Implications Of COVID-19 On The Liver In Healthy And Diseased States
While lung lesions have been considered as the major damage caused by SARS-CoV-2 infection, liver injury has also been reported to occur during the course of the disease in severe cases.
Recent studies on Covid-19 have shown that the incidence of liver injury ranged from 14.8 – 53%, mainly indicated by abnormal ALT/AST levels accompanied by slightly elevated bilirubin levels.
A case control study of electronic health records of 62.2 million patients (age >18 years) in US has reported that patients with chronic liver disease (CLD) were at significantly increased risk for Covid-19 compared with patients without CLD, with the strongest effect in patients with chronic non-alcoholic liver disease and non-alcoholic cirrhosis, followed by chronic hepatitis C, alcoholic liver damage, alcoholic liver cirrhosis and chronic hepatitis B. Furthermore, patients with Covid-19 and a recent encounter for CLD had a death rate of 10.3% (vs 5.5% among Covid-19 patients without CLD) and hospitalization rate of 41.0% (vs 23.9% among Covid-19 patients without CLD) (1).
Hospitalization and death rates in Covid-19 patients with or without chronic liver disease (CLD) [Adapted from Wang 2021]
Several possible mechanisms of liver injury:
(i) SARS-CoV-2 binds to hepatic cells containing ACE2 receptor leading to active viral replication
SARS-CoV-2 enters cells through the ACE2 molecule, which is abundantly expressed in the liver and, in particular, in bile epithelial cells. Based on this expression, the liver is a potential target for direct infection with this virus .
(ii) Covid-19 drug-induced liver injury
An increasing number of drugs, including Remdesivir, was associated with an increase in liver enzymes in one published report. Drugs could activate the endoplasmic reticulum stress pathway in the liver and induce hepatocyte apoptosis through the caspase cascade system and induce inflammatory reactions and oxidative stress by accelerating liver damage .
(iii) Localized & Systemic Inflammatory Responses
The massive release of cytokines by the immune system in response to the viral infection can result in a cytokine storm and symptoms of sepsis that are the cause of death in 28% of fatal COVID-19 cases. In these cases, uncontrolled inflammation induces multiorgan damage leading including liver failure. Biomarkers of inflammation, such as C-reactive protein (PCR), serum ferritin, LDH, d-dimer, IL-6, IL-2, are have been found to be significantly elevated in critically ill patients with COVID-19 .
(iv) Congestive hepatopathy may occur as a consequence of an acute cardiomyopathy
Cardiomyopathy is a well-described consequence of Covid-19, which was reported in 33% of individuals in one recent study. Thus, the cardiac dysfunction and hepatic congestion from venous outflow obstruction and resulting hypertension and decreased oxygen delivery from an impaired cardiac output contribute to hepatic injury in severe Covid-19 infection .
Mechanisms of Covid-19 associated liver injury [Adapted from Zhong 2020]
Hepatoprotective Vitamin & Supplement
1. Vitamin D
Studies have shown that vitamin D could reduce liver inflammation by reducing the secretion of pro-inflammatory cytokines as well as improving adipose tissue oxidative stress and inflammatory parameters. Besides that, vitamin D exert its anti-fibrogenic effect on hepatic cells via vitamin D receptor signaling, inhibiting expression of pro-fibrogenic genes. Furthermore, large numbers of clinical studies documented high incidence of low circulating vitamin D levels in patients with chronic liver disease, establishing the possible influence of low vitamin D levels in the development of liver fibrosis .
2. Omega 3
Omega 3 are known to downregulate sterol regulatory element binding protein 1c (SREBP-1c) and upregulate peroxisome proliferator activated receptor which would favour fatty acid oxidation and reduce steatosis. Omega 3 supplementation in some studies has also shown to be effective for liver fat reduction .
3. Silybum marianum
The natural compound in silybum marianum, silymarin, has been used traditionally to treat hepatic diseases due to its anti-oxidant, anti-inflammatory and anti-fibrotic activities. Inhibition of cyclooxygenase cycle, leukotrienes, and free radical production contribute to its cytoprotective effects in liver. Improvement in ALT, AST, liver function parameters and liver histology have been seen after consumption of silymarin in patients with liver disease .
(i) Powerlife Vitamin D3: Anti-inflammatory and anti-fibrotic
Dosage: Healthy adults - 1 capsule/day
Vitamin D deficiency – 2 capsules / day
Powerlife Vitamin K2D3: Better option for patient with comorbidity of heart/kidney/bones (NOT for individual taking warfarin)
Dosage: 2 capsules/day
Dosage: Healthy adults – 1 softgel/day ; Liver disease patients - 2 softgels/day
(iii) Powerlife Hepapho: Hepatoprotective effect
Dosage: Liver disease patients: 1 capsule/day
Close monitoring on Covid patient liver profile is essential, as well as keeping a healthy liver during this pandemic.
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