Longitudinal Association Between Markers of Liver Injury and Mortality in COVID‐19 in China

Abstract

Background and Aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon co morbidities. Its pro le in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Methods: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with con rmed COVID-19. Result: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR=2.1(1.1-3.7), p=0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR=8.1(1.9-38.8), p=0.002) predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5(11.6%)] or acute decompensation [4(9%)]. Liver related complications increased (p<0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC-0.94, HR=19.2(95CI 2.3-163.3), p<0.001, sensitivity 85.7% and speci city 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis. Conclusions: SARS-Cov-2 infection causes signi cant liver injury in CLD patients, decompensating one fth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Predictors of mortality in patients with coronavirus disease 2019: a systematic review and meta-analysis

“…In a large-sample longitudinal study evaluating 5771 patients with COVID-19 infection, elevation of AST was correlated with the highest mortality risk compared to other markers of liver injury, such as ALT, TBIL and alkaline phosphatas. In addition, the elevation of AST occurred before the elevation of ALT [55]. These ndings indicate that AST may be a better liver injury marker for predicting clinical outcomes than the other markers, and frequent monitoring of AST and early detection of liver injury are suggested.…”

High Aspartate Aminotransferase to Alanine Aminotransferase Ratio on Admission as Risk Factor for Poor Prognosis in COVID-19 Patients

“…Among a variety of recent publications about COVID-19, accumulated evidence suggests that SARS-CoV-2 infections might cause multiple and systemic injuries, including acute renal failure, myocardial dysfunction, and acute liver injury 20,24,25 . Additionally, there are recent studies analyzing COVID-19 patients in detail with respect to liver enzymes, such as ALT and AST 20,26 . The underlying mechanism of elevated liver enzymes in COVID-19 patients remains unclear.…”

“…Several studies have suggested that ACE2 is possibly expressed in the liver 14,27,28 and might serve as the entry point for SARS-CoV-2 virus to the liver. Additionally, elevated liver enzymes may also be associated with hypoxemia and systemic in ammation response 20 . However, the relationship between COVID-19 and AST/ALT ratio was still not revealed.…”

“…To assess the AST/ALT ratio on poor prognosis of patients with different liver enzyme levels 20 , we separated the COVID-19 patients into two groups according to their AST levels (≤ 40 or > 40 U/L) on admission ( Table 5). Of the patients with normal liver enzyme levels and AST/ALT < 2 (n = 420), 42 (10%) patients had poor prognosis, while of the patients with AST/ALT ≥ 2 (n = 40), 11 (27.5%) patients had poor prognosis (crude OR = 3.4; 95% CI [1.6-7.4]; P = 0.002).…”

“…Clinical studies have reported that approximately 20%-30% of COVID-19 patients have liver dysfunction, which is represented by elevated levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 8,19 . Although higher AST levels are likely to associate with death in COVID-19 patients 20 , there is still a lack of clinical studies on AST/ALT ratio to predict disease course in COVID-19 patients. In addition to individual values of ALT and AST, the AST/ALT ratio has been explored as an important indicator for assessing liver diseases.…”