Buchok O. Clinical and pathogenetic features and rationale for treating patients with chronic hepatitis C in comorbidity with chronic pancreatitis.

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U001220

Applicant for

Specialization

  • 222 - Медицина

02-05-2024

Specialized Academic Board

ДФ 61.051.132

Uzhhorod National University State Higher Educational Institution

Essay

The aim of the study was to enhance the effectiveness of treatment for patients with chronic hepatitis C and chronic pancreatitis by investigating the correlation between clinical and biochemical parameters, the activity of the inflammatory process, the expressiveness of morphological changes and pancreatic enzymatic activity. To fulfill the goal, 2 groups of patients were included in the study: group 1 – patients with CHC comorbid with CP (n=72), group 2 – patients with CHC (n=48), which were further divided into group 1a (n=52) – patients with CHC+CP with pancreatic exocrine insufficiency (EPI) and group 1b (n=20) – patients with CHC+CP without EPI. In order to study the effectiveness of complex therapy, 46 patients with CHC+CP with mild and moderate EPI were divided into group A (n=21) and group B (n=26). All patients received daclatasvir+sofosbuvir, rabeprazole and a polyenzyme drug with a minimum lipase activity of 25 thousand units. EF., and patients of group A additionally received vitamin D in a dose of 4000 IU for 24 weeks. As a result of the obtained data, it was established that the features of the clinical course of CHC+CP are a significant predominance of intestinal dyspepsia which is manifested by flatulence and defecation disorders in 75.0% and 68.1% of patients. In patients with CHC+CP with EPI, high degrees of necroinflammatory activity of the liver (A2-3 (p<0.05)) were registered 4.6 times more often and liver fibrosis degree F2-3 was 2.8 times more often (p<0, 05), than in patients with preserved exocrine function of the pancreas. It has been found that more pronounced changes in the cytokine profile are observed in patients with CHC+CP with EPI, due to the predominance of the pro-inflammatory and pro-fibrogenic component. It was found that the levels of IL-6 and neopterin are positively correlated with viral load (ρ=0.869, p<0.001; ρ=0.723, p<0.001) and inversely correlated with the level of fecal elastase-1 (FE-1) (ρ=-0.649 , p<0.001; ρ=-0.534, p<0.001). The established strong inverse correlation (ρ=–0.832, p<0.001) between the viral load and the level of FE-1 confirms the influence of the replicative activity of the hepatitis C virus and inflammation on the pancreatocyte with the formation of exocrine pancreatic insufficiency. It has been proven that probably lower levels of vitamin D are observed in patients with CHC+CP compared to patients with CHC without CP (p<0.001) and it is established that the level of vitamin D is the lowest in the condition of EPI and with high necroinflammatory activity of the liver (A2-3 and A3- 4) and severe fibrosis (F3-4). It was found that the level of vitamin D in patients with CHC+CP with EPI with fibrosis F3-4 is 26.8% lower than in patients with initial stages of fibrosis F0-1 (p<0.05). A positive correlation was registered between vitamin D levels and FE-1 levels (ρ=0.431, p=0.001), a negative correlation - between vitamin D levels and viral load (ρ=-0.447, p<0.001) and profibrogenic cytokine (TGF-β) levels. (ρ=-0.745, p<0.001), confirms the role of vitamin D in the regulation of the processes of both fibrogenesis and the formation of exocrine pancreatic insufficiency in patients with CHC. It was found that indicators of quality of life (QoL) in patients with CHC+CP are positively correlated with levels of vitamin D - when the level of vitamin D is increased, QoL improves according to the following indicators: integral index; physical health; mental health, and the level of situational anxiety is negatively correlated with the level of vitamin D (ρ=-0.660, p<0.001). A positive correlation was also established between the level of FE-1 and all indicators of the quality of life in patients with CHC+CP with EPI: integral; physical health; mental health. It has been proven that the inclusion of a polyenzyme drug with minimal lipase activity of 25,000 and vitamin D in a dose of 4,000 IU/day to the complex treatment of patients with CHC combined with CP leads to rapid normalization of ALT, AST, total bilirubin, helps to eliminate cytokine imbalance, improves the exocrine function of the pancreas and contributes to the marked regression of manifestations of hepatobiliary dysfunction, thereby reducing situational anxiety and increasing the quality of life of these patients.

Research papers

1. Дербак МА, Бучок ОВ. Оцінка зовнішньосекреторної функції підшлункової залози у хворих на хронічний гепатит С. Науковий вісник Ужгородського університету. Серія «Медицина». 2023;68(2):181-5.

2. Derbak MA, Buchok OV, Ganych TM, Rishko OA, Timashev VV. Assessment of the influence of vitamin D level on the course of chronic hepatitis C in comorbidity with chronic pancreatitis. Mìžnarodnij endokrinologìčnij žurnal. 2023;19(7):478-84.

3. Дербак MA, Бучок ОВ, Болдіжар OO, Рішко OA, Блецкан MM. Динаміка основних клініко-імунологічних показників у хворих на ХГС поєднаний із хронічним панкреатитом в результаті використання комплексної терапії із включенням вітаміну D. Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії. 2023;23(4):84–8.

4. Derbak MA, Buchok OV, Boldizhar OO, Bletskan MM, Svistak VV. The effect of complex therapy including vitamin D on the quality of life of patients with chronic hepatitis C combined with chronic pancreatitis. Bulletin of problems in biology and medicine. 2023;1(2):166-171.

5. Derbak MA, Buchok OV, Ganich TM, Rivis MV, Lazur YV, Polyak-Tovt VM, Timashev VV. Peculiarities of the functional state of the liver in patients with chronic hepatitis С in the presence of chronic pancreatitis. Wiadomosci Lekarskie. 2023;76(11):2359-64.

6. Дербак МА, Бучок ОВ. Особливості цитокінового профілю у хворих на хронічний гепатит С, поєднаний із хронічним панкреатитом. Проблеми клінічної педіатрії. 2023;61(3):6-12.

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