Key points
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Infections with new genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose an ongoing threat to both infected patients and healthcare systems. In what represents the largest global health crisis since the 1918 flu pandemic, around 766 million confirmed COVID-19 infections have led to a staggering 6.9 million deaths worldwide.
In recent months, the severity of individual cases has eased due to the spread of the highly contagious but less clinically consequential omicron variant, as well as increased (repeat) immunization rates. The need to analyze both the dynamics of the pandemic and individual risk profiles to protect potential high-risk patients remains essential.
Numerous studies have identified advanced age, underlying respiratory diseases, impaired renal function, cardiovascular disease, obesity, type 2 diabetes mellitus, and immunosuppression as risk factors for disease progression, hospitalization, and deaths from COVID-19. Unfortunately, the COVID-19 pandemic is intersecting with a steady increase in the prevalence of metabolic syndrome (i.e., obesity, diabetes, hypertension, dyslipidemia, or hyperlipidemia) and nonalcoholic fatty liver disease (NAFLD). In fact, the new nomenclature of ’metabolic dysfunction-associated steatotic liver disease’ (MASLD) requires the presence of ≥ 1 characteristic cardiometabolic comorbidity in individuals with fatty liver to establish the diagnosis.
Background and objectives
Nonalcoholic fatty liver disease ( NAFLD) and nonalcoholic steatohepatitis (NASH) are potential risk factors for severe pneumonia and other infections. Available data on the role of NAFLD/NASH in worsening COVID-19 outcomes are controversial and could be confounded by comorbidities.
Methods
We used PINC AI™ Health Data Special Release (PHD-SR) to identify patients with COVID-19 (ICD-10) in approximately 900 hospitals in the United States.
We performed exact matching (age, gender, and ethnicity) for patients with or without NAFLD/NASH, adjusting for demographics (admission type, region) and comorbidities (e.g., obesity, diabetes) using inverse probability weighting of treatment and then we analyze the hospitalization with the related outcomes.
Results
Among 513,623 patients with SARS-CoV-2 (COVID-19), we identified 14,667 with NAFLD/NASH who could match 14,667 controls. The mean age was 57.6 (±14.9) years, 50.8% were women, and 43.7% were non-Hispanic white.
After matching, baseline characteristics (e.g., age, ethnicity, and gender) and comorbidities (e.g., hypertension, obesity, diabetes, and cardiovascular disease) were well balanced (standard difference (SD) <0. 10), except cirrhosis and malignant neoplasms.
Patients with COVID-19 and NAFLD/NASH had higher FIB-4 scores, significantly longer length of hospital stay (LOS) and intensive care stay than controls (9.4 vs. 8.3 days and 10.3 days). 4 vs. 9.3, respectively), even after adjustment for cirrhosis and malignancy.
Patients with COVID-19 and NAFLD/NASH also had a significantly increased risk of requiring invasive mandatory ventilation (IMV) (odds ratio 1.0727; 95% CI 1.0095–1.1400). Other results were similar in both groups.
Conclusions
In this large real-world cohort of patients hospitalized with COVID-19 in the United States, NAFLD/NASH were obesity-independent risk factors for complicated disease courses.
Discussion
Our findings confirm that patients hospitalized and coded with COVID-19 and hepatic steatosis require longer periods of hospitalization, longer ICU stays, and more use of mechanical ventilation (MIV), even after adjusting for comorbidities such as obesity, hypertension, diabetes or cardiovascular diseases while also assuming the underdiagnosis of NAFLD/NASH and the limitation of a significant number of NAFLD cases in the control cohort. As a relevant number of NAFLD/NASH cases could have been included in the control cohort, we performed a FIB-4 analysis and believe that the level of fibrosis may play an important role in transmitting susceptibility.
Interestingly, this was not associated with increased mortality or readmission, possibly due to better treatment options. A recent meta-analysis of 18 studies reported that NAFLD was a risk factor for severe COVID-19 in younger patients (<60 years), but not in older patients >60 years.
