SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups

Abstract

Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with “bystander hepatitis”, cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.

Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting

“…Liver injury was the most frequently described extrapulmonary manifestation (17.28%) in our study group, as presented in Table 1. The data on liver injury in COVID-19 patients are heterogeneous [1]-a systematic review indicated mild liver function in every fourth to fifth patient [25]. In our analyses, liver injury was associated with obesity and therapy (corticosteroids, anakinra, favipiravir, and remdesivir), while the highest OR was associated with the Delta wave, as presented in Table 5.…”

“…The pulmonary manifestations of COVID-19 are well recognized, but COVID-19 is associated with deleterious effects on many other organ systems. The liver is the second most common organ affected after the lung [1]. While it is now widely established that acute kidney injury (AKI) is an important complication of SARS-CoV-2 infection, there is marked variability in its reported incidence.…”

Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre

“…COVID-19 death predictors have been extensively evaluated in large databases all over the world, with age being the most important factor along with male sex, number of preexisting diseases, and many comorbidities like cardiovascular and/or cerebrovascular, obesity, diabetes, and dementia [ 11 , 38 , 39 , 40 , 41 , 42 ]. Fortunately, even in immunocompromised patients, SARS-CoV-2 infection severity was much lower in the Omicron wave compared with the previous waves, as demonstrated by the WHO ISARIC UK prospective cohort study [ 43 ].…”

“…Low albumin is a marker of severity and poor outcomes [ 9 ]. The incidence of acute or acute-on-chronic liver failure (ACLF) in COVID-19 patients with chronic liver disease (CLD) was widely reported (10% to 50%), with a high mortality rate of up to 65% [ 10 , 11 , 12 ]. Patients with a SARS-CoV-2 infection may develop hepatic manifestations due to direct viral action, drug-induced liver injury (DILI), hyperinflammation, the hypoxic-ischemic mechanism [ 12 , 13 ], or exacerbation of associated liver disease; yet, it has not been possible to separate the impact of each mechanism [ 5 ].…”

Insight into COVID-19 associated liver injury: Mechanisms, evaluation, and clinical implications

“…Similarly, chronic hepatitis C (HCV) patients with COVID-19 are more prone to hospitalization but not at a higher risk of death. [ 46 ] The results of a comprehensive meta-analysis by Hariyanto et al [ 47 ] have also shown an association of viral hepatitis with severe COVID-19. COVID-19 can reactivate or cause a sudden increase in HBV DNA levels in the blood, hepatitis failure, and flare of acute hepatitis in patients with chronic HBV.…”