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Jiao H, Wang H, Li J, Yang Z, Sun C. The Molecular Pathogenesis of Sarcopenia/Frailty in Cirrhosis. Semin Liver Dis 2025. [PMID: 40239708 DOI: 10.1055/a-2564-7551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
Cirrhosis is an important cause of morbidity and death in patients with chronic liver disease. It can be divided into compensatory and decompensated stages. During the decompensation period, complications such as esophageal and gastric varices hemorrhage, hepatic encephalopathy, infection, and hepatorenal syndrome are often incurred, which has a high mortality rate and leverages huge economic burden on society, healthcare resources, and individuals. Sarcopenia and frailty are common in patients with cirrhosis. The pathogenesis of sarcopenia and frailty in the context of cirrhosis is complicated and multifactorial, including overwhelming systemic inflammation, imbalance of muscle protein metabolism, malnutrition, endocrine and metabolic dysfunctions, intestinal microecological disorders, lack of physical exercise, and other aspects. Notably, accumulating evidence implicates that many patients experience sarcopenia/frailty even before the onset of liver cirrhosis. In this regard, the magnitude of liver fibrosis is closely linked to the progression of sarcopenia with reciprocal impact. In conclusion, this review article will shed light on the pathogenesis of cirrhosis complicated with sarcopenia/frailty, aimed at facilitating early diagnosis and effective management.
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Affiliation(s)
- Huanli Jiao
- Department of Health Management, Tianjin Hospital, Hexi District, Tianjin, People's Republic of China
| | - Han Wang
- Department of Health Management, Tianjin Hospital, Hexi District, Tianjin, People's Republic of China
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
| | - Ziyi Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, People's Republic of China
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Koh HH, Lee M, Kang M, Yim SH, Choi MC, Min EK, Lee JG, Joo DJ, Kim MS, Lee JS, Kim DG. Association between low fasting glucose of the living donor and risk of graft loss in the recipient after liver transplantation. Sci Rep 2025; 15:951. [PMID: 39762289 PMCID: PMC11704233 DOI: 10.1038/s41598-024-80604-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025] Open
Abstract
Several donor-specific factors influence the functional recovery and long-term outcomes of liver grafts. This study investigated the association between donor fasting glucose (DFG) and recipient outcomes after living donor liver transplantation (LDLT) in 950 cases at a single center. Patients were divided into two groups: low-DFG (< 85 mg/dL, n = 120) and control (≥ 85 mg/dL, n = 830). The five-year graft survival rate was significantly lower in the low-DFG group (71.5%) compared to the control group (80.0%) (P = 0.02). Multivariable Cox regression analysis showed that low DFG was independently associated with graft loss (hazard ratio 1.72, 95% CI 1.15-2.56, P = 0.008). In propensity score-matched groups, the low-DFG group also had lower survival rates (71% vs. 83.1%, P = 0.004). The presence of additional risk factors, such as low graft-to-recipient weight ratio, older donor age, and longer cold ischemic time, further reduced graft survival in the low-DFG group. A DFG level < 85 mg/dL is associated with higher risk of graft failure after LDLT, especially when combined with other risk factors. Low DFG should be considered a prognostic marker in LDLT planning, with potential to improve patient outcomes as further research clarifies the underlying pathophysiological mechanisms.
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Affiliation(s)
- Hwa-Hee Koh
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Minyoung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Minyu Kang
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Hyuk Yim
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Mun Chae Choi
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun-Ki Min
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Geun Lee
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Dong Jin Joo
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
| | - Deok-Gie Kim
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea.
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Ata F, Choudry H, Khan AA, Anum, Khamees I, Al-Sadi A, Mohamed A, Malkawi L, Aljaloudi E. A systematic review of literature on Insulin-like growth factor-2-mediated hypoglycaemia in non-islet cell tumours. Endocrinol Diabetes Metab 2024; 7:e00471. [PMID: 38411039 PMCID: PMC10897872 DOI: 10.1002/edm2.471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/17/2024] [Accepted: 01/21/2024] [Indexed: 02/28/2024] Open
Abstract
INTRODUCTION Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication. METHODS Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16. RESULTS The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes. CONCLUSION This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates.
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Affiliation(s)
- Fateen Ata
- Department of Endocrinology and Metabolism, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Hassan Choudry
- Internal Medicine, University Hospital of Coventry and Warwickshire (UHCW), Coventry, UK
| | - Adeel Ahmad Khan
- Department of Endocrinology and Metabolism, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Anum
- Department of Internal Medicine, Punjab Medical College/Faisalabad Medical University, Faisalabad, Pakistan
| | - Ibrahim Khamees
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Anas Al-Sadi
- Department of Internal Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Abdelaziz Mohamed
- Department of Internal Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Lujain Malkawi
- Department of infectious diseases, University of Missouri-Kansas City, Missouri, USA
| | - Esra'a Aljaloudi
- Department of Family Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
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Fang LZ, Jin HX, Zhao N, Wu YP, Shi YQ. Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports. World J Clin Cases 2024; 12:157-162. [PMID: 38292637 PMCID: PMC10824187 DOI: 10.12998/wjcc.v12.i1.157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/07/2023] [Accepted: 12/19/2023] [Indexed: 01/02/2024] Open
Abstract
BACKGROUND Glucose imbalance is common in total parenteral nutrition (TPN). Hypoglycemia seems to be less frequent than hyperglycemia, but it influences the clinical outcome to a greater extent. Therefore, it should be effectively prevented and treated. However, there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury. CASE SUMMARY We present three patients with liver cell injury who developed severe hypoglycemia during or after TPN infusion. The causes of severe hypoglycemia and glucose-raising strategies were discussed. According to the physiological characteristics of the hepatocellular injury, the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases. We simultaneously reduced the dose of insulin and fat emulsion, and increased the dose of glucose in TPN. The blood glucose level was restored to normal range and clinical symptoms were eliminated. CONCLUSION When hypoglycemia occurs during or after TPN in patients with hepatocellular injury, physicians need to simultaneously reduce insulin and fat emulsion, and increase glucose, and correct severe hypoglycemia in time to reduce its adverse consequences.
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Affiliation(s)
- Ling-Zhi Fang
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Hui-Xin Jin
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Na Zhao
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Yu-Pei Wu
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Ying-Qin Shi
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
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Weiler N, Bojunga J. Ernährung bei fortgeschrittener Leberzirrhose und perioperativ bei Lebertransplantation. DIE GASTROENTEROLOGIE 2023; 18:308-316. [DOI: 10.1007/s11377-023-00706-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/16/2023] [Indexed: 01/04/2025]
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Liu Q, Gong C, Geng Y, You J. Elevated alanine transaminase is nonlinearly associated with in-hospital death in ICU-admitted diabetic ketoacidosis patients. Diabetes Res Clin Pract 2023; 197:110555. [PMID: 36738833 DOI: 10.1016/j.diabres.2023.110555] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 01/18/2023] [Accepted: 01/23/2023] [Indexed: 02/05/2023]
Abstract
AIMS To investigate the association between alanine transaminase (ALT) and in-hospital death in patients admitted to the intensive care unit for diabetic ketoacidosis (DKA). METHODS A cohort of 2,684 patients was constructed from the eICU Collaborative Research Database. Baseline demographic and clinical characteristics were summarized. Cox regressions with restricted cubic spline functions were modelled to explore the association between alanine transaminase and in-hospital death. Subgroup analyses were conducted between sexes, age groups, and people with/without obesity. RESULTS After adjusting multiple confounders, a nonlinear, S-shaped association between ALT and in-hospital death was found. Compared to patients at median ALT, patients at the 90th percentile of ALT have a 1.88 (95 % confidence interval [CI]: 1.34-2.62) times higher hazard of in-hospital death in the unstratified cohort. Similar results were found in males (hazard ratio [HR] = 1.69, 95 % CI: 1.24-2.30); patients aged under 65 years (HR = 1.65, 95 % CI: 1.09-2.49); patients aged 65 years or above (HR = 3.45, 95 % CI: 1.67-7.14); non-obese patients (HR = 1.52, 95 % CI: 1.00-2.32); and obese patients (HR = 2.76, 95 % CI: 1.38-5.54). CONCLUSIONS Elevated ALT is robustly associated with in-hospital death in ICU-admitted DKA patients across several subgroups. Close monitoring of ALT in these patients is recommended.
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Affiliation(s)
- Qiaoling Liu
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom.
| | - Chen Gong
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yunjie Geng
- Research Institute of Statistical Sciences, National Bureau of Statistics, Beijing, China
| | - Jiuhong You
- Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Reshetnyak VI, Maev IV. Mechanism for development of malnutrition in primary biliary cholangitis. World J Meta-Anal 2022; 10:81-98. [DOI: 10.13105/wjma.v10.i3.81] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 04/14/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that is associated with impaired biliary excretion processes. Along with the development of cholestasis, there is a deficient flow of bile acids into the intestinal lumen causing malnutrition (MN) that is manifested in deficiencies of both macro- and micronutrients. The mechanism for development of trophological insufficiency is multifactorial. However, the trigger of MN in PBC is impaired enterohepatic circulation of bile acids. The ingress of bile acids with a detergent effect into the general bloodstream, followed by elimination via the kidneys and skin, triggers a cascade of metabolic disturbances, which leads to the gradual development and progression of calorie MN. The latter gradually transforms into protein-calorie MN (PСM) (as marasmus) due to the insufficient entry of bile acids into the duodenum, which is accompanied by a decrease in the emulsification, hydrolysis, and absorption of fats and fat-soluble vitamins, as well as disturbance of intestinal motility and bacterial overgrowth. Fat-soluble vitamin deficiencies complement PСM with vitamin and mineral MN. The development of hepatocellular failure enhances the progression of PСM due to the impaired protein synthetic function of hepatocytes in the advanced stage of PBC, which results in deficiency of not only the somatic but also the visceral pool of proteins. A mixed PСM form of marasmus and kwashiorkor develops. Early recognition of energy, protein, micronutrient, and macronutrient deficiencies is of great importance because timely nutritional support can improve liver function and quality of life in patients with PBC. In this case, it is important to know what type (energy, protein-calorie, vitamin, and vitamin-mineral) and form (marasmus, marasmus-kwashiorkor) of MN is present in the patient and how it is associated with the stage of the disease. Therefore, it is recommended to screen all patients with PBC for MN, from the early asymptomatic stage of the disease in order to identify and avoid preventable complications, such as fatigue, malaise, performance decrement, sarcopenia, osteoporosis, and hepatic encephalopathy, which will be able to provide appropriate nutritional support for correction of the trophological status.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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Non-Invasive Analysis of Human Liver Metabolism by Magnetic Resonance Spectroscopy. Metabolites 2021; 11:metabo11110751. [PMID: 34822409 PMCID: PMC8623827 DOI: 10.3390/metabo11110751] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 10/26/2021] [Accepted: 10/26/2021] [Indexed: 11/16/2022] Open
Abstract
The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform on the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.
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Traub J, Reiss L, Aliwa B, Stadlbauer V. Malnutrition in Patients with Liver Cirrhosis. Nutrients 2021; 13:540. [PMID: 33562292 PMCID: PMC7915767 DOI: 10.3390/nu13020540] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 02/04/2021] [Accepted: 02/04/2021] [Indexed: 12/13/2022] Open
Abstract
Liver cirrhosis is an increasing public health threat worldwide. Malnutrition is a serious complication of cirrhosis and is associated with worse outcomes. With this review, we aim to describe the prevalence of malnutrition, pathophysiological mechanisms, diagnostic tools and therapeutic targets to treat malnutrition. Malnutrition is frequently underdiagnosed and occurs-depending on the screening methods used and patient populations studied-in 5-92% of patients. Decreased energy and protein intake, inflammation, malabsorption, altered nutrient metabolism, hypermetabolism, hormonal disturbances and gut microbiome dysbiosis can contribute to malnutrition. The stepwise diagnostic approach includes a rapid prescreen, the use of a specific screening tool, such as the Royal Free Hospital Nutritional Prioritizing Tool and a nutritional assessment by dieticians. General dietary measures-especially the timing of meals-oral nutritional supplements, micronutrient supplementation and the role of amino acids are discussed. In summary malnutrition in cirrhosis is common and needs more attention by health care professionals involved in the care of patients with cirrhosis. Screening and assessment for malnutrition should be carried out regularly in cirrhotic patients, ideally by a multidisciplinary team. Further research is needed to better clarify pathogenic mechanisms such as the role of the gut-liver-axis and to develop targeted therapeutic strategies.
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Affiliation(s)
- Julia Traub
- Department of Clinical Medical Nutrition, University Hospital Graz, 8036 Graz, Austria; (J.T.); (L.R.)
| | - Lisa Reiss
- Department of Clinical Medical Nutrition, University Hospital Graz, 8036 Graz, Austria; (J.T.); (L.R.)
| | - Benard Aliwa
- Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria;
| | - Vanessa Stadlbauer
- Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria;
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10
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Marco-Rius I, Wright AJ, Hu DE, Savic D, Miller JJ, Timm KN, Tyler D, Brindle KM, Comment A. Probing hepatic metabolism of [2- 13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR. MAGMA (NEW YORK, N.Y.) 2021; 34:49-56. [PMID: 32910316 PMCID: PMC7910257 DOI: 10.1007/s10334-020-00884-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 08/07/2020] [Accepted: 08/27/2020] [Indexed: 01/06/2023]
Abstract
OBJECTIVES To enhance detection of the products of hyperpolarized [2-13C]dihydroxyacetone metabolism for assessment of three metabolic pathways in the liver in vivo. Hyperpolarized [2-13C]DHAc emerged as a promising substrate to follow gluconeogenesis, glycolysis and the glycerol pathways. However, the use of [2-13C]DHAc in vivo has not taken off because (i) the chemical shift range of [2-13C]DHAc and its metabolic products span over 144 ppm, and (ii) 1H decoupling is required to increase spectral resolution and sensitivity. While these issues are trivial for high-field vertical-bore NMR spectrometers, horizontal-bore small-animal MR scanners are seldom equipped for such experiments. METHODS Real-time hepatic metabolism of three fed mice was probed by 1H-decoupled 13C-MR following injection of hyperpolarized [2-13C]DHAc. The spectra of [2-13C]DHAc and its metabolic products were acquired in a 7 T small-animal MR scanner using three purpose-designed spectral-spatial radiofrequency pulses that excited a spatial bandwidth of 8 mm with varying spectral bandwidths and central frequencies (chemical shifts). RESULTS The metabolic products detected in vivo include glycerol 3-phosphate, glycerol, phosphoenolpyruvate, lactate, alanine, glyceraldehyde 3-phosphate and glucose 6-phosphate. The metabolite-to-substrate ratios were comparable to those reported previously in perfused liver. DISCUSSION Three metabolic pathways can be probed simultaneously in the mouse liver in vivo, in real time, using hyperpolarized DHAc.
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Affiliation(s)
- Irene Marco-Rius
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
- Institute for Bioengineering of Catalonia, Barcelona, Spain.
| | - Alan J Wright
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | - De-En Hu
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | - Dragana Savic
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Division of Medicine, University of Oxford, Oxford, UK
| | - Jack J Miller
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
- Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Division of Medicine, University of Oxford, Oxford, UK
| | - Kerstin N Timm
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
| | - Damian Tyler
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Division of Medicine, University of Oxford, Oxford, UK
| | - Kevin M Brindle
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | - Arnaud Comment
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
- General Electric Healthcare, Chalfont St Giles, UK
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11
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Philips CA, Ahamed R, Rajesh S, George T, Mohanan M, Augustine P. Update on diagnosis and management of sepsis in cirrhosis: Current advances. World J Hepatol 2020; 12:451-474. [PMID: 32952873 PMCID: PMC7475781 DOI: 10.4254/wjh.v12.i8.451] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 05/28/2020] [Accepted: 06/27/2020] [Indexed: 02/06/2023] Open
Abstract
Sepsis and septic shock are catastrophic disease entities that portend high mortality in patients with cirrhosis. In cirrhosis, hemodynamic perturbations, immune dysregulation, and persistent systemic inflammation with altered gut microbiota in the background of portal hypertension enhance the risk of infections and resistance to antimicrobials. Patients with cirrhosis develop recurrent life-threatening infections that progress to multiple organ failure. The definition, pathophysiology, and treatment options for sepsis have been ever evolving. In this exhaustive review, we discuss novel advances in the understanding of sepsis, describe current and future biomarkers and scoring systems for sepsis, and delineate newer modalities and adjuvant therapies for the treatment of sepsis from existing literature to extrapolate the same concerning the management of sepsis in cirrhosis. We also provide insights into the role of gut microbiota in initiation and progression of sepsis and finally, propose a treatment algorithm for management of sepsis in patients with cirrhosis.
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Affiliation(s)
- Cyriac Abby Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Rizwan Ahamed
- Gastroenterology and Advanced G.I Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Sasidharan Rajesh
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Tom George
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Meera Mohanan
- Anaesthesia and Critical Care, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Philip Augustine
- Gastroenterology and Advanced G.I Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
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12
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Meyer F, Bannert K, Wiese M, Esau S, Sautter LF, Ehlers L, Aghdassi AA, Metges CC, Garbe LA, Jaster R, Lerch MM, Lamprecht G, Valentini L. Molecular Mechanism Contributing to Malnutrition and Sarcopenia in Patients with Liver Cirrhosis. Int J Mol Sci 2020; 21:E5357. [PMID: 32731496 PMCID: PMC7432938 DOI: 10.3390/ijms21155357] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 07/24/2020] [Accepted: 07/24/2020] [Indexed: 02/07/2023] Open
Abstract
Liver cirrhosis is frequently accompanied by disease-related malnutrition (DRM) and sarcopenia, defined as loss of skeletal muscle mass and function. DRM and sarcopenia often coexist in cirrhotic patients and are associated with increased morbidity and mortality. The clinical manifestation of both comorbidities are triggered by multifactorial mechanisms including reduced nutrient and energy intake caused by dietary restrictions, anorexia, neuroendocrine deregulation, olfactory and gustatory deficits. Maldigestion and malabsorption due to small intestinal bacterial overgrowth, pancreatic insufficiency or cholestasis may also contribute to DRM and sarcopenia. Decreased protein synthesis and increased protein degradation is the cornerstone mechanism to muscle loss, among others mediated by disease- and inflammation-mediated metabolic changes, hyperammonemia, increased myostatin and reduced human growth hormone. The concise pathophysiological mechanisms and interactions of DRM and sarcopenia in liver cirrhosis are not completely understood. Furthermore, most knowledge in this field are based on experimental models, but only few data in humans exist. This review summarizes known and proposed molecular mechanisms contributing to malnutrition and sarcopenia in liver cirrhosis and highlights remaining knowledge gaps. Since, in the prevention and treatment of DRM and sarcopenia in cirrhotic patients, more research is needed to identify potential biomarkers for diagnosis and development of targeted therapeutic strategies.
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Affiliation(s)
- Fatuma Meyer
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
| | - Karen Bannert
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Mats Wiese
- Division of Gastroenterology, Endocrinology and Nutritional Medicine, Department of Internal Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany; (M.W.); (A.A.A.); (M.M.L.)
| | - Susanne Esau
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
| | - Lea F. Sautter
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Luise Ehlers
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Ali A. Aghdassi
- Division of Gastroenterology, Endocrinology and Nutritional Medicine, Department of Internal Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany; (M.W.); (A.A.A.); (M.M.L.)
| | - Cornelia C. Metges
- Institute of Nutritional Physiology ‘Oskar Kellner’, Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany;
| | - Leif-A. Garbe
- Department of Agriculture and Food Sciences, University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany;
| | - Robert Jaster
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Markus M. Lerch
- Division of Gastroenterology, Endocrinology and Nutritional Medicine, Department of Internal Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany; (M.W.); (A.A.A.); (M.M.L.)
| | - Georg Lamprecht
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Luzia Valentini
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
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Myeloid cell deletion of Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) induces non-alcoholic steatohepatitis. PLoS One 2019; 14:e0225332. [PMID: 31800592 PMCID: PMC6892561 DOI: 10.1371/journal.pone.0225332] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 11/01/2019] [Indexed: 12/12/2022] Open
Abstract
Background and aim Non-alcoholic steatohepatitis (NASH) is predicted to become the most common cause of cirrhosis and liver failure. Risk factors include obesity, insulin resistance and diabetes. Macrophages and other myeloid cells play crucial roles in initiating and driving inflammation. Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) is a transcription factor which binds to a range of partners to mediate responses to environmental signals, including the diet. In people with diabetes it is decreased in liver. We hypothesised that myeloid cell ARNT activity may contribute to the development of liver pathology. Methods Floxed-ARNT mice were bred with LysM-Cre mice to generate mice with reduced ARNT in myeloid cells. Animals were fed a high fat diet (HFD) and liver pathology was assessed. Histology, mRNA, fat accumulation and metabolism were studied. Results Animals with reduced myeloid ARNT developed steatohepatitis on a HFD, with additional alterations of metabolism and fat deposition. Steatohepatitis was accompanied by hepatic macrophage infiltration and expression of both M1 and M2 markers. Expression of mRNAs for Cxcl1, Mcp-1, Tnf-α and Tgf-β1 were increased. Human livers from controls and people with NASH were tested; ARNT mRNA was decreased by 80% (p = 0.0004). Conclusions Decreased myeloid ARNT may play a role in the conversion from non-alcoholic fatty liver to steatohepatitis. Increasing ARNT may be a therapeutic strategy to reduce NASH.
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Takeda Y, Fujita Y, Bessho R, Sato M, Abe T, Yanagimachi T, Sakagami H, Abiko A, Takiyama Y, Ota T, Haneda M. Increment of plasma glucose by exogenous glucagon is associated with present and future renal function in type 2 diabetes:a retrospective study from glucagon stimulation test. BMC Endocr Disord 2019; 19:99. [PMID: 31615494 PMCID: PMC6792190 DOI: 10.1186/s12902-019-0428-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 09/16/2019] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Glucagon stimulation test (GST) is often employed to assess the insulin reserve of the pancreatic beta cells in diabetic subjects. The clinical significance of the increment of plasma glucose (Δglucose) by exogenous glucagon during GST has not been elucidated. We investigated the relationship between Δglucose and clinical parameters including the liver and renal function in type 2 diabetic subjects, since we hypothesized that Δglucose is associated with the liver and renal function reflecting the capacity for gluconeogenesis in the organs. METHODS A total of 209 subjects with type 2 diabetes who underwent GST during admission were included in this cross-sectional study. We defined the difference between plasma glucose at fasting and 6 min after intravenous injection of 1 mg glucagon as Δglucose. We assessed correlations between Δglucose and clinical parameters such as diabetic duration, BMI, HbA1c, beta cell function, serum free fatty acids (FFA) which is known to stimulate gluconeogenesis, liver function, the indices of liver function, renal function, and urinary albumin excretion (UAE). RESULTS In correlation analysis, Δglucose positively correlated to FFA and estimated glomerular filtration rate (eGFR), but inversely to serum creatinine and cystatin C, although Δglucose showed no correlation with both liver function and the indices of residual liver function. Multiple regression analysis revealed that Δglucose was an independent determinant for the eGFR after 1 year, equally BMI, HbA1c, serum lipids, and UAE, which are known as the predictors for the development of chronic kidney disease. CONCLUSION Our results suggest that Δglucose during GST might be related to gluconeogenesis in the kidney and could be the determinant of future renal function in type 2 diabetes.
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Affiliation(s)
- Yasutaka Takeda
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Yukihiro Fujita
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan.
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
| | - Ryoichi Bessho
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Mao Sato
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Tomoe Abe
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Tsuyoshi Yanagimachi
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan
| | - Hidemitsu Sakagami
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Atsuko Abiko
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Yumi Takiyama
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Tsuguhito Ota
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Masakazu Haneda
- Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
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Yao J, Han W, Ren X, Yuan L, Xu J, Duan Z. Improvement of energy substrate metabolism by late evening snack supplementation in patients with liver cirrhosis: a meta-analysis. Ther Clin Risk Manag 2019; 15:659-668. [PMID: 31190846 PMCID: PMC6526777 DOI: 10.2147/tcrm.s201564] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 04/08/2019] [Indexed: 12/11/2022] Open
Abstract
Aim: Malnutrition is one of the most common complications in patients with liver cirrhosis. Abnormal energy substrate metabolism may contribute to aggravation of malnutrition. Late evening snack (LESs) supplementation has been recommended as an intervention to reduce starvation time and improve nutritional status. Published studies have analyzed the effect of LESs on the branched-chain amino acid (BCAA)/tyrosine ratio (BTR) and oxidation rate of fat and carbohydrate in patients with liver cirrhosis. Methods: We searched PubMed, Cochrane Library, Web of Science and Embase for relevant research from January 2000 to October 2018. The primary outcome for this analysis was changes in BTR and fat and carbohydrate oxidation in patients with liver cirrhosis. Results: A total of 9 articles, containing 211 patients, were included in this analysis. The results supported that supplementation with BCAA-enriched LESs improved BTR, and long-term supplementation with BCAAs (>1 month) may be more beneficial than short-term supplementation (<1 month) in patients with liver cirrhosis. In addition, supplementation with BCAAs may increase the oxidation rate of carbohydrates and decrease the oxidation rate of fat. Furthermore, compared with liquid-enriched LESs, BCAA was a better choice for increasing the oxidation of carbohydrates and decreasing the rate of fat oxidation. Conclusion: BCAA-enriched LES supplementation is an appropriate nutritional intervention to improve abnormal energy substrate metabolism, which may improve malnutrition in patients with liver cirrhosis. Further research is needed on the long-term benefit and improved survival in patients with liver cirrhosis.
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Affiliation(s)
- Jia Yao
- Department of Gastroenterology and General Surgery, Shanxi Dayi Hospital, Taiyuan, People's Republic of China
| | - Weijia Han
- Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, People's Republic of China
| | - Xiaojing Ren
- Department of Gastroenterology and General Surgery, Shanxi Dayi Hospital, Taiyuan, People's Republic of China
| | - Lili Yuan
- Department of Gastroenterology and General Surgery, Shanxi Dayi Hospital, Taiyuan, People's Republic of China
| | - Jun Xu
- Department of Gastroenterology and General Surgery, Shanxi Dayi Hospital, Taiyuan, People's Republic of China
| | - Zhongping Duan
- Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, People's Republic of China
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Mathioudakis NN, Everett E, Routh S, Pronovost PJ, Yeh HC, Golden SH, Saria S. Development and validation of a prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults. BMJ Open Diabetes Res Care 2018; 6:e000499. [PMID: 29527311 PMCID: PMC5841507 DOI: 10.1136/bmjdrc-2017-000499] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 02/02/2018] [Accepted: 02/10/2018] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE To develop and validate a multivariable prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults. RESEARCH DESIGN AND METHODS We collected pharmacologic, demographic, laboratory, and diagnostic data from 128 657 inpatient days in which at least 1 unit of subcutaneous insulin was administered in the absence of intravenous insulin, total parenteral nutrition, or insulin pump use (index days). These data were used to develop multivariable prediction models for biochemical and clinically significant hypoglycemia (blood glucose (BG) of ≤70 mg/dL and <54 mg/dL, respectively) occurring within 24 hours of the index day. Split-sample internal validation was performed, with 70% and 30% of index days used for model development and validation, respectively. RESULTS Using predictors of age, weight, admitting service, insulin doses, mean BG, nadir BG, BG coefficient of variation (CVBG), diet status, type 1 diabetes, type 2 diabetes, acute kidney injury, chronic kidney disease (CKD), liver disease, and digestive disease, our model achieved a c-statistic of 0.77 (95% CI 0.75 to 0.78), positive likelihood ratio (+LR) of 3.5 (95% CI 3.4 to 3.6) and negative likelihood ratio (-LR) of 0.32 (95% CI 0.30 to 0.35) for prediction of biochemical hypoglycemia. Using predictors of sex, weight, insulin doses, mean BG, nadir BG, CVBG, diet status, type 1 diabetes, type 2 diabetes, CKD stage, and steroid use, our model achieved a c-statistic of 0.80 (95% CI 0.78 to 0.82), +LR of 3.8 (95% CI 3.7 to 4.0) and -LR of 0.2 (95% CI 0.2 to 0.3) for prediction of clinically significant hypoglycemia. CONCLUSIONS Hospitalized patients at risk of insulin-associated hypoglycemia can be identified using validated prediction models, which may support the development of real-time preventive interventions.
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Affiliation(s)
- Nestoras Nicolas Mathioudakis
- Division of Endocrinology, Diabetes and Metabolism, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Estelle Everett
- Division of Endocrinology, Diabetes and Metabolism, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Shuvodra Routh
- Division of Endocrinology, Diabetes and Metabolism, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Peter J Pronovost
- Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Hsin-Chieh Yeh
- Division of Endocrinology, Diabetes and Metabolism, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Sherita Hill Golden
- Division of Endocrinology, Diabetes and Metabolism, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Suchi Saria
- Department of Computer Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA
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Salam OMA, Sleem AA, Omara EA, Hassan NS. Effect of Ribavirin Alone or Combined with Silymarin on Carbon Tetrachloride Induced Hepatic Damage in Rats. Drug Target Insights 2017. [DOI: 10.1177/117739280700200014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Omar M.E. Abdel Salam
- Department of Pharmacology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
| | - Amany A. Sleem
- Department of Pharmacology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
| | - Enayat A. Omara
- Department of Pathology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
| | - Nabila S. Hassan
- Department of Pathology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
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18
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Yang CH, Perumpail BJ, Yoo ER, Ahmed A, Kerner JA. Nutritional Needs and Support for Children with Chronic Liver Disease. Nutrients 2017; 9:nu9101127. [PMID: 29035331 PMCID: PMC5691743 DOI: 10.3390/nu9101127] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 10/08/2017] [Accepted: 10/11/2017] [Indexed: 12/31/2022] Open
Abstract
Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional.
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Affiliation(s)
- Christine H Yang
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Lucile Packard Children's Hospital, Palo Alto, Stanford, CA 94304, USA.
| | - Brandon J Perumpail
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
| | - Eric R Yoo
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, USA.
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - John A Kerner
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Lucile Packard Children's Hospital, Palo Alto, Stanford, CA 94304, USA.
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19
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Affiliation(s)
- Wednesday Marie A Sevilla
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA
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20
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Pershina AG, Ivanov VV, Efimova LV, Shevelev OB, Vtorushin SV, Perevozchikova TV, Sazonov AE, Ogorodova LM. Magnetic resonance imaging and spectroscopy for differential assessment of liver abnormalities induced by Opisthorchis felineus in an animal model. PLoS Negl Trop Dis 2017; 11:e0005778. [PMID: 28708894 PMCID: PMC5529022 DOI: 10.1371/journal.pntd.0005778] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 07/26/2017] [Accepted: 07/05/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND European liver fluke Opisthorchis felineus, causing opisthorchiasis disease, is widespread in Russia, Ukraine, Kazakhstan and sporadically detected in the EU countries. O. felineus infection leads to hepatobiliary pathological changes, cholangitis, fibrosis and, in severe cases, malignant transformation of bile ducts. Due to absence of specific symptoms, the infection is frequently neglected for a long period. The association of opisthorchiasis with almost incurable bile duct cancer and rising international migration of people that increases the risk of the parasitic etiology of liver fibrosis in non-endemic regions determine high demand for development of approaches to opisthorchiasis detection. METHODOLOGY/PRINCIPAL FINDINGS In vivo magnetic resonance imaging and spectroscopy (MRI and MRS) were applied for differential assessment of hepatic abnormalities induced by O. felineus in an experimental animal model. Correlations of the MR-findings with the histological data as well as the data of the biochemical analysis of liver tissue were found. MRI provides valuable information about the severity of liver impairments induced by opisthorchiasis. An MR image of O. felineus infected liver has a characteristic pattern that differs from that of closely related liver fluke infections. 1H and 31P MRS in combination with biochemical analysis data showed that O. felineus infection disturbed hepatic metabolism of the host, which was accompanied by cholesterol accumulation in the liver. CONCLUSIONS A non-invasive approach based on the magnetic resonance technique is very advantageous and may be successfully used not only for diagnosing and evaluating liver damage induced by O. felineus, but also for investigating metabolic changes arising in the infected organ. Since damages induced by the liver fluke take place in different liver lobes, MRI has the potential to overcome liver biopsy sampling variability that limits predictive validity of biopsy analysis for staging liver fluke-induced fibrosis.
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Affiliation(s)
- Alexandra G. Pershina
- Central Research Laboratory, Siberian State Medical University, Tomsk, Russia
- Department of Biotechnology and Organic Chemistry, National Research Tomsk Polytechnic University, Tomsk, Russia
- * E-mail:
| | - Vladimir V. Ivanov
- Central Research Laboratory, Siberian State Medical University, Tomsk, Russia
| | - Lina V. Efimova
- Central Research Laboratory, Siberian State Medical University, Tomsk, Russia
| | - Oleg B. Shevelev
- Center for Genetic Resources of Laboratory Animals, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
| | - Sergey V. Vtorushin
- Central Research Laboratory, Siberian State Medical University, Tomsk, Russia
| | | | - Alexey E. Sazonov
- Central Research Laboratory, Siberian State Medical University, Tomsk, Russia
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21
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Zheng Z, Gelling RW. Attenuation of Carbon Tetrachloride-Induced Hepatic Toxicity by a Dietary Supplement. J Diet Suppl 2017; 14:121-131. [PMID: 27471884 DOI: 10.1080/19390211.2016.1205702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Advanced liver disease (ALD) is often characterized with overt malnutrition and liver fibrosis. In this study, a dietary supplement (DS) was first developed, including branch chain amino acids, fat soluble vitamins, zinc, medium chain triglycerides, soy lecithin, L-carnitine, and n-3 polyunsaturated fatty acids. Benefits of DS were then tested using an ALD rat model treated with carbon tetrachloride (CCl4) for 6, 8, and 10 weeks, respectively. Our study showed that CCl4-induced drop of serum albumin and ratio of branch chain to aromatic amino acids were significantly prevented at all three time points. DS also mitigated CCl4-induced elevation of classical liver function markers (alanine aminotransferase, aspartate aminotransferase, and bilirubin) at certain time points, depending on specific liver function markers. Moreover, CCl4-induced liver fibrosis was strongly inhibited at all three time points in a transforming growth factor beta (TGF-β) independent manner. These findings indicated multi-faceted benefits of DS in this animal model, suggesting that it could be a useful adjunctive treatment of ALD in clinic.
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Affiliation(s)
- Zhiqiang Zheng
- a Abbott Nutrition Research & Development Center , Shanghai , P. R. China
| | - Richard W Gelling
- b Abbott Nutrition Research & Development Center , Singapore , Singapore
- c Department of Medicine, Yong Loo Lin School of Medicine , National University of Singapore , Singapore , Singapore
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Valkovič L, Chmelík M, Krššák M. In-vivo 31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism. Anal Biochem 2017; 529:193-215. [PMID: 28119063 PMCID: PMC5478074 DOI: 10.1016/j.ab.2017.01.018] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 01/13/2017] [Accepted: 01/19/2017] [Indexed: 01/18/2023]
Abstract
In addition to direct assessment of high energy phosphorus containing metabolite content within tissues, phosphorus magnetic resonance spectroscopy (31P-MRS) provides options to measure phospholipid metabolites and cellular pH, as well as the kinetics of chemical reactions of energy metabolism in vivo. Even though the great potential of 31P-MR was recognized over 30 years ago, modern MR systems, as well as new, dedicated hardware and measurement techniques provide further opportunities for research of human biochemistry. This paper presents a methodological overview of the 31P-MR techniques that can be used for basic, physiological, or clinical research of human skeletal muscle and liver in vivo. Practical issues of 31P-MRS experiments and examples of potential applications are also provided. As signal localization is essential for liver 31P-MRS and is important for dynamic muscle examinations as well, typical localization strategies for 31P-MR are also described.
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Affiliation(s)
- Ladislav Valkovič
- High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, Oxford, United Kingdom; Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia.
| | - Marek Chmelík
- High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria; Institute for Clinical Molecular MRI in Musculoskeletal System, Karl Landsteiner Society, Vienna, Austria
| | - Martin Krššák
- High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria; Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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23
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Marco-Rius I, von Morze C, Sriram R, Cao P, Chang GY, Milshteyn E, Bok RA, Ohliger MA, Pearce D, Kurhanewicz J, Larson PEZ, Vigneron DB, Merritt M. Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2- 13 C]dihydroxyacetone. Magn Reson Med 2016; 77:65-73. [PMID: 27859575 DOI: 10.1002/mrm.26525] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 10/02/2016] [Accepted: 10/03/2016] [Indexed: 01/18/2023]
Abstract
PURPOSE To investigate acute changes in glucose metabolism in liver and kidneys in vivo after a bolus injection of either fructose or glucose, using hyperpolarized [2-13 C]dihydroxyacetone. METHODS Spatially registered, dynamic, multislice MR spectroscopy was acquired for the metabolic products of [2-13 C]dihydroxyacetone in liver and kidneys. Metabolism was probed in 13 fasted rats at three time points: 0, 70, and 140 min. At 60 min, rats were injected intravenously with fructose (n = 5) or glucose (n = 4) at 0.8 g/kg to initiate acute response. Controls (n = 4) did not receive a carbohydrate challenge. RESULTS Ten minutes after fructose infusion, levels of [2-13 C]phosphoenolpyruvate and [2-13 C]glycerol-3-phosphate halved in liver: 51% (P = 0.0010) and 47% (P = 0.0001) of baseline, respectively. Seventy minutes later, levels returned to baseline. The glucose challenge did not alter the signals significantly, nor did repeated administration of the dihydroxyacetone imaging bolus. In kidneys, no statistically significant changes were detected after sugar infusion other than a 20% increase of the glycerol-3-phosphate signal between 10 and 80 min after fructose injection (P = 0.0028). CONCLUSION Hyperpolarized [2-13 C]dihydroxyacetone detects a real-time, transient metabolic response of the liver to an acute fructose challenge. Observed effects possibly include ATP depletion and changes in the unlabeled pool sizes of glycolytic intermediates. Magn Reson Med 77:65-73, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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Affiliation(s)
- Irene Marco-Rius
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Cornelius von Morze
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Renuka Sriram
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Peng Cao
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Gene-Yuan Chang
- Department of Medicine, Division of Nephrology, University of California San Francisco, San Francisco, California, USA
| | - Eugene Milshteyn
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Robert A Bok
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Michael A Ohliger
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - David Pearce
- Department of Medicine, Division of Nephrology, University of California San Francisco, San Francisco, California, USA
| | - John Kurhanewicz
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Peder E Z Larson
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Daniel B Vigneron
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA
| | - Matthew Merritt
- Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA
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Ursini F, D’Angelo S, Padula A, Gilio M, Russo E, Naty S, De Sarro G, Grembiale RD, Olivieri I. Retrospective analysis of type 2 diabetes prevalence in a systemic sclerosis cohort from southern Italy: Comment on “Reduced incidence of Type 1 diabetes and Type 2 diabetes in systemic sclerosis: A nationwide cohort study” by Tseng et al., Joint Bone Spine 2016;83:307–13. Joint Bone Spine 2016; 83:611-2. [DOI: 10.1016/j.jbspin.2016.07.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Accepted: 07/06/2016] [Indexed: 10/21/2022]
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Abstract
OPINION STATEMENT Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, malnutrition and muscle wasting (sarcopenia) constitute common complications which negatively impact survival, quality of life, and response to stressors, such as infection and surgery in patients with cirrhosis. Despite the important role that malnutrition and sarcopenia play in the prognosis of patients with cirrhosis, they are frequently overlooked, in part because nutritional assessment can be a difficult task in patients with cirrhosis due to fluid retention and/or overweight. Moreover, patients with cirrhosis may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of "sarcopenic obesity." In addition, muscle depletion is characterized by both a reduction in muscle size and increased proportion of intermuscular and intramuscular fat-denominated "myosteatosis." Sarcopenia in cirrhotic patients has been associated with increased mortality, sepsis complications, hyperammonemia, overt hepatic encephalopathy, and increased length of stay after liver transplantation. Muscularity assessment with cross-sectional imaging studies has become an attractive index of nutritional status evaluation in cirrhosis, as sarcopenia reflects a chronic detriment in general physical condition, rather than acute severity of the liver disease. In this review, we discuss the current diagnostic methods to evaluate malnutrition and muscle abnormalities in cirrhosis and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and muscle abnormalities in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduce morbidity related to cirrhosis. Finally, we analyze new studies including sarcopenia with the MELD score that seems to allow better prediction of mortality among cirrhotic patients waiting for liver transplantation.
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Affiliation(s)
- Ragesh B Thandassery
- From the Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Zeidler Ledcor Centre, 130 University Campus, Edmonton, AB, T6G 2X8, Canada
| | - Aldo J Montano-Loza
- From the Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Zeidler Ledcor Centre, 130 University Campus, Edmonton, AB, T6G 2X8, Canada.
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Nishikawa H, Yoh K, Enomoto H, Iwata Y, Kishino K, Shimono Y, Hasegawa K, Nakano C, Takata R, Nishimura T, Aizawa N, Sakai Y, Ikeda N, Takashima T, Ishii A, Iijima H, Nishiguchi S. Factors Associated With Protein-energy Malnutrition in Chronic Liver Disease: Analysis Using Indirect Calorimetry. Medicine (Baltimore) 2016; 95:e2442. [PMID: 26765430 PMCID: PMC4718256 DOI: 10.1097/md.0000000000002442] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
We aimed to elucidate the incidence of protein-energy malnutrition (PEM) in patients with chronic liver disease and to identify factors linked to the presence of PEM.A total of 432 patients with chronic liver disease were analyzed in the current analysis. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient (npRQ) value using indirect calorimetry less than 0.85 as those with PEM. We compared between patients with PEM and those without PEM in baseline characteristics and examined factors linked to the presence of PEM using univariate and multivariate analyses.There are 216 patients with chronic hepatitis, 123 with Child-Pugh A, 80 with Child-Pugh B, and 13 with Child-Pugh C. Six patients (2.8%) had PEM in patients with chronic hepatitis, 17 (13.8%) in patients with Child-Pugh A, 42 (52.5%) in patients with Child-Pugh B, and 10 (76.9%) in patients with Child-Pugh C (P < 0.001). Multivariate analysis revealed that Child-Pugh classification (P < 0.001), age ≥64 years (P = 0.0428), aspartate aminotransferase (AST) ≥40 IU/L (P = 0.0023), and branched-chain amino acid to tyrosine ratio (BTR) ≤5.2 (P = 0.0328) were independent predictors linked to the presence of PEM. On the basis of numbers of above risk factors (age, AST, and BTR), the proportions of patients with PEM were well stratified especially in patients with early chronic hepatitis or Child-Pugh A (n = 339, P < 0.0001), while the proportions of patients with PEM tended to be well stratified in patients with Child-Pugh B or C (n = 93, P = 0.0673).Age, AST, and BTR can be useful markers for identifying PEM especially in patients with early stage of chronic liver disease.
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Affiliation(s)
- Hiroki Nishikawa
- From the Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
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Chmelik M, Považan M, Krššák M, Gruber S, Tkačov M, Trattnig S, Bogner W. In vivo (31)P magnetic resonance spectroscopy of the human liver at 7 T: an initial experience. NMR IN BIOMEDICINE 2014; 27:478-85. [PMID: 24615903 DOI: 10.1002/nbm.3084] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2012] [Revised: 12/11/2013] [Accepted: 01/07/2014] [Indexed: 05/12/2023]
Abstract
Phosphorus ((31) P) MRS is a powerful tool for the non-invasive investigation of human liver metabolism. Four in vivo (31) P localization approaches (single voxel image selected in vivo spectroscopy (3D-ISIS), slab selective 1D-ISIS, 2D chemical shift imaging (CSI), and 3D-CSI) with different voxel volumes and acquisition times were demonstrated in nine healthy volunteers. Localization techniques provided comparable signal-to-noise ratios normalized for voxel volume and acquisition time differences, Cramer-Rao lower bounds (8.7 ± 3.3%1D-ISIS , 7.6 ± 2.5%3D-ISIS , 8.6 ± 4.2%2D-CSI , 10.3 ± 2.7%3D-CSI ), and linewidths (50 ± 24 Hz1D-ISIS , 34 ± 10 Hz3D-ISIS , 33 ± 10 Hz2D-CSI , 34 ± 11 Hz3D-CSI ). Longitudinal (T1 ) relaxation times of human liver metabolites at 7 T were assessed by 1D-ISIS inversion recovery in the same volunteers (n = 9). T1 relaxation times of hepatic (31) P metabolites at 7 T were the following: phosphorylethanolamine - 4.41 ± 1.55 s; phosphorylcholine - 3.74 ± 1.31 s; inorganic phosphate - 0.70 ± 0.33 s; glycerol 3-phosphorylethanolamine - 6.19 ± 0.91 s; glycerol 3-phosphorylcholine - 5.94 ± 0.73 s; γ-adenosine triphosphate (ATP) - 0.50 ± 0.08 s; α-ATP - 0.46 ± 0.07 s; β-ATP - 0.56 ± 0.07 s. The improved spectral resolution at 7 T enabled separation of resonances in the phosphomonoester and phosphodiester spectral region as well as nicotinamide adenine dinucleotide and uridine diphosphoglucose signals. An additional resonance at 2.06 ppm previously assigned to phosphoenolpyruvate or phosphatidylcholine is also detectable. These are the first (31) P metabolite relaxation time measurements at 7 T in human liver, and they will help in the exploration of new, exciting questions in metabolic research with 7 T MR.
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Affiliation(s)
- Marek Chmelik
- High Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
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Kwarta E, Nagle S, Welstead L. Update on Malnutrition in Liver Cirrhosis: Assessment and Treatment. ACTA ACUST UNITED AC 2014. [DOI: 10.1007/s11901-014-0230-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Franz CC, Hildbrand C, Born C, Egger S, Rätz Bravo AE, Krähenbühl S. Dose adjustment in patients with liver cirrhosis: impact on adverse drug reactions and hospitalizations. Eur J Clin Pharmacol 2013; 69:1565-73. [DOI: 10.1007/s00228-013-1502-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2012] [Accepted: 12/14/2012] [Indexed: 12/15/2022]
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Glass C, Hipskind P, Tsien C, Malin SK, Kasumov T, Shah SN, Kirwan JP, Dasarathy S. Sarcopenia and a physiologically low respiratory quotient in patients with cirrhosis: a prospective controlled study. J Appl Physiol (1985) 2013; 114:559-65. [PMID: 23288550 DOI: 10.1152/japplphysiol.01042.2012] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Patients with cirrhosis have increased gluconeogenesis and fatty acid oxidation that may contribute to a low respiratory quotient (RQ), and this may be linked to sarcopenia and metabolic decompensation when these patients are hospitalized. Therefore, we conducted a prospective study to measure RQ and its impact on skeletal muscle mass, survival, and related complications in hospitalized cirrhotic patients. Fasting RQ and resting energy expenditure (REE) were determined by indirect calorimetry in cirrhotic patients (n = 25), and age, sex, and weight-matched healthy controls (n = 25). Abdominal muscle area was quantified by computed tomography scanning. In cirrhotic patients we also examined the impact of RQ on mortality, repeat hospitalizations, and liver transplantation. Mean RQ in patients with cirrhosis (0.63 ± 0.05) was significantly lower (P < 0.0001) than healthy matched controls (0.84 ± 0.06). Psoas muscle area in cirrhosis (24.0 ± 6.6 cm(2)) was significantly (P < 0.001) lower than in controls (35.9 ± 9.5 cm(2)). RQ correlated with the reduction in psoas muscle area (r(2) = 0.41; P = 0.01). However, in patients with cirrhosis a reduced RQ did not predict short-term survival or risk of developing complications. When REE was normalized to psoas area, energy expenditure was significantly higher (P < 0.001) in patients with cirrhosis (66.7 ± 17.8 kcal/cm(2)) compared with controls (47.7 ± 7.9 kcal/cm(2)). We conclude that hospitalized patients with cirrhosis have RQs well below the traditional lowest physiological value of 0.69, and this metabolic state is accompanied by reduced skeletal muscle area. Although low RQ does not predict short-term mortality in these patients, it may reflect a decompensated metabolic state that requires careful nutritional management with appropriate consideration for preservation of skeletal muscle mass.
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Affiliation(s)
- Cathy Glass
- Department of Nutrition Therapy, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
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31
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Abstract
The liver plays an important role in the metabolism, synthesis, storage, and absorption of nutrients. Patients with cirrhosis are prone to nutritional deficiencies and malnutrition, with a higher prevalence among patients with decompensated disease. Mechanisms of nutritional deficiencies in patients with liver disease are not completely understood and probably multifactorial. Malnutrition among patients with cirrhosis or alcoholic liver disease correlates with poor quality of life, increased risk of infections, frequent hospitalizations, complications, mortality, poor graft and patient survival after liver transplantation, and economic burden. Physicians, including gastroenterologists and hepatologists, should be conversant with assessment and management of malnutrition and nutritional supplementation.
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Mpabanzi L, Deutz N, Hayes PC, Dejong CHC, Olde Damink SWM, Jalan R. Overnight glucose infusion suppresses renal ammoniagenesis and reduces hyperammonaemia induced by a simulated bleed in cirrhotic patients. Aliment Pharmacol Ther 2012; 35:921-8. [PMID: 22360430 DOI: 10.1111/j.1365-2036.2012.05044.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Revised: 12/23/2011] [Accepted: 02/02/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND A simulated upper gastrointestinal (UGI) bleed in cirrhotic patients has been shown to induce hyperammonaemia. The kidney was the site of this exaggerated ammoniagenesis with alanine as substrate. Administration of alanine to decompensated cirrhotic patients did not change hepatic gluconeogenesis, but resulted in increased ammoniagenesis. We hypothesise that reduced hepatic glycogen stores result in hyperglucagonaemia which may drive increased renal gluconeogenesis and therefore alanine uptake and renal ammoniagenesis. AIM To determine whether an overnight glucose infusion lowers renal ammoniagenesis by reducing hyperglucagonaemia and renal ammoniagenesis. METHODS Patients with decompensated cirrhosis were studied in a cross-over design. An UGI bleed was simulated via intragastric administration of an amino acids mixture mimicking the haemoglobin molecule after a 12-h overnight fast (F-group) or after a 12-h treatment with 20% glucose solution (G-group). RESULTS Before the simulated bleed the glucagon levels were 21 (15-31) pmol/L in the F-group and 15 (9-21) pmol/L in the G-group (P < 0.01). After the simulated bleed, arterial ammonia levels increased in both groups [F-group: 73-118 μmol/L (P = 0.01); G-group 64-87 μmol/L (P = 0.01)]. The enhancement of hyperammonaemia was significantly higher in the F-group (45 [19-71] μmol/L) compared with the G-group (23 [13-39] μmol/L) (P = 0.01). The difference in renal ammoniagenesis during the simulated bleed in the F-group was 399 (260-655) nmol/kg/bwt/min and was significantly higher than in the G-group 313 (1-498) nmol/kg/bwt/min (P = 0.05). CONCLUSIONS Overnight glucose infusion results in reduced renal ammoniagenesis and attenuates ammonia levels. These observations have implications for the development of nutritional strategies in hyperammonaemic patients.
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Affiliation(s)
- L Mpabanzi
- Department of Surgery, Maastricht University Medical Centre, NUTRIM School of Nutrition, Toxicology and Metabolism, Maastricht University, The Netherlands
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Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol 2012; 10:117-25. [PMID: 21893127 DOI: 10.1016/j.cgh.2011.08.016] [Citation(s) in RCA: 232] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2011] [Revised: 07/22/2011] [Accepted: 08/24/2011] [Indexed: 02/07/2023]
Abstract
Malnutrition is prevalent among cirrhotic patients and is an important prognostic factor. Etiologic factors include hypermetabolism, malabsorption, altered nutrient metabolism, and anorexia. It is a challenge to manage nutrition in cirrhotic patients because of alterations to metabolic and storage functions of the liver; use of traditional assessment tools, such as anthropometric and biometric measures, is difficult because of complications such as ascites and inflammation. In addition to meeting macro- and micronutrient requirements, the composition and timing of supplements have been proposed to affect efficacy of nutrition support. Studies have indicated that branched chain aromatic acid can be given as therapeutic nutrients, and that probiotics and nocturnal feeding improve patient outcomes.
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Affiliation(s)
- Kally Cheung
- Alberta Health Services, Calgary, Alberta, Canada
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34
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Smart KM, Alex G, Hardikar W. Feeding the child with liver disease: a review and practical clinical guide. J Gastroenterol Hepatol 2011; 26:810-5. [PMID: 21299619 DOI: 10.1111/j.1440-1746.2011.06687.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nourishing children with liver disease is a challenging task; however, appropriate assessment and well-timed nutritional interventions are paramount for a good long-term outcome in these patients. An appropriate balance of macronutrients, micronutrients, and vitamins is important, as is the route of administration. This review aims to highlight the practical points in nutrition assessment and also provides a guide to the various nutritional interventions available for children with chronic liver disease.
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Role of nutrition in the management of hepatic encephalopathy in end-stage liver failure. J Nutr Metab 2010; 2010:489823. [PMID: 21234351 PMCID: PMC3017957 DOI: 10.1155/2010/489823] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2010] [Accepted: 11/11/2010] [Indexed: 02/07/2023] Open
Abstract
Malnutrition is common in patients with end-stage liver failure and hepatic encephalopathy, and is considered a significant prognostic factor affecting quality of life, outcome, and survival. The liver plays a crucial role in the regulation of nutrition by trafficking the metabolism of nutrients, their distribution and appropriate use by the body. Nutritional consequences with the potential to cause nervous system dysfunction occur in liver failure, and many factors contribute to malnutrition in hepatic failure. Among them are inadequate dietary intake, malabsorption, increased protein losses, hypermetabolism, insulin resistance, gastrointestinal bleeding, ascites, inflammation/infection, and hyponatremia. Patients at risk of malnutrition are relatively difficult to identify since liver disease may interfere with biomarkers of malnutrition. The supplementation of the diet with amino acids, antioxidants, vitamins as well as probiotics in addition to meeting energy and protein requirements may improve nutritional status, liver function, and hepatic encephalopathy in patients with end-stage liver failure.
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Sevastianova K, Hakkarainen A, Kotronen A, Cornér A, Arkkila P, Arola J, Westerbacka J, Bergholm R, Lundbom J, Lundbom N, Yki-Järvinen H. Nonalcoholic Fatty Liver Disease: Detection of Elevated Nicotinamide Adenine Dinucleotide Phosphate with in Vivo 3.0-T 31P MR Spectroscopy with Proton Decoupling. Radiology 2010; 256:466-473. [DOI: 10.1148/radiol.10091351] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Nightingale S, Ng VL. Optimizing nutritional management in children with chronic liver disease. Pediatr Clin North Am 2009; 56:1161-83. [PMID: 19931069 DOI: 10.1016/j.pcl.2009.06.005] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Malnutrition is common in infants and children with chronic liver disease (CLD) and may easily be underestimated by clinical appearance alone. The cause of malnutrition in CLD is multifactorial, although insufficient dietary intake is probably the most important factor and is correctable. Fat malabsorption occurs in cholestatic disorders, and one must also consider any accompanying fat-soluble vitamin and essential fatty acid deficiencies. The clinician should proactively evaluate, treat, and re-evaluate response to treatment of nutritional deficiencies. Because a better nutritional state is associated with better survival before and after liver transplantation, aggressive nutritional management is an important part of the care of these children.
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Affiliation(s)
- Scott Nightingale
- SickKids Transplant Center, Division of Gastroenterology, Hepatology, and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
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Sharma R, Sinha S, Danishad K, Vikram NK, Gupta A, Ahuja V, Jagannathan N, Pandey R, Misra A. Investigation of hepatic gluconeogenesis pathway in non-diabetic Asian Indians with non-alcoholic fatty liver disease using in vivo (31P) phosphorus magnetic resonance spectroscopy. Atherosclerosis 2009; 203:291-7. [DOI: 10.1016/j.atherosclerosis.2008.06.016] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2008] [Revised: 06/09/2008] [Accepted: 06/13/2008] [Indexed: 02/03/2023]
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Bianchi G, Marzocchi R, Lorusso C, Ridolfi V, Marchesini G. Nutritional treatment of chronic liver failure. Hepatol Res 2008; 38 Suppl 1:S93-S101. [PMID: 19125960 DOI: 10.1111/j.1872-034x.2008.00433.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The liver plays a central role in the regulation of nutrition by trafficking the metabolism of nutrients, their distribution and appropriate use. Accordingly, protein-energy malnutrition is common in patients with advanced liver disease, and it is a significant prognostic factor, affecting survival, the success of liver transplantation and quality of life. Clinical guidelines for the assessment and treatment of malnutrition have been issued by International societies, suggesting that nutritional therapy should be instituted in all patients where requirements are not adequately met by diet. The supplementation of the diet with amino acids (mainly branched-chain amino acids) and trace elements may improve nutritional status, liver function and hepatic encephalopathy. Nutritional issues should be carefully considered in Liver Units treating patients with advanced cirrhosis, and long-term, carefully controlled studies are needed to better define the type of nutritional support and the amount and timing of administration.
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Affiliation(s)
- Giampaolo Bianchi
- Unit of Internal Medicine, Alma MAter Studiorum University, Bologna, Italy
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40
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Chmelík M, Schmid AI, Gruber S, Szendroedi J, Krššák M, Trattnig S, Moser E, Roden M. Three-dimensional high-resolution magnetic resonance spectroscopic imaging for absolute quantification of31P metabolites in human liver. Magn Reson Med 2008; 60:796-802. [DOI: 10.1002/mrm.21762] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Solga SF, Horska A, Hemker S, Crawford S, Diggs C, Diehl AM, Brancati FL, Clark JM. Hepatic fat and adenosine triphosphate measurement in overweight and obese adults using 1H and 31P magnetic resonance spectroscopy. Liver Int 2008; 28:675-81. [PMID: 18331237 PMCID: PMC3096527 DOI: 10.1111/j.1478-3231.2008.01705.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND/AIMS Magnetic resonance spectroscopy (MRS) measures hepatic fat and adenosine triphosphate (ATP), but magnetic resonance studies are challenging in obese subjects. We aimed to evaluate the inter- and intrarater reliability and stability of hepatic fat and ATP measurements in a cohort of overweight and obese adults. METHODS We measured hepatic fat and ATP using proton MRS ((1)H MRS) and phosphorus MRS ((31)P MRS) at baseline in adults enrolled in the Action for Health in Diabetes (Look AHEAD) clinical trial at one site. Using logistic regression, we determined factors associated with successful MRS data acquisition. We calculated the intra- and inter-rater reliability for hepatic fat and ATP based on 20 scans analysed twice by two readers. We also calculated the stability of these measures three times on five healthy volunteers. RESULTS Of 244 participants recruited into our ancillary study, 185 agreed to MRS. We obtained usable hepatic fat data from 151 (82%) and ATP data from 105 (58%). Obesity was the strongest predictor of failed data acquisition; every unit increase in the body mass index reduced the likelihood of successful fat data by 11% and ATP data by 14%. The inter- and intrarater reliability were excellent for fat (intraclass correlation coefficient=0.99), but substantially more variable for ATP. Fat measures appeared relatively stable, but this was less true for ATP. CONCLUSIONS Obesity can hinder (1)H and (31)P MRS data acquisition and subsequent analysis. This impact was greater for hepatic ATP than hepatic fat.
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Affiliation(s)
- Steven F. Solga
- Department of Medicine, Division of Gastroenterology, Johns Hopkins University, Baltimore, MD, USA
| | - Alena Horska
- Russel H. Morgan Department of Radiology and Radiologic Science, Johns Hopkins University, Baltimore, MD, USA
| | - Susanne Hemker
- Russel H. Morgan Department of Radiology and Radiologic Science, Johns Hopkins University, Baltimore, MD, USA
| | - Stephen Crawford
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
| | - Charalett Diggs
- Department of Medicine, Division of Gastroenterology, Johns Hopkins University, Baltimore, MD, USA
| | - Anna Mae Diehl
- Department of Medicine, Duke University, Durham, NC, USA
| | - Frederick L. Brancati
- Department of Medicine, Division of Gastroenterology, Johns Hopkins University, Baltimore, MD, USA,Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
| | - Jeanne M. Clark
- Department of Medicine, Division of Gastroenterology, Johns Hopkins University, Baltimore, MD, USA,Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
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Salam OMA, Sleem AA, Omara EA, Hassan NS. Effect of ribavirin alone or combined with silymarin on carbon tetrachloride induced hepatic damage in rats. Drug Target Insights 2007; 2:19-27. [PMID: 21901059 PMCID: PMC3155230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
The effect of the antiviral agent ribavirin given alone or in combination with silymarin on the development of liver injury induced in rats with carbon tetrachloride (CCl(4); 2.8 ml/kg followed by 1.4 ml/kg after one week) was studied. Ribavirin at three dose levels (30, 60 or 90 mg/kg), silymarin (25 mg/kg) or combination of ribavirin (60 mg/kg) and silymarin (25 mg/kg) was administered once daily orally for 14 days, starting at time of administration of CCl(4). The administration of ribavirin decreased the elevations in serum alanine aminotransferase (ALT) by 78.5, 82.1, 75.1%, aspartate aminotransferase (AST) 47.5, 37.4, 38.8%, and alkaline phosphatase (ALP) by 23.4, 16, 21.6%, respectively and also pre-vented the development of hepatic necrosis caused by CCl(4). In comparison, the elevated serum ALT, AST and ALP levels decreased to 43.3%, 46%, and 37.5% of controls, respectively by silymarin. When silymarin was combined with ribavirin, the serum activities of AST and ALP were further decreased, indicating a beneficial additive effect. Morphometric analysis indicated significant reduction in the area of necrosis and fibrosis on ribavirin treatment and this was further reduced after the addition of silymarin. Metabolic pertuberations caused by CCl(4) as reflected in a decrease in intracellular protein content in hepatocytes were improved by ribavirin monotherapy and to higher extent by combined silymarin and ribavirin therapy. Proliferating cell nuclear antigen was reduced in nuclei of hepatocytes by ribavirin montherapy or the combination of ribavirin and silymarin compared with CCl(4)-control group. The study demonstrates that ribavirin treatment in the model of CCl(4)-induced liver injury results in less liver damage. Results also indicate that the combined application of ribavirin and sily-marin is likely to be a useful additive in reducing liver injury.
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Affiliation(s)
- Omar M.E. Abdel Salam
- Department of Pharmacology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
| | - Amany A. Sleem
- Department of Pharmacology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
| | - Enayat A. Omara
- Department of Pathology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
| | - Nabila S. Hassan
- Department of Pathology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt
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Takahara Y, Takahashi M, Wagatsuma H, Yokoya F, Zhang QW, Yamaguchi M, Aburatani H, Kawada N. Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis. World J Gastroenterol 2006; 12:6473-99. [PMID: 17072980 PMCID: PMC4100637 DOI: 10.3748/wjg.v12.i40.6473] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the gene expression profile data for the whole liver during development of dimethylni-trosamine (DMN)-induced hepatic fibrosis.
METHODS: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells), and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells.
RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSC-specific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis, suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocyte-specific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis.
CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibrogenesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.
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Affiliation(s)
- Yoshiyuki Takahara
- Exploratory and Applied Pharmaceutical Research Department, Pharmaceutical Company, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan.
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Abstract
Patients with cirrhosis develop metabolic derangements of protein, carbohydrate, and lipid metabolism. Malnutrition is commonplace and is associated with morbidity and mortality. Specific nutrient deficiencies may occur and enteral or parenteral nutritional support may improve outcome in appropriately selected patients. Parenteral nutrition itself has been associated with hepatic dysfunction, although the preponderance of evidence suggests that hepatic dysfunction is more a function of the underlying disorder and malabsorption. Intravenously infused organic nutrients may be metabolized differently than the same nutrient consumed enterally. The pathophysiology of total parenteral nutrition-associated liver disease is discussed as well as potential management options.
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Affiliation(s)
- A L Buchman
- Division of Gastroenterology, Intestinal Rehabilitation Center, Feinberg School of Medicine, Northwestern University, 676 N. St. Clair Street, Chicago, Illinois, USA.
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45
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Young TA, Bailey SM, Van Horn CG, Cunningham CC. Chronic ethanol consumption decreases mitochondrial and glycolytic production of ATP in liver. Alcohol Alcohol 2006; 41:254-60. [PMID: 16571619 DOI: 10.1093/alcalc/agl017] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
AIMS The synthesis of ATP in the liver of the chronic ethanol consumer is suppressed, particularly if the tissue becomes hypoxic. Moreover, the perivenous region of the liver lobule becomes even more oxygen deficient as a result of ethanol consumption. Synthesis of ATP in the perivenous region of the lobule may be depressed in the chronic ethanol consumer due to decreases in both mitochondrial and glycolytic activities. In this study the effects of hypoxia on hepatic ATP levels derived from synthesis by both oxidative phosphorylation and the glycolytic mechanisms were investigated. METHODS Rats were pair-fed liquid diets containing 36% of calories as ethanol or an isocaloric control diet. The contributions of glycolysis and mitochondria to ATP production were assessed employing oligomycin, an inhibitor of oxidative phosphorylation. In order to localize the ethanol-elicited lesion in the glycolytic pathway, the metabolism of [3-(3)H] D-glucose was followed in hepatocytes from ethanol-fed and control animals. RESULTS Under both hypoxic and normoxic conditions ATP losses were due to decreases in both glycolytic and mitochondrial ATP production. The rate of production of tritiated water from [3-(3)H] D-glucose was significantly decreased in hepatocytes from ethanol-fed animals, which indicates there is an ethanol-elicited lesion in glycolysis between glucose and glyceraldehyde-3-phosphate.
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Affiliation(s)
- Tracey A Young
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
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47
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Khan SA, Cox IJ, Hamilton G, Thomas HC, Taylor-Robinson SD. In vivo and in vitro nuclear magnetic resonance spectroscopy as a tool for investigating hepatobiliary disease: a review of H and P MRS applications. Liver Int 2005; 25:273-81. [PMID: 15780050 DOI: 10.1111/j.1478-3231.2005.01090.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Nuclear magnetic resonance (NMR) spectroscopy is a non-invasive technique, which allows the study of cellular biochemistry and metabolism. It is a diverse research tool, widely used by biochemists to investigate pathophysiological processes in vitro and, more recently, by physicians to determine disease abnormalities in vivo. This article reviews the basics of the NMR phenomenon and summarises previous research on the hepatobiliary system using both laboratory-based and clinical methodologies. The role of proton and phosphorus-31 ((31)P) NMR spectroscopy in the study of malignant and non-malignant liver disease and studies of bile composition are discussed. In vivo techniques (magnetic resonance spectroscopy, MRS) can be performed as an adjunct to standard MR examination of the liver. Although still primarily a research tool, the in vivo technique provides non-invasive biochemical information on disease severity and holds promise in its use to gauge response to treatment regimens.
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Affiliation(s)
- Shahid A Khan
- Liver Unit, Department of Medicine A, St Mary's Hospital Campus, Imperial College London, 10th Floor, QEQM Building, London W2 1NY, UK.
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48
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Corbin IR, Ryner LN, Singh H, Minuk GY. Quantitative hepatic phosphorus-31 magnetic resonance spectroscopy in compensated and decompensated cirrhosis. Am J Physiol Gastrointest Liver Physiol 2004; 287:G379-84. [PMID: 15191882 DOI: 10.1152/ajpgi.00418.2003] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Few studies have examined the physiological/biochemical status of hepatocytes in patients with compensated and decompensated cirrhosis in situ. Phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) is a noninvasive technique that permits direct assessments of tissue bioenergetics and phospholipid metabolism. Quantitative (31)P MRS was employed to document differences in the hepatic metabolite concentrations among patients with compensated and decompensated cirrhosis as well as healthy controls. All MRS examinations were performed on a 1.5-T General Electric Signa whole body scanner. The concentration of hepatic phosphorylated metabolites among patients with compensated cirrhosis (n = 7) was similar to that among healthy controls (n = 8). However, patients with decompensated cirrhosis (n = 6) had significantly lower levels of hepatic ATP compared with patients with compensated cirrhosis and healthy controls (P < 0.02 and P < 0.009, respectively) and a higher phosphomonoester/phosphodiester ratio than controls (P < 0.003). The results of this study indicate that metabolic disturbances in hepatic energy and phospholipid metabolism exist in patients with decompensated cirrhosis that are not present in patients with compensated cirrhosis or healthy controls. These findings provide new insights into the pathophysiology of hepatic decompensation.
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Affiliation(s)
- I R Corbin
- John Buhler Research Centre, 803F-715 McDermot Ave., Winnipeg, Manitoba, Canada.
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49
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Dhanjal NS, Cox IJ, Taylor-Robinson SD. In vivo electron spin resonance spectroscopy: what use is it to gastroenterologists? Gut 2003; 52:1236-7. [PMID: 12912850 PMCID: PMC1773809 DOI: 10.1136/gut.52.9.1236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- N S Dhanjal
- Department of Medicine A, Division of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
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50
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Hamilton G, Patel N, Forton DM, Hajnal JV, Taylor-Robinson SD. Prior knowledge for time domain quantification of in vivo brain or liver 31P MR spectra. NMR IN BIOMEDICINE 2003; 16:168-176. [PMID: 12884361 DOI: 10.1002/nbm.821] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Prior knowledge is required when quantifying in vivo (31)P magnetic resonance spectra from the brain or liver. The prior knowledge system we have used models both the phosphomonoester and phosphodiester resonances as two peaks of equal linewidth and fixed relative chemical shift. The analysis of the data is carried out in the time domain, which allows the broad component of the spectra to be modelled. This prior knowledge method has been tested for analysis of in vivo (31)P MR spectra from the liver and brain and gives results consistent with other methods that are also used to analyse the spectra, but with reduced variability. This technique may be utilized for studies requiring serial MR spectroscopy examinations, before and after patient treatment.
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Affiliation(s)
- Gavin Hamilton
- Robert Steiner MR Unit, Imaging Sciences Department, MRC Clinical Sciences Centre Imperial College London, London, UK.
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