Cognitive impairment in patients with moderate and advanced liver fibrosis in the background of metabolic dysfunction-associated steatotic liver disease

Objective — to study cognitive impairment in patients with moderate and advanced liver fibrosis due to metabolically associated steatotic liver disease (MASLD) using various cognitive tests, as well as to investigate possible ways to correct such disorders. Materials and methods. A total of 86 patients (43 men and 43 women aged 24 to 55 years) were examined, in whom the diagnosis of MASLD with fibrosis of the 2nd (46 people) and 3rd (40 people) degrees was confirmed. Patients underwent an initial (screening) clinical, psychometric and laboratory examination before the start of treatment, as well as a repeat examination after 1 month. At the beginning of the observation, these patients were randomized into 2 groups, matched by age, gender and severity of clinical manifestations. 43 patients in group 1 received standard recommendations for patients with MASLD, which included advice on lifestyle changes (diet and physical activity). Patients in group 2 (43 people) additionally received Hepamerz (L-ornithine-L-aspartate) 1 sachet (3 g) 2 times a day with meals for 1 month. Non-invasive psychometric tests were used during the study. Each patient underwent standardized tests for objective assessment of cognitive functions. The tests were selected in collaboration with a clinical psychologist. Each participant underwent evaluation in a separate, quiet examination room with a qualified research assistant. The assessment was carried out in the following order: Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), 10-point clock drawing test. Statistical analysis was performed using Statistica software. Results. The vast majority of them did not have characteristic complaints from the digestive system, most of them actively complained only about physical weakness and fatigue. As for cognitive changes and decreased mental performance, most of them associated this group of symptoms with such causes as stress, lack of sleep, prolonged overload. Patients reported such changes mostly only when actively questioned by the doctor. Changes in laboratory liver tests were also mild and uncharacteristic in such patients. The use of standard cognitive tests revealed mild cognitive impairment even in patients with moderate liver fibrosis. The most sensitive for their detection was the 10-point clock test, the MoCA test was less effective. The standard MMSE test was practically uninformative for detecting minimal cognitive impairment. We conducted these tests again after the patient read the text aloud for 15 minutes. This modification allowed us to objectively detect the phenomenon of rapid cognitive fatigue. In healthy volunteers, such cognitive load had practically no effect on the performance of all three tests. In contrast, patients with moderate liver fibrosis showed a sharp decrease in the performance of all three tests (p < 0.05). In patients with advanced liver fibrosis (F3), the performance of cognitive tests was reduced to a much greater extent than in F2. At the screening stage, all results were significantly lower compared to the data of the control group (p < 0.05). These indicators were even lower when conducting cognitive tests after 15-minute reading aloud of the text by the patient (p < 0.05). The use of L-ornithine-L-aspartate 1 sachet (3 g) 2 times a day during meals for 1 month contributed to a significant improvement in cognitive performance in patients with MASLD. The indicated therapeutic effect was faster in patients with moderately severe liver fibrosis, indicating the potential advantage of earlier prescription of the drug. Conclusions. The presence of MASLD is accompanied by mild cognitive impairment even in the presence of moderately severe fibrotic changes in the liver (F2). The 10-point clock test turned out to be the most sensitive for their detection. Patients with moderately expressed fibrotic changes in the liver (F2) show rapid cognitive fatigue, which can be effectively detected by using the above-mentioned cognitive tests after 15-minute reading of the text. Such changes can significantly affect the working capacity of patients, especially in the case of intellectual activities or professions that require constant attention and concentration. In the case of advanced liver fibrosis (F3), almost all examined patients showed not only rapid cognitive fatigue, but also a significant decrease in the results of all cognitive tests we used. The changes we detected corresponded to the stage of moderate cognitive impairment, which can disrupt not only professional activities, but also everyday life and social adaptation of such patients. The use of L-ornithine-L-aspartate for 1 month significantly improved cognitive performance in patients with MASLD. The therapeutic effect was more rapid in patients with moderate liver fibrosis.

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