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Campbell KA, Trivedi HD, Chopra S. Infections in Cirrhosis: A Guide for the Clinician. Am J Med 2021; 134:727-734. [PMID: 33607090 DOI: 10.1016/j.amjmed.2021.01.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 12/31/2020] [Accepted: 01/25/2021] [Indexed: 12/13/2022]
Abstract
Cirrhosis contributes significantly to morbidity and mortality worldwide. Infections in patients with cirrhosis are common and significantly impact health-related quality of life. As our understanding of immune dysfunction associated with cirrhosis grows and as rates of drug-resistant organisms increase, the management of infections in cirrhosis has become increasingly nuanced. In this review, we discuss the current understanding of cirrhosis-associated immune deficiency, review the most common infections in patients with cirrhosis, and highlight techniques for the general clinician in the prevention and treatment of infections in this high-risk population.
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Affiliation(s)
- Kirsti A Campbell
- Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Boston, Mass.
| | - Hirsh D Trivedi
- Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Boston, Mass
| | - Sanjiv Chopra
- Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Boston, Mass
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Schiavo L, Busetto L, Cesaretti M, Zelber-Sagi S, Deutsch L, Iannelli A. Nutritional issues in patients with obesity and cirrhosis. World J Gastroenterol 2018; 24:3330-3346. [PMID: 30122874 PMCID: PMC6092576 DOI: 10.3748/wjg.v24.i30.3330] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/15/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.
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Affiliation(s)
- Luigi Schiavo
- Department of Translational Medical Science, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
- IX Division of General Surgery, Vascular Surgery and Applied Biotechnology, Naples University Policlinic, Naples 80131, Italy
| | - Luca Busetto
- Department of Medicine, University of Padua, Padua 35128, Italy
- Center for the Study and the Integrated Management of Obesity, University Hospital of Padua, Padua 35128, Italy
| | - Manuela Cesaretti
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, AP-HP, Clichy 92110, France
- Department of Nanophysics, Italian Institute of Technology, Genova 16163, Italy
| | - Shira Zelber-Sagi
- School of Public Health, University of Haifa, Haifa 3498838, Israel
- Department of Gastroenterology and Liver disease, Tel Aviv Medical Center, 62431, Tel-Aviv 62431, Israel
| | - Liat Deutsch
- Department of Gastroenterology and Liver disease, Tel Aviv Medical Center, 62431, Tel-Aviv 62431, Israel
- The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 62431, Israel
| | - Antonio Iannelli
- Digestive Unit, Archet 2 Hospital, University Hospital of Nice, F-06202, Nice, France; Inserm, U1065, Team 8 “Hepatic complications of obesity”, Nice F-06204, France
- University of Nice Sophia-Antipolis, Nice F-06107, France
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In vitro assessment of nutraceutical compounds and novel nutraceutical formulations in a liver-steatosis-based model. Lipids Health Dis 2018; 17:24. [PMID: 29402273 PMCID: PMC5800044 DOI: 10.1186/s12944-018-0663-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 01/15/2018] [Indexed: 12/19/2022] Open
Abstract
Background Steatosis is a chronic liver disease that depends on the accumulation of intracellular fatty acids. Currently, no drug treatment has been licensed for steatosis; thus, only nutritional guidelines are indicated to reduce its progression. The aim of this study is to combine different nutraceutical compounds in order to evaluate their synergistic effects on a steatosis in vitro model compared to their separate use. In particular, three different formulations based on silymarin, curcumin, vitamin E, docosahexaenoic acid (DHA), choline, and phosphatidylcholine were assayed. Methods Human hepatocellular carcinoma cells (HepG2 cell line) were treated with a mixture of fatty acids in order to induce an in vitro model of steatosic cells, and then the amount of intracellular fat was evaluated by Oil Red O staining. The peroxisome proliferator-activated receptors α and γ (PPARα and γ) expression, closely correlated to lipid metabolism, was evaluated. The efficiency of these receptors was evaluated through the study of LPL mRNA expression, a marker involved in the lipolysis mechanism. Superoxide dismutase (SOD-2) and malondialdehydes (MDA) in lipid peroxidation were assayed as specific biomarkers of oxidative stress. In addition, experiments were performed using human liver cells stressed to obtain a steatosis model. In particular, the content of the intracellular fat was assayed using Oil Red O staining, the activation of PPARα and γ was evaluated through western blotting analyses, and the LPL mRNA expression level was analyzed through qRT-PCR. Results All formulations proved effective on lipid content reduction of about 35%. The oxidative stress damage was reduced by all the substances separately and even more efficiently by the same in formulation (i.e. Formulation 1 and Formulation 3, which reduced the SOD-2 expression and induced the PPARs activation). Lipid peroxidation, was reduced about 2 fold by foormulation2 and up to 5 fold by the others compared to the cells pretreated with H2O2.Formulation 1, was more effective on PPARγ expression (2.5 fold increase) respect to the other compounds on FA treated hepathocytes. Beside, LPL was activated also by Formulation 3 and resulted in a 5 to 9 fold-increase respect to FA treated control. Conclusions Our results proved that the formulations tested could be considered suitable support to face steatosis disease beside the mandatory dietetic regimen.
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Hung CK, Bodenheimer HC. Current Treatment of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis. Clin Liver Dis 2018; 22:175-187. [PMID: 29128055 DOI: 10.1016/j.cld.2017.08.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Treatment of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is focused on patients with NASH because they are at highest risk for progressive liver disease. Current first-line treatment consists of lifestyle modifications. Patients should lose at least 7% to 10% of body weight via a combination of physical exercise and calorie restriction dieting. Surgical or endoscopic surgery for weight loss can be considered in obese patients, depending on degree of excess body weight and comorbidities. There is no currently approved pharmacotherapy for NASH. Vitamin E and pioglitazone have the most evidence of therapeutic efficacy but have limitations. The treatment modality chosen should be individualized.
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Affiliation(s)
- Chun Kit Hung
- Division of Gastroenterology, Department of Medicine, Northwell Health, 270-05 76th, Avenue, New Hyde Park, NY 11040, USA
| | - Henry C Bodenheimer
- Department of Medicine, Zucker Hofstra Northwell School of Medicine, Sandra Atlas Bass Center for Liver Diseases, Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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Abstract
Purpose of Review The purpose of this review article is to raise awareness of the significance of steatosis that exist within the spectrum of nonalcoholic fatty liver disease (NAFLD). While the impact of nonalcoholic steatohepatitis (NASH), and its potential for histologic progression to cirrhosis and hepatocellular carcinoma is widely appreciated, the impact of non-NASH NAFLD (steatosis) on morbidity and mortality is less well recognized. Recent Findings NAFLD is a spectrum of hepatic pathology with a rising prevalence worldwide. Steatosis without fibrosis carries a low risk of progression to cirrhosis but likely confers an increased risk of diabetes mellitus and cardiovascular disease. Summary About a quarter of the world population is affected by NAFLD. NAFLD represents a burden to affected individuals, economics of the health care system and contributes significantly to morbidity and mortality worldwide. An increased level of awareness and knowledge about risk factors and diagnostic strategies is needed to identify patients affected with disease.
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Perumpail BJ, Li AA, Cholankeril G, Kumari R, Ahmed A. Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis. Nutrients 2017; 9:nu9101114. [PMID: 29027963 PMCID: PMC5691730 DOI: 10.3390/nu9101114] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 09/25/2017] [Accepted: 10/09/2017] [Indexed: 12/22/2022] Open
Abstract
Aim: The aim of this work is to develop a pragmatic approach in the assessment and management strategies of patients with cirrhosis in order to optimize the outcomes in this patient population. Method: A systematic review of literature was conducted through 8 July 2017 on the PubMed Database looking for key terms, such as malnutrition, nutrition, assessment, treatment, and cirrhosis. Articles and studies looking at associations between nutrition and cirrhosis were reviewed. Results: An assessment of malnutrition should be conducted in two stages: the first, to identify patients at risk for malnutrition based on the severity of liver disease, and the second, to perform a complete multidisciplinary nutritional evaluation of these patients. Optimal management of malnutrition should focus on meeting recommended daily goals for caloric intake and inclusion of various nutrients in the diet. The nutritional goals should be pursued by encouraging and increasing oral intake or using other measures, such as oral supplementation, enteral nutrition, or parenteral nutrition. Conclusions: Although these strategies to improve nutritional support have been well established, current literature on the topic is limited in scope. Further research should be implemented to test if this enhanced approach is effective.
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Affiliation(s)
- Brandon J Perumpail
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
| | - Andrew A Li
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - Radhika Kumari
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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Cantero I, Abete I, Monreal JI, Martinez JA, Zulet MA. Fruit Fiber Consumption Specifically Improves Liver Health Status in Obese Subjects under Energy Restriction. Nutrients 2017; 9:nu9070667. [PMID: 28657604 PMCID: PMC5537782 DOI: 10.3390/nu9070667] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 06/19/2017] [Accepted: 06/22/2017] [Indexed: 02/06/2023] Open
Abstract
The prevalence of non-alcoholic-fatty-liver-disease (NAFLD) is associated with obesity, diabetes, and metabolic syndrome (MS). This study aimed to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in obese individuals with features of MS after six months of follow-up and to assess the role of fiber content in metabolic outcomes. Seventy obese individuals from the RESMENA (Reduction of Metabolic Syndrome in Navarra) study were evaluated at baseline and after six months of energy-restricted nutritional intervention (American Heart Association (AHA) and RESMENA dietary groups). Dietary records, anthropometrical data, body composition by dual energy X-ray absorptiometry (DXA), and routine laboratory measurements were analyzed by standardized methods. Regarding liver status, cytokeratin-18 fragments and several non-invasive scores of fatty liver were also assessed. The RESMENA strategy was a good and complementary alternative to AHA for the treatment of obesity-related comorbidities. Participants with higher insoluble fiber consumption (≥7.5 g/day) showed improvements in fatty liver index (FLI), hepatic steatosis index (HIS), and NAFLD liver fat score (NAFLD_LFS), while gamma-glutamyl transferase (GGT) and transaminases evidenced significant improvements as a result of fruit fiber consumption (≥8.8 g/day). Remarkably, a regression model evidenced a relationship between liver status and fiber from fruits. These results support the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction for the management of obese patients suffering fatty liver disease.
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Affiliation(s)
- Irene Cantero
- Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - Itziar Abete
- Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- CIBERObn, Physiopathology of obesity and nutrition, Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - J Ignacio Monreal
- Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
- Clinical Chemistry Department, University Clinic of Navarra, University of Navarra, 31008 Pamplona, Spain.
| | - J Alfredo Martinez
- Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- CIBERObn, Physiopathology of obesity and nutrition, Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
| | - M Angeles Zulet
- Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- CIBERObn, Physiopathology of obesity and nutrition, Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
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Abstract
Non alcoholic fatty liver disease is linked to obesity and the metabolic syndrome. As rates of obesity rise it has become the major etiology of liver dysfunction. Despite intense study the molecular mechanisms contributing to the onset of fatty liver remain debatable. Furthermore, few therapies exist and as a result dietary therapy is commonly prescribed and remains problematic. Fibroblast growth factor is a complex metabolic regulator that is synthesized in multiple organs including the liver, with resulting complex systemic effects. Several lines of evidence suggest that effects in the liver lead to decreased fat accumulation and that treatment results in reduced inflammation and fibrosis. Understanding the physiology of FGF21 is important to the understanding of liver disease and may also provide targets for future therapy.
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Affiliation(s)
- Eleftheria Maratos-Flier
- Harvard Medical School, Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, CLS 7 3 Blackfan Circle, Boston, MA 02215, United States.
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