key: cord-0906382-izkhcygc
authors: Philips, Cyriac Abby; Ahamed, Rizwan; Augustine, Philip
title: SARS-CoV-2 related liver impairment – perception may not be the reality
date: 2020-05-23
journal: J Hepatol
DOI: 10.1016/j.jhep.2020.05.025
sha: 5f94eacb28871fe42e1da525d8ba8239133893dc
doc_id: 906382
cord_uid: izkhcygc

nan

The authors associate very minimal elevations in alanine (ALT) and aspartate aminotransferase (AST; ALT > AST) to disease severity and demonstrate 'specific' findings of Covid-19 related cytopathic changes and virus-like particles on post-mortem liver histopathology (n=2).They found that SARS-Cov-2 caused massive apoptosis and binucleation of hepatocytes, resulting in liver enzyme abnormality and synthetic liver dysfunction, the latter in the form of hypoalbuminemia. Their painstaking work is commendable, but the perception and surmise of clinical and investigational events may not be quite the reality. It is recommended that the ideal cut-off for diagnosing acute hepatic injury is 200 U/L and 300 U/L for AST and ALT respectively. (2) The degree of elevation in AST and ALT in the current study can only be considered an 'altered' liver test, not akin to acute hepatic injury. In hepatic impairment, there must be very clear evidence for metabolic (hypoglycaemia, hyperammonemia), secretory (hyperbilirubinemia) and synthetic (hypoalbuminemia, raised prothrombin time) dysfunction. Except for a mild rise in ALT and hypoalbuminemia, significant liver dysfunction is elusive in the current study. Importantly, hypoalbuminemia, in the absence of other significant liver test abnormalities, virtually rules out the hepatic origin of this abnormality. Acute liver injury is best identified by international normalized ratio (INR) >2.0 which was conspicuously absent in the current study. (3) The liver biopsy findings of hepatocyte apoptosis, binuclear or occasional multinuclear syncytial hepatocytes, in the absence of viral inclusions and presence of moderate steatosis, with mild focal lobular or portal inflammation are non-specific findings that may not be related to viral cytopathy.

These findings can be undoubtfully seen in sepsis and multi-organ dysfunction associated with critical illness (moderate to severe apoptosis, steatosis, lobular and portal inflammation) and aging, sepsis, drug-induced liver injury and fatty liver disease (binucleation or polyploidy-a feature of liver cell renewal and not injury). (4, 5, 6) The liver biopsy does not correlate with increased gammaglutamyl transpeptidase, which could have been secondary to the systemic illness or drug toxicity. drug-induced liver injury. (8, 9) . In non-hepatotropic viral infection, such as cytomegalovirushepatitis, the liver involvement occur as part of the disseminated systemic disease or secondary organ dysfunction that could be true for the SARS-CoV-2.(10) To conclude, even though intriguing, the study by Wang et al. might have suffered unintentional, but unfounded assumptions of SARS-CoV-2 related liver injury. Hepatic impairment is not confirmed, and multiple viral cytopathic effects described on liver histology may be misleading in presence of high age and multiple comorbidities.

The use of 'Covid-19 induced liver injury' may be illusory, and its use needs caution. Current research has not confirmed direct SARS-CoV-2 related liver injury, and the features described may only suggest hepatic involvement of severe systemic inflammatory disease with or without sepsis driven by Covid-19.

SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19

Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring

The natural history of severe acute liver injury

Liver histology in ICU patients dying from sepsis: a clinicopathological study

Hepatocyte polyploidization and its association with pathophysiological processes

Pathological polyploidy in liver disease

Macrophage Phenotype and Function in Liver Disorder

Hepatic cholesterol crystals, and crown-like structures distinguish NASH from simple steatosis

Central role of mitochondria in drug-induced liver injury

Role of non-hepatotropic viruses in acute sporadic viral hepatitis and acute-on-chronic liver failure in adults