High prevalence of hepatic steatosis and vascular thrombosis in COVID-19: A systematic review and meta-analysis of autopsy data

Abstract

Background: Coronavirus disease 2019 (COVID-19) disease can frequently affect the liver. Data on hepatic histopathological findings in COVID-19 is scarce.

Aim: To characterize hepatic pathological findings in patients with COVID-19.

Methods: We conducted a systematic review with meta-analysis registered on PROSPERO (CRD42020192813), following PRISMA guidelines. Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test. Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed. Articles including less than ten patients were excluded. Proportions were pooled using random-effects models. Q statistic and I ² were used to assess heterogeneity and levels of evidence, respectively.

Results: We identified 18 studies from 7 countries; all were case reports and case series from autopsies. All the patients were over 15 years old, and 67.2% were male. We performed a meta-analysis of 5 studies, including 116 patients. Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1% [95% confidence interval (CI): 46.2-63.8], congestion of hepatic sinuses 34.7% (95%CI: 7.9-68.4), vascular thrombosis 29.4% (95%CI: 0.4-87.2), fibrosis 20.5% (95%CI: 0.6-57.9), Kupffer cell hyperplasia 13.5% (95%CI: 0.6-54.3), portal inflammation 13.2% (95%CI: 0.1-48.8), and lobular inflammation 11.6% (95%CI: 0.3-35.7). We also identified the presence of venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis.

Conclusion: We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features. Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation. Further studies are needed to establish the mechanisms and implications of these findings.

Keywords: Autopsies; COVID-19; Liver; Liver biopsies; Pathology; SARS-CoV-2.

Figure 1

Study selection for the systematic review.

Figure 2

Major liver histological features observed in 6 studies (n = 116 autopsies from deceased coronavirus disease 2019 patients). Steatosis was the most frequent finding (55.1%). Studies also reported congestion of hepatic sinuses (34.6%), vascular thrombosis (29.4%), fibrosis (20.5%), Kupffer cell hyperplasia (13.5%), portal inflammation (13.2%), and lobular inflammation (11.6%), Other findings observed were venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis.

Figure 3

Forest plots of major liver histological features from deceased coronavirus disease 2019 patients. A-D: The figure includes forest plots of hepatic steatosis (A), congestion of hepatic sinuses (B), vascular thrombosis (C), and fibrosis (D). Heterogeneity was assessed using I² and Q statistics. CI: Confidence interval.

Figure 4

Forest plots of inflammatory liver histological features from deceased coronavirus disease 2019 patients. A-C: The figure includes forest plots of Kupffer cell hyperplasia (A), portal inflammation (B), and lobular inflammation (C). Heterogeneity was assessed using I² and Q statistics. CI: Confidence interval.