Fatty liver disease may increase risk of severe COVID-19 disease

Keith Alcorn
Published:
27 April 2020
Image: Bru-nO/Pixabay

A preliminary analysis of people admitted to hospital in China with COVID-19 symptoms shows that people with non-alcoholic fatty liver disease (NAFLD) were six times more likely to progress to severe COVID-19 illness than people without NAFLD and remained potentially infectious for longer, Chinese researchers report in the Journal of Hepatology.

COVID-19 is the disease caused by SARS-CoV-2, the new coronavirus identified in China in January 2020. SARS-CoV-2 causes a spectrum of clinical illness ranging from mild symptoms (cough, fever) to severe pneumonia, lung damage and death.

People with pre-existing health conditions including chronic kidney disease, cardiovascular disease and chronic obstructive pulmonary disease are at higher risk of developing serious illness that requires hospital admission and ventilation.

Whereas early concerns about the effects of underlying conditions on COVID-19 outcomes focused on respiratory conditions such as chronic obstructive pulmonary disease and asthma, attention has shifted to cardiovascular disease, obesity, diabetes and chronic kidney disease as more is learnt about the interaction between underlying inflammation, vascular disease and severe COVID-19 illness.

The impact of underlying liver disease on COVID-19 outcomes is still unclear. Preliminary analysis of Chinese cases published in March 2020 did not show a high prevalence of liver disease among people admitted to hospital with COVID-19 symptoms.

But that analysis did not differentiate between causes of liver disease. NAFLD is often accompanied by metabolic syndrome and obesity and so might lead to worse outcomes than other forms of liver disease.

It’s also unclear if SARS-CoV-2 causes liver injury in the same way as some other respiratory viruses, in which virus-specific effector T-cells damage liver cells.

Researchers at two hospitals designated for care of COVID-19 patients in Beijing and Fuyang have now reported on liver injury and underlying liver health in patients admitted to hospital with confirmed SARS-CoV-2 infection between 20 January and 18 February 2020.

A total of 202 patients had confirmed infection (55% male, median age 44 years, 83% with moderate symptoms and 14% with severe or critical illness). One hundred and one had liver injury, defined as ALT > 30 IU/l in men and > 19 IU/l in women, or elevated liver enzymes and ductular enzymes.

Thirty-seven per cent had NAFLD and 23% had at least one underlying co-morbidity (hypertension, diabetes, cardiovascular disease, chronic lung disease or HIV).

Thirty-nine experienced progression of illness after admission to hospital, defined as one of: increase in respiratory rate above 30 breaths a minute, oxygen saturation reduced below 93%, worsening lung X-ray findings or PaO2/Fi02<300mmHg.

People with NAFLD, or underlying co-morbidities were significantly more likely to experience worsening of illness after admission (p < 0.001), as were older people and people with higher body mass index (p < 0.001). People admitted with severe symptoms were also more likely to suffer worsening symptoms.

People with NAFLD also had a longer viral shedding period after admission to hospital (17 vs 12 days), suggesting that the condition increases the duration of infectiousness.

Multivariate analysis showed that people with NAFLD were at least six times more likely to progress (odds ratio 6.4, 95% CI 1.5-31.2) and underlying co-morbidity was associated with a similar increase in risk (OR 6.3, 95% CI 2.3-18.8). Male sex (OR 3.1, 95% CI 1.1-9.4) and age over 60 years (OR 4.8, 95% CI 1.5-16.2) were also associated with progression.

NAFLD was also associated with a higher frequency of liver injury (abnormal liver function during hospitalisation) (70% vs 11%), although liver enzyme increases were mild to moderate. A postmortem liver biopsy in one patient who died showed no evidence of the cytopathic damage reported in cases of other respiratory viruses.

The study authors say that NAFLD may promote a pro-inflammatory environment in the liver, impairing innate immunity and leading to more severe COVID-19 illness.

Reference

Dong J et al. Implication of non-alcoholic fatty liver diseases (NAFLD) in patienst with COVID-19: a preliminary analysis. Journal of Hepatology, https://doi.org/10.1016/j.jhep.2020.03.044