Liver enzyme elevation and acute liver injury are independently associated with adverse clinical outcomes in patients with COVID-19: A territory-wide cohort study of 1,040 patients in Hong Kong

ABSTRACT

Background: Different degrees of liver injury were reported in patients infected by Coronavirus disease 2019 (COVID-19) It is possibly caused by systemic inflammation and adverse drug reactions in severe COVID-19 patients under different medical treatments However, the impact of liver injury on adverse clinical outcomes remains unclear We aimed to examine the impact of liver injury on clinical outcomes in COVID-19 patients Methods: All COVID-19 patients reported to the Department of Health between 23 January 2020 and 1 May 2020 in Hong Kong were identified using an electronic database managed by Hospital Authority, Hong Kong, and retrospectively studied Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2x upper limit of normal (ULN) (i.e. 80 U/L) Acute liver injury was defined as ALT and/or AST ≥2xULN, with total bilirubin ≥2xULN (i.e. 38 μmol/L) and/or international normalized ratio (INR) ≥1.7. The primary endpoint was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation, and/or death Results: 1,040 COVID-19 patients were identified. Their mean age was 38±18 years, 560 (53 8%) were male, 4 1% and 0 3% had hepatitis B and C virus infection, respectively;53 (5 1%) were admitted to ICU, 22 (2 1%) received invasive mechanical ventilation, and 4 (0 4%) died Among 816 COVID-19 patients who had serial measurement of liver biochemistries, 184 (22 5%) had ALT/ AST elevation and 15 (1 8%) had acute liver injury Acute liver injury was more common in patients who had hepatitis B/C virus infection than those who did not have (9 4% vs. 1 8%, P=0 026) ALT/AST elevation (adjusted odds ratio [aOR] 7 92, 95% CI 4 14-15 14, P<0 001) and acute liver injury (aOR 6 40, 95% CI 1 78-23 07, P=0 005) were independently associated with development of primary endpoint (Table) Use of lopinavirritonavir ± ribavirin + interferon beta (aOR 1 94, 95% CI 1 20- 3 13, P=0 006) and corticosteroids (aOR 3 92, 95% CI 2 14- 7 16, P<0 001) were independently associated with ALT/AST elevation Use of corticosteroids was associated with acute liver injury (aOR 4 76, 95% CI 1 56-14 50, P=0 006), while all 15 patients who developed acute liver injury also usedlopinavir-ritonavir ± ribavirin ± interferon beta Conclusion: ALT/AST elevation and acute liver injury were independently associated with adverse clinical outcomes in COVID-19 patients Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids were associated with ALT/AST elevation and acute liver injury in COVID-19 patients.