Introduction
Liver damage is often observed in COVID-19 patients, especially in severe cases. It may be caused by a systemic inflammatory response, cytokine storm, immune dysregulation, hypoxemia, multiorgan dysfunction syndrome , and the use of COVID-19 drugs (1). Abnormal liver function tests were observed in up to 52% of COVID-19 patients (2). Ursodeoxycholic acid (UDCA) inhibits the production of pro-inflammatory cytokines involved in the cytokine storm development. Thus, it may be beneficial in restoring liver function in patients with COVID-19 and hepatic injury
Aims & Methods
This non-interventional prospective study aimed to evaluate efficacy and safety of UDCA in adult patients with signs of liver damage and COVID-19 infection.
140 patients (mean age 67,43 ± 14,40; 67 males) with laboratory-confirmed COVID-19 and hepatic injury were enrolled, 93% of them had moderate COVID-19. Hepatic injury referred to elevated level of at least one of the following parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) or total bilirubin. UDCA was prescribed to 70 patients for up to 2 months. The control group comprised of 70 patients with COVID-19 and hepatic injury who were not prescribed UDCA
Results
At baseline, both ALT and AST levels were elevated above the upper limit of normal (ULN) dualfold in 25% of patients of the total population, by three-fold in 20%. Isolated elevation of ALT by more than 2-3 times above the ULN was observed in 31% of patients, isolated elevation of AST – in 8%. Hepatocellular liver injury was diagnosed in 62.85% of patients in the UDCA group and 57.14% in the control. Mean ± standard deviation (SD) ALT levels at baseline were 79.44 ± 81.43 and 66.98 ± 32.34 IU/L in the UDCA and control groups, respectively (not significant, NS). On day 10, the ALT levels were 45.75 ± 39.17 and 69.72 ± 64.99 IU/L (p = 0.002 between the groups), on day 60 – 17.39 ± 7.61 and 21.59 ± 9.14 IU/L (p = 0.011). Mean AST levels at baseline were 82.57 ± 97.12 and 62.24 ± 50.77 IU/L in the UDCA and control groups, respectively (NS), a significant difference between the groups was noted on day 60: 17.39 ± 7.42 and 22.68 ± 7.62 IU/L respectively (p < 0.001). A significantly lower ALP and total bilirubin levels were observed in the UDCA group compared to control on day 60 (ALP: 57.49 ± 27.91 vs. 74.09 ± 21.85 IU/L, p < 0.001; total bilirubin: 10.32 ± 3.60 vs. 15.03 ± 10.34 µmol/L, p < 0.001). GGT levels were similar in both groups on all visits.
At baseline, hepatomegaly was observed onsonography in 48,57% and 51,43% (NS) of patients in the UDCA and control groups, respectively. By day 60 hepatomegaly remained in only 21,43% patients in the UDCA group but in 48,57% in the control group (p < 0.001 between the group). Biliary dyskinesia was initially observed in 24,29% and 27,14% of patients in the UDCA and control groups respectively, by day 60 it persisted in 1,43% and 15,71% of patients, respectively (p = 0.007). Positive dynamics on ultrasound and normalization of liver size during treatment were observed in 60.0% of patients in the UDCA group and 7.1% in the control group, while negative dynamics were observed in 0% and 25.7% of patients, respectively. No changes were seen in 27.1% and 50.0% of patients, respectively
Conclusion
Oral administration of UDCA to patients with COVID-19 and liver damage demonstrated a faster normalization of liver function, as evidenced by the reduction in elevated levels of ALT, AST, ALP, and total bilirubin, as well as the restoration of liver size.
References
1. Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut. 2023 Sep 1;72(9):1783–94.
2. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061–9.
3. Ko WK, Lee SH, Kim SJ, Jo MJ, Kumar H, Han IB, et al. Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages. PLOS ONE. 2017;12(6):e0180673.
4. Talebian R, Panahipour L, Gruber R. Ursodeoxycholic acid attenuates the expression of proinflammatory cytokines in periodontal cells. J Periodontol. 2020 Aug;91(8):1098–104.
Disclosure
Current study was conducted with the financial support of Binnopharm Group