New Onset of Acute and Chronic Hepatic Diseases Post-COVID-19 Infection: A Systematic Review

Abstract

The SARS-CoV-2 virus caused a pandemic in the 2020s, which affected almost every aspect of life. As the world is recovering from the effect of the coronavirus, the concept of post-COVID-19 syndrome has emerged. Multiple organ systems have been implicated, including the liver. We aim to identify and analyze the reported cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 22 studies met our inclusion criteria. Our results revealed that liver steatosis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis were the most reported liver associated complications post-COVID-19 infection. Moreover, complications like acute liver failure, hepatitis, and liver hemorrhage were also reported. The mechanism of liver injury post-COVID-19 infection is not fully understood. The leading proposed mechanisms include the involvement of the angiotensin-converting enzyme-2 (ACE-2) receptor expressed in the liver and the overall inflammatory state caused by COVID-19 infection. Future studies should incorporate longer follow-up periods, spanning several years, for better insight into the progression and management of such diseases.

Keywords: COVID-19; SARS-CoV-2; hepatic injury; liver injury; long-COVID; parenchymal liver disease; post-COVID-19 sequelae.

Figure 1

Protocol of database search, screening, and study selection.

Figure 2

Types of the reported parenchymal liver injury post-COVID-19 infection and the reported outcomes. Only 1 death was reported by the 22 included studies. NAFLD: non-alcoholic fatty liver disease, NR: not reported.

Figure 3

Types of post-COVID-19 parenchymal liver injury as reported by 22 included studies. The numbers in the figures show the reported number of patients. (a) Post-COVID-19 steatosis and NAFLD as reported by 7 included studies. (b) Post-COVID-19 acute hepatitis with cholestasis and autoimmune hepatitis as reported by 4 included studies. (c) Post-COVID-19 hepatomegaly and increased liver volume as reported by 2 included studies. (d) Post-COVID-19 endothelial damage, sinus dilation, chronic liver disease, or other disorders as reported by 11 included studies. The other disorders were reported only in 8 patients, such as autoimmune hemolytic anemia, acute liver injury with calcified liver nodule, portal venous thrombosis, liver abscesses, hemophagocytic lymphohistiocytosis, deranged LFTs with ascites, and congestive hepatopathy. Liver stiffness was also reported but the number of patients was not reported (NR). Liver fibrosis was reported in 7 patients while sclerosis and cirrhosis post-COVID-19 were reported without reporting the number of patients (4 studies). Acute liver failure was reported by 3 case reports and liver inflammation (by imaging) was reported in 29 patients by 2 studies. The last 3 categories were not presented as pie charts due to the lack of number of patients or because there were no different types to show on the pie chart. NAFLD: non-alcoholic fatty liver disease, NR: not reported.