Advances in the diagnosis and therapy of liver cirrhosis: a systematic review / Avanços no diagnóstico e terapia da cirrose hepática: uma revisão sistemática

Hepatic cirrhosis (HC) is a diffuse pathophysiological state of the liver considered to be the end-stage of several liver injuries. It is essential to highlight the need to implement new diagnostic and treatment methods to contain subsequent damage to liver cirrhosis, so that we can better understand the pathophysiological process of the disease and obtain better therapeutic results. Thus, this study aimed to identify advances in diagnostic methods and treatments for liver cirrhosis. This is a systematic literature review study, conducted by searching the descriptors “Liver cirrhosis”, “Alcoholic liver cirrhosis”, “Liver fibrosis” and “Liver”, in the databases: Scielo- Scientific Electronic Library Online, Lilacs - Latin American and Caribbean Center on Health Sciences Information, NIH-NCBI-Pubmed- National Center for Biotechnological Information – National Library of Medicine, following a search strategy according to descriptors in Portuguese and English, years 2015 to 2021. At the end of the search with the descriptors, 835 articles were found in the databases, of which 88 were in the Scielo platform, 286 in Lilacs and 461 in Pubmed. After the three selection steps, 811 articles were excluded and 23 articles that met the inclusion and exclusion criteria were selected for analysis. Based on this systematic review, it is pointed out that there has been a lot of development regarding the diagnosis and treatment of cirrhosis that, for many years, required scientific evidence to combat morbidity and mortality and reverse the condition of liver cirrhosis.

Protective Effects of Chlorogenic Acid against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

The protective effects of chlorogenic acid (CGA) against liver injury were evaluated by its reduction in carbon tetrachloride (CCl4)-induced hepatic damage in ICR mice. The animals were orally given CGA (60, 100, and 200 mg/kg, respectively) or silymairn (200 mg/kg) daily with 0.3% CCl4 administration (3 mL/kg, dissolved in olive oil) after medicament treatment on the 7th day. Compared with the normal group, CCl4 caused severe impairment in liver according to the evidence of significant reduction in the level of total albumin and expansion (p < 0.05) of the activities in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cholesterol, triglyceride (TG), and total albumin in serum, decreased the level of glutathione (GSH), and diminished the activities of catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), and glutathione peroxidase (GSH-Px) in liver while increasing the level of hepatic thiobarbituric acid-reactive substances (TBARS). However, oral administration of CGA or silymarin could significantly (p < 0.05) decrease the serum levels of AST, ALT, cholesterol, TG, and total albumin and elevated the serum total albumin and the activities of GSH, catalase, SOD, GSH-Rd, and GSH-Px while leading to decline the TBARS in liver compared with CCl4-intoxicated group. Moreover, histopathology displayed that CGA decreased the formation of lesions in liver resulted from CCl4. The outcomes indicate that CGA shows the efficiency hepatoprotective consequences for CCl4-incited liver injuries in mice by the elevation of the activities of antioxidant enzymes and hindrance of lipid peroxidation.

MODERN PRINCIPLES OF DIAGNOSIS AND TREATMENT OF PATIENTS WITH SEVERE INJURIES OF LIVER

Авторы анализируют свой опыт лечения открытых и закрытых травм печени, вопросы диагностики, информативность инвазивных и неинвазивных методов диагностики и делятся накопленным опытом лечения. Используя современный алгоритм диагностики и лечения авторам удалось снизить летальность до 8,8%. The authors analyze their experience in the treatment of open and closed liver injuries, diagnostic issues, the informative value of invasive and non-invasive diagnostic methods and share their experience in treatment. Using a modern diagnostic and treatment algorithms, the authors managed to reduce the mortality rate to 8.8%.

Regenerative Potential of Mesenchymal Stem Cells’ (MSCs) Secretome for Liver Fibrosis Therapies

Chronic liver injuries lead to liver fibrosis and then to end-stage liver cirrhosis. Liver transplantation is often needed as a course of treatment for patients in critical conditions, but limitations associated with transplantation prompted the continuous search for alternative therapeutic strategies. Cell therapy with stem cells has emerged as an attractive option in order to stimulate tissue regeneration and liver repair. Transplanted mesenchymal stem cells (MSCs) could trans-differentiate into hepatocyte-like cells and, moreover, show anti-fibrotic and immunomodulatory effects. However, cell transplantation may lead to some uncontrolled side effects, risks associated with tumorigenesis, and cell rejection. MSCs’ secretome includes a large number of soluble factors and extracellular vesicles (EVs), through which they exert their therapeutic role. This could represent a cell-free strategy, which is safer and more effective than MSC transplantation. In this review, we focus on cell therapies based on MSCs and how the MSCs’ secretome impacts the mechanisms associated with liver diseases. Moreover, we discuss the important therapeutic role of EVs and how their properties could be further used in liver regeneration.

Medicinal plants with hepatoprotective potentials against carbon tetrachloride-induced toxicity: a review

Background Carbon tetrachloride (CCl4) is a well-characterized hepatotoxic agent. With rising cases of liver diseases, the identification, assessment, and development of hepatoprotective agents from plants source has become imperative. Main body With arrays of literature on plants with hepatoprotective potentials, this review sourced published literatures between 1998 and 2020 and systematically highlighted about 92 medicinal plants that have been reported to protect against CCl4-induced liver injury in animal models. The results show that herbal plants provide protection for the liver against CCl4 by downregulation of the liver marker enzymes and activation of antioxidant capacity of the liver cells with the restoration of liver architecture. We also provided the traditional and accompanying pharmacological uses of the plants. A variety of phytochemicals mostly flavonoids and polyphenols compounds were suggested to offer protection against liver injuries. Conclusion It can be concluded that there are a variety of phytochemicals in plant products with hepatoprotective activity against CCl4-induced toxicity in animal models.

Emerging Roles on Immunological Effect of Indoleamine 2,3-Dioxygenase in Liver Injuries

Indoleamine 2,3-dioxygenase (IDO) is one of the initial rate-limiting enzymes of the kynurenine pathway (KP), which causes immune suppression and induction of T cell anergy. It is associated with the imbalance of immune homeostasis in numerous diseases including cancer, chronic viral infection, allergy, and autoimmune diseases. Recently, IDO has extended its role to liver field. In this review, we summarize the dysregulation and potentials of IDO in the emerging field of liver injuries, as well as current challenges for IDO targets. In particular, we discuss unexpected conclusions against previous work published. IDO is induced by pro-inflammatory cytokines in liver dysfunction and exerts an immunosuppressive effect, whereas the improvement of liver injury may require consideration of multiple factors besides IDO.

LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome

Extracellular vesicles (EVs) have emerged as important vectors of intercellular dialogue. High mobility group box protein 1 (HMGB1) is a typical damage-associated molecular pattern (DAMP) molecule, which is cytotoxic and leads to cell death and tissue injury. Whether EVs are involved in the release of HMGB1 in lipopolysaccharide (LPS)-induced acute liver injuries need more investigation. EVs were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The co-localization of HMGB1, RAGE (receptor for advanced glycation end-products), EEA1, Rab5, Rab7, Lamp1 and transferrin were detected by confocal microscopy. The interaction of HMGB1 and RAGE were investigated by co-immunoprecipitation. EVs were labeled with the PKH67 and used for uptake experiments. The pyroptotic cell death was determined by FLICA 660-YVAD-FMK. The expression of NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasomes were analyzed by western-blot or immunohistochemistry. Serum HMGB1, ALT (alanine aminotransferase), AST (aspartate aminotransferase), LDH (lactate dehydrogenase) and MPO (myeloperoxidase) were measured using a commercial kit. The extracellular vesicle HMGB1 was detected in the serums of sepsis patients. Macrophages were found to contribute to HMGB1 release through the EVs. HMGB1-RAGE interactions participated in the loading of HMGB1 into the EVs. These EVs shuttled HMGB1 to target cells by transferrin-mediated endocytosis leading to hepatocyte pyroptosis by the activation of NLRP3 inflammasomes. Moreover, a positive correlation was verified between the sepsis serum EVs-HMGB1 level and clinical liver damage. This finding provides insights for the development of novel diagnostic and therapeutic strategies for acute liver injuries.