Liver diseases remain an important global health problem. Postoperative liver fibrosis develops in 35-45% of patients after its resection or transplantation, as well as after laparoscopic interventions. The aim of the study is to identify the main cellular mechanisms of development and determine optimal diagnostic methods for postoperative liver fibrosis. Materials and methods. A literature review was conducted using the electronic databases PubMed, Google Scholar, Scopus, and elibrary. The work includes original research, systematic reviews and meta-analyses, 51 of the initially identified 117 sources. Results. Modern instrumental diagnostic methods make it possible to effectively determine the presence of existing fibrosis, respectively, their use is justified only in the IV phase of fibrogenesis. The possibility of using biochemical markers in the I-III phases of fibrogenesis is associated with traumatic damage and death of hepatocytes, as well as their apoptosis. And the use of direct biochemical markers in the III-IV phases of fibrogenesis is justified by the active synthesis and stabilization of the extracellular matrix, crosslinking of collagen fibers and their retraction. It should be noted that the biochemical markers M2BPGi and sTREM2 can effectively stratify patients according to the risk of complications in the postoperative period, and the use of FIB-4 and sTREM2 can significantly improve the preoperative assessment of the risk of liver failure. Conclusion. The most reliable diagnostic method is morphological analysis, which allows not only to identify the presence of fibrous changes in liver tissue and accurately determine the phase of fibrogenesis, but also to predict the progressive development of fibrosis in the postoperative period. Thus, knowledge of the morphopathogenetic foundations of the formation of postoperative liver fibrosis can not only provide early diagnosis, but will also allow the development of prevention and treatment measures based on the impact on the key links of fibrogenesis.
Regular moderate physical activity improves liver health, while excessively prolonged exercise has adverse effects on cells. Understanding the cellular mechanisms underlying liver injury and recovery after varying degrees of physical activity is important for developing effective therapeutic strategies. Aim: study of the number of binuclear cells, markers of cell proliferation, and the specific area of vimentin-positive cells in the liver during physical exertion of varying intensity and after taking meldonium. Methods. The experiments were conducted on male Wistar rats, which were subjected to physical activity of varying intensity. The animals of the first series swam for 15 minutes. The rats of the second series spent 30 minutes in the bath; this activity was considered moderate. To simulate heavy physical activity (the third series), the animals swam in the bath until they began to lose strength and drown. This usually occurred 55-59 minutes after the animals were in the water. To compare the results, three control (experimental) series of rats were used (8 per series), which also performed similar activity of varying intensity; meldonium was added to the food throughout the experiment (10 days) at the rate of 100-120 mg/kg of weight. The animals of all series completed 10 sessions of water loading, after which they were taken out of the experiment immediately after the last session and 30 days after the end of the experiments. After the animals were removed from the experiment, the liver was removed, paraffin blocks were prepared, stained with hematoxylin and eosin, and immunohistochemical studies were performed. Results. The study revealed that after 10 days of using meldonium and 30 days after the experiment in all series in which meldonium was used, the morphological structure of the liver was similar to the liver of intact animals. With light and moderate physical activity, mitotically dividing cells were determined, cells in different phases of the cell cycle were encountered; the number of binuclear cells, the mitotic index, and the alteration index were within the values of the intact series. In animals with heavy physical exertion involving meldonium, 30 days after the experiment, an increase in the number of binuclear cells was noted, vimenti-positive cells appeared, the alteration index was reduced in comparison with the indicators of animals in which meldonium was not used. Conclusion. During heavy physical activity with the use of meldonium, recovery processes are observed with an increase in the proportion of binuclear hepatocytes, mitoses, cell proliferation (Ki-67), a change in the specific area of vimentin with a simultaneous decrease in alterative processes.
Objective - To conduct a comparative evaluation of the efficacy of prophylactic correction using ademetionine and a complex of oxymethyluracil with N-acetylcysteine in a model of thioacetamide-induced toxicity. Materials and Methods. The study was performed on 56 male rats. Toxicity was induced by intraperitoneal administration of thioacetamide at 50 mg/kg body weight twice weekly for 100 days. The animals were assigned to four groups: negative control, positive control, and two experimental groups receiving thioacetamide in combination with either ademetionine or the oxymethyluracil-N-acetylcysteine complex. The corrective agents were administered one hour prior to the toxicant. On days 50 and 100, serum and urine biochemical parameters were assessed, along with gene expression in the liver and kidneys related to antioxidant defense, the glutathione system, apoptosis, and the cell cycle. Histological and morphometric tissue analyses were also performed. Results. The positive control group confirmed the development of chronic toxic hepatitis with progressive liver fibrosis. The use of a complex of oxymethyluracil and acetylcysteine demonstrated superiority over ademetionine in preventing long-term outcomes, with ademetionine primarily exerting an early metabolic effect without affecting the progression of liver fibrosis or structural tissue remodeling in the later stages. Regarding the kidneys, morphometric stress was observed by the end of the treatment period, most noticeable in the positive control group and during prophylactic administration of ademetionine. Conclusion. Under the conditions of intoxication considered, both compounds demonstrated a certain ability to modify late structural outcomes. The complex compound of oxymethyluracil with acetylcysteine demonstrated a more favorable profile at the late stage, while ademetionine was more effective at the early stages. These findings highlight the potential of antioxidant-targeted strategies for the prevention of adverse outcomes in chronic toxic injury.
The article presents a clinical case of hemochromatosis diagnosis with the presence of a heterozygous HFE His63Asp (H63D) mutation in a patient with liver damage. In our opinion, the reason leading to secondary iron retention in this case was the long-term intake of allopurinol. Correction of urate-lowering therapy led to a decrease in ferritin levels and normalization of liver parameters.
Aim: To identify predictors for early liver fibrosis in patients with metabolically associated steatotic liver disease (MASLD). Materials and methods: A prospective cohort study included 131 patients with MASLD (77 females, 54 males; mean age 48.5 ± 0.95 years). Fibrosis stages were verified using transient elastography (FibroScan). Patients were divided into two groups: those without fibrosis (F0, n = 91) and those with early fibrosis (F1-F2, n = 40). Statistical analysis was performed using R (v. 4.3.3) with binary logistic regression and ROC analysis. Results: Early fibrosis was identified in 30.1% of the participants. Type 2 diabetes mellitus (OR = 12.0; 95% CI: 3.94-36.53), a positive family history (OR = 7.75), and hyperlipidemia (OR = 5.77) were established as key risk factors. Obesity (BMI > 30 kg/m²) acted as an obligatory prerequisite for the presence of fibrosis. The most significant quantitative predictors were glycemia level (OR = 2.34) and HOMA-IR index (OR = 1.89). According to the ROC analysis, AST (AUC = 0.832, threshold > 48.5 U/L) and glycemia level (AUC = 0.826, threshold > 7.05 mmol/L) showed the highest diagnostic accuracy. The developed predictive model based on metabolic factors demonstrated high accuracy (AUC = 0.902; sensitivity - 82.5%, specificity - 83.5%), significantly outperforming the international NFS (AUC = 0.829) and FIB-4 (AUC = 0.617) indices. Conclusion: The inclusion of metabolic parameters in the developed algorithm allows for high-accuracy prediction of early changes in liver tissue, making the model an effective screening tool for primary healthcare.
