COVID-19 experiencing some form of hepatic dysfunction. [[4], [5], [6]]

The mechanism by which SARS-CoV-2 causes liver injury is not fully understood and likely is multifactorial. Angiotensin-converting enzymes 2 (ACE2) receptors, located in cells from multiple organ sites, including lung, gastrointestinal tract and liver, have been documented to have strong affinity for the SARS-CoV-2 virus. Their interaction with the virus has also been reported to account, in large part, for the direct cytopathic pulmonary injury related to COVID-19 pneumonia. [7] Interestingly, while ACE2 receptors are significantly enriched on cholangiocytes of the liver, only a low level of hepatocytes express ACE2. Secondary injury, whether due to cytokine release syndrome, dysregulated immune response, hypoperfusion, or drug induced liver injury, also seems plausible. [8]

Previous autopsy series have described histologic hepatic features in patients with COVID-19, with steatosis, portal and lobular inflammation, and microvascular thrombi being reported in many. [[9], [10], [11], [12], [13], [14], [15], [16]] Most of the prior autopsy series have lacked a control group, and therefore it is unclear whether the reported histologic features are specific to COVID-19 or secondary findings in critically ill patients. The goal of this study was to describe the hepatic pathology in a large cohort of deceased patients with COVID-19 as compared to a control group of deceased patients without COVID-19.