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  The Liver Meeting
Digital Experience
November 13 - 16 - 2020
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Abnormal Liver Tests at COVID Hospitalization Tied to Severe Disease, Death
  AASLD The Liver Meeting Digital Experience, November 13-16, 2020
Mark Mascolini
An abnormal liver function test upon hospital admission for COVID-19 boosted chances of severe COVID-19 and death in a 1611-person 11-country Latin American study [1]. These associations held true in people without diagnosed chronic liver disease. Liver test changes were usually mild but affected 45% of study participants.
Clinicians have diagnosed COVID-19 in more than 8 million people in Latin America. An international team who conducted this study noted that 1 in 5 people with COVID-19 had abnormal liver function test results in a systematic review. But little is known about how abnormal liver test results affect COVID-19 outcomes.
To address that question, the authors designed a prospective observational study of people at least 17 years old and admitted to the hospital with SARS-CoV-2 detected by PCR from April 15 through July 31, 2020 [2]. Follow-up continued until hospital discharge or death. The researchers defined abnormal liver function as total bilirubin, alanine aminotransferase (ALT), or alkaline phosphatase above the upper limit of normal.
Death from any cause was the primary outcome. The investigators used multivariable logistic regression to pinpoint variables independently associated with that outcome and with development of severe COVID-19.
Researchers identified 1611 people admitted to the hospital with COVID-19 in 40 institutions in 11 countries. While 1421 (88.2%) of these people had no liver disease, 135 (8.4%) had chronic liver disease, and 55 (3.4%) had cirrhosis. The entire study group averaged 52.3 years in age (+/- 17.4) and 58% were men. The most frequent comorbidities were hypertension (29.9%), diabetes (17.7%), obesity (17.2%), and cardiovascular disease (6.7%). One in 5 people used tobacco.
At hospital admission, 729 people (45.2%) had an abnormal liver function test. Among the 35.3% with elevated ALT, 11% had a reading more than 5 times the upper limit of normal (severe), 33% were 2 to 5 times the upper limit of normal (moderate), and 57% under 2 times the upper limit of normal (57%).
Compared with 882 people who had normal liver function test results, 729 with abnormal readings were significantly older (average 54.2 vs 50.7 years, P = 0.0001), more likely to be men (63.6% vs 52.9%, P < 0.0001), more likely to take antibiotics (14.9% vs 8%, P < 0.0001), and more likely to have chronic liver disease (13.4% vs 4.4%, P < 0.0001), cirrhosis (5.5% vs 1.7%, P < 0.0001), hypertension, diabetes, or obesity. Cerebrovascular disease was more frequent in people with normal liver function tests (2.8% vs 1.1%, P = 0.03). C-reactive protein, an inflammation marker, was twice higher in people with abnormal liver tests (average 68.7 vs 32.6 mg/dL, P < 0.0001).
Compared with the normal liver function test group, significantly higher proportions with abnormal function tests received steroids (41% vs 22%, P < 0.0001), antibiotics (71% vs 41%, P < 0.0001), low molecular weight heparin (51% vs 37%, P < 0.0001), hydroxychloroquine (32% vs 22%, P < 0.0001), and the antiparasitic ivermectine (9% vs 5%, P = 0.001). People with normal liver function tests received the immunosuppressant tocilizumab significantly more often than those with an abnormal result (4% vs 2%, P = 0.02).
Major clinical outcomes all affected significantly higher proportions of people with abnormal liver test results, including pneumonia, severe acute respiratory distress syndrome, multiple organ failure, and bacterial infection (P < 0.0001 for all comparisons). Significantly higher proportions of the abnormal liver function group went to the intensive care unit (30% vs 17%) and required intubation (24% vs 13%), hemodialysis (5% vs 3%), or vasopressors (17% vs 8%) (P < 0.0001 for all comparisons).
Severe COVID-19 proved significantly more frequent in people with abnormal liver test results than in the normal group (58% vs 32%, P < 0.0001), as did death (19% vs 12%, P < 0.0001).
Adjusted logistic regression determined that people with abnormal liver tests had a 40% higher risk of all-cause mortality than did the normal-liver group (adjusted odds ratio [aOR] 1.4, 95% confidence interval [CI] 1.06 to 1.9, P = 0.02). This analysis also determined that the abnormal liver group had significantly higher odds of pneumonia (aOR 2.3, 95% CI 1.6 to 3.2, P < 0.0001), obesity (aOR 1.4, 95% CI 1.02 to 2.1, P = 0.04), and diabetes (aOR 1.6, 95% CI 1.1 to 2.2, P = 0.007). People with abnormal liver function results were 50% more likely to be men than women (aOR 1.5, 95% CI 1.1 to 2.1, P = 0.006) and more likely to be 50 to 65 years old (vs under 50) (aOR 1.8, 95% CI 1.2 to 2.8, P = 0.003) or older than 65 (aOR 5.4, 95% CI 3.7 to 8.0, P < 0.0001).
Participants with severe ALT elevation (more than 5 times the upper limit of normal) had a doubled risk of death compared with people with normal ALT (aOR 2.0, 95% CI 1.1 to 3.7, P = 0.026). In an analysis excluding people with chronic liver disease or cirrhosis at hospital admission, abnormal liver test results still independently raised odds of all-cause mortality 50% (aOR 1.5, 95% CI 1.2 to 2.0, P = 0.01). In a similar analysis excluding people with those diagnoses at admission, abnormal liver tests more than doubled the odds of severe COVID-19 (aOR 2.6, 95% CI 1.9 to 3.3).
The researchers believe their results suggest the liver may be another target of the cytokine storm seen with uncontrolled COVID-19. They proposed that inexpensive and accessible liver function tests may be a useful tool to predict development of severe COVID-19 in people who require hospital admission.
1. Mendizabal M, Ridruejo E, Piņero F, et al. Abnormal liver function tests on admission are associated with increased mortality in hospitalized patients with COVID-19: preliminary results from a large Latin American cohort. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 107.
2. ClinicalTrials.gov. Liver injury in patients with COVID-19. ClinicalTrials.gov identifier NCT04358380. https://clinicaltrials.gov/ct2/show/NCT04358380