|
1
|
Singal AK, Wong RJ, Dasarathy S, Abdelmalek MF, Neuschwander-Tetri BA, Limketkai BN, Petrey J, McClain CJ. ACG Clinical Guideline: Malnutrition and Nutritional Recommendations in Liver Disease. Am J Gastroenterol 2025; 120:950-972. [PMID: 40314389 DOI: 10.14309/ajg.0000000000003379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 01/29/2025] [Indexed: 05/03/2025]
Abstract
Malnutrition, defined as deficiency, excess, or imbalance of nutrients, is a common complication in patients with liver disease, especially those with cirrhosis. Malnutrition may present as an isolated micronutrient deficiency, such as zinc deficiency, and it commonly presents as frailty and/or sarcopenia in patients with advanced liver disease. Patients with cirrhosis and/or alcohol-associated hepatitis should be assessed for malnutrition because it adversely affects patient outcomes including mortality, as well as waitlist and posttransplant outcomes among liver transplant candidates. The prevalence of malnutrition varies based on the method of assessment and disease severity, being higher in those with advanced liver disease. Among stable outpatients with cirrhosis, counseling should be done to eat small frequent meals, a night-time snack between 7 PM and 10 PM, and 2 or more cups of coffee daily. In selected patients with metabolic dysfunction-associated steatohepatitis, vitamin E 800 IU/d should be provided. Among hospitalized patients with cirrhosis, nutritional supplementation preferably by enteral route should be implemented in those with poor oral intake of daily requirements of proteins and/or calories. Protein intake should not be restricted including patients with decompensated cirrhosis and hepatic encephalopathy. A vegetable source of protein seems to be better tolerated than an animal source of protein in patients with hepatic encephalopathy. Branched chain amino acids augment the efficacy of lactulose and rifaximin in the treatment of hepatic encephalopathy. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the auspices of the American College of Gastroenterology Practice Parameters Committee.
Collapse
Affiliation(s)
- Ashwani K Singal
- Department of Medicine, University of Louisville, Louisville, Kentucky, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Srinivasan Dasarathy
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, Ohio, USA
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Brent A Neuschwander-Tetri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA
| | - Berkeley N Limketkai
- Divisions of Digestive Diseases and Clinical Nutrition, UCLA School of Medicine, Los Angeles, California, USA
| | - Jessica Petrey
- Kornhauser Health Sciences Library, University of Louisville, Louisville, Kentucky, USA; and
| | - Craig J McClain
- Departments of Medicine and Pharmacology & Toxicology, Chief of Research Affairs, Division of Gastroenterology, Hepatology and Nutrition, Associate Vice President for Health Affairs/Research, Associate Vice President for Translational Research, Louisville, Kentucky, USA
| |
Collapse
|
|
2
|
Shasthry SM, Sarin SK. Alcohol-Associated Liver Diseases: Spectrum, Nomenclature, and Definitions. Clin Liver Dis 2024; 28:621-631. [PMID: 39362711 DOI: 10.1016/j.cld.2024.06.003] [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] [Indexed: 10/05/2024]
Abstract
Alcohol-associated liver disease (AALD) is a global health problem with increasing incidence with associated high morbidity and mortality. Patients with AALD have varied clinical presentation encompassing a spectrum ranging from alcoholic steatosis, alcoholic steatohepatitis to alcohol-associated fibrosis/cirrhosis, which can be either compensated or decompensated. We need uniformity in defining each of the stages of AALD, which will help in both research and patient care. Algorithmic approach using noninvasive tests like enhanced liver fibrosis score, elastography, and fibrosis-4 scores can help in early diagnosis in addition to the presence of any red flags (low albumin, low platelet count, and raised transaminases).
Collapse
Affiliation(s)
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Sector D1, Vasantkunj, New Delhi 110070, India.
| |
Collapse
|
|
3
|
Ebrahim MA, Zaher EA, Patel P, Ahmed MK, Ahmed K. Non-cirrhotic Ascites: A Case of Severe Alcoholic Hepatitis. Cureus 2024; 16:e58187. [PMID: 38741864 PMCID: PMC11089831 DOI: 10.7759/cureus.58187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2024] [Indexed: 05/16/2024] Open
Abstract
This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation excluded alternative etiologies, pinpointing sinusoidal non-cirrhotic portal hypertension. Present therapeutic modalities for AH, including steroids and pentoxifylline, offer limited efficacy, necessitating ongoing investigation. Liver transplantation may be contemplated in refractory cases. This case underscores the intricate nature of AH presentations and the challenges in their management, emphasizing the imperative need for continued research to delineate optimal therapeutic strategies. Early intervention remains pivotal in addressing AH complications, underscoring the need for heightened clinical vigilance and proactive treatment approaches in such cases.
Collapse
Affiliation(s)
| | - Eli A Zaher
- Internal Medicine, Ascension Saint Joseph - Chicago, Chicago, USA
| | - Parth Patel
- Internal Medicine, Ascension Saint Joseph - Chicago, Chicago, USA
| | - Marwan K Ahmed
- Internal Medicine, Ascension Saint Joseph - Chicago, Chicago, USA
| | - Kanwal Ahmed
- Internal Medicine, Ascension Saint Joseph - Chicago, Chicago, USA
| |
Collapse
|
|
4
|
Condon S, Jophlin LL. Past, Present, and Future Therapies for Alcohol-associated Hepatitis. Clin Ther 2023; 45:1171-1176. [PMID: 37980219 PMCID: PMC10842010 DOI: 10.1016/j.clinthera.2023.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 10/10/2023] [Accepted: 10/11/2023] [Indexed: 11/20/2023]
Abstract
PURPOSE Alcohol-associated hepatitis (AH) is a unique presentation of cholestatic steatohepatitis with liver dysfunction and malaise preceded by heavy alcohol intake. Although AH exists on a spectrum, in its most severe form, 28-day mortality approaches 50%. Clinical trials of therapeutic interventions over the last 50 years have yielded few durable therapies, none of which convey benefit beyond the short term. METHODS A qualitative systematic review was performed via searches of PubMed, the International Clinical Trials Registry Platform, and ClinicalTrials.gov for therapeutic interventions for AH. FINDINGS Prior to 2005, clinical trial results for AH were identified within PubMed. From 2005 to the present, trials were well catalogued within online registries and included information regarding trial status (eg, complete, terminated, actively enrolling). Most clinical trials for AH have used existing medications broadly targeting pathogenic themes of AH (eg, inflammation, cell death) in an off-label manner. The trend of initially promising pilot studies answered by larger trials showing lack of efficacy or safety signals have ended the hopes of many new therapeutics. The emergence of theragnostics to identify patients who may benefit from existing therapies and trials of agents with novel mechanisms of action, including epigenetic modifications and hyaluronic acid signaling targeted to AH pathogenesis, are currently under investigation. IMPLICATIONS This review of AH treatments details the historical interventions and clinical trials that have led to the current treatment algorithm and active studies shaping the therapeutic pipeline for AH.
Collapse
Affiliation(s)
- Sally Condon
- Department of Medicine, Division of Gastroenterology Hepatology and Nutrition, University of Louisville, Louisville, Kentucky, USA
| | - Loretta L Jophlin
- Department of Medicine, Division of Gastroenterology Hepatology and Nutrition, University of Louisville, Louisville, Kentucky, USA.
| |
Collapse
|
|
5
|
Rondanelli M, Gasparri C, Razza C, Ferraris C, Perna S, Ferrarotti I, Corsico AG. Practical dietary advices for subjects with alpha-1 antitrypsin deficiency. Biomed Pharmacother 2023; 163:114753. [PMID: 37119738 DOI: 10.1016/j.biopha.2023.114753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/01/2023] Open
Abstract
Congenital alpha-1 antitrypsin deficiency (AATD) is a rare inherited disorder caused by the mutation of the SERPINA1 gene on chromosome 14. At pulmonary level, AAT deficiency leads to an increased risk of chronic obstructive pulmonary disease (COPD) and emphysema, starting from the third-fourth decade of life. At hepatic level, some variants of the allelic, in particular PI*Z, cause a conformational change of the AAT molecule, which polymerizes within the hepatocytes. Excessive hepatic accumulation of these abnormal molecules can lead to liver disease in both adults and children, with clinical presentation ranging from cholestatic jaundice in the newborn to abnormal blood indices of liver function in children and adults, up to fatty liver, cirrhosis and hepatocarcinoma. Nutritional interventions in AATD aim to provide the necessary calories, stop protein catabolism, prevent and treat malnutrition as in the case of common COPD, and even take into account any liver disease that is a distinctive trait, compared to common COPD. Actually, there is a lack of formal research regarding the effects of specific nutritional recommendations in patients with AATD, proper eating habits may help to preserve lung and liver function. For practical dietary advice in patients with AATD and COPD, recently a food pyramid proposal has been published. It has been observed that there is a marked overlap between AATD liver disease and obesity-related liver disease, suggesting shared molecular basis and, therefore, similar nutritional strategies. In this narrative review dietary advice for all possible stages of liver disease have been reported.
Collapse
Affiliation(s)
- Mariangela Rondanelli
- IRCCS Mondino Foundation, Pavia 27100, Italy; Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, Pavia 27100, Italy.
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona "Istituto Santa Margherita", University of Pavia, Pavia 27100, Italy
| | - Claudia Razza
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona "Istituto Santa Margherita", University of Pavia, Pavia 27100, Italy
| | - Cinzia Ferraris
- Laboratory of Food Education and Sport Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
| | - Simone Perna
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain
| | - Ilaria Ferrarotti
- Center for Diagnosis of Inherited Alpha 1-Antitrypsin Deficiency, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy; Division of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation, Pavia 27100, Italy
| | - Angelo Guido Corsico
- Center for Diagnosis of Inherited Alpha 1-Antitrypsin Deficiency, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy; Division of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation, Pavia 27100, Italy
| |
Collapse
|
|
6
|
Tadokoro T, Morishita A, Himoto T, Masaki T. Nutritional Support for Alcoholic Liver Disease. Nutrients 2023; 15:nu15061360. [PMID: 36986091 PMCID: PMC10059060 DOI: 10.3390/nu15061360] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/09/2023] [Accepted: 03/09/2023] [Indexed: 03/16/2023] Open
Abstract
Malnutrition is a common finding in alcohol use disorders and is associated with the prognosis of patients with alcoholic liver disease (ALD). These patients also frequently show deficiencies in vitamins and trace elements, increasing the likelihood of anemia and altered cognitive status. The etiology of malnutrition in ALD patients is multifactorial and complex and includes inadequate dietary intake, abnormal absorption and digestion, increased skeletal and visceral protein catabolism, and abnormal interactions between ethanol and lipid metabolism. Most nutritional measures derive from general chronic liver disease recommendations. Recently, many patients with ALD have been diagnosed with metabolic syndrome, which requires individualized treatment via nutritional therapy to avoid overnutrition. As ALD progresses to cirrhosis, it is frequently complicated by protein–energy malnutrition and sarcopenia. Nutritional therapy is also important in the management of ascites and hepatic encephalopathy as liver failure progresses. The purpose of the review is to summarize important nutritional therapies for the treatment of ALD.
Collapse
Affiliation(s)
- Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita 761-0793, Kagawa, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita 761-0793, Kagawa, Japan
- Correspondence: ; Tel.: +81-87-891-2156
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu 761-0123, Kagawa, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita 761-0793, Kagawa, Japan
| |
Collapse
|
|
7
|
Habib S, Murakami T, Takyar V, Patel K, Dominguez C, Zhan Y, Mehrpour O, Hsu CH. The Impact of Metabolic Syndrome on the Prognosis of High-Risk Alcoholic Hepatitis Patients: Redefining Alcoholic Hepatitis. Gastroenterology Res 2023; 16:25-36. [PMID: 36895697 PMCID: PMC9990531 DOI: 10.14740/gr1556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 10/03/2022] [Indexed: 03/11/2023] Open
Abstract
Background Alcoholic hepatitis (AH) is characterized by acute symptomatic hepatitis associated with heavy alcohol use. This study was designed to assess the impact of metabolic syndrome on high-risk patients with AH with discriminant function (DF) score ≥ 32 and its effect on mortality. Methods We searched the hospital database for ICD-9 diagnosis codes of acute AH, alcoholic liver cirrhosis, and alcoholic liver damage. The entire cohort was categorized into two groups: AH and AH with metabolic syndrome. The effect of metabolic syndrome on mortality was evaluated. Also, an exploratory analysis was used to create a novel risk measure score to assess mortality. Results A large proportion (75.5%) of the patients identified in the database who had been treated as AH had other etiologies and did not meet the American College of Gastroenterology (ACG)-defined diagnosis of acute AH, thus had been misdiagnosed as AH. Such patients were excluded from analysis. The mean body mass index (BMI), hemoglobin (Hb), hematocrit (HCT), and alcoholic liver disease/non-alcoholic fatty liver disease index (ANI) were significantly different between two groups (P < 0.05). The results of a univariate Cox regression model showed that age, BMI, white blood cells (WBCs), creatinine (Cr), international normalized ratio (INR), prothrombin time (PT), albumin levels, albumin < 3.5, total bilirubin, Na, Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), MELD ≥ 21, MELD ≥ 18, DF score, and DF ≥ 32 had a significant effect on mortality. Patients with a MELD greater than 21 had a hazard ratio (HR) (95% confidence interval (CI) of 5.81 (2.74 - 12.30) (P < 0.001). The adjusted Cox regression model results showed that age, Hb, Cr, INR, Na, MELD score, DF score, and metabolic syndrome were independently associated with high patient mortality. However, the increase in BMI and mean corpuscular volume (MCV) and sodium significantly reduced the risk of death. We found that a model including age, MELD ≥ 21, and albumin < 3.5 was the best model in identifying patient mortality. Our study showed that patients admitted with a diagnosis of alcoholic liver disease with metabolic syndrome had an increased mortality risk compared to patients without metabolic syndrome, in high-risk patients with DF ≥ 32 and MELD ≥ 21. A bivariate correlation analysis revealed that patients with AH with metabolic syndrome were more likely to have infection (43%) compared to AH (26%) with correlation coefficient of 0.176 (P = 0.03, CI: 0.018 - 1.0). Conclusion In clinical practice, the diagnosis of AH is inaccurately applied. Metabolic syndrome significantly increases the mortality risk in high-risk AH. It signifies that the presence of features of metabolic syndrome modifies the behavior of AH in acute settings, warranting different therapeutic strategies. We propose that in defining AH, patients overlapping with metabolic syndrome may need to be excluded as their outcome is different with regard to risk of renal dysfunctions, infections and death.
Collapse
Affiliation(s)
| | | | | | | | | | - Yongcheng Zhan
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
| | | | - Chiu-Hsieh Hsu
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
| |
Collapse
|
|
8
|
Abstract
Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness.
Collapse
Affiliation(s)
- Thomas N Smith
- Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Alice Gallo de Moraes
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
| |
Collapse
|
|
9
|
Jalkh APC, Eastmond AK, Shetty C, Rizvi SMHA, Sharaf J, Williams KAD, Tariq M, Acharekar MV, Guerrero Saldivia SE, Unnikrishnan SN, Chavarria YY, Akindele AO, Hamid P. Oxandrolone Efficacy in Wound Healing in Burned and Decubitus Ulcer Patients: A Systematic Review. Cureus 2022; 14:e28079. [PMID: 36127967 PMCID: PMC9477554 DOI: 10.7759/cureus.28079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/15/2022] [Indexed: 11/18/2022] Open
Abstract
Wounds with delayed or impaired healing represent a considerable challenge in medical practice. These patients develop a sustained hypermetabolic and catabolic state, directly impacting the wound healing process. The use of oxandrolone has been studied to control this metabolic imbalance and protect lean body mass as a beneficial resource in wound healing. This systematic review aims to analyze previously conducted randomized controlled trials to evaluate the evidence of the applicability of oxandrolone therapy. We compared its use in adult patients with burns and adult patients with pressure ulcers in terms of wound healing and healing time of the skin graft donor site in days. The digital searches were done from March 23-28, 2022, within the databases: Google Scholar, PubMed/MEDLINE, and EBSCO (Elton B. Stephens Company). Data from six studies were analyzed and included in this review. Analysis of the available data demonstrated a significant advantage in skin healing using oxandrolone in adult burn patients as an adjunct. For adult patients with pressure ulcers, the drug showed no benefit on wound healing and skin graft site healing. Importantly, we found only one study evaluating the use of oxandrolone in patients with decubitus ulcers that met our eligibility criteria, and the certainty of the evidence was low. Thus, further prospective randomized studies with larger samples and standard wound care protocols are needed to produce more solid results, allowing more definitive conclusions to be made on this theme.
Collapse
|
|
10
|
Hyun JY, Kim SK, Yoon SJ, Lee SB, Jeong JJ, Gupta H, Sharma SP, Oh KK, Won SM, Kwon GH, Cha MG, Kim DJ, Ganesan R, Suk KT. Microbiome-Based Metabolic Therapeutic Approaches in Alcoholic Liver Disease. Int J Mol Sci 2022; 23:8749. [PMID: 35955885 PMCID: PMC9368757 DOI: 10.3390/ijms23158749] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/21/2022] [Accepted: 08/03/2022] [Indexed: 11/21/2022] Open
Abstract
Alcohol consumption is a global healthcare problem. Chronic alcohol consumption generates a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, fibrosis, and cirrhosis. Alcoholic liver diseases (ALD) refer to liver damage and metabolomic changes caused by excessive alcohol intake. ALD present several clinical stages of severity found in liver metabolisms. With increased alcohol consumption, the gut microbiome promotes a leaky gut, metabolic dysfunction, oxidative stress, liver inflammation, and hepatocellular injury. Much attention has focused on ALD, such as alcoholic fatty liver (AFL), alcoholic steatohepatitis (ASH), alcoholic cirrhosis (AC), hepatocellular carcinoma (HCC), a partnership that reflects the metabolomic significance. Here, we report on the global function of inflammation, inhibition, oxidative stress, and reactive oxygen species (ROS) mechanisms in the liver biology framework. In this tutorial review, we hypothetically revisit therapeutic gut microbiota-derived alcoholic oxidative stress, liver inflammation, inflammatory cytokines, and metabolic regulation. We summarize the perspective of microbial therapy of genes, gut microbes, and metabolic role in ALD. The end stage is liver transplantation or death. This review may inspire a summary of the gut microbial genes, critical inflammatory molecules, oxidative stress, and metabolic routes, which will offer future promising therapeutic compounds in ALD.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Raja Ganesan
- Institute for Liver and Digestive Disease, College of Medicine, Hallym University, Chuncheon 24253, Korea
| | - Ki Tae Suk
- Institute for Liver and Digestive Disease, College of Medicine, Hallym University, Chuncheon 24253, Korea
| |
Collapse
|
|
11
|
Limon-Miro AT, Jackson CD, Eslamparast T, Yamanaka-Okumura H, Plank LD, Henry CJ, Madden AM, Ferreira LG, Kalaitzakis E, Prieto de Frías C, Knudsen AW, Gramlich L, Raman M, Alberda C, Belland D, Den Heyer V, Tandon P, Morgan MY. Predicted estimates of resting energy expenditure have limited clinical utility in patients with cirrhosis. J Hepatol 2022; 77:98-107. [PMID: 35090958 DOI: 10.1016/j.jhep.2022.01.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Malnutrition is associated with adverse clinical outcomes in patients with cirrhosis. Accurate assessment of energy requirements is needed to optimize dietary intake. Resting energy expenditure (REE), the major component of total energy expenditure, can be measured using indirect calorimetry (mREE) or estimated using prediction equations (pREE). This study assessed the usefulness of predicted estimates of REE in this patient population. METHODS Individual mREE data were available for 900 patients with cirrhosis (mean [±1 SD] age 55.7±11.6 years-old; 70% men; 52% south-east Asian) and 282 healthy controls (mean age 36.0±12.8 years-old; 52% men; 18% south-east Asian). Metabolic status was classified using thresholds based on the mean ± 1 SD of the mREE in the healthy controls. Comparisons were made between mREE and pREE estimates obtained using the Harris-Benedict, Mifflin, Schofield and Henry equations. Stepwise regression was used to build 3 new prediction models which included sex, ethnicity, body composition measures, and model for end-stage liver disease scores. RESULTS The mean mREE was significantly higher in patients than controls when referenced to dry body weight (22.4±3.8 cf. 20.8±2.6 kcal/kg/24 hr; p <0.001); there were no significant sex differences. The mean mREE was significantly higher in Caucasian than Asian patients (23.1±4.4 cf. 21.7±2.9 kcal/kg/24 hr; p <0.001). Overall, 37.1% of Caucasian and 25.3% of Asian patients were classified as hypermetabolic. The differences between mREE and pREE were both statistically and clinically relevant; in the total patient population, pREE estimates ranged from 501 kcal/24 hr less to 548 kcal/24 hr more than the mREE. Newly derived prediction equations provided better estimates of mREE but still had limited clinical utility. CONCLUSIONS Prediction equations do not provide useful estimates of REE in patients with cirrhosis. REE should be directly measured. LAY SUMMARY People with cirrhosis are often malnourished and this has a detrimental effect on outcome. Provision of an adequate diet is very important and is best achieved by measuring daily energy requirements and adjusting dietary intake accordingly. Prediction equations, which use information on age, sex, weight, and height can be used to estimate energy requirements; however, the results they provide are not accurate enough for clinical use, particularly as they vary according to sex and ethnicity.
Collapse
Affiliation(s)
| | - Clive Douglas Jackson
- Department of Clinical Neurophysiology, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | | | - Hisami Yamanaka-Okumura
- Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho, Tokushima, Japan
| | | | | | - Angela Mary Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Livia Garcia Ferreira
- Graduate Program in Nutrition and Health, Department of Nutrition, Universidade Federal de Lavras, Brazil
| | - Evangelos Kalaitzakis
- Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Denmark; Department of Gastroenterology, University Hospital of Heraklion, University of Crete, Heraklion, Greece
| | | | - Anne Wilkens Knudsen
- Gastrounit, Medical Division, Copenhagen University Hospital - Hvidovre, Denmark
| | - Leah Gramlich
- Department of Medicine, University of Alberta, Edmonton, Canada
| | - Maitreyi Raman
- Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Cathy Alberda
- Royal Alexandra Hospital, Alberta Health Services, Edmonton, Alberta, Canada
| | - Dawn Belland
- University of Alberta Hospital, Alberta Health Services Nutrition Services, Edmonton, Canada
| | - Vanessa Den Heyer
- University of Alberta Hospital, Alberta Health Services Nutrition Services, Edmonton, Canada
| | - Puneeta Tandon
- Department of Medicine, University of Alberta, Edmonton, Canada.
| | - Marsha Yvonne Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, UK.
| |
Collapse
|
|
12
|
Phase Angle Is a Stronger Predictor of Hospital Outcome than Subjective Global Assessment-Results from the Prospective Dessau Hospital Malnutrition Study. Nutrients 2022; 14:nu14091780. [PMID: 35565747 PMCID: PMC9100773 DOI: 10.3390/nu14091780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
This prospective cohort study of 16,943 consecutive patients compared phase angle (PhA, foot-to-hand at 50 kHz) and subjective global assessment (SGA) to predict outcomes length of hospital stay (LOS) and in-hospital mortality in patients at risk of malnutrition (NRS-2002 ≥ 3). In 1505 patients, the independent effects on LOS were determined by competing risk analysis and on mortality by logistic regression. In model I, including influence factors age, sex, BMI, and diagnoses, malnourished (SGA B and C) patients had a lower chance for a regular discharge (HR 0.74; 95%CI 0.69−0.79) and an increased risk of mortality (OR 2.87; 95%CI 1.38−5.94). The association of SGA and outcomes regular discharge and mortality was completely abrogated when PhA was added (model II). Low PhA reduced the chance of a regular discharge by 53% in patients with a PhA ≤ 3° (HR 0.47; 95%CI 0.39−0.56) as compared to PhA > 5°. Mortality was reduced by 56% for each 1° of PhA (OR 0.44; 95%CI 0.32−0.61). Even when CRP was added in model III, PhA ≤ 3° was associated with a 41% lower chance for a regular discharge (HR 0.59; 95%CI 0.48−0.72). In patients at risk of malnutrition, the objective measure PhA was a stronger predictor of LOS and mortality than SGA.
Collapse
|
|
13
|
Baldwin C, de van der Schueren MA, Kruizenga HM, Weekes CE. Dietary advice with or without oral nutritional supplements for disease-related malnutrition in adults. Cochrane Database Syst Rev 2021; 12:CD002008. [PMID: 34931696 PMCID: PMC8691169 DOI: 10.1002/14651858.cd002008.pub5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Disease-related malnutrition has been reported in 10% to 55% of people in hospital and the community and is associated with significant health and social-care costs. Dietary advice (DA) encouraging consumption of energy- and nutrient-rich foods rather than oral nutritional supplements (ONS) may be an initial treatment. OBJECTIVES To examine evidence that DA with/without ONS in adults with disease-related malnutrition improves survival, weight, anthropometry and quality of life (QoL). SEARCH METHODS We identified relevant publications from comprehensive electronic database searches and handsearching. Last search: 01 March 2021. SELECTION CRITERIA Randomised controlled trials (RCTs) of DA with/without ONS in adults with disease-related malnutrition in any healthcare setting compared with no advice, ONS or DA alone. DATA COLLECTION AND ANALYSIS Two authors independently assessed study eligibility, risk of bias, extracted data and graded evidence. MAIN RESULTS We included 94, mostly parallel, RCTs (102 comparisons; 10,284 adults) across many conditions possibly explaining the high heterogeneity. Participants were mostly older people in hospital, residential care and the community, with limited reporting on their sex. Studies lasted from one month to 6.5 years. DA versus no advice - 24 RCTs (3523 participants) Most outcomes had low-certainty evidence. There may be little or no effect on mortality after three months, RR 0.87 (95% confidence interval (CI) 0.26 to 2.96), or at later time points. We had no three-month data, but advice may make little or no difference to hospitalisations, or days in hospital after four to six months and up to 12 months. A similar effect was seen for complications at up to three months, MD 0.00 (95% CI -0.32 to 0.32) and between four and six months. Advice may improve weight after three months, MD 0.97 kg (95% CI 0.06 to 1.87) continuing at four to six months and up to 12 months; and may result in a greater gain in fat-free mass (FFM) after 12 months, but not earlier. It may also improve global QoL at up to three months, MD 3.30 (95% CI 1.47 to 5.13), but not later. DA versus ONS - 12 RCTs (852 participants) All outcomes had low-certainty evidence. There may be little or no effect on mortality after three months, RR 0.66 (95% CI 0.34 to 1.26), or at later time points. Either intervention may make little or no difference to hospitalisations at three months, RR 0.36 (95% CI 0.04 to 3.24), but ONS may reduce hospitalisations up to six months. There was little or no difference between groups in weight change at three months, MD -0.14 kg (95% CI -2.01 to 1.74), or between four to six months. Advice (one study) may lead to better global QoL scores but only after 12 months. No study reported days in hospital, complications or FFM. DA versus DA plus ONS - 22 RCTs (1286 participants) Most outcomes had low-certainty evidence. There may be little or no effect on mortality after three months, RR 0.92 (95% CI 0.47 to 1.80) or at later time points. At three months advice may lead to fewer hospitalisations, RR 1.70 (95% CI 1.04 to 2.77), but not at up to six months. There may be little or no effect on length of hospital stay at up to three months, MD -1.07 (95% CI -4.10 to 1.97). At three months DA plus ONS may lead to fewer complications, RR 0.75 (95% CI o.56 to 0.99); greater weight gain, MD 1.15 kg (95% CI 0.42 to 1.87); and better global QoL scores, MD 0.33 (95% CI 0.09 to 0.57), but this was not seen at other time points. There was no effect on FFM at three months. DA plus ONS if required versus no advice or ONS - 31 RCTs (3308 participants) Evidence was moderate- to low-certainty. There may be little or no effect on mortality at three months, RR 0.82 (95% CI 0.58 to 1.16) or at later time points. Similarly, little or no effect on hospitalisations at three months, RR 0.83 (95% CI 0.59 to 1.15), at four to six months and up to 12 months; on days in hospital at three months, MD -0.12 (95% CI -2.48 to 2.25) or for complications at any time point. At three months, advice plus ONS probably improve weight, MD 1.25 kg (95% CI 0.73 to 1.76) and may improve FFM, 0.82 (95% CI 0.35 to 1.29), but these effects were not seen later. There may be little or no effect of either intervention on global QoL scores at three months, but advice plus ONS may improve scores at up to 12 months. DA plus ONS versus no advice or ONS - 13 RCTs (1315 participants) Evidence was low- to very low-certainty. There may be little or no effect on mortality after three months, RR 0.91 (95% CI 0.55 to 1.52) or at later time points. No study reported hospitalisations and there may be little or no effect on days in hospital after three months, MD -1.81 (95% CI -3.65 to 0.04) or six months. Advice plus ONS may lead to fewer complications up to three months, MD 0.42 (95% CI 0.20 to 0.89) (one study). Interventions may make little or no difference to weight at three months, MD 1.08 kg (95% CI -0.17 to 2.33); however, advice plus ONS may improve weight at four to six months and up to 12 months. Interventions may make little or no difference in FFM or global QoL scores at any time point. AUTHORS' CONCLUSIONS We found no evidence of an effect of any intervention on mortality. There may be weight gain with DA and with DA plus ONS in the short term, but the benefits of DA when compared with ONS are uncertain. The size and direction of effect and the length of intervention and follow-up required for benefits to emerge were inconsistent for all other outcomes. There were too few data for many outcomes to allow meaningful conclusions. Studies focusing on both patient-centred and healthcare outcomes are needed to address the questions in this review.
Collapse
Affiliation(s)
- Christine Baldwin
- Department of Nutritional Sciences, Facutly of Life Sciences & Medicine, King's College London, London, UK
| | - Marian Ae de van der Schueren
- Department of Nutrition, Dietetics and Lifestyle, HAN University of Applied Sciences, Nijmegen, Netherlands
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
| | - Hinke M Kruizenga
- Department of Nutrition and Dietetics, VU University Medical Center, Amsterdam, Netherlands
| | | |
Collapse
|
|
14
|
Siddiqui ATS, Parkash O, Hashmi SA. Malnutrition and liver disease in a developing country. World J Gastroenterol 2021; 27:4985-4998. [PMID: 34497430 PMCID: PMC8384735 DOI: 10.3748/wjg.v27.i30.4985] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/19/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
Malnutrition is a highly prevalent and under recognized condition in developing countries of South Asia. The presence of malnutrition causes a severe impact on patients with liver cirrhosis. The etiology of cirrhosis differs in the South Asian region compared to the West, with hepatitis B and C still being the leading causes and the prevalence of nonalcoholic fatty liver disease increasing over time. Comorbid malnutrition worsens outcomes for cirrhosis patients. Urgent attention to address malnutrition is needed to improve patient outcomes. The etiology and pathophysiology of malnutrition in liver diseases is multifactorial, as reduction in liver function affects both macronutrients and micronutrients. A need for nutritional status assessment for liver disease patients exists in all parts of the world. There are many widely studied tools in use to perform a thorough nutritional assessment, of which some tools are low cost and do not require extensive training. These tools can be studied and evaluated for use in the resource limited setting of a country like Pakistan. Treatment guidelines for proper nutrition maintenance in chronic liver disease exist for all parts of the world, but the knowledge and practice of nutritional counseling in Pakistan is poor, both amongst patients and physicians. Emphasis on assessment for nutritional status at the initial visit with recording of vital signs is needed. Simultaneously, treating physicians need to be made aware of the misconceptions surrounding nutritional restrictions in cirrhosis so that patient education is done correctly based on proper scientific evidence.
Collapse
Affiliation(s)
| | - Om Parkash
- Department of Medicine, Division of Gastroenterology, The Aga Khan University, Karachi 74800, Pakistan
| | | |
Collapse
|
|
15
|
Abstract
Malnutrition is common in alcohol-associated hepatitis (AH); almost all patients with severe AH have some component of malnutrition. The classic phenotype of malnutrition in AH is sarcopenia, but this has become more difficult to discern clinically as patients have become more obese. Patients with AH are often drinking 10 to 15 standard drinks per day. This substantial alcohol consumption becomes a major source of calories, but these are considered "empty" calories that contain little nutritional value. Malnutrition is associated with liver complications, such as hepatic encephalopathy, and worse liver outcomes. Nutrition support can improve nutrition status and reduce complications.
Collapse
Affiliation(s)
- Craig J. McClain
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY;,UofL Alcohol Research Center, University of Louisville, Louisville, KY;,Department of Medicine, University of Louisville, Louisville, KY;,Hepatobiology and Toxicology Center, University of Louisville, Louisville, KY;,Robely Rex Veterans Affairs Medical Center, Louisville, KY 40207
| | - Cristian D. Rios
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY
| | - Sally Condon
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY
| | - Luis S. Marsano
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY;,Department of Medicine, University of Louisville, Louisville, KY
| |
Collapse
|
|
16
|
Ali YH, Ali T. Nandrolone decanoate safely combats catabolism in burned patients: A new potential indication after recall. Burns 2021; 48:59-68. [PMID: 34172326 DOI: 10.1016/j.burns.2021.04.011] [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: 06/14/2020] [Revised: 03/12/2021] [Accepted: 04/12/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION The hyper-catabolic state is a devastating pathophysiological response to severe injury, infection or burns. Nandrolone decanoate (ND) is a potent anabolic steroid have many clinical indications, but not investigated in burn injuries yet. PATIENTS AND METHODS A prospective randomized control study included 40 burned patients who were treated in Burn unit from burn injuries ranged from 20 to 40%. Both groups are objectively assessed, clinically and laboratory during treatment period till full recovery from burns' injury. Recall assessment of the drug safety after many years is achieved. RESULTS ND showed highly significant results supporting its use in combating catabolic insults in burns patient. Both clinical findings and laboratory findings are correlated and highly support the use of ND in burns as new effective and safe long-lasting indication. CONCLUSION This study results showed preservation of lean body mass and protein partition, as well as the near normal nitrogen balance in burn patients. Study proposes that nandrolone decanoate could be used in safe and effective way to combat hypercatabolic impact in burn injury.
Collapse
Affiliation(s)
- Yasser Helmy Ali
- Al-Azhar University, Faculty of Medicine, Naser City, Cairo, Egypt.
| | - Tasnim Ali
- Nile University, Faculty of Biotechnology, 6th of October City, Egypt.
| |
Collapse
|
|
17
|
Galba J, Piešťanský J, Kováč A, Olešová D, Cehlár O, Kertys M, Kozlík P, Chaľová P, Tirčová B, Slíž K, Mikuš P. Fast and Sensitive Screening of Oxandrolone and Its Major Metabolite 17-Epi-Oxandrolone in Human Urine by UHPLC-MS/MS with On-Line SPE Sample Pretreatment. Molecules 2021; 26:molecules26020480. [PMID: 33477515 PMCID: PMC7831107 DOI: 10.3390/molecules26020480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/08/2021] [Accepted: 01/11/2021] [Indexed: 11/24/2022] Open
Abstract
Oxandrolone, a synthetic testosterone analog, is used for the treatment of several diseases associated with weight loss. Unfortunately, oxandrolone is abused by many athletes and bodybuilders due to its strong anabolic effect. We have developed and validated a highly sensitive and rapid on-line SPE-UHPLC-MS/MS method for the determination of oxandrolone and simultaneous identification of its major metabolite 17-epi-oxandrolone in urine matrices. Enrichment of the analytes via an integrated solid-phase extraction was achieved using an Acquity UPLC BEH C18 Column. Subsequently, the chromatographic separation of the on-line preconcentrated sample fraction was achieved using an Acquity HSS T3 C18 Column. For the structural identification of these analytes, a high-resolution mass spectrometer Synapt-G2Si coupled to the Acquity M-class nano-LC system with ionKey source was used. A highly sensitive determination of oxandrolone was achieved using a tandem quadrupole mass spectrometer XEVO TQD. The method was successfully validated in the linear range of oxandrolone from 81.63 pg·mL−1 (limit of quantification, LOQ) to 5000 pg·mL−1 in the human urine matrix. It was applied to the analysis of real urine samples obtained from a healthy volunteer after the oral administration of one dose (10 mg) of oxandrolone. Concentration vs. time dependence was tested in the time interval of 4 h–12 days (after oral administration) to demonstrate the ability of the method to detect the renal elimination of oxandrolone from the human body. Favorable performance parameters along with successful application indicate the usefulness of the proposed method for its routine use in antidoping control labs.
Collapse
Affiliation(s)
- Jaroslav Galba
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia; (J.G.); (J.P.); (P.C.); (K.S.)
- Biomedical Research Center of the Slovak Academy of Sciences in Bratislava, 84510 Bratislava, Slovakia
| | - Juraj Piešťanský
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia; (J.G.); (J.P.); (P.C.); (K.S.)
- Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia
| | - Andrej Kováč
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 84510 Bratislava, Slovakia; (A.K.); (D.O.); (O.C.)
| | - Dominika Olešová
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 84510 Bratislava, Slovakia; (A.K.); (D.O.); (O.C.)
| | - Ondrej Cehlár
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 84510 Bratislava, Slovakia; (A.K.); (D.O.); (O.C.)
| | - Martin Kertys
- Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 01 Martin, Slovakia;
- Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 01 Martin, Slovakia
| | - Petr Kozlík
- Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Prague 2, Czech Republic;
| | - Petra Chaľová
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia; (J.G.); (J.P.); (P.C.); (K.S.)
| | - Barbora Tirčová
- Department of Chemistry, Faculty of Natural Science, Matej Bel University in Banska Bystrica, 974 09 Banska Bystrica, Slovakia;
| | - Kristián Slíž
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia; (J.G.); (J.P.); (P.C.); (K.S.)
- Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia
| | - Peter Mikuš
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia; (J.G.); (J.P.); (P.C.); (K.S.)
- Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia
- Correspondence: ; Tel.: +421-2-50-117-243
| |
Collapse
|
|
18
|
Verna EC, Serper M, Chu J, Corey K, Fix OK, Hoyt K, Page KA, Loomba R, Li M, Everson GT, Fried MW, Garcia‐Tsao G, Terrault N, Lok AS, Chung RT, Reddy KR. Clinical Research in Hepatology in the COVID-19 Pandemic and Post-Pandemic Era: Challenges and the Need for Innovation. Hepatology 2020; 72:1819-1837. [PMID: 32740969 PMCID: PMC7435542 DOI: 10.1002/hep.31491] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/22/2020] [Accepted: 07/24/2020] [Indexed: 12/14/2022]
Abstract
The severe acute respiratory syndrome coronavirus 2 pandemic has drastically altered all facets of clinical care and research. Clinical research in hepatology has had a rich tradition in several domains, including the discovery and therapeutic development for diseases such as hepatitis B and C and studying the natural history of many forms of chronic liver disease. National Institutes of Health, foundation, and industry funding have provided important opportunities to advance the academic careers of young investigators while they strived to make contributions to the field. Instantaneously, however, all nonessential research activities were halted when the pandemic started, forcing those involved in clinical research to rethink their research strategy, including a shift to coronavirus disease 2019 research while endeavoring to maintain their preexisting agenda. Strategies to maintain the integrity of ongoing studies, including patient follow-up, safety assessments, and continuation of investigational products, have included a shift to telemedicine, remote safety laboratory monitoring, and shipping of investigational products to study subjects. As a revamp of research is being planned, unique issues that face the research community include maintenance of infrastructure, funding, completion of studies in the predetermined time frame, and the need to reprogram career path timelines. Real-world databases, biomarker and long-term follow up studies, and research involving special groups (children, the homeless, and other marginalized populations) are likely to face unique challenges. The implementation of telemedicine has been dramatically accelerated and will serve as a backbone for the future of clinical research. As we move forward, innovation in clinical trial design will be essential for conducting optimized clinical research.
Collapse
Affiliation(s)
- Elizabeth C. Verna
- Center for Liver Disease and TransplantationColumbia University Irving Medical CenterNew YorkNY
| | - Marina Serper
- Division of Gastroenterology and HepatologyUniversity of PennsylvaniaPhiladelphiaPA
| | - Jaime Chu
- Division of Pediatric HepatologyMt. Sinai School of MedicineNew YorkNY
| | | | - Oren K. Fix
- Organ Transplant and Liver CenterSwedish Medical CenterSeattleWA
| | | | - Kimberly A. Page
- Division of Epidemiology, Biostatistics and Preventive Medicine, Department of Internal MedicineUniversity of New Mexico School of MedicineAlbuquerqueNM
| | - Rohit Loomba
- Division of GastroenterologyUC San Diego School of MedicineSan DiegoCA
| | - Ming Li
- Keck School of Medicine of USCLos AngelesCA
| | - Gregory T. Everson
- Division of Gastroenterology and Hepatology, Department of Internal MedicineUniversity of Colorado Denver School of MedicineAuroraCO
- HepQuant LLCGreenwood VillageCO
| | - Michael W. Fried
- Division of Gastroenterology and HepatologyUniversity of North Carolina School of MedicineChapel HillNC
| | | | | | - Anna S. Lok
- Division of GastroenterologyUniversity of Michigan Medical SchoolAnn ArborMI
| | | | - K. Rajender Reddy
- Division of Gastroenterology and HepatologyUniversity of PennsylvaniaPhiladelphiaPA
| |
Collapse
|
|
19
|
Bischoff SC, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Plauth M. ESPEN practical guideline: Clinical nutrition in liver disease. Clin Nutr 2020; 39:3533-3562. [PMID: 33213977 DOI: 10.1016/j.clnu.2020.09.001] [Citation(s) in RCA: 188] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease. METHODS It has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. RESULTS A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition. CONCLUSION This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care.
Collapse
Affiliation(s)
- Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany
| |
Collapse
|
|
20
|
Kamran U, Towey J, Khanna A, Chauhan A, Rajoriya N, Holt A. Nutrition in alcohol-related liver disease: Physiopathology and management. World J Gastroenterol 2020; 26:2916-2930. [PMID: 32587439 PMCID: PMC7304106 DOI: 10.3748/wjg.v26.i22.2916] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/08/2020] [Accepted: 05/21/2020] [Indexed: 02/06/2023] Open
Abstract
Malnutrition encompassing both macro- and micro-nutrient deficiency, remains one of the most frequent complications of alcohol-related liver disease (ArLD). Protein-energy malnutrition can cause significant complications including sarcopenia, frailty and immunodepression in cirrhotic patients. Malnutrition reduces patient’s survival and negatively affects the quality of life of individuals with ArLD. Moreover, nutritional deficit increases the likelihood of hepatic decompensation in cirrhosis. Prompt recognition of at-risk individuals, early diagnosis and treatment of malnutrition remains a key component of ArLD management. In this review, we describe the pathophysiology of malnutrition in ArLD, review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD, ranging from acute alcoholic hepatitis through to decompensated end stage liver disease.
Collapse
Affiliation(s)
- Umair Kamran
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, United Kingdom
| | - Jennifer Towey
- Department of Dietetics, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, United Kingdom
| | - Amardeep Khanna
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, United Kingdom
| | - Abhishek Chauhan
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, United Kingdom
- Centre for Liver Research, Institute of Immunology and Inflammation, and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, The Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Neil Rajoriya
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, United Kingdom
| | - Andrew Holt
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, United Kingdom
| |
Collapse
|
|
21
|
Coker MS, Ladd KR, Kim J, Murphy CJ, DeCort R, Newcomer BR, Wolfe RR, Coker RH. Essential Amino Acid Supplement Lowers Intrahepatic Lipid despite Excess Alcohol Consumption. Nutrients 2020; 12:E254. [PMID: 31963802 PMCID: PMC7019240 DOI: 10.3390/nu12010254] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/07/2020] [Accepted: 01/09/2020] [Indexed: 12/18/2022] Open
Abstract
Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this exploratory pilot study was to initiate the evaluation of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38 ± 15 years/age and 7 females at 34 ± 18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 g of EAAS twice/day (BID)) or high dose (HD: 13 g of EAAS BID). Five of the twenty-five enrolled participants dropped out of the intervention. Both groups consumed the supplement BID for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual-energy X-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at p < 0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p = 0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407 ± 141 ng/mL and HD at 429 ± 196 ng/mL, indicating chronic and excess alcohol consumption. The HD of the proprietary EAAS formulation consumed BID seemed to lower IHL in individuals with mild to moderate AUD. We suggest that further studies in a larger cohort be conducted to more completely address this important area of investigation.
Collapse
Affiliation(s)
- Melynda S. Coker
- Department of Natural Resources and Environment, University of Alaska Fairbanks, 505 South Chandalar Drive, Fairbanks, AK 99775, USA;
| | - Kaylee R. Ladd
- Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775, USA; (K.R.L.); (J.K.)
| | - Jimin Kim
- Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775, USA; (K.R.L.); (J.K.)
| | - Carl J. Murphy
- Institute of Arctic Biology, Department of Chemistry & Biochemistry, University of Alaska Fairbanks1930 Yukon Dr. Room 136, Fairbanks, AK 99775, USA;
| | - Ryan DeCort
- Bassett Army Community Hospital, 4076 Neely Road, FortWainwright, United States Army, Fairbanks, AK 99703, USA;
| | - Bradley R. Newcomer
- Honors College, 1501 251Warren Service Drive, Room 105, James Madison University, Harrisonburg, VA 22807, USA;
| | - Robert R. Wolfe
- Department of Geriatrics, Center for Translational Research in Aging & Longevity, Donald W. Reynolds Institute on Aging, 4301 West Markham, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA;
| | - Robert H. Coker
- Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775, USA; (K.R.L.); (J.K.)
- Institute of Arctic Biology, Department of Chemistry & Biochemistry, University of Alaska Fairbanks1930 Yukon Dr. Room 136, Fairbanks, AK 99775, USA;
| |
Collapse
|
|
22
|
Abstract
PURPOSE OF REVIEW This review discusses the prevalence of malnutrition in cirrhosis, metabolic functions of the liver and alterations in cirrhosis, malnutrition screening tools, and common macronutrient and micronutrient deficiencies encountered in individuals with chronic liver disease and their impact on morbidity and mortality. RECENT FINDINGS Several meta-analyses and international society guidelines recommend malnutrition screening and nutrition interventions to improve outcomes in all patients with chronic liver disease given their high risk of malnutrition which is often under recognized. Malnutrition is common in individuals with chronic liver disease and has a significant impact on patient outcomes. Thus, it is critical that validated malnutrition screening tools are used routinely in this patient population in order to identify high-risk patients and implement nutrition and exercise interventions early.
Collapse
Affiliation(s)
- Lena B Palmer
- Division of Gastroenterology, Southeast Louisiana Veterans Affairs Healthcare System, 2400 Canal St, New Orleans, LA, 70119, USA.
| | - Gabriela Kuftinec
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, University of Miami Health Systems, Miller School of Medicine, Miami, FL, USA
| | - Michelle Pearlman
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, University of Miami Health Systems, Miller School of Medicine, Miami, FL, USA
| | - Caitlin Homberger Green
- Division of Gastroenterology & Hepatology, Medical University of South Carolina, Charleston, SC, USA
| |
Collapse
|
|
23
|
Kiracofe B, Zavala S, Gayed RM, Foster CJ, Jones KM, Oltrogge Pape K, Hill DM, Reger M, Porter K, Murphy CV. Risk Factors Associated with the Development of Transaminitis in Oxandrolone-Treated Adult Burn Patients. J Burn Care Res 2019; 40:406-411. [PMID: 31220261 DOI: 10.1093/jbcr/irz041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Oxandrolone has proven benefits in thermal burn injury and has become a standard of care. Transaminitis is the most frequent side effect of oxandrolone use, although no risk factors have been identified that increase the risk of transaminitis. The objective was to evaluate the frequency of transaminitis while on oxandrolone and to identify risk factors leading to an increased risk of transaminitis in adult burn patients. This multicenter retrospective risk factor analysis compared two patient groups with and without occurrence of transaminitis, which was detected by an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >100 mg/dL. Secondary outcomes included percentage increase from baseline for AST/ALT, length of stay, and mortality. After univariable analysis, a multivariable logistic regression analysis was performed to detect possible risk factors leading to transaminitis. A total of 309 patients were included, with transaminitis occurring in 128 patients (41.4%) after 13 (interquartile range [IQR] 8-23) days on oxandrolone. After multivariable analysis, age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.84-0.99 for a 5-year increase in age), intravenous vasopressor use (OR 1.85; 95% CI 1.05-3.27), and amiodarone use (OR 2.51; 95% CI 1.09-5.77) were independent predictors of transaminitis, controlling for TBSA%. Transaminitis was not significantly associated with length of stay or mortality after adjusting for age and TBSA%. We conclude that patients who are younger and have concurrent amiodarone or vasopressor use have the highest risk of developing oxandrolone induced transaminitis and should be monitored closely.
Collapse
Affiliation(s)
| | - Sarah Zavala
- Department of Pharmacy, Loyola University Medical Center, Maywood, Illinois
| | - Rita M Gayed
- Department of Pharmacy, Grady Hospital, Atlanta, Georgia
| | - Charles J Foster
- Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado
| | - Kendrea M Jones
- Department of Pharmacy Practice, University of Arkansas Medical Sciences College of Pharmacy, Little Rock, Arkansas
| | - Kate Oltrogge Pape
- Department of Pharmaceutical Care, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - David M Hill
- Department of Pharmacy, Regional One Health, Memphis, Tennessee
| | - Melissa Reger
- Department of Pharmacy, Community Regional Medical Center, Fresno, California
| | - Kyle Porter
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio
| | - Claire V Murphy
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| |
Collapse
|
|
24
|
|
|
25
|
Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Bischoff SC. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr 2019; 38:485-521. [PMID: 30712783 DOI: 10.1016/j.clnu.2018.12.022] [Citation(s) in RCA: 392] [Impact Index Per Article: 65.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023]
Abstract
This update of evidence-based guidelines (GL) aims to translate current evidence and expert opinion into recommendations for multidisciplinary teams responsible for the optimal nutritional and metabolic management of adult patients with liver disease. The GL was commissioned and financially supported by ESPEN. Members of the guideline group were selected by ESPEN. We searched for meta-analyses, systematic reviews and single clinical trials based on clinical questions according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing the SIGN method. A total of 85 recommendations were made for the nutritional and metabolic management of patients with acute liver failure, severe alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver cirrhosis, liver surgery and transplantation as well as nutrition associated liver injury distinct from fatty liver disease. The recommendations are preceded by statements covering current knowledge of the underlying pathophysiology and pathobiochemistry as well as pertinent methods for the assessment of nutritional status and body composition.
Collapse
Affiliation(s)
- Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany
| |
Collapse
|
|
26
|
Treatment retention in a specialized alcohol programme after an episode of alcoholic hepatitis: Impact on alcohol relapse. J Psychosom Res 2019; 116:75-82. [PMID: 30654998 DOI: 10.1016/j.jpsychores.2018.11.020] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 11/27/2018] [Indexed: 12/20/2022]
Abstract
AIMS Alcoholic hepatitis (AH) is a life-threatening complication of alcohol use disorder (AUD). Alcohol abstinence is the main predictor of the long-term prognosis of AH. It is unknown whether AUD treatment retention (TR) after an AH episode impacts alcohol relapse and mortality or what baseline factors influence TR. METHODS Design: case-control study; Study population: hospitalized patients (1999-2012) with an episode of biopsy-proven AH were included (n = 120); Assessment: demographic and clinical data, the High-Risk Alcoholism Relapse (HRAR) scale, mortality and alcohol relapse were assessed through clinical records and telephone or personal interviews; Follow-up period: short-term and long-term TRs were assessed at 12 and 24 months, respectively. RESULTS The overall short-term and long-term TRs were 37% and 27.8%, respectively. The severity of liver disease at baseline predicted both short-term and long-term TR (OR 3.7 and 3.3, respectively), whereas HRAR >3 and a history of psychiatric disorders predicted long-term TR (OR 2.9 and 2.6, respectively). Moreover, HRAR >3 (OR 3.0) and previous treatment for AUD (OR 2.9) increased the risk of relapse in the short term. Importantly, receiving alcohol therapy in a centre different from the hospital where the patient was admitted was associated with increased risk of alcohol relapse over the long term (OR 5.4). CONCLUSION Experiencing an alcohol-related life-threatening complication is insufficient motivation to seek treatment for AUD. AUD treatment after an episode of AH is suboptimal, with a low TR rate, high risk of alcohol relapse and poor impact of treatment on alcohol relapse.
Collapse
|
|
27
|
Kiracofe B, Coffey R, Jones LM, Bailey JK, Thomas S, Porter K, Murphy CV. Incidence of oxandrolone induced hepatic transaminitis in patients with burn injury. Burns 2018; 45:891-897. [PMID: 30545697 DOI: 10.1016/j.burns.2018.10.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 09/24/2018] [Accepted: 10/31/2018] [Indexed: 11/16/2022]
Abstract
The benefits of oxandrolone in burn patients has led to its accepted use in the burn care community, however details regarding the most common adverse effect, transaminitis, remains unclear. The purpose of this study was to determine the incidence of transaminitis in patients with burn injury and identify risk factors associated with the development of transaminitis. This single-center, retrospective risk factor analysis compared burn patients on oxandrolone with and without the development of transaminitis, defined as any aspartate aminotransferase or alanine aminotransferase value >100mg/dL. Patient demographics, past medical history, lab values, and burn characteristics were recorded. Overall 28 out of 66 (42%) patients developed transaminitis. The transaminitis group had a significantly higher proportion of other concomitant medications with a transaminitis risk (p=0.045). No significant difference in liver dysfunction or length of stay was observed between the two groups. Oxandrolone induced transaminitis is occurring in patients significantly more frequently than previously reported warranting further research to guide monitoring requirements, use of concomitant medications, and to determine if rechallenging after resolution should be considered.
Collapse
Affiliation(s)
- Brittany Kiracofe
- Department of Pharmacy, Spectrum Health, Grand Rapids, MI, United States
| | - Rebecca Coffey
- Department of Surgery, Division of Trauma, Critical Care, and Burn, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Larry M Jones
- Department of Surgery, Division of Trauma, Critical Care, and Burn, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - J Kevin Bailey
- Department of Surgery, Division of Trauma, Critical Care, and Burn, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Sheela Thomas
- Department of Nutrition Services, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Kyle Porter
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States
| | - Claire V Murphy
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
| |
Collapse
|
|
28
|
Marroni CA, Fleck Jr ADM, Fernandes SA, Galant LH, Mucenic M, de Mattos Meine MH, Mariante-Neto G, Brandão ABDM. Liver transplantation and alcoholic liver disease: History, controversies, and considerations. World J Gastroenterol 2018; 24:2785-2805. [PMID: 30018475 PMCID: PMC6048431 DOI: 10.3748/wjg.v24.i26.2785] [Citation(s) in RCA: 108] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 05/23/2018] [Accepted: 06/16/2018] [Indexed: 02/06/2023] Open
Abstract
Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease (ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation (LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a "self-inflicted disease". One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this "6-mo rule" is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.
Collapse
Affiliation(s)
- Claudio Augusto Marroni
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Alfeu de Medeiros Fleck Jr
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Sabrina Alves Fernandes
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
- Nutrition at the Centro Universitário Metodista (IPA), Porto Alegre 90420-060, RS, Brazil
| | - Lucas Homercher Galant
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Marcos Mucenic
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Mario Henrique de Mattos Meine
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Guilherme Mariante-Neto
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Ajacio Bandeira de Mello Brandão
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| |
Collapse
|
|
29
|
Kharbanda KK, Ronis MJJ, Shearn CT, Petersen DR, Zakhari S, Warner DR, Feldstein AE, McClain CJ, Kirpich IA. Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 Congress. Biomolecules 2018; 8:16. [PMID: 29587455 PMCID: PMC6022870 DOI: 10.3390/biom8020016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023] Open
Abstract
The symposium, "Role of Nutrition in Alcoholic Liver Disease", was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances and developments in the field of alcohol and nutrition. The symposium was focused on experimental and clinical aspects in relation to the role of different types of dietary nutrients and malnutrition in the pathogenesis of alcoholic liver disease (ALD). The following is a summary of key research presented at this session. The speakers discussed the role of dietary fats and carbohydrates in the development and progression of alcohol-induced multi-organ pathology in animal models of ALD, analyzed novel nutrition-related therapeutics (specifically, betaine and zinc) in the treatment of ALD, and addressed clinical relevance of malnutrition and nutrition support in ALD. This summary of the symposium will benefit junior and senior faculty currently investigating alcohol-induced organ pathology as well as undergraduate, graduate, and post-graduate students and fellows.
Collapse
Affiliation(s)
- Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68105, USA.
| | - Martin J J Ronis
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
| | - Colin T Shearn
- Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Denver, CO 80045, USA.
| | - Dennis R Petersen
- Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Denver, CO 80045, USA.
| | - Samir Zakhari
- Distilled Spirits Council, Washington, DC 20005, USA.
| | - Dennis R Warner
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
| | - Ariel E Feldstein
- Division of Gastroenterology, Department of Pediatrics, University of California, San Diego, CA 92037, USA.
| | - Craig J McClain
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 402202, USA;.
- University of Louisville Alcohol Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
- Robley Rex Veterans Medical Center, Louisville, KY 40202, USA.
- Hepatobiology and Toxicology Program, University of Louisville, Louisville, KY 402202, USA.
| | - Irina A Kirpich
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 402202, USA;.
- University of Louisville Alcohol Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
- Hepatobiology and Toxicology Program, University of Louisville, Louisville, KY 402202, USA.
| |
Collapse
|
|
30
|
Current therapies in alleviating liver disorders and cancers with a special focus on the potential of vitamin D. Nutr Metab (Lond) 2018; 15:13. [PMID: 29449867 PMCID: PMC5807831 DOI: 10.1186/s12986-018-0251-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 01/30/2018] [Indexed: 02/06/2023] Open
Abstract
Background Liver dysfunction is a topic of global concern with many advancing therapies being researched. Though vitamin D takes a center place, other therapies especially nutritional are also gaining ground. Vitamin D has gone beyond its role in skeletal disorders by showcasing its associations in other metabolic dysfunctions too. Result Epidemiological evidences show a correlation between the status of vitamin D and different forms of cancer. Vitamin D receptors and alterations in gene expression appear decisive in the development of chronic liver disorders. Nutritional status therefore plays a significant role in avoiding the complications related to liver dysfunctions, making it mandatory in maintaining vitamin D sufficiency in the body. Therapies with omega-3 fatty acids, antioxidants, amino acids, steroids also render benefits which could be further explored. Recent research on the progression of certain forms of liver cancer using vitamin D analogs like Seocalcitol EB 1089 has shown good promise. Conclusion The anti-inflammatory and immuno- regulatory properties of vitamin D makes its analogs, suitable candidates of better choice for the prevention and treatment of liver disorders and cancer.
Collapse
|
|
31
|
Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol 2018; 113:175-194. [PMID: 29336434 PMCID: PMC6524956 DOI: 10.1038/ajg.2017.469] [Citation(s) in RCA: 549] [Impact Index Per Article: 78.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 11/08/2017] [Indexed: 02/07/2023]
Abstract
Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most patients are diagnosed at advanced stages and data on the prevalence and profile of patients with early disease are limited. Diagnosis of ALD requires documentation of chronic heavy alcohol use and exclusion of other causes of liver disease. Prolonged abstinence is the most effective strategy to prevent disease progression. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients hospitalized with ALD include inpatient management of liver disease complications, management of alcohol withdrawal syndrome, surveillance for infections and early effective antibiotic therapy, nutritional supplementation, and treatment of the underlying alcohol-use disorder. Liver transplantation, a definitive treatment option in patients with advanced alcoholic cirrhosis, may also be considered in selected patients with AH cases, who do not respond to medical therapy. There is a clinical unmet need to develop more effective and safer therapies for patients with ALD.
Collapse
Affiliation(s)
- Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham School of Medicine , Birmingham , Alabama , USA
| | - Ramon Bataller
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Liver Research Center , Pittsburgh , Pennsylvania , USA
| | - Joseph Ahn
- Division of Gastroenterology and Hepatology, Oregon Health and Science University , Portland , Oregon , USA
| | - Patrick S. Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester , Minnesota ,USA
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester , Minnesota ,USA
| |
Collapse
|
|
32
|
|
|
33
|
Hammad A, Kaido T, Aliyev V, Mandato C, Uemoto S. Nutritional Therapy in Liver Transplantation. Nutrients 2017; 9:E1126. [PMID: 29035319 PMCID: PMC5691742 DOI: 10.3390/nu9101126] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 10/10/2017] [Accepted: 10/12/2017] [Indexed: 12/11/2022] Open
Abstract
Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.
Collapse
Affiliation(s)
- Ahmed Hammad
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
- Department of General Surgery, Mansoura University, Mansoura 35516, Egypt.
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
| | - Vusal Aliyev
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
| | - Claudia Mandato
- L'AORN Children's Hospital Santobono and Pausilipon, Napoli 80122, Italy.
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
| |
Collapse
|
|
34
|
Abstract
Purpose of Review Nutritional status in patients with cirrhosis is very frequently associated with macro- and micronutrient deficiencies. Cirrhosis itself is the cause of malnutrition and nutritional deficiencies but these conditions have to be identified and addressed properly as they can worsen the prognosis of cirrhosis. The goals of this review are to 1) identify and describe the challenges associated with nutritional assessment in cirrhosis and 2) describe recent advancements when using clinical, laboratory, and instrumental tools in the evaluation of malnourished patients with liver diseases. Recent Findings The most promising tools for nutritional assessment in cirrhosis include the evaluation of body composition with phase angle obtained by bioelectrical impedance analysis, computed tomography transverse images at the level of third lumbar vertebra. The Royal-Free Hospital global assessment algorithm appears to be helpful but needs further validation. Summary Nutritional assessment in cirrhosis is challenging as several factors, including edema, can interfere with it and because of lack of a validated gold standard. Regardless, nutritional assessment methods have been developed in recent years and should gain relevance in the clinical practice.
Collapse
|
|
35
|
Dasarathy J, McCullough AJ, Dasarathy S. Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances. Alcohol Clin Exp Res 2017; 41:1419-1431. [PMID: 28557005 DOI: 10.1111/acer.13425] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 05/16/2017] [Indexed: 12/18/2022]
Abstract
Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current "deficiency replacement" approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in general, and ALD, specifically. Translation of these data to human studies and clinical application requires priority for allocation of resources.
Collapse
Affiliation(s)
| | - Arthur J McCullough
- Department of Gastreoenterology, Hepatology and Pathobiology, Cleveland Clinic, Cleveland, Ohio
| | - Srinivasan Dasarathy
- Department of Gastreoenterology, Hepatology and Pathobiology, Cleveland Clinic, Cleveland, Ohio
| |
Collapse
|
|
36
|
Abstract
With aging and other muscle wasting diseases, men and women undergo similar pathological changes in skeletal muscle: increased inflammation, enhanced oxidative stress, mitochondrial dysfunction, satellite cell senescence, elevated apoptosis and proteasome activity, and suppressed protein synthesis and myocyte regeneration. Decreased food intake and physical activity also indirectly contribute to muscle wasting. Sex hormones also play important roles in maintaining skeletal muscle homeostasis. Testosterone is a potent anabolic factor promoting muscle protein synthesis and muscular regeneration. Estrogens have a protective effect on skeletal muscle by attenuating inflammation; however, the mechanisms of estrogen action in skeletal muscle are less well characterized than those of testosterone. Age- and/or disease-induced alterations in sex hormones are major contributors to muscle wasting. Hence, men and women may respond differently to catabolic conditions because of their hormonal profiles. Here we review the similarities and differences between men and women with common wasting conditions including sarcopenia and cachexia due to cancer, end-stage renal disease/chronic kidney disease, liver disease, chronic heart failure, and chronic obstructive pulmonary disease based on the literature in clinical studies. In addition, the responses in men and women to the commonly used therapeutic agents and their efficacy to improve muscle mass and function are also reviewed.
Collapse
|
|
37
|
Dasarathy S. Nutrition and Alcoholic Liver Disease: Effects of Alcoholism on Nutrition, Effects of Nutrition on Alcoholic Liver Disease, and Nutritional Therapies for Alcoholic Liver Disease. Clin Liver Dis 2016; 20:535-50. [PMID: 27373615 PMCID: PMC4934388 DOI: 10.1016/j.cld.2016.02.010] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Malnutrition is the most frequent and nearly universal consequence in alcoholic liver disease (ALD) that adversely affects clinical outcomes. Sarcopenia or skeletal muscle loss is the major component of malnutrition in liver disease. There are no effective therapies to prevent or reverse sarcopenia in ALD because the mechanisms are not well understood. Consequences of liver disease including hyperammonemia, hormonal perturbations, endotoxemia and cytokine abnormalities as well as the direct effects of alcohol and its metabolites contribute to sarcopenia in ALD. This article focuses on the prevalence, methods to quantify malnutrition, specifically sarcopenia and potential therapies including novel molecular targeted treatments.
Collapse
Affiliation(s)
- Srinivasan Dasarathy
- Departments of Gastroenterology, Hepatology and Pathobiology, Cleveland Clinic, Cleveland, Ohio
| |
Collapse
|
|
38
|
Singal AK, Kodali S, Vucovich LA, Darley-Usmar V, Schiano TD. Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic Review. Alcohol Clin Exp Res 2016; 40:1390-402. [PMID: 27254289 PMCID: PMC4930399 DOI: 10.1111/acer.13108] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 04/24/2016] [Indexed: 12/16/2022]
Abstract
Alcoholic hepatitis (AH) occurs in about one-third of individuals reporting long-term heavy alcohol use. It is associated with high short-term mortality, economic burden, and hospital resources utilization. We performed this systematic review to (i) describe clinical characteristics and genomics associated with the risk of AH; (ii) discuss role and limitations of liver biopsy and prognostic scoring systems; (iii) summarize evidence regarding the currently available therapies including liver transplantation; and (iv) outline emerging therapies with areas of unmet need. Literature search was performed for studies published in English language (January 1971 through March 2016). The following search engines were used: PubMed, Elsevier Embase, PsycINFO, and Cochrane Library. For the treatment section, only randomized controlled studies were included for this review. A total of 138 studies (59 randomized, 22 systematic reviews or meta-analyses, 7 surveys or guidelines, 7 population-based, and 43 prospective cohorts) were cited. There are over 325,000 annual admissions with AH contributing to about 0.8% of all hospitalizations in the United States. Liver biopsy may be required in about 25 to 30% cases for uncertain clinical diagnosis. Corticosteroids with or without N-acetylcysteine remains the only available therapy for severe episodes. Data are emerging on the role of liver transplantation as salvage therapy for select patients. Abstinence remains the most important factor impacting long-term prognosis. Results from the ongoing clinical trials within the National Institute on Alcohol Abuse and Alcoholism-funded consortia are awaited for more effective and safer therapies. AH is a potentially lethal condition with a significant short-term mortality. A high index of suspicion is required. There remains an unmet need for noninvasive biomarkers for the diagnosis, and predicting prognosis and response to therapy.
Collapse
Affiliation(s)
- Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Sudha Kodali
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Lee A Vucovich
- UAB Lister Hill Library of the Health Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | - Victor Darley-Usmar
- Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Thomas D Schiano
- Division of Liver Diseases, Mount Sinai School of Medicine, New York City, New York
| |
Collapse
|
|
39
|
Detection and treatment of medical inpatients with or at-risk of malnutrition: Suggested procedures based on validated guidelines. Nutrition 2016; 32:790-8. [DOI: 10.1016/j.nut.2016.01.019] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 12/22/2015] [Accepted: 01/25/2016] [Indexed: 12/21/2022]
|
|
40
|
Thursz M, Morgan TR. Treatment of Severe Alcoholic Hepatitis. Gastroenterology 2016; 150:1823-34. [PMID: 26948886 PMCID: PMC5828019 DOI: 10.1053/j.gastro.2016.02.074] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 02/22/2016] [Accepted: 02/24/2016] [Indexed: 12/18/2022]
Abstract
Alcoholic hepatitis (AH) is a syndrome of jaundice and liver failure that occurs in a minority of heavy consumers of alcohol. The diagnosis usually is based on a history of heavy alcohol use, findings from blood tests, and exclusion of other liver diseases by blood and imaging analyses. Liver biopsy specimens, usually collected via the transjugular route, should be analyzed to confirm a diagnosis of AH in patients with an atypical history or presentation. The optimal treatment for patients with severe AH is prednisolone, possibly in combination with N-acetyl cysteine. At present, only short-term increases in survival can be expected-no treatment has been found to increase patient survival beyond 3 months. Abstinence is essential for long-term survival. New treatment options, including liver transplantation, are being tested in trials and results eagerly are awaited.
Collapse
Affiliation(s)
- Mark Thursz
- Division of Digestive Diseases, Imperial College, St Mary's Hospital Campus, London, United Kingdom.
| | - Timothy R Morgan
- Gastroenterology Services, VA Long Beach Healthcare, VA Long Beach Healthcare System, Long Beach, California.
| |
Collapse
|
|
41
|
CRABB DAVIDW, BATALLER RAMON, CHALASANI NAGAP, KAMATH PATRICKS, LUCEY MICHAEL, MATHURIN PHILIPPE, MCCLAIN CRAIG, MCCULLOUGH ARTHUR, MITCHELL MACKC, MORGAN TIMOTHYR, NAGY LAURA, RADAEVA SVETLANA, SANYAL ARUN, SHAH VIJAY, SZABO GYONGYI. Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia. Gastroenterology 2016; 150:785-90. [PMID: 26921783 PMCID: PMC5287362 DOI: 10.1053/j.gastro.2016.02.042] [Citation(s) in RCA: 401] [Impact Index Per Article: 44.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- DAVID W. CRABB
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, School of Medicine, Indianapolis, Indiana
| | - RAMON BATALLER
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - NAGA P. CHALASANI
- Division of Gastroenterology and Hepatology Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - PATRICK S. KAMATH
- Gastroenterology Research Unit, Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - MICHAEL LUCEY
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin, Madison, Wisconsin
| | - PHILIPPE MATHURIN
- Service Maladie de l’Appareil Digestif and INSERM U995 Univ Lille 2, CHRU Lille, France
| | - CRAIG MCCLAIN
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky
| | - ARTHUR MCCULLOUGH
- Departments of Gastroenterology, Hepatology and Transplant Surgery, Cleveland Clinic, Cleveland, Ohio
| | - MACK C. MITCHELL
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | | | - LAURA NAGY
- Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
| | - SVETLANA RADAEVA
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - ARUN SANYAL
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - VIJAY SHAH
- Gastroenterology Research Unit, Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - GYONGYI SZABO
- Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
| | | |
Collapse
|
|
42
|
Anastácio LR, Davisson Correia MIT. Nutrition therapy: Integral part of liver transplant care. World J Gastroenterol 2016; 22:1513-1522. [PMID: 26819518 PMCID: PMC4721984 DOI: 10.3748/wjg.v22.i4.1513] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/08/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Managing malnutrition before liver transplantation (LTx) while on the waiting list and, excessive weight gain/metabolic disturbances in post-surgery are still a challenge in LTx care. The aim of this review is to support an interdisciplinary nutrition approach of these patients. Cirrhotic patients are frequently malnourished before LTx and this is associated with a poor prognosis. Although the relation between nutritional status versus survival, successful operation and recovery after LTx is well established, prevalence of malnutrition before the operation is still very high. Emerging research has also demonstrated that sarcopenia pre and post-transplant is highly prevalent, despite the weight gain in the postoperative period. The diagnosis of the nutritional status is the first step to address the adequate nutritional therapy. Nutritional recommendations and therapy to manage the nutritional status of LTx patients are discussed in this review, regarding counseling on adequate diets and findings of the latest research on using certain immunonutrients in these patients (branched chain amino-acids, pre and probiotics). Nutrition associated complications observed after transplantation is also described. They are commonly related to the adverse effects of immunosuppressive drugs, leading to hyperkalemia, hyperglycemia and weight gain. Excessive weight gain and post-transplant metabolic disorders have long been described in post-LTx and should be addressed in order to reduce associated morbidity and mortality.
Collapse
|
|
43
|
Corticosteroids Versus Pentoxifylline for Severe Alcoholic Hepatitis: A Sequential Analysis of Randomized Controlled Trials. J Clin Gastroenterol 2016; 50:871-881. [PMID: 27404293 PMCID: PMC5065367 DOI: 10.1097/mcg.0000000000000585] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Despite the significant morbidity and mortality associated with alcoholic hepatitis, a consensus or generally accepted therapeutic strategy has not yet been reached. The purpose of this analysis was to evaluate the effects of corticosteroids and pentoxifylline on short-term mortality, incidence of hepatorenal syndrome, and sepsis in patients with severe alcoholic hepatitis. MATERIALS AND METHODS We conducted a comprehensive search of the Cochrane library, PUBMED, Scopus, EMBASE, and published proceedings from major hepatology and gastrointestinal meetings from January 1970 to June 2015. All relevant articles irrespective of language, year of publication, type of publication, or publication status were included. Two independent reviewers extracted data and scored publications; a third investigator adjudicated discrepancies. The κ scores were measured to assess the agreement between the 2 initial reviewers. The review and meta-analyses were performed following the recommendations of The Cochrane Collaboration. Conventional meta-analysis and Trial sequential analysis were performed. GRADEpro version 3.6 was used to appraise the quality of epidemiologic evidence. RESULTS A total of 14 studies satisfied inclusion criteria comparing corticosteroids, pentoxifylline, or placebo. Compared with placebo, corticosteroids reduced 28-day mortality (RR=0.53; 95% CI, 0.33-0.84; P=0.006). There was no statistically significant difference in short-term mortality between pentoxifylline and placebo (RR=0.74; 95% CI, 0.46-1.18; P=0.21). Neither corticosteroids nor pentoxifylline impacted the incidence of hepatorenal syndrome or sepsis. Trial sequential analysis confirmed the results of our conventional meta-analysis. CONCLUSIONS AND RELEVANCE Corticosteroids demonstrated a decrease in 28-day mortality in patients with severe alcoholic hepatitis. The evidence from this study is insufficient to support any recommendations regarding the mortality benefit of pentoxifylline in severe alcoholic hepatitis.
Collapse
|
|
44
|
Rossi RE, Conte D, Massironi S. Diagnosis and treatment of nutritional deficiencies in alcoholic liver disease: Overview of available evidence and open issues. Dig Liver Dis 2015; 47:819-825. [PMID: 26164399 DOI: 10.1016/j.dld.2015.05.021] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/28/2015] [Accepted: 05/30/2015] [Indexed: 02/08/2023]
Abstract
Malnutrition is common in alcoholic liver disease and is associated with high rates of complications and mortality. In this article, the current literature was reviewed to highlight the relevance of proper nutritional management providing levels of evidence, when available. A PubMed search was performed for English-language publications from 1980 through 2014 with the keywords: alcoholic liver disease, nutritional deficiencies, nutritional support, enteral nutrition, parenteral nutrition, and protein-energy malnutrition. Manuscripts focused on nutritional approach in patients with alcoholic liver disease were selected. Although nutritional support for malnourished patients improves the outcome of hospitalization, surgery, transplantation and reduces the complications of liver disease and the length of hospital stay, specific guidelines are scanty. Both enteral and parenteral nutrition appear to improve nutritional parameters and liver function; however data on survival is often conflicting. As micronutrient depletion is common in alcoholic liver disease and each deficiency produces specific sequelae, all cirrhotic patients should be screened at baseline for deficiencies of micronutrient and supplemented as needed. In summary, protein-energy malnutrition and micronutrient depletion are clinical concerns in alcoholic liver disease. Nutritional therapy, including enteral nutrition, parenteral nutrition and micronutrient supplementation should be part of the multidisciplinary management of these patients.
Collapse
Affiliation(s)
- Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Italy
| |
Collapse
|
|
45
|
Pang JXQ, Ross E, Borman MA, Zimmer S, Kaplan GG, Heitman SJ, Swain MG, Burak KW, Quan H, Myers RP. Validation of coding algorithms for the identification of patients hospitalized for alcoholic hepatitis using administrative data. BMC Gastroenterol 2015; 15:116. [PMID: 26362871 PMCID: PMC4566395 DOI: 10.1186/s12876-015-0348-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 09/09/2015] [Indexed: 12/20/2022] Open
Abstract
Background Epidemiologic studies of alcoholic hepatitis (AH) have been hindered by the lack of a validated International Classification of Disease (ICD) coding algorithm for use with administrative data. Our objective was to validate coding algorithms for AH using a hospitalization database. Methods The Hospital Discharge Abstract Database (DAD) was used to identify consecutive adults (≥18 years) hospitalized in the Calgary region with a diagnosis code for AH (ICD-10, K70.1) between 01/2008 and 08/2012. Medical records were reviewed to confirm the diagnosis of AH, defined as a history of heavy alcohol consumption, elevated AST and/or ALT (<300 U/L), serum bilirubin >34 μmol/L, and elevated INR. Subgroup analyses were performed according to the diagnosis field in which the code was recorded (primary vs. secondary) and AH severity. Algorithms that incorporated ICD-10 codes for cirrhosis and its complications were also examined. Results Of 228 potential AH cases, 122 patients had confirmed AH, corresponding to a positive predictive value (PPV) of 54 % (95 % CI 47–60 %). PPV improved when AH was the primary versus a secondary diagnosis (67 % vs. 21 %; P < 0.001). Algorithms that included diagnosis codes for ascites (PPV 75 %; 95 % CI 63–86 %), cirrhosis (PPV 60 %; 47–73 %), and gastrointestinal hemorrhage (PPV 62 %; 51–73 %) had improved performance, however, the prevalence of these diagnoses in confirmed AH cases was low (29–39 %). Conclusions In conclusion the low PPV of the diagnosis code for AH suggests that caution is necessary if this hospitalization database is used in large-scale epidemiologic studies of this condition.
Collapse
Affiliation(s)
- Jack X Q Pang
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada. .,Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
| | - Erin Ross
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.
| | - Meredith A Borman
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.
| | - Scott Zimmer
- Medical Services, Alberta Health Services, Calgary, AB, Canada.
| | - Gilaad G Kaplan
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada. .,Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
| | - Steven J Heitman
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada. .,Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
| | - Mark G Swain
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.
| | - Kelly W Burak
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada. .,Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
| | - Hude Quan
- Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
| | - Robert P Myers
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada. .,Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
| |
Collapse
|
|
46
|
Nguyen DL, Morgan T. Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view. Hepatol Int 2015; 8:447-51. [PMID: 25525477 DOI: 10.1007/s12072-013-9497-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Since the late nineteenth century, protein restriction has been shown to improve hepatic encephalopathy. However, malnutrition has been described in up to 60 % of cirrhotic patients and is associated with increased mortality. Furthermore, emerging clinical evidence has revealed that a large proportion of cirrhotic patients may tolerate normal protein intake. However, approximately one third of cirrhotic patients with hepatic encephalopathy may need a short course of protein restriction, in addition to maximum medical therapy, to ameliorate the clinical course of their hepatic encephalopathy. For patients with chronic hepatic encephalopathy who are protein-sensitive, modifying their sources of nitrogen by using more vegetable protein, less animal protein, and branched-chain amino acids may improve their encephalopathy without further loss of lean body mass. In conclusion, among cirrhotics with hepatic encephalopathy, modulation of normal protein intake must take into account the patient's hepatic reserve, severity of hepatic encephalopathy, and current nutritional status.
Collapse
Affiliation(s)
- Douglas L Nguyen
- Gastroenterology Service, VA Long Beach Healthcare System, 11, 5901 E. Seventh Street, Long Beach, CA 90822, USA, Gastroenterology Division, University of California, Irvine, CA, USA
| | - Timothy Morgan
- Gastroenterology Service, VA Long Beach Healthcare System, 11, 5901 E. Seventh Street, Long Beach, CA 90822, USA, Gastroenterology Division, University of California, Irvine, CA, USA
| |
Collapse
|
|
47
|
Abstract
Alcoholic hepatitis (AH) is caused by acute inflammation of the liver in patients that consume excessive amounts of alcohol, usually in a background of cirrhosis. AH can range from mild to severe, life threatening disease with a high rate of short and long-term mortality. Prognostic models have been used to estimate mortality in order to identify those that may benefit from corticosteroids or pentoxifylline. This review focuses on the different prognostic models proposed. While limitations of the prognostic models exist, combining models may be beneficial in order to identify responders to therapy versus non-responders.
Collapse
Affiliation(s)
- Erik Rahimi
- Division of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX 77030 USA
| | - Jen-Jung Pan
- Division of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX 77030 USA
| |
Collapse
|
|
48
|
Ye BD. [Parenteral Nutritional Support in Gastrointestinal and Liver Diseases]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2015; 65:346-53. [PMID: 26087689 DOI: 10.4166/kjg.2015.65.6.346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Protein-calorie malnutrition and deficiencies of specific nutrients could commonly occur in various types of gastrointestinal diseases. These nutritional problems could delay recovery from diseases, resulting in increased morbidity and mortality, and impairment of quality of life. Parenteral nutrition (PN) is one of the methods of nutritional support through which macronutrients (glucose, amino acids, and triglycerides), micronutrients (vitamins and trace elements), water, and electrolytes are administered via peripheral or central venous route. PN could play an important role for patients for whom enteral/oral feeding is contraindicated or cannot meet the patients' requirement for adequate nutrition due to anatomical and/or functional problems. Since insufficient and excessive PN supplement could both be harmful for patients, it is very important to adhere to correct indication, optimal timing, and dosage/composition of PN. In this article, the current role of PN for various gastrointestinal diseases will be reviewed and discussed.
Collapse
Affiliation(s)
- Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
49
|
Risk factors for mortality in patients with alcoholic hepatitis and assessment of prognostic models: A population-based study. Can J Gastroenterol Hepatol 2015; 29:131-8. [PMID: 25855876 PMCID: PMC4399372 DOI: 10.1155/2015/814827] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Severe alcoholic hepatitis (AH) is associated with a substantial risk for short-term mortality. OBJECTIVES To identify prognostic factors and validate well-known prognostic models in a Canadian population of patients hospitalized for AH. METHODS In the present retrospective study, patients hospitalized for AH in Calgary, Alberta, between January 2008 and August 2012 were included. Stepwise logistic regression models identified independent risk factors for 90-day mortality, and the discrimination of prognostic models (Model for End-stage Liver Disease [MELD] and Maddrey discriminant function [DF]) were examined using areas under the ROC curves. RESULTS A total of 122 patients with AH were hospitalized during the study period; the median age was 49 years (interquartile range [IQR] 42 to 55 years) and 60% were men. Median MELD score and Maddrey DF on admission were 21 (IQR 18 to 24) and 45 (IQR 26 to 62), respectively. Seventy-three percent of patients received corticosteroids and⁄or pentoxifylline, and the 90-day mortality was 17%. Independent predictors of mortality included older age, female sex, international normalized ratio, MELD score and Maddrey DF (all P<0.05). For discrimination of 90-day mortality, the areas under the ROC curves of the prognostic models (MELD 0.64; Maddrey DF 0.68) were similar (P>0.05). At optimal cut-offs of ≥22 for MELD score and ≥37 for Maddrey DF, both models excluded death with high certainty (negative predictive values 90% and 96%, respectively). CONCLUSIONS In patients hospitalized for AH, well-known prognostic models can be used to predict 90-day mortality, particularly to identify patients with a low risk for death.
Collapse
|
|
50
|
Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G, Cochrane Neuromuscular Group. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. Cochrane Database Syst Rev 2014; 2014:CD006832. [PMID: 24477672 PMCID: PMC7390458 DOI: 10.1002/14651858.cd006832.pub3] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Critical illness polyneuropathy or myopathy (CIP/CIM) is a frequent complication in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, longer ICU stay and increased mortality. This is an interim update of a review first published in 2009 (Hermans 2009). It has been updated to October 2011, with further potentially eligible studies from a December 2013 search characterised as awaiting assessment. OBJECTIVES To systematically review the evidence from RCTs concerning the ability of any intervention to reduce the incidence of CIP or CIM in critically ill individuals. SEARCH METHODS On 4 October 2011, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE. We checked the bibliographies of identified trials and contacted trial authors and experts in the field. We carried out an additional search of these databases on 6 December 2013 to identify recent studies. SELECTION CRITERIA All randomised controlled trials (RCTs), examining the effect of any intervention on the incidence of CIP/CIM in people admitted to adult medical or surgical ICUs. The primary outcome was the incidence of CIP/CIM in ICU, based on electrophysiological or clinical examination. Secondary outcomes included duration of mechanical ventilation, duration of ICU stay, death at 30 and 180 days after ICU admission and serious adverse events from the treatment regimens. DATA COLLECTION AND ANALYSIS Two authors independently extracted the data and assessed the risk of bias in included studies. MAIN RESULTS We identified five trials that met our inclusion criteria. Two trials compared intensive insulin therapy (IIT) to conventional insulin therapy (CIT). IIT significantly reduced CIP/CIM in the screened (n = 825; risk ratio (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.77) and total (n = 2748; RR 0.70, 95% CI 0.60 to 0.82) population randomised. IIT reduced duration of mechanical ventilation, ICU stay and 180-day mortality, but not 30-day mortality compared with CIT. Hypoglycaemia increased with IIT but did not cause early deaths.One trial compared corticosteroids with placebo (n = 180). The trial found no effect of treatment on CIP/CIM (RR 1.27, 95% CI 0.77 to 2.08), 180-day mortality, new infections, glycaemia at day seven, or episodes of pneumonia, but did show a reduction of new shock events.In the fourth trial, early physical therapy reduced CIP/CIM in 82/104 evaluable participants in ICU (RR 0.62. 95% CI 0.39 to 0.96). Statistical significance was lost when we performed a full intention-to-treat analysis (RR 0.81, 95% CI 0.60 to 1.08). Duration of mechanical ventilation but not ICU stay was significantly shorter in the intervention group. Hospital mortality was not affected but 30- and 180-day mortality results were not available. No adverse effects were noticed.The last trial found a reduced incidence of CIP/CIM in 52 evaluable participants out of a total of 140 who were randomised to electrical muscle stimulation (EMS) versus no stimulation (RR 0.32, 95% CI 0.10 to 1.01). These data were prone to bias due to imbalances between treatment groups in this subgroup of participants. After we imputed missing data and performed an intention-to-treat analysis, there was still no significant effect (RR 0.94, 95% CI 0.78 to 1.15). The investigators found no effect on duration of mechanical ventilation and noted no difference in ICU mortality, but did not report 30- and 180-day mortality.We updated the searches in December 2013 and identified nine potentially eligible studies that will be assessed for inclusion in the next update of the review. AUTHORS' CONCLUSIONS There is moderate quality evidence from two large trials that intensive insulin therapy reduces CIP/CIM, and high quality evidence that it reduces duration of mechanical ventilation, ICU stay and 180-day mortality, at the expense of hypoglycaemia. Consequences and prevention of hypoglycaemia need further study. There is moderate quality evidence which suggests no effect of corticosteroids on CIP/CIM and high quality evidence that steroids do not affect secondary outcomes, except for fewer new shock episodes. Moderate quality evidence suggests a potential benefit of early rehabilitation on CIP/CIM which is accompanied by a shorter duration of mechanical ventilation but without an effect on ICU stay. Very low quality evidence suggests no effect of EMS, although data are prone to bias. Strict diagnostic criteria for CIP/CIM are urgently needed for research purposes. Large RCTs need to be conducted to further explore the role of early rehabilitation and EMS and to develop new preventive strategies.
Collapse
Affiliation(s)
- Greet Hermans
- KU LeuvenDepartment of Cellular and Molecular MedicineHerestraat 49, 3000 LeuvenLeuvenBelgium
| | - Bernard De Jonghe
- Centre Hospitalier de Poissy‐Saint‐GermainRéanimation Médico‐Chirurgicale10 rue du Champ Gaillard, F‐78300PoissyFrance
| | - Frans Bruyninckx
- KU Leuven, University HospitalsPhysical Medicine and RehabilitationHerestraat 49, 3000LeuvenBelgium
| | - Greet Van den Berghe
- KU Leuven, University HospitalsDepartment of Intensive Care MedicineHerestraat 49,3000LeuvenBelgium
| | | |
Collapse
|