Nutrition: Chronic Disease Management.

Dietary modifications can help to prevent and manage many chronic diseases. The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets emphasize consumption of fruits and vegetables while reducing intake of red meat. These diets are supported by well-established evidence for patients with cardiovascular disease and hypertension, respectively. Whole-food, plant-based diets have been shown to result in reduced body weight, lower A1c levels, and decreased insulin resistance in patients with diabetes. Patients with diabetes and hypertension should adhere to a heart-healthy diet, such as the DASH diet. For patients with diabetes and at risk of diabetes, key nutritional recommendations include emphasizing intake of nonstarchy vegetables, minimizing intake of added sugars and refined grains, and choosing whole foods instead of processed foods. The Dietary Guidelines for Americans, 2020-2025 recommend that adults limit sodium intake to less than 2,300 mg/day. Patients with chronic kidney or liver disease should follow sodium restriction and protein intake guidelines. Patients with irritable bowel syndrome should follow a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet with fiber supplementation. For patients with gastrointestinal symptoms, fiber can effectively manage constipation and stool irregularity. Probiotic supplements or foods can be useful for digestive problems.

METABOLIC AND NUTRITIONAL REPERCUSSIONS OF LIVER DISEASE ON CHILDREN: HOW TO MINIMIZE THEM?

OBJECTIVE: To describe the metabolic and nutritional repercussions of chronic liver disease (CLD), proposing strategies that optimize nutritional therapy in the pre- and post-liver transplantation (LT) period, in order to promote favorable clinical outcomes and adequate growth and development, respectively. DATA SOURCES: Bibliographic search in the PubMed, Lilacs and SciELO databases of the last 12 years, in English and Portuguese; target population: children from early childhood to adolescence; keywords in Portuguese and their correlates in English: "Liver Transplant," "Biliary Atresia," "Nutrition Therapy," "Nutritional Status," and "Child"; in addition to Boolean logics "and" and "or," and the manual search of articles. DATA SYNTHESIS: Malnutrition in children with CLD is a very common condition and an important risk factor for morbidity and mortality. There is an increase in energy and protein demand, as well as difficulties in the absorption of carbohydrates, lipids and micronutrients such as fat-soluble vitamins and some minerals. An increase in the supply of energy, carbohydrates and proteins and micronutrients, especially fat-soluble vitamins, iron, zinc and calcium, is suggested, except in cases of hepatic encephalopathy (this restriction is indicated for a short period). CONCLUSIONS: Based on metabolic changes and anthropometric and body composition monitoring, a treatment plan should be developed, following the nutritional recommendations available, in order to minimize the negative impact of malnutrition on clinical outcomes during and after LT.

Effects of silybin supplementation on nutrient digestibility, hematological parameters, liver function indices, and liver-specific mi-RNA concentration in dogs.

BACKGROUND: Hepatopathies are an important group of disorders in dogs where proper nutritional care is crucial. Supplementation with a hepatoprotectant like silybin can improve liver function and should not interfere with nutrient digestibility. The purpose of this study was to investigate the effect of both pure silybin and commercial hepatoprotectant on nutrients digestibility, liver function indices and health status in healthy dogs (EXP1). Moreover, the second experiment (EXP2) investigated the effect of commercial hepatoprotectant on liver function tests and liver-associated miRNAs concentration in dogs with idiopathic liver disorder. RESULTS: Nutrient digestibility was not affected by treatment in EXP1. Supplementation did alter the serum fatty acid profile, with no clinical relevance. The levels of liver markers such as ALT, AST and GGT significantly decreased. In EXP2, supplementation with commercial hepatoprotectant containing silybin improved liver function tests. A decrease was observed in liver serum markers such as ALT, AST and miR122 concentration. CONCLUSIONS: EXP1 confirmed that silybin (whether pure or as a commercial hepatoprotectant) does not interfere with digestion which subsequently exerts no detrimental effect on dogs' health and metabolism. In EXP2, dietary supplementation with commercial hepatoprotectant containing silybin resulted in a decreased activity of serum liver markers, accompanied by a decrease in the concentration of liver-specific miRNA molecules. Liver function indices were consequently improved. Silybin supplementation can thus serve as an effective therapeutical tool in dogs with hepatopathies.

Biomedical applications of methionine-based systems.

Methionine (Met), an essential amino acid in the human body, possesses versatile features based on its chemical modification, cell metabolism and metabolic derivatives. Benefitting from its multifunctional properties, Met holds immense potential for biomedical applications. In this review, we systematically summarize the recent progress in Met-based strategies for biomedical applications. First, given the unique structural characteristics of Met, two chemical modification methods are briefly introduced. Subsequently, due to the disordered metabolic state of tumor cells, applications of Met in cancer treatment and diagnosis are summarized in detail. Furthermore, the efficacy of S-adenosylmethionine (SAM), as the most important metabolic derivative of Met, for treating liver diseases is mentioned. Finally, we analyze the current challenges and development trends of Met in the biomedical field, and suggest that Met-restriction therapy might be a promising approach to treat COVID-19.

Liver Damage Produced by Malnutrition is Improved by Dietary Supplementation in Mice: Assessment of a Supplement Based on Buriti (A Cerrado Fruit) and Dairy By-products.

BACKGROUND: Malnutrition induced by dietary restriction produces several metabolic changes that affect body weight, the digestive system, and annex organs, including the liver. Malnutrition generates an inflammatory state and increases oxidative stress. The liver is one of the body vital organs, becoming necessary to analyze the impact of food supplementation on the repair of possible changes that may occur in this organ due to malnutrition. AIMS: To evaluate the effects of a low-cost supplementation derived from Buriti and dairy byproducts on liver recovery in malnourished mice, focusing on the expression of oxidative stressrelated genes, as well as biochemical and histological parameters. METHODS: Swiss mice were divided into six groups and submitted to two treatment phases: food restriction, for malnutrition onset; and renutrition, with mice being fed with different diets. RESULTS: Our results indicate that dietary supplementation was successful in recovering liver damage caused by malnutrition in animal models. The new supplement has been shown to recover liver damage with similar or superior results compared to the commercial reference supplement on the market. CONCLUSION: Our work presents a new composition of low cost food supplement based on buriti and dairy by-products, proven to be effective in the malnutrition treatment of malnutrition. The improvements were proven through the recovery of body weight, reduction of inflammation and oxidative stress.

Assessment of the Clinical Impact of a Liver-Specific, BCAA-Enriched Diet in Major Liver Surgery.

BACKGROUND: The relationship between nutrition and liver disease is relevant for the outcome after surgery. Patients with liver cirrhosis characteristically show protein-energy malnutrition with decreased levels of branched-chain amino acids (BCAA) and increased levels of aromatic amino acids. MATERIALS AND METHODS: We conducted a prospective controlled clinical trial including 57 patients after liver transplantation or major liver resection surgery in order to test the effect of early postoperative nutrition on the outcome and nutrition profile of these patients. The test group received a dietetic program composed of ingredients naturally rich in BCAA (BCAA group), and the control group received standard hospital meals. Patient survival, liver function tests, subjective well-being, and a nutritional status including amino acid profiles were analyzed immediately and 14 days after major liver surgery (secondary end points). General health and well-being were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (primary end point). RESULTS: In-depth analysis of amino acid profiles was performed for patients undergoing liver resection (n = 21) and liver transplantation (n = 36). Interestingly, amino acid profiles did not correlate with body mass index or the Model for End-Stage Liver Disease score. Patients scheduled for liver transplantation showed significantly lower levels of BCAA pretransplant compared to patients undergoing liver resection. Patients in the liver resection subgroup were more likely to benefit from the BCAA cuisine in terms of significantly higher food intake and subjective rating. The clinical liver function tests, however, did not show statistical difference between the BCAA group and the control group in the examination period of 14 days. CONCLUSION: Our specifically designed BCAA-enriched diet resulted in greater patient satisfaction and compliance with nutrition. A larger trial or longer-term follow-up may be required to identify an effect on survival, recovery, surgical complications, protein profiles, and amino acid profiles.

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication.

As one of the bicyclic metabolic pathways of one-carbon metabolism, methionine metabolism is the pivot linking the folate cycle to the transsulfuration pathway. In addition to being a precursor for glutathione synthesis, and the principal methyl donor for nucleic acid, phospholipid, histone, biogenic amine, and protein methylation, methionine metabolites can participate in polyamine synthesis. Methionine metabolism disorder can aggravate the damage in the pathological state of a disease. In the occurrence and development of chronic liver diseases (CLDs), changes in various components involved in methionine metabolism can affect the pathological state through various mechanisms. A methionine-deficient diet is commonly used for building CLD models. The conversion of key enzymes of methionine metabolism methionine adenosyltransferase (MAT) 1 A and MAT2A/MAT2B is closely related to fibrosis and hepatocellular carcinoma. In vivo and in vitro experiments have shown that by intervening related enzymes or downstream metabolites to interfere with methionine metabolism, the liver injuries could be reduced. Recently, methionine supplementation has gradually attracted the attention of many clinical researchers. Most researchers agree that adequate methionine supplementation can help reduce liver damage. Retrospective analysis of recently conducted relevant studies is of profound significance. This paper reviews the latest achievements related to methionine metabolism and CLD, from molecular mechanisms to clinical research, and provides some insights into the future direction of basic and clinical research.

Associations of linoleic acid with markers of glucose metabolism and liver function in South African adults.

BACKGROUND: The relation between dietary and circulating linoleic acid (18:2 n-6, LA), glucose metabolism and liver function is not yet clear. Associations of dietary and circulating LA with glucose metabolism and liver function markers were investigated. METHODS: Cross-sectional analyses in 633 black South Africans (aged > 30 years, 62% female, 51% urban) without type 2 diabetes at baseline of the Prospective Urban Rural Epidemiology study. A cultural-sensitive 145-item food-frequency questionnaire was used to collect dietary data, including LA (percentage of energy; en%). Blood samples were collected to measure circulating LA (% total fatty acids (FA); plasma phospholipids), plasma glucose, glycosylated hemoglobin (HbA1c), serum gamma-glutamyl transferase (GGT), alanine (ALT) and aspartate aminotransferase (AST). Associations per 1 standard deviation (SD) and in tertiles were analyzed using multivariable regression. RESULTS: Mean (±SD) dietary and circulating LA was 6.8 (±3.1) en% and 16.0 (±3.5) % total FA, respectively. Dietary and circulating LA were not associated with plasma glucose or HbA1c (ß per 1 SD: - 0.005 to 0.010, P > 0.20). Higher dietary LA was generally associated with lower serum liver enzymes levels. One SD higher circulating LA was associated with 22% lower serum GGT (ß (95% confidence interval): - 0.25 (- 0.31, - 0.18), P < 0.001), but only ≤9% lower for ALT and AST. Circulating LA and serum GGT associations differed by alcohol use and locality. CONCLUSION: Dietary and circulating LA were inversely associated with markers of impaired liver function, but not with glucose metabolism. Alcohol use may play a role in the association between LA and liver function. TRIAL REGISTRATION: PURE North-West Province South Africa study described in this manuscript is part of the PURE study. The PURE study is registered in ClinicalTrials.gov (Identifier: NCT03225586; URL).

Omega-3 derivatives, specialized pro-resolving mediators: Promising therapeutic tools for the treatment of pain in chronic liver disease.

The main causes of liver injury are associated with inflammation and permanent damage. They can cause chronic liver disease (CLD), which is mainly related to viral hepatitis, alcohol consumption and non-alcoholic steatohepatitis, leading to fibrosis, cirrhosis and hepatocellular carcinoma. These conditions prevent the liver from working normally and make it begin to fail, which in turn may prompt a liver transplant. CLD and cirrhosis are the eleventh cause of death worldwide. At present, there are no approved pharmacological treatments to prevent, treat or resolve liver fibrosis. The prevalence of pain in the hepatic disease is elevated with ranges between 30% and 40%. Most of the pain drugs require hepatic function; therefore, the suitable control of pain is still a clinical challenge. Specialized pro-resolving mediators (SPM): lipoxins, resolvins, protectins and maresins, are potent endogenous molecules (nM concentrations) that modulate inflammatory body responses by reducing neutrophil infiltration, macrophage activity and pain sensitization. SPM have anti-inflammatory properties, stimulate tissue resolution, repair and regeneration, and exhibit anti-nociceptive actions. Furthermore, SPM were tried on different cellular, animal models and human observational data of liver injury, improving the pathogenesis of inflammation and fibrosis. In the present work, we will describe recent evidence that suggests that SPM can be used as a therapeutic option for CLD. Additionally, we will examine the role of SPM in the control of pain in pathologies associated with liver injury.

Review article: malnutrition/sarcopenia and frailty in patients with cirrhosis.

BACKGROUND: Malnutrition/sarcopenia and frailty are common in patients with cirrhosis and are associated with poor outcomes. AIM: To provide an overview of data on the importance, assessment and management of malnutrition/sarcopenia and frailty in cirrhosis. METHODS: A literature search was conducted in PubMed and other sources, using the search terms "sarcopenia," "muscle," "malnutrition," "cirrhosis," "liver" and "frailty" from inception to April 2019, to identify the relevant studies and international guidelines. RESULTS: The prevalence of malnutrition/sarcopenia in cirrhosis is 23%-60%. Frailty generally overlaps with malnutrition/sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition/sarcopenia in cirrhosis is complex/multifactorial and not just reduction in protein/calorie intake. Hyperammonemia appears to be the main driver of sarcopenia in cirrhosis through several molecular signalling pathways. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, they, and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. CONCLUSIONS: Malnutrition/sarcopenia and frailty are unique, inter-related and multi-dimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.

Calorie Restriction in Adulthood Reduces Hepatic Disorders Induced by Transient Postnatal Overfeeding in Mice.

Impaired early nutrition influences the risk of developing metabolic disorders in later life. We observed that transient postnatal overfeeding (OF) in mice induces long-term hepatic alterations, characterized by microsteatosis, fibrosis associated with oxidative stress (OS), and stress-induced premature senescence (SIPS). In this study, we investigated whether such changes can be reversed by moderate calorie restriction (CR). C57BL/6 male mice pups were maintained during lactation in litters adjusted to nine pups in the normal feeding (NF) group and three pups in the transient postnatal OF group. At six months of age, adult mice from the NF and OF groups were randomly assigned to an ad libitum diet or CR (daily energy supply reduced by 20%) for one month. In each group, at the age of seven months, analysis of liver structure, liver markers of OS (superoxide anion, antioxidant defenses), and SIPS (lipofuscin, p53, p21, p16, pRb/Rb, Acp53, sirtuin-1) were performed. CR in the OF group reduced microsteatosis, decreased levels of superoxide anion, and increased protein expression of catalase and superoxide dismutase. Moreover, CR decreased lipofuscin staining, p21, p53, Acp53, and p16 but increased pRb/Rb and sirtuin-1 protein expression. CR did not affect the NF group. These results suggest that CR reduces hepatic disorders induced by OF.

The Liver and Celiac Disease.

Celiac disease is a multisystem disorder. Celiac hepatitis characterized by gluten-responsive mild elevation of transaminases is the more common liver manifestation of celiac disease. Celiac disease may also be associated or coexist with other chronic liver disorders. Shared genetic risk and increased intestinal permeability have been suggested to be the most relevant events in the pathogenesis of liver injury in celiac disease. The aim of this article is to review the full spectrum of liver disorders in patients with celiac disease.

Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment.

PURPOSE: This study characterized the effects of hepatic impairment on the pharmacokinetics and safety of glecaprevir and pibrentasvir, two direct-acting antivirals used for treatment of chronic HCV infection. METHODS: HCV-negative subjects with normal hepatic function, or with mild (Child-Pugh [CP]-A), moderate (CP-B), or severe (CP-C) hepatic impairment received single doses of pibrentasvir 120 mg alone or with glecaprevir 200 mg or 300 mg (n = 6/functional group/dose). Plasma pharmacokinetics and protein binding were evaluated. Doses were separated by ≥ 14 days of washout. RESULTS: For the approved combination of glecaprevir 300 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 33% (CP-A), to 2.0-fold (CP-B), and to 11-fold (CP-C) relative to normal subjects; pibrentasvir AUC was ≤ 26% different (CP-A or CP-B) and increased to 2.1-fold (CP-C). For glecaprevir 200 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 80% (CP-A) or to 2.8-fold (CP-B), while pibrentasvir AUC was unaffected in the same subjects (≤ 12% difference). Pibrentasvir 120 mg alone AUC increased 51% (CP-A), 31% (CP-B), and to 5.2-fold (CP-C). The unbound fraction of glecaprevir was higher in CP-C subjects than normal subjects and pibrentasvir protein binding was similar across groups. The most common adverse event was headache; no events were serious. CONCLUSION: This study supported evaluation of the glecaprevir 300 mg with pibrentasvir 120-mg combination in HCV-infected subjects with CP-A hepatic impairment without dose adjustment. Elevated glecaprevir and/or pibrentasvir exposures are expected in HCV-infected patients with CP-B or CP-C hepatic impairment.

Probiotics for Gastrointestinal and Liver Diseases: An Updated Review of the Published Literature.

BACKGROUND: Probiotics can be viewed as biological agents that modify the intestinal microbiota and certain cytokine profiles, which can lead to an improvement in certain gastrointestinal diseases, including diarrhea, inflammatory bowel disease, and liver disease. DISCUSSION: Consumption of probiotics in their various forms, including yogurt, functional foods, and dietary supplements, is frequently encountered worldwide. Often, however, the correct prescription of these agents is dampened due to a lack of knowledge of the scientific evidence and the different presentations and microbial compositions of the currently available probiotic options. Here, we provide an up-to-date review of the evidence of probiotics in the prevention and treatment of various gastrointestinal diseases. OBJECTIVE: Consumption of probiotics in their various forms, including yogurt, functional foods, and dietary supplements, is frequently encountered worldwide. Often, however, the correct prescription of these agents is dampened due to a lack of knowledge of the scientific evidence and the different presentations and microbial compositions of the currently available probiotic options. METHODS/RESULTS: Here, we provide an up-to-date review of the evidence of probiotics in the prevention and treatment of various gastrointestinal diseases. CONCLUSION: While not efficacious in every disease process studied, probiotics have demonstrated some benefit in several specific gastrointestinal and liver diseases.

Nutrition in Pediatric Chronic Liver Disease.

More than one-half of children with chronic liver disease suffer from malnutrition, which leads not only to a poor quality of life and even possibly catastrophic complications, but also to poor outcomes after a liver transplantation. These children have increased metabolic demands but often decreased intake with malabsorption and altered nutrient utilization, all of which make it difficult to keep up with nutritional demands. Assessment of a patient's nutritional status should be timely, and it should be performed routinely and proactively. When specific nutritional needs are identified, these should be addressed with a multidisciplinary team approach and with the close guidance of an experienced pediatric dietician. The assessment includes anthropometric and laboratory assessments, in addition to a careful physical examination and a detailed patient history. The specific nutritional needs vary, but generally dietary intervention focuses on increasing caloric intake, supplementation with medium-chain triglycerides, and prevention of essential fatty acid and fat-soluble vitamin deficiencies. [Pediatr Ann. 2018;47(11):e445-e451.].

Prevalence of Chronic Liver Disease Among the Patients of Celiac Disease and Effect of Gluten-Free Diet on Outcome of Liver Disease: A Prospective Study.

Objectives: Descriptive reports of liver involvement in celiac disease (CD) are sparse, and the effect of a strict gluten-free diet (GFD) on the course of liver injury is also poorly understood. We conducted a study on 94 adult patients with CD and found that 39 of them were having chronic liver disease as well. We further followed patients of 'CD with CLD' with strict Gluten-free diet (GFD) for six months. Methods: We screened 94 patients of CD for CLD and found 39 patients to have CLD as well. We further followed these 39 patients of 'CD with CLD' for six month with strict gluten-free diet. Follow up was done in terms of Child Pugh score. We recorded their clinical as well as laboratory findings after 1 month, 3 months and 6 months and compared them with those at the time of recruitment. Results: The liver involvement was found in 39(41.5%) out of 94 patients celiac disease. Mean Child-Pugh score on admission was 10.22±1.09 and on first follow-up mean Child-Pugh score was 7.38±1.47 was found to be statistically highly significant (p <0.001) Mean Child-Pugh score on admission was 10.15±1.09 and on second follow-up 7.33±1.33 respectively and was statistically highly significant (p <0.001) Mean Child-Pugh score on admission was 10.12±1.09 and on third follow-up mean Child-Pugh score was 6.31±0.93 respectively was statistically highly significant (p <0.001).

Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases.

In the therapeutic strategies, the role of diet is a well-established factor that can also have an important role in liver diseases. Melatonin, identified in animals, has many antioxidant properties and it was after discovered also in plants, named phytomelatonin. These substances have a positive effect during aging and in pathological conditions too. In particular, it is important to underline that the amount of melatonin produced by pineal gland in human decreases during lifetime and its reduction in blood could be related to pathological conditions in which mitochondria and oxidative stress play a pivotal role. Moreover, it has been indicated that melatonin/phytomelatonin containing foods may provide dietary melatonin, so their ingestion through balanced diets could be sufficient to confer health benefits. In this review, the classification of liver diseases and an overview of the most important aspects of melatonin/phytomelatonin, concerning the differences among their synthesis, their presence in foods and their role in health and diseases, are summarized. The findings suggest that melatonin/phytomelatonin supplementation with diet should be considered important in preventing different disease settings, in particular in liver. Currently, more studies are needed to strengthen the potential beneficial effects of melatonin/phytomelatonin in liver diseases and to better clarify the molecular mechanisms of action.

Hepatic Complications of Anorexia Nervosa.

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric illnesses due to the widespread organ dysfunction caused by the underlying severe malnutrition. Starvation causes hepatocyte injury and death leading to a rise in aminotransferases. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases. Acute liver failure associated with coagulopathy and encephalopathy can rarely occur. Liver enzymes may also less commonly increase as part of the refeeding process due to hepatic steatosis and can be distinguished from starvation hepatitis by the finding of a fatty liver on ultrasonography. Individuals with AN and starvation-induced hepatitis are at increased risk of hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis. Gastroenterology and hepatology consultations are often requested when patients with AN and signs of hepatitis are hospitalized. It should be noted that additional laboratory testing, imaging, or liver biopsy all have low diagnostic yield, are costly, and potentially invasive, therefore, not generally recommended for diagnostic purposes. While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.

Lactobacillus rhamnosus GG reduces hepatic fibrosis in a model of chronic liver disease in rats / El Lactobacillus rhamnosus GG reduce la fibrosis hepática en un modelo de enfermedad hepática crónica en ratas

Background: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. Aim: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. Methods: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups).Two weeks after surgery, each group was randomly divided to receive 1 ml of PBS (Ctrl and BDL) or PBS containing 2.5 x 107 CFU of LGG (Ctrl-P and BDL-P) through gavages for 14 days. Euthanasia occurred 33 days after surgery when samples of blood and liver tissue were collected. Results: The hepatic gene expression of Tlr4, Tnfα, IL-6, Tgfβ, and metalloproteinase-2 and -9 were higher in the BDL groups in comparison to Ctrl. The ductular reaction evaluated by immunocontent of cytokeratin-7 (CK7) and the content of collagen were increased in BDL groups. Also, there was an imbalance in the antioxidant defenses (superoxide dismutase and catalase) and an increase in the oxidative stress marker sulfhydryl in BDL groups. The treatment with LGG significantly reduced gene expression of IL-6, collagen deposition, and ductular reaction in hepatic tissue of animals from BDL-P groups. Conclusion: The treatment with the probiotic LGG was able to reduce liver fibrosis, ductular reaction, and hepatic gene expression of IL-6 in a model of cholestatic liver disease in rats (AU)

Introducción: la disbiosis intestinal es común en la enfermedad hepática crónica y puede inducir respuestas inflamatorias y mediar la deposición hepática de colágeno. Objetivo: evaluar el efecto del probiótico Lactobacillus rhamnosus GG (LGG) en el tratamiento de la fibrosis hepática en un modelo de enfermedad hepática colestásica en ratas. Métodos: se sometió a ratas Wistar macho adultas (n = 29) a ligadura del conducto biliar común (grupo BDL) o a manipulación del conducto biliar sin ligadura (grupo Ctrl). Dos semanas después, cada grupo se dividió aleatoriamente para recibir 1 ml de PBS (Ctrl y BDL) o PBS con 2,5 x 107 UFC de LGG (Ctrl-P y BDL-P) durante 14 días. Se aplicó la eutanasia 33 días después de la cirugía y se recogieron muestras de sangre y de tejido hepático. Resultados: las expresiones hepáticas de Tlr4, Tnfα, IL-6, Tgfβ, metaloproteinasa-2 y -9 fueron mayores en los grupos BDL. La reacción ductular evaluada por el inmunocontenido de citoqueratina 7 (CK7) y el contenido de colágeno se aumentó en los grupos BDL. Además, hubo un desequilibrio en las defensas antioxidantes (superóxido dismutasa y catalasa) y un aumento en el estrés oxidativo (sulfhidrilo) en los grupos BDL. El tratamiento con LGG redujo la expresión génica de IL-6, la deposición de colágeno y la reacción ductular en el hígado de los animales del grupo BDL-P. Conclusión: el tratamiento con LGG redujo la expresión génica de IL-6 en el hígado, la fibrosis hepática y la reacción ductular en un modelo de enfermedad hepática colestásica en ratas (AU)