Changes in zonulin levels and possibilities for its correction in patients with liver cirrhosis and hepatic encephalopathy after COVID-19

Abstract

Background. The liver is frequently affected in coronavirus disease 2019 (COVID-19), which can range from a simple increase in transaminase levels to the development of acute liver failure. The study of the peculiarities of the course of liver cirrhosis (LC) and its complications, especially hepatic encephalopathy (HE), in COVID-19 and the study of possible markers indica­ting the progression of the disease and the development of effective methods for their correction is an urgent task today. Aim of the research: to study the features of changes in serum and faecal zonulin levels and its dynamics in patients with LC and HE after COVID-19 on the background of a comprehensive therapy with a butyric acid preparation. Materials and methods. The study was conducted in two stages. At the first stage, 126 patients with LC were examined to determine the features of HE course, colonic dysbiosis, and zonulin levels in blood serum and faeces at discharge from the hospital after COVID-19, as well as after 1 month of outpatient follow-up. At the second stage of the study, patients with LC and HE after COVID-19 were divided into two groups depending on the treatment: group I (n = 56) received only basic therapy for LC, which included constant use of the β-blocker bisoprolol, lactulose, as well as a combined hepatoprotective agent, melatonin and rifaximin; group II (n = 70) in addition to basic therapy took a combined probiotic preparation containing butyric acid. Results. During the first month after COVID-19, progression of the HE severity was diagnosed in patients with LC. Among participants with LC classes B and C, an increase in the number of patients with grade II HE (up to 57.2 and 72.2 %, respectively) was found a month after COVID-19, and in 16.7 % of patients with decompensated LC, grade III HE was diagnosed. Colonic dysbiosis progression was detected in patients with LC and HE after COVID-19. In one month of the follow-up, a repeated microbiological exami­nation of faeces revealed a significant increase in the number of patients with LC and HE after COVID-19 with grade III colonic dysbiosis, regardless of the stage of the disease, which, accordingly, occurred against the background of a decrease in patients with grade I and II colonic dysbiosis. Among patients with LC and HE after COVID-19, a significant increase in serum and faecal zonulin was found with maximum values in patients with class C according to the Child-Pugh score, which also tended to increase during the first month of observation (up to (171.4 ± 2.2) ng/ml in serum and up to (198.2 ± 3.4 ng/ml) in faeces). The administration of a probiotic complex containing butyric acid contributed to a decrease in both blood and faecal zonulin levels in patients with LC and HE after COVID-19 during a one-month course of treatment. Conclusions. In patients with LC after COVID-19, a progression of HE and colonic dysbiosis severity was diagnosed during the first month of outpatient follow-up. Participants with LC and HE after COVID-19 reported an increase in the level of zonulin in the blood serum and faeces (up to (102.7 ± 1.4) ng/ml, p < 0.01, and up to (131.4 ± 2.6), p < 0.001, respectively), which tends to increase depending on the progression of the disease severity. Comprehensive therapy with the use of a drug containing butyric acid is an effective method to reduce the level of blood and faecal zonulin in patients with LC and HE after COVID-19.

Keywords

• liver cirrhosis
• hepatic encephalopathy
• covid-19
• zonulin
• colonic dysbiosis
• treatment