To the Editor:
We read with interest the article by Mushtaq et al. 1 Both their study and ours1 , 2 used similar inclusion criteria and the hepatic steatosis index as a surrogate marker for the presence of NAFLD. We found that NAFLD is an independent predictor of disease progression. However, their study showed that when controlled for covariates in multivariate analysis, NAFLD was not a predictor of mortality, disease severity, or markers of disease progression. Mushtaq et al. correctly pointed out the different conclusions may be due to the different criteria used to define COVID-19 disease progression, development of tachypnea and requirement of oxygen supplements in our study as opposed to development of acute respiratory distress syndrome, intensive care unit (ICU) admission, and the need for mechanical ventilation in their study. We chose a less stringent criteria for disease progression because our main purpose was to identify those patients who were absolutely safe to be managed at home or community facilities (no need for supplementary oxygen) as opposed to identifying patients that may require mechanical ventilation or ICU requirement. Zhou et al., using a definition of severe COVID-19 similar to ours, also showed that metabolic dysfunction-associated fatty liver disease (MAFLD) was associated with severe COVID-19 in patients age <60.3 Also, the prevalence of diabetes and hypertension in their NAFLD population were 50% and 42%, respectively, compared with 17.1% and 26.3%, respectively, in our and Zhou et al.'s studies. This may affect the impact of NAFLD in multivariate analysis. We agreed with the authors' suggestion that there is a need to study the outcomes in large scale studies with histologically confirmed cases of NAFLD and COVID-19 disease. Recently, Lax et al. reported hepatic steatosis, involving 50% to 60% of hepatocytes, in all 12 COVID-19 patients with pulmonary embolism on autopsy.4 NAFLD patients had elevated plasma levels of von Willebrand factor and circulating plasminogen activator inhibitor type 1.5 The liver is a frontline immune organ and increased production of pro-inflammatory cytokines by adipose cells and Kupffer cells has been reported in patients with NAFLD.6 We had also observed that the mean admission and peak D-dimer levels were also significantly higher in COVID-19 patients with NAFLD than in those without NAFLD, 0.72 ± 1.10 ug/ml vs. 0.38 ± 0.46 ug/ml, p = 0.003 and 1.81 ± 4.1 mg/ml vs. 0.63 ± 0.41 mg/ml, p = 0.003 respectively. Therefore, the likelihood of activation of the coagulation cascade by pro-inflammatory cytokines, and subsequent thrombosis, may be higher in COVID-19 patients with underlying NAFLD. This NAFLD-associated hypercoagulable state may contribute to disease progression in COVID-19.
Financial support
This work is funded by the Capital Characteristic Clinic Project of Beijing Municipal Science and Technology Commission (Z181100001718034).
Authors' contributions
DJ and GC wrote the manuscript; GL provided guidance and proof-read the manuscript; all authors revised and approved the final version.
Conflict of interest
The authors declare no conflicts of interest that pertain to this work.
Please refer to the accompanying ICMJE disclosure forms for further details.
Acknowledgments
We acknowledge all patients and health-care workers involved in the diagnosis and treatment of patients with COVID-19 in our hospitals.
Footnotes
Author names in bold designate shared co-first authorship
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jhep.2020.10.020.
Supplementary data
References
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