J Korean Med Sci.  2021 Oct;36(41):e291. 10.3346/jkms.2021.36.e291.

Non-alcoholic Fatty Liver Disease and COVID-19 Susceptibility and Outcomes: a Korean Nationwide Cohort

• Yoo HW
• Jin HY
• Yon DK
• Effenberger M
• Shin YH
• Kim SY
• Yang JM
• Kim MS
• Koyanagi A
• Jacob L
• Smith L
• Yoo IK
• Shin JI
• Lee SW

• KMID: 2521474
• DOI: http://doi.org/10.3346/jkms.2021.36.e291

Abstract

Background
Evidence for the association between underlying non-alcoholic fatty liver disease (NAFLD), the risk of testing severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) positive, and the clinical consequences of coronavirus disease 2019 (COVID-19) is controversial and scarce. We aimed to investigate the association between the presence of NAFLD and the risk of SARS-CoV-2 infectivity and COVID-19-related outcomes.
Methods
We used the population-based, nationwide cohort in South Korea linked with the general health examination records between January 1, 2018 and July 30, 2020. Data for 212,768 adults older than 20 years who underwent SARS-CoV-2 testing from January 1 to May 30, 2020, were obtained. The presence of NAFLDs was defined using three definitions, namely hepatic steatosis index (HSI), fatty liver index (FLI), and claims-based definition. The outcomes were SARS-CoV-2 test positive, COVID-19 severe illness, and related death.
Results
Among 74,244 adults who completed the general health examination, there were 2,251 (3.0%) who were SARS-CoV-2 positive, 438 (0.6%) with severe COVID-19 illness, and 45 (0.06%) COVID-19-related deaths. After exposure-driven propensity score matching, patients with pre-existing HSI-NAFLD, FLI-NAFLD, or claims-based NAFLD had an 11–23% increased risk of SARS-CoV-2 infection (HSI-NAFLD 95% confidence interval [CI], 1–28%; FLI-NAFLD 95% CI, 2–27%; and claims-based NAFLD 95% CI, 2–31%) and a 35–41% increased risk of severe COVID-19 illness (HSI-NAFLD 95% CI, 8–83%; FLI-NAFLD 95% CI, 5–71%; and claims-based NAFLD 95% CI, 1–92%). These associations are more evident as liver fibrosis advanced (based on the BARD scoring system). Similar patterns were observed in several sensitivity analyses including the full-unmatched cohort.
Conclusion
Patients with pre-existing NAFLDs have a higher likelihood of testing SARSCoV-2 positive and severe COVID-19 illness; this association was more evident in patients with NAFLD with advanced fibrosis. Our results suggest that extra attention should be given to the management of patients with NAFLD during the COVID-19 pandemic.

Keyword

COVID-19; SARS-CoV-2; Non-alcoholic Fatty Liver Disease; Hepatic Steatosis Index; Fatty Liver Index; BARD Scoring System

Figure

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  Fig. 1 Study profile.SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, HSI = hepatic steatosis index, FLI = fatty liver index, NAFLD = non-alcoholic fatty liver disease.

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  Fig. 2 Flowchart of the study.SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, COVID-19 = coronavirus disease 2019.

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  Fig. 3 The association between NAFLD and positive SARS-CoV-2 test results, severe COVID-19 illness, and COVID-19-related death in nationwide cohort of South Korea.The x-axis indicates a log-scale; horizontal bars denote 95% CIs for each of the results; and blue dots indicate propensity score matched results. Severe COVID-19 comprised requirement of oxygen therapy, admission to the intensive care unit, invasive ventilation, or death. The figure was generated from our previous research and made further advance.15COVID-19 = coronavirus disease 2019, HSI = hepatic steatosis index, FLI = fatty liver index, NAFLD = non-alcoholic fatty liver disease, OR = odds ratio, CI = confidence interval, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

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