Longitudinal analysis of the utility of liver biochemistry in hospitalised COVID-19 patients as prognostic markers

Background

COVID-19, the clinical syndrome caused by infection with SARS-CoV-2, has been associated with deranged liver biochemistry in studies from China, Italy and the USA. However, the clinical utility of liver biochemistry as a prognostic marker of outcome for COVID-19 is currently debated.

Methods

We extracted routinely collected clinical data from a large teaching hospital in the UK, matching 585 hospitalised SARS-CoV-2 RT-PCR-positive patients to 1165 hospitalised SARS-CoV-2 RT-PCR-negative patients for age, gender, ethnicity and pre-existing comorbidities. Liver biochemistry was compared between groups over time to determine whether derangement was associated with outcome.

Results

26.8% (157/585) of COVID-19 patients died, compared to 11.9% (139/1165) in the non-COVID-19 group (p<0.001). At presentation, a significantly higher proportion of the COVID-19 group had elevated alanine aminotransferase (20.7% vs. 14.6%, p=0.004) and hypoalbuminaemia (58.7% vs. 35.0%, p<0.001), compared to the non-COVID-19 group. Within the COVID-19 group, those with hypoalbuminaemia at presentation had 1.83-fold increased hazards of death compared to those with normal albumin (adjusted hazard ratio [HR] 1.83, 95% CI 1.25-2.67), whilst the hazard of death was ~4-fold higher in those aged ≥75 years (adjusted HR 3.96, 95% CI 2.59-6.04) and ~3-fold higher in those with pre-existing liver disease (adjusted HR 3.37, 95% CI 1.58-7.16). In the COVID-19 group, alkaline phosphatase increased (R=0.192, p<0.0001) and albumin declined (R=-0.123, p=0.0004) over time in patients who died. We did not find a significant association between other liver biochemistry and death.

Conclusion

In this UK population, liver biochemistry is commonly deranged in patients with COVID-19 but only baseline low albumin and a rising alkaline phosphatase over time are prognostic markers for death.

Key Points

• Age ≥ 75 years and low albumin at the time of a positive SARS-CoV-2 RT-PCR test can predict poor clinical outcome in COVID-19 patients.

• Liver biochemistry is more likely to be abnormal in patients with COVID-19 than in patients without COVID-19.

• Patients with COVID-19 who died showed a greater decline in albumin and a greater increase in alkaline phosphatase over time, compared to those who survived.

• Patients with pre-existing liver disease and COVID-19 had an increased mortality.

Lay Summary

We used routinely collected hospital data from a large UK teaching hospital to compare liver biochemistry (markers of liver inflammation or damage) between 585 patients with COVID-19 and 1165 patients of the same age and sex admitted to hospital but without COVID-19. Patients with COVID-19 were more likely to die than those without COVID-19, and deaths were significantly higher in those aged ≥75 years. We found that patients with COVID-19 were more likely to have abnormal liver biochemistry. Low albumin (a blood protein) at the time of being diagnosed with COVID-19 was associated with an increased chance of death.