THE DISCREPANCY BETWEEN GGT AND ALKALINE PHOSPHATASE IN COVID-19 PATIENTS: CHOLESTASIS OR DISEASE SEVERITY?

Introduction

COVID-19 patients with abnormal liver tests, especially ALT and AST, are at higher risk of progressing to severe disease. There is a discrepancy between gamma glutamyl transferase (GGT) and alkaline phosphatase elevation (ALP) in COVID-19 patients. We hypothesized that elevated GGT at admission in COVID-19 patients is independently associated with disease severity and adverse outcomes.

Methods

We studied 232 patients with confirmed symptomatic COVID-19 who were consecutively hospitalized in the first half of March 2021 in our hospital in Qatar. We categorized them into three groups; borderline if GGT was normal or less than twice the upper limit of normal (ULN), mild if elevated 2-5 times, and moderate if more than five times the ULN. The primary outcome was mortality, and secondary outcomes were disease severity on presentation and intensive Care Unit (ICU) admission. The Medical Research Centre of Hamad Medical Corporation approved the study.

Results

Patients with moderate GGT elevation were not different in age, BMI, gender distribution, Charlson comorbid index, transaminase levels, albumin, and bilirubin levels but had elevated ferritin and LDH levels. For ALP levels, 75% of the patients had normal levels, 18% had borderline elevation (less than twice the ULN), and the remaining had mild elevation (2x -5x). In univariate analysis, COVID-19 patients with moderate GGT elevation had higher mortality (p = 0.006) and more severe disease at presentation (p=0.003), but no statically increased risk of ICU admission and requirement of mechanical ventilation. In multivariate regression analysis, patients with moderate GGT elevation remained at increased risk of mortality odds ratio (OR) 3.09 (C.I. 1.1-9.67 p = 0.04) and severe disease at presentation OR 1.57 (C.I.1.2 – 2.65 p=0.048).

Conclusions

In COVID-19 patients, the moderate elevation of GGT at presentation is an independent predictor of disease severity and increased mortality. Elevated GGT levels are a marker of disease severity rather than cholestasis in COVID-19 patients.