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Clinical Characteristics and Outcomes of Coronavirus Disease 2019 Among Patients with Preexisting Liver Disease in the United States: A Multicenter Research Network Study

Our take —

This retrospective cohort study from the early phase of the pandemic (January-April 2020) showed that signs of new onset liver injury were common across US patients with COVID-19 disease, and patients with preexisting liver disease, especially cirrhosis, were at greater risk for mortality and hospitalization compared to patients without preexisting liver disease. However, these results should be interpreted with caution given probable selection bias and residual confounding.

Study design

Retrospective cohort

Study population and setting

This study used the TriNetX Research Network (Cambridge, MA), which has access to the electronic health records (EHR) of 49 million patients across 37 health care organizations to evaluate the impact of preexisting liver disease on COVID-19 outcomes. TriNetX patients with COVID-19 diagnoses recorded in the EHR according to CDC guidelines between January 20 and April 12, 2020 were included. Preexisting liver disease was defined by ICD-10-CM codes. 1:1 propensity score matching (n=250 per group) was used to control for confounding for the following variables: body mass index, hypertension, diabetes, age, race, and nicotine use. Primary outcomes for this study included mortality, hospitalization, and laboratory findings up to 30 days after diagnosis.

Summary of Main Findings

Among 2780 patients diagnosed with COVID-19 across 34 health care organizations (mean age: 52 years, 49% white, 61% female), 250 (9%) had preexisting liver disease (LD), including 50 with cirrhosis. Among a subset of patients with laboratory values following COVID-19 diagnosis, there existed substantial elevations in liver enzyme values compared to baseline values (most recent results >14 days before COVID-19 diagnosis) including in alanine aminotransferase (ALT) and aspartate alanine aminotransferase (AST) values. ALT elevations of >50 U/L were seen in 46.1% of LD (n=130) and 50.6% of non-LD groups (n=770). AST elevations of >50 U/L were seen in 61.5% and 67.5% of LD and non-LD groups respectively. Similar elevations in markers of liver function and inflammation including gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, ferritin, C-reactive protein, lactate dehydrogenase, interleukin 6, creatinine kinase, and D-dimer were seen in both groups. After propensity score matching, the LD group demonstrated significantly higher risk of mortality (risk ratio [RR]=3.0; 95% confidence interval [CI] = 1.5-6.0) and hospitalization (RR=1.3; 95% CI=1.1-1.6) than the non-LD group. Patients with cirrhosis had an even higher risk of mortality (RR=4.6; 95% CI=2.6-8.3)

Study Strengths

This study included a large and racially diverse cohort of patients cared for across a multitude of U.S. health care centers, increasing the generalizability to those most impacted by severe COVID-19 outcomes across the United States. Propensity matching accounted for some differences between LD and non-LD groups.

Limitations

Due to the use of electronic medical record data early in the COVID-19 pandemic when coding for diagnoses of COVID-19 changed rapidly and reliable testing was not widespread, there is potential for errors in patient selection that bias toward those with severe disease and classic symptoms. Patient counts were also rounded to the nearest 10 for the purpose of analysis, which may affect measures of associations in more infrequent outcomes. Laboratory results before and after COVID-19 diagnosis were not available for most patients, therefore differences in laboratory results may be overestimated, as patients with a more severe course of disease are more likely to receive laboratory testing. As this study was not randomized, confounding cannot be ruled out and residual confounding despite propensity score matching is likely.

Value added

To the best of our knowledge, this study is among the first to substantially investigate the relationship between COVID-19 disease and preexisting or chronic liver disease, and the first to do so in a large cohort.

This review was posted on: 20 November 2020