Differentiated approach to correction of metabolic disorders in chronic hepatitis С

Introduction

Metabolic syndrome (MS) is a medical problem at the population level. Its relevance is due to its high prevalence and a significant increase in the risk of developing cardiovascular diseases, type 2 diabetes mellitus, and other serious complications. Every fourth resident in developed countries suffers from this condition, and over the next 25 years, the incidence rate is expected to increase by 50% [1].

The combination of chronic hepatitis C (CHC) and metabolic syndrome can adversely affect the rate of HCV infection progression and reduce the effectiveness of antiviral therapy. There is evidence that HCV infection contributes to the development of hepatic steatosis, one of the organ manifestations of MS, leading some authors to consider CHC a "metabolic disease" [2, 3]. It has been noted that patients with CHC (with a disease duration in the liver of more than 6 months) present with a greater number of metabolic syndrome components [4].

The nutritional status of patients with metabolic syndrome and CHC can be studied using bioimpedance analysis of body composition components. It is possible to search for criteria for the effectiveness of therapy for metabolic disorders in CHC using this method [5]. In addition to the main parameters, it is necessary to consider the bioimpedance phase angle (PhA) as a significant diagnostic marker reflecting the nature of metabolic processes and the intensity of metabolism. Studies indicate that a phase angle value of less than 5° correlates with an unfavorable survival prognosis in patients with gastrointestinal cancers [6]. Furthermore, the dynamics of phase angle changes have been studied for use as a prognostic criterion in several clinical conditions, such as acquired immunodeficiency syndrome, chronic obstructive pulmonary disease, and sepsis [7, 8]. The phase angle, along with the skeletal muscle index, is a predictor of mortality in patients with liver cirrhosis [9].

The use of hepatoprotective drugs in the treatment of chronic viral hepatitis remains a subject of debate. The study and comparative evaluation of the clinical and laboratory effects of several drugs from this group with multidirectional effects on metabolic processes in patients with a combination of CHC and MS appears highly relevant.

Quality of life is an integral summary characteristic of physical, psychological, emotional, and social functioning. It is known that the quality of life in patients with chronic viral hepatitis is reduced across all health components: physical and psychological [10]. The influence of various hepatoprotective therapy regimens on the quality of life of patients with CHC is of interest [11, 12].

Objective

The aim of this study is to investigate the parameters of bioimpedance analysis and quality of life (QoL) in patients with chronic hepatitis C and metabolic syndrome using different regimens of hepatoprotective therapy.

Materials and methods

The study included 120 patients with CHC, aged 18 to 51 years, who were treated at the Regional Infectious Diseases Clinical Hospital in Yaroslavl. Diagnoses were confirmed by detecting markers using ELISA (anti-HCV panel: anti-core, anti-NS3, anti-NS4, anti-NS5) and PCR (HCV RNA). Patients were evenly distributed by gender — 60 women and 60 men. Mean age was 35.7±2.8 years. All patients exhibited a marked degree of hepatitis activity, confirmed by a significant elevation of aminotransferases (ALT, AST) above 400 U/L, as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). Bilirubin levels were within normal limits.

Nutritional status was studied using bioimpedance analysis of body composition components with the device "Analyzer for assessing the balance of body water sectors 'ABC-01 Medass'" with the basic body composition assessment program ABC01-03612, according to the recommendations of the Scientific and Technical Center "Medass". Analysis was performed on all patients before starting therapy and at the end of the course.

Quality of life was assessed using the SF-36 (The Short Form-36) questionnaire before and after hepatoprotective therapy. Statistical processing was performed using methods of parametric and nonparametric statistics with the data processing software "STATISTICA" (version 10.0). The significance of differences was determined using Student's t-test, Mann-Whitney U test, and Wilcoxon test (to assess the dynamics of indicators within groups). Differences were considered statistically significant at p <0.05.

In accordance with the study's aim, patients were randomized into treatment groups: 1) glycyrrhizic acid (GA) + essential phospholipids (EPL) (n=30); 2) ademetionine (n=30); 3) UDCA (n=30); 4) comparison group (n=30). Drug doses recommended by the instructions were used. Results were evaluated according to clinical-biochemical and instrumental criteria after 4 weeks.

Results and discussion

A statistically significant positive dynamic was found in the mean levels of AST and ALT in the group receiving GA+EPL — 40-45%, while ALP and GGT levels remained virtually unchanged. With UDCA administration, the positive dynamic of transaminases was 40%, but cholestasis parameters decreased to a greater extent (up to 60%, p <0.05). In the ademetionine group, the reduction in ALT level reached 65%, AST — 50%, GGT, ALP — 70% (p <0.05). The effectiveness of ademetionine in correcting cholestasis syndrome and improving clinical symptoms (weakness, malaise, reduced work capacity) should be specifically emphasized. There were no side effects. Adverse events possibly related to UDCA intake were episodic: moderate discomfort in the upper abdomen (3 patients), loose stools up to 3–5 times a day (2 patients), which did not lead to treatment discontinuation. In the control group, no significant changes were observed.

Baseline quality of life values in the groups were comparable (p >0.05): a decrease was found in the indicators assessing general health and mental health (40.43±13.83 and 63.02±0.58, respectively). Along with a decrease in the "vitality" scale (61.04±0.74), low scores were found on the physical functioning (80.45±0.54) and bodily pain (74.11±0.96) scales. This reflects the degree of individual psycho-emotional and physical discomfort caused by the underlying disease.

By the end of treatment, statistically significant improvements in QoL were observed in groups 1 and 2 across most scales: EF (energy/fatigue), EW (emotional well-being), SF (social functioning), and BP (bodily pain). Meanwhile, the apparent improvement in group 3 did not achieve statistical significance. It is important to note the absence of significant differences in the control group (p >0.05).

Bioimpedance analysis parameters were studied, from which the following were selected for monitoring: phase angle at 50 kHz (% of normal), fat mass (FM) percentage (% of normal), waist-to-hip ratio (WHR) (% of normal) before treatment and after completion of therapy.

Some body composition analysis parameters in patients before therapy are presented in the figure.

Fig. Body composition analysis in patients before therapy

According to the obtained data, before therapy, the fat mass percentage and waist-to-hip ratio were significantly higher than normal (p <0.05), which can be considered a sign of the severity of metabolic syndrome. Excess body weight predominates due to increased adipose tissue volume. At the same time, the phase angle value as a percentage of normal indicates high adaptive capacity and level of metabolic activity.

Before treatment, the mean PhA was 6.08±0.08°, with 6.28±0.1° in men (n=60) and 5.68±0.13° in women (n=60). After the course of hepatoprotective therapy, a significant increase (p <0.05) in PhA was noted, to 6.43±0.09° (men 6.66±0.11°, women 5.98±0.09°). No significant differences were found in PhA dynamics among the groups of patients receiving different drugs. A positive trend was noted in group 2; however, it was not statistically significant. In the control group of patients, no significant changes in bioimpedance analysis results were detected.

The administration of hepatoprotective therapy did not have a significant positive or negative effect on the qualitative body composition of patients. No significant changes were obtained in any group for the WHR and fat mass percentage parameters; presumably, this is related to the short course of drug administration, requiring longer study periods and larger group sizes. Only a positive trend was noted in patients of group 2, which requires further investigation.

Conclusion

Chronic hepatitis C is often combined with metabolic syndrome, particularly with signs of viscero-abdominal obesity. This study allows us to note the positive effect of hepatoprotectors in patients with CHC and metabolic syndrome on the degree of hepatitis activity, quality of life, and body composition components (phase angle).

The assessment of QoL and body composition using screening methods during dynamic follow-up demonstrates positive changes during treatment, no less clearly than traditional biochemical parameters. Moreover, these evaluation criteria allow us to see treatment results as a complex effect on all aspects of a person's health. The screening methods used for determining QoL and body composition are particularly useful in the context of long-term outpatient follow-up of patients with chronic pathology.

The use of hepatoprotectors (glycyrrhizic acid + essential phospholipids, ademetionine, or ursodeoxycholic acid preparations) in standard therapeutic doses for 4 weeks led to an improvement in both traditional indicators of treatment effectiveness (clinical symptoms, functional liver tests) and a statistically significant improvement in quality of life (groups 1 and 2). In the ademetionine group, positive dynamics were also noted in the results of bioimpedance analysis.