Liver function test abnormalities at admission associated with severe course of SARS-CoV-2 infection

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Liver function test (LFT) abnormalities at hospital admission, in particular gamma-glutamyltransferase (GGT) and albumin, were associated with a severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, according to a study published in Gut.

“In our prospective coronavirus disease 2019 (COVID-19) cohort, 58% of patients had LFT abnormalities at the time of hospital admission. Hypoalbuminaemia, in particular in combination with an elevation of aminotransferases or GGT, was [a] highly significant independent risk [factor] for a severe course,” reported Sabine Weber, University Hospital Munich, Munich, Bavaria, Germany, and colleagues.

In a cohort of 217 patients (median age, 63 years) with SARS-CoV-2 infection and without pre-existing liver disease, abnormal LFT at hospital admission was present in 125 (58%) patients, with a predominant elevation of aspartate aminotransferase (AST; 42%), GGT (37%) and alanine aminotransferase (ALT; 27%), while hypoalbuminaemia was observed in 33% of the patients. Of the 217 patients, 36% required treatment in the intensive care unit (ICU) and 32% underwent mechanical ventilation, with a total fatality rate of 14.7%, mostly related to COVID-19.

After adjusting for age, gender and relevant comorbidities, the researchers found that baseline LFT abnormality of any kind was associated with an increased risk for the composite endpoint of ICU admission and/or COVID-19-related death (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.30-4.82; P = 0.006), particularly hypoalbuminaemia (OR, 9.95; 95% CI, 4.40-22.78; P<0.001 ), elevation of AST (OR, 2.54; 95% CI, 1.33 to 4.84; P = 0.005) and ALT (OR, 2.10; 95% CI, 1.07 to 4.11; P = 0.030 ). Meanwhile, elevated levels of AST, ALT, GGT as well as hypoalbuminaemia were also associated with an increased risk for ICU admission with odds ratio ranging from 2.06 to 13.95. On the other hand, hyperbilirubinaemia, although rare at admission, was an independent risk factor for COVID-19-related death (OR, 4.80, 95% CI, 1.14-20.16; P = 0.032).

Further, the researchers noted that when hypoalbuminaemia was combined with elevation of any LFT abnormality, the risk of ICU admission was markedly increased with the highest risk observed for the combination of hypoalbuminaemia and AST (OR, 46.22; 95% CI, 13.33-160.29; P <0.001), followed by the combination of hypoalbuminaemia and GGT (OR, 38.82; 95% CI, 8.31-181.35; P<0.001) and the combination of hypoalbuminaemia and ALT (OR, 20.37; 95% CI, 5.34-77.73; P<0.001). Similarly, hypoalbuminaemia combined with abnormal AST (OR, 42.04; 95% CI, 11.08-159.57; P<0.001), GGT (OR, 26.85; 95% CI, 5.82-123.89; P<0.001) or ALT (OR, 12.39; 95% CI, 3.37-45.54; P<0.001) at admission were a significant independent risk factor for a composite endpoint of ICU admission and/or COVID-19-related death. Meanwhile, when hyperbilirubinaemia and hypoalbuminaemia were combined, the association with COVID-19-related mortality was also increased (OR, 9.64; 95% CI 1.35-68.96; P = 0.024).

“During infection with SARS-CoV-2 liver injury occurs in a relevant proportion of patients. As yet, mainly elevation of aminotransferases has been described, while abnormalities of cholestatic parameters, that is, GGT and alkaline phosphatase were reported less frequently,” the authors wrote. “LFT peak levels correlate with severity and/or outcome in COVID-19 patients. However, the association of baseline LFT abnormalities with the course of the disease has not been prospectively evaluated.”

“We exhibit the impact of hypoalbuminaemia in SARS-CoV-2-infected patients for the first time in a prospective cohort in line with recent retrospective analysis. We found that hypoalbuminaemia on admission correlated strongly with more severe SARS-CoV-2 infections, even after adjusting for other risk factors such as age, gender and relevant comorbidities,” the authors noted. “With a cut-off of 3.55 mg/dL, which is the lower limit of normal in our laboratory institute, albumin could differentiate between less and more severe cases with a sensitivity and specificity of 80%, respectively.”

“Thus, baseline hypoalbuminaemia when combined with other abnormal LFT in particular with abnormal AST or GGT should be regarded as a red flag indicating a more severe course of the disease and could support clinical decisions regarding closer monitoring and intensive care of patients with COVID-19,” the authors added.