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Enciu VT, Ologeanu PM, Constantinescu A, Fierbinteanu-Braticevici C. Latest Insights in Alcohol-Related Liver Disease and Alcoholic Hepatitis. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2025:rjim-2025-0007. [PMID: 40245287 DOI: 10.2478/rjim-2025-0007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Indexed: 04/19/2025]
Abstract
Alcohol-related liver disease (ALD) is still to this date one of the leading causes of chronic liver disease globally. ALD comprises a wide disease spectrum, from the benign liver steatosis, to the life-threatening inflammatory acute phenotype of alcoholic hepatitis (AH) and ultimately, advanced liver fibrosis and cirrhosis. AH represents an acute inflammatory liver condition caused by prolonged high quantities of alcohol intake. Disease outcome varies from mild to severe, with systemic implication and high mortality. Although the pathogenesis has been extensively studied over the years, little progress has been made regarding therapeutic options. In over 50 years, steroid treatment is still the cornerstone therapeutic option, albeit having multiple limitations and a low success rate. On the other hand, important progress has been made regarding disease management and severity stratification with the implementation of different prognostic score. Although highly prevalent, AH still has many unmet needs, with a growing necessity for novel non-invasive diagnosis, prognosis biomarkers and impactful treatment options.
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Affiliation(s)
- Vlad-Teodor Enciu
- 1Internal Medicine II and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 2Emergency University Hospital, 050098 Bucharest, Romania
| | - Priscila Madalina Ologeanu
- 1Internal Medicine II and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 2Emergency University Hospital, 050098 Bucharest, Romania
| | - Alexandru Constantinescu
- 2Emergency University Hospital, 050098 Bucharest, Romania
- 3Internal Medicine I and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474, Bucharest, Romania
| | - Carmen Fierbinteanu-Braticevici
- 1Internal Medicine II and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 2Emergency University Hospital, 050098 Bucharest, Romania
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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: 396] [Impact Index Per Article: 66.0] [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.
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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
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Trieu JA, Bilal M, Lewis B, Gou E, Sonstein L, Parupudi S. Adherence to Appropriate Nutrition in Acute Alcoholic Hepatitis is Low. Ann Hepatol 2018; 17:752-755. [PMID: 30145576 DOI: 10.5604/01.3001.0012.3132] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Malnutrition is a common cause of impeding recovery in patients with acute alcoholic hepatitis (AAH). Previous reports have shown that appropriate nutritional supplementation reduce short and long-term mortality in patients with AAH. Despite these clear recommendations, the element of nutrition in AAH is often neglected. We designed a quality improvement project to evaluate and improve compliance with appropriate nutrition in patients presenting with AAH at our institution. Patients admitted with AAH between December 2015 to December 2016 were included. Our primary outcome was compliance with appropriate nutrition. Secondary outcomes included nutrition consultation and hepatology consultation. A total of fifty-four patients were included. Nine of the 53 patients (17%) received high calorie and high protein diets. Hepatology was consulted in 72% (38/53) of the patients, and 21% (8/38) of these patients received appropriate nutrition as compared to only 8.3% (1/12) in whom hepatology was not consulted. Nutrition was consulted in 55% (29/53) of these patients and 67% (19/28) of those patients received appropriate nutrition. In conclusion, our compliance of appropriate nutrition in AAH is low. Our initial investigation suggests that hepatology and nutrition consultation improved compliance with appropriate nutrition. The next step will be to implement protocolized care for appropriate nutrition in AAH by incorporating consultation of hepatology and nutrition services, assess the effect on adherence to appropriate nutrition, and determine the impact on patient outcomes.
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Affiliation(s)
- Judy A Trieu
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States
| | - Mohammad Bilal
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, United States
| | - Briana Lewis
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States
| | - Eric Gou
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, United States
| | - Lindsay Sonstein
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States
| | - Sreeram Parupudi
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, United States
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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.
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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
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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.
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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.
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Silva M, Gomes S, Peixoto A, Torres-Ramalho P, Cardoso H, Azevedo R, Cunha C, Macedo G. Nutrition in Chronic Liver Disease. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2015; 22:268-276. [PMID: 28868418 PMCID: PMC5580118 DOI: 10.1016/j.jpge.2015.06.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 06/25/2015] [Indexed: 12/12/2022]
Abstract
Protein-calorie malnutrition is a transversal condition to all stages of chronic liver disease. Early recognition of micro or macronutrient deficiencies is essential, because the use of nutritional supplements reduces the risk of complications. The diet of patients with chronic liver disease is based on a standard diet with supplements addition as necessary. Restrictions may be harmful and should be individualized. Treatment management should aim to maintain an adequate protein and caloric intake and to correct nutrient deficiencies. The large majority of patients with grade I/II hepatic encephalopathy can tolerate a regular diet. Protein restriction can aggravate malnutrition and is not recommended, except in cases of hepatic encephalopathy unresponsive to optimized therapy.
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Affiliation(s)
- Marco Silva
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
| | - Sara Gomes
- General Practice Department, Unidade Saúde Familiar Alfena, Porto, Portugal
| | - Armando Peixoto
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
| | | | - Hélder Cardoso
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
| | - Rosa Azevedo
- Nutrition Department, Centro Hospitalar São João, Porto, Portugal
| | - Carla Cunha
- Nutrition Department, Centro Hospitalar São João, Porto, Portugal
| | - Guilherme Macedo
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
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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.
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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
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Abstract
PURPOSE OF REVIEW The burden of alcohol on global health is increasing, and there is a strong relationship between population alcohol consumption and liver-related deaths. As alcohol-related liver disease (ArLD) often develops with no signs or symptoms, the prevention of liver disease relies on the recognition of harmful drinking and screening of those patients at risk for early markers of liver disease. RECENT FINDINGS A robust method of screening patients at risk of ArLD is essential. Once a patient develops ArLD, abstinence and early recognition of its complications are keys to improving outcomes. Corticosteroids remain the mainstay treatment in alcoholic hepatitis pending the results from large multicentre trials. More recently, there has been an increased interest in the use of rifaximin and albumin in various settings of ArLD. SUMMARY Advances in the treatment of ArLD and its complications, such as alcoholic hepatitis, will allow a greater proportion of patients chance for their liver to recover. However, new strategies to detect and intervene in those patients at higher risk of ArLD are likely to have the greatest overall impact.
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Abstract
The liver plays an important role in the metabolism, synthesis, storage, and absorption of nutrients. Patients with cirrhosis are prone to nutritional deficiencies and malnutrition, with a higher prevalence among patients with decompensated disease. Mechanisms of nutritional deficiencies in patients with liver disease are not completely understood and probably multifactorial. Malnutrition among patients with cirrhosis or alcoholic liver disease correlates with poor quality of life, increased risk of infections, frequent hospitalizations, complications, mortality, poor graft and patient survival after liver transplantation, and economic burden. Physicians, including gastroenterologists and hepatologists, should be conversant with assessment and management of malnutrition and nutritional supplementation.
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Abstract
BACKGROUND Weight loss and muscle wasting are commonly found in patients with end-stage liver disease. Since there is an association between malnutrition and poor clinical outcome, such patients (or those at risk of becoming malnourished) are often given parenteral nutrition, enteral nutrition, or oral nutritional supplements. These interventions have costs and adverse effects, so it is important to prove that their use results in improved morbidity or mortality, or both. OBJECTIVES To assess the beneficial and harmful effects of parenteral nutrition, enteral nutrition, and oral nutritional supplements on the mortality and morbidity of patients with underlying liver disease. SEARCH METHODS The following computerised databases were searched: the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, and Science Citation Index Expanded (January 2012). In addition, reference lists of identified trials and review articles and Clinicaltrials.gov were searched. Trials identified in a previous systematic handsearch of Index Medicus were also considered. Handsearches of a number of medical journals, including abstracts from annual meetings, were done. Experts in the field and manufacturers of nutrient formulations were contacted for potential references. SELECTION CRITERIA Randomised clinical trials (parallel or cross-over design) comparing groups of patients with any underlying liver disease who received, or did not receive, enteral or parenteral nutrition or oral nutritional supplements were identified without restriction on date, language, or publication status. Six categories of trials were separately considered: medical or surgical patients receiving parenteral nutrition, enteral nutrition, or supplements. DATA COLLECTION AND ANALYSIS The following data were sought in each report: date of publication; geographical location; inclusion and exclusion criteria; the type of nutritional support and constitution of the nutrient formulation; duration of treatment; any nutrition provided to the controls; other interventions provided to the patients; number, sex, age of the study participants; hospital or outpatient status; underlying liver disease; risks of bias (sequence generation, allocation concealment, blinding, incomplete outcome reporting, intention-to-treat analysis, selective outcome reporting, others (vested interests, baseline imbalance, early stopping)); mortality; hepatic morbidity (development or resolution of ascites or hepatic encephalopathy, occurrence of gastrointestinal bleeding); quality of life scores; adverse events; infections; lengths of stay in the hospital or intensive care unit; costs; serum bilirubin; postoperative complications (surgical trials only); and nutritional outcomes (nitrogen balance, anthropometric measurements, body weight). The primary outcomes of this review were mortality, hepatic morbidity, quality of life, and adverse events. Data were extracted in duplicate; differences were resolved by consensus.Data for each outcome were combined in a meta-analysis (RevMan 5.1). Estimates were reported using risk ratios or mean differences, along with the 95% confidence intervals (CI). Both fixed-effect and random-effects models were employed; fixed-effect models were reported unless one model, but not the other, found a significant difference (in which case both were reported). Heterogeneity was assessed by the Chi(2) test and I(2) statistic. Subgroup analyses were planned to assess specific liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma), acute or chronic liver diseases, and trials employing standard or branched-chain amino acid formulations (for the hepatic encephalopathy outcomes). Sensitivity analyses were planned to compare trials at low and high risk of bias and trials reported as full papers. The following exploratory analyses were undertaken: 1) medical and surgical trials were combined for each nutritional intervention; 2) intention-to-treat analyses in which missing dichotomous data were imputed as best- and worst-case scenarios; 3) all trials were combined to assess mortality; 4) effects were estimated by absolute risk reductions. MAIN RESULTS Thirty-seven trials were identified; only one was at low risk of bias. Most of the analyses failed to find any significant differences. The significant findings that were found were the following: 1) icteric medical patients receiving parenteral nutrition had a reduced serum bilirubin (mean difference (MD) -2.86 mg%, 95% CI -3.82 mg% to -1.89 mg%, 3 trials) and better nitrogen balance (MD 3.60 g/day, 95% CI 0.86 g/day to 6.34 g/day, 1 trial); 2) surgical patients receiving parenteral nutrition had a reduced incidence of postoperative ascites only in the fixed-effect model (RR 0.65, 95% CI 0.48 to 0.87, 2 trials, I(2) = 70%) and one trial demonstrated a reduction in postoperative complications, especially infections (pneumonia in particular); 3) enteral nutrition may have improved nitrogen balance in medical patients (although a combination of the three trials was not possible); 4) one surgical trial of enteral nutrition found a reduction in postoperative complications; and 5) oral nutritional supplements had several effects in medical patients (reduced occurrence of ascites (RR 0.57, 95% CI 0.37 to 0.88, 3 trials), possibly (significant differences only seen in the fixed-effect model) reduced rates of infection (RR 0.49, 95% CI 0.24 to 0.99, 3 trials, I(2) = 14%), and improved resolution of hepatic encephalopathy (RR 3.75, 95% CI 1.15 to 12.18, 2 trials, I(2) = 79%). While there was no overall effect of the supplements on mortality in medical patients, the one low risk of bias trial found an increased risk of death in the recipients of the supplements. Three trials of supplements in surgical patients failed to show any significant differences. No new information was derived from the various subgroup or sensitivity analyses. The exploratory analyses were also unrevealing except for a logical conundrum. There was no difference in mortality when all of the trials were combined, but the trials of parenteral nutrition found that those recipients had better survival (RR 0.53, 95% CI 0.29 to 0.98, 10 trials). Either the former observation represents a type II error or the latter one a type I error. AUTHORS' CONCLUSIONS The data do not compellingly justify the routine use of parenteral nutrition, enteral nutrition, or oral nutritional supplements in patients with liver disease. The fact that all but one of these trials were at high risks of bias even casts doubt on the few benefits that were demonstrated. Data from well-designed and executed randomised trials that include an untreated control group are needed before any such recommendation can be made. Future trials have to be powered adequately to see small, but clinically important, differences.
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Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2012. [PMID: 22592729 DOI: 10.1002/14651858.cd008344] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Weight loss and muscle wasting are commonly found in patients with end-stage liver disease. Since there is an association between malnutrition and poor clinical outcome, such patients (or those at risk of becoming malnourished) are often given parenteral nutrition, enteral nutrition, or oral nutritional supplements. These interventions have costs and adverse effects, so it is important to prove that their use results in improved morbidity or mortality, or both. OBJECTIVES To assess the beneficial and harmful effects of parenteral nutrition, enteral nutrition, and oral nutritional supplements on the mortality and morbidity of patients with underlying liver disease. SEARCH METHODS The following computerised databases were searched: the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, and Science Citation Index Expanded (January 2012). In addition, reference lists of identified trials and review articles and Clinicaltrials.gov were searched. Trials identified in a previous systematic handsearch of Index Medicus were also considered. Handsearches of a number of medical journals, including abstracts from annual meetings, were done. Experts in the field and manufacturers of nutrient formulations were contacted for potential references. SELECTION CRITERIA Randomised clinical trials (parallel or cross-over design) comparing groups of patients with any underlying liver disease who received, or did not receive, enteral or parenteral nutrition or oral nutritional supplements were identified without restriction on date, language, or publication status. Six categories of trials were separately considered: medical or surgical patients receiving parenteral nutrition, enteral nutrition, or supplements. DATA COLLECTION AND ANALYSIS The following data were sought in each report: date of publication; geographical location; inclusion and exclusion criteria; the type of nutritional support and constitution of the nutrient formulation; duration of treatment; any nutrition provided to the controls; other interventions provided to the patients; number, sex, age of the study participants; hospital or outpatient status; underlying liver disease; risks of bias (sequence generation, allocation concealment, blinding, incomplete outcome reporting, intention-to-treat analysis, selective outcome reporting, others (vested interests, baseline imbalance, early stopping)); mortality; hepatic morbidity (development or resolution of ascites or hepatic encephalopathy, occurrence of gastrointestinal bleeding); quality of life scores; adverse events; infections; lengths of stay in the hospital or intensive care unit; costs; serum bilirubin; postoperative complications (surgical trials only); and nutritional outcomes (nitrogen balance, anthropometric measurements, body weight). The primary outcomes of this review were mortality, hepatic morbidity, quality of life, and adverse events. Data were extracted in duplicate; differences were resolved by consensus.Data for each outcome were combined in a meta-analysis (RevMan 5.1). Estimates were reported using risk ratios or mean differences, along with the 95% confidence intervals (CI). Both fixed-effect and random-effects models were employed; fixed-effect models were reported unless one model, but not the other, found a significant difference (in which case both were reported). Heterogeneity was assessed by the Chi(2) test and I(2) statistic. Subgroup analyses were planned to assess specific liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma), acute or chronic liver diseases, and trials employing standard or branched-chain amino acid formulations (for the hepatic encephalopathy outcomes). Sensitivity analyses were planned to compare trials at low and high risk of bias and trials reported as full papers. The following exploratory analyses were undertaken: 1) medical and surgical trials were combined for each nutritional intervention; 2) intention-to-treat analyses in which missing dichotomous data were imputed as best- and worst-case scenarios; 3) all trials were combined to assess mortality; 4) effects were estimated by absolute risk reductions. MAIN RESULTS Thirty-seven trials were identified; only one was at low risk of bias. Most of the analyses failed to find any significant differences. The significant findings that were found were the following: 1) icteric medical patients receiving parenteral nutrition had a reduced serum bilirubin (mean difference (MD) -2.86 mg%, 95% CI -3.82 mg% to -1.89 mg%, 3 trials) and better nitrogen balance (MD 3.60 g/day, 95% CI 0.86 g/day to 6.34 g/day, 1 trial); 2) surgical patients receiving parenteral nutrition had a reduced incidence of postoperative ascites only in the fixed-effect model (RR 0.65, 95% CI 0.48 to 0.87, 2 trials, I(2) = 70%) and one trial demonstrated a reduction in postoperative complications, especially infections (pneumonia in particular); 3) enteral nutrition may have improved nitrogen balance in medical patients (although a combination of the three trials was not possible); 4) one surgical trial of enteral nutrition found a reduction in postoperative complications; and 5) oral nutritional supplements had several effects in medical patients (reduced occurrence of ascites (RR 0.57, 95% CI 0.37 to 0.88, 3 trials), possibly (significant differences only seen in the fixed-effect model) reduced rates of infection (RR 0.49, 95% CI 0.24 to 0.99, 3 trials, I(2) = 14%), and improved resolution of hepatic encephalopathy (RR 3.75, 95% CI 1.15 to 12.18, 2 trials, I(2) = 79%). While there was no overall effect of the supplements on mortality in medical patients, the one low risk of bias trial found an increased risk of death in the recipients of the supplements. Three trials of supplements in surgical patients failed to show any significant differences. No new information was derived from the various subgroup or sensitivity analyses. The exploratory analyses were also unrevealing except for a logical conundrum. There was no difference in mortality when all of the trials were combined, but the trials of parenteral nutrition found that those recipients had better survival (RR 0.53, 95% CI 0.29 to 0.98, 10 trials). Either the former observation represents a type II error or the latter one a type I error. AUTHORS' CONCLUSIONS The data do not compellingly justify the routine use of parenteral nutrition, enteral nutrition, or oral nutritional supplements in patients with liver disease. The fact that all but one of these trials were at high risks of bias even casts doubt on the few benefits that were demonstrated. Data from well-designed and executed randomised trials that include an untreated control group are needed before any such recommendation can be made. Future trials have to be powered adequately to see small, but clinically important, differences.
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Tan HH, Virmani S, Martin P. Controversies in the management of alcoholic liver disease. ACTA ACUST UNITED AC 2011; 76:484-98. [PMID: 19787655 DOI: 10.1002/msj.20135] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Alcohol is a risk factor for chronic disease burden in developed countries. Alcoholic liver disease affects 1% of the North American population and is the second most frequent indication for liver transplantation in the United States. It is a spectrum that ranges from simple hepatic steatosis to alcoholic hepatitis to steatohepatitis and eventually cirrhosis. The clinical spectrum of alcoholic hepatitis is wide and ranges from the asymptomatic patient to overt liver failure and death. Liver biopsy as a means of prognostication in alcoholic hepatitis has mostly been replaced with less invasive scoring systems. The management of alcoholic liver disease is challenging. Abstinence is the cornerstone of therapy and should include rehabilitation with a multidisciplinary approach. No specific treatment is required in mild to moderate alcoholic hepatitis. In patients with severe hepatitis, there appears to be a moderate survival benefit from the use of either corticosteroids or pentoxifylline in the absence of contraindications to their use. Nonresponders should have steroid therapy withdrawn by day 7, as persistence with therapy is not beneficial. Orthotopic liver transplantation remains the definitive therapy for decompensated alcoholic cirrhosis despite alcohol abstinence. More studies are needed to define the optimal timing of orthotopic liver transplantation and patients at risk of alcohol relapse post-transplant. Mt Sinai J Med 76:484-498, 2009. (c) 2009 Mount Sinai School of Medicine.
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Affiliation(s)
- Hui-Hui Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.
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Yu CH, Xu CF, Ye H, Li L, Li YM. Early mortality of alcoholic hepatitis: a review of data from placebo-controlled clinical trials. World J Gastroenterol 2010; 16:2435-2439. [PMID: 20480532 PMCID: PMC2874151 DOI: 10.3748/wjg.v16.i19.2435] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2010] [Revised: 02/07/2010] [Accepted: 02/14/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the early mortality of placebo-treated alcoholic hepatitis patients. METHODS Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. RESULTS A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infection were the three main causes of death, accounting for 55.47%, 21.17% and 7.30% of all deaths, respectively. One-month mortality data about 324 placebo-treated alcoholic hepatitis patients in 10 trials were reported with a pooled mortality rate of 20.37%. The one-month mortality rate of patients with moderate to severe alcoholic hepatitis tended to be higher than that of general patients (22.69% vs 10.93%, P < 0.05), whereas no significant difference was observed between the patients from North America or Europe (22.43% vs 18.45%, P > 0.05), neither any difference was found between the studies published before and after 1990 (18.18% vs 21.88%, P > 0.05). CONCLUSION Alcoholic hepatitis is a severe liver disease with a high mortality rate, and hepatic failure, gastrointestinal bleeding and infection are the three main causes of death.
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Plauth M, Schuetz T. Hepatology - Guidelines on Parenteral Nutrition, Chapter 16. GERMAN MEDICAL SCIENCE : GMS E-JOURNAL 2009; 7:Doc12. [PMID: 20049084 PMCID: PMC2795384 DOI: 10.3205/000071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2009] [Indexed: 12/13/2022]
Abstract
Parenteral nutrition (PN) is indicated in alcoholic steatohepatitis (ASH) and in cirrhotic patients with moderate or severe malnutrition. PN should be started immediately when sufficientl oral or enteral feeding is not possible. ASH and cirrhosis patients who can be sufficiently fed either orally or enterally, but who have to abstain from food over a period of more than 12 hours (including nocturnal fasting) should receive basal glucose infusion (2–3 g/kg/d). Total PN is required if such fasting periods last longer than 72 h. PN in patients with higher-grade hepatic encephalopathy (HE); particularly in HE IV° with malfunction of swallowing and cough reflexes, and unprotected airways. Cirrhotic patients or patients after liver transplantation should receive early postoperative PN after surgery if they cannot be sufficiently rally or enterally nourished. No recommendation can be made on donor or organ conditioning by parenteral administration of glutamine and arginine, aiming at minimising ischemia/reperfusion damage. In acute liver failure artificial nutrition should be considered irrespective of the nutritional state and should be commenced when oral nutrition cannot be restarted within 5 to 7 days. Whenever feasible, enteral nutrition should be administered via a nasoduodenal feeding tube.
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Affiliation(s)
- M Plauth
- Dept. of Internal Medicine, Municipal Clinic Dessau, Germany
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15
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ESPEN Guidelines on Parenteral Nutrition: hepatology. Clin Nutr 2009; 28:436-44. [PMID: 19520466 DOI: 10.1016/j.clnu.2009.04.019] [Citation(s) in RCA: 145] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 04/27/2009] [Indexed: 12/13/2022]
Abstract
Parenteral nutrition (PN) offers the possibility to increase or to ensure nutrient intake in patients, in whom sufficient nutrition by oral or enteral alone is insufficient or impossible. Complementary to the ESPEN guideline on enteral nutrition of liver disease (LD) patients the present guideline is intended to give evidence-based recommendations for the use of PN in LD. For this purpose three paradigm conditions of LD were chosen: alcoholic steatohepatitis (ASH), liver cirrhosis and acute liver failure. The guideline was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was presented on the ESPEN website and visitors' criticism and suggestions were welcome and included in the final revision. PN improves nutritional state and liver function in malnourished patients with ASH. PN is safe and improves mental state in patients with cirrhosis and severe HE. Perioperative (including liver transplantation) PN is safe and reduces the rate of complications. In acute liver failure PN is a safe second-line option to adequately feed patients in whom enteral nutrition is insufficient or impossible.
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16
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Abstract
PURPOSE OF REVIEW To describe the evidences for and against the different nutritional and nonnutritional therapeutic approaches for severe alcoholic steatohepatitis, based on data from randomized controlled trials, in order to answer the question posed in the title: 'more of the same or something new?'. RECENT FINDINGS Very few papers assessing old or new therapeutic strategies for severe alcoholic steatohepatitis have been published in the last 18 months. In addition, all of them provide negative results. A meta-analysis of the trials using anabolic steroids in alcoholic steatohepatitis confirmed the lack of benefit associated with this therapy. Also, two randomized controlled trials failed to disclose any positive effect of different antioxidant mixture in these patients. SUMMARY The answer to the question posed in the title of this review must unfortunately be 'nothing new, but just the same!'.
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Affiliation(s)
- Eduard Cabré
- Department of Gastroenterology, Hospital Universitari Germans Trias i PujolBadalona, Catalonia, Spain.
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17
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Jung Y, Brown KD, Witek RP, Omenetti A, Yang L, Vandongen M, Milton RJ, Hines IN, Rippe RA, Spahr L, Rubbia–Brandt L, Diehl AM. Accumulation of hedgehog-responsive progenitors parallels alcoholic liver disease severity in mice and humans. Gastroenterology 2008; 134:1532-43. [PMID: 18471524 PMCID: PMC3611332 DOI: 10.1053/j.gastro.2008.02.022] [Citation(s) in RCA: 125] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2007] [Accepted: 01/31/2008] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Improving outcomes in alcoholic liver disease (ALD) necessitates better understanding of how habitual ethanol (EtOH) consumption alters normal regenerative mechanisms within the liver. Hedgehog (Hh) pathway activation promotes expansion of progenitor populations in other tissues. We evaluated the hypothesis that chronic EtOH exposure activates Hh signaling in liver. METHODS Hh signaling, liver progenitors, transforming growth factor (TGF)-beta induction, and liver damage were compared in mice fed chow, high-fat diets (HF), or HF + EtOH for 4 weeks. Susceptibility to TGF-beta-mediated apoptosis was compared in Hh-responsive liver cells (eg, immature cholangiocytes and oval cells) and mature hepatocytes (which are unresponsive to Hh). Hepatic accumulation of Hh-responsive cells were compared in controls and ALD patients and correlated with a discriminant function (DF) that predicts subacute mortality. RESULTS Hh signaling and numbers of Hh-responsive cells were increased in HF mice and greatest in HF+EtOH mice. In both, progenitor and stromal cell populations harbored Hh-responsive cells. More ductular-type progenitors and fibrosis markers were noted in HF+EtOH mice than in HF mice. The former also expressed more TGF-beta-1. TGF-beta-1 treatment selectively promoted the viability of Hh-responsive immature liver cells and caused mature hepatocytes that survived to produce Hh ligands. Hh-responsive cells were increased in ALD patients. Lobular accumulation of Hh-responsive immature ductular cells was greater in those with a DF >32 than those with a DF <32. CONCLUSIONS Hh signaling is increased in ALD and may influence ALD outcomes by promoting hepatic accumulation of immature ductular cells.
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Affiliation(s)
- Youngmi Jung
- Department of Medicine, Duke University, Durham, North Carolina
| | - Kevin D. Brown
- Department of Medicine, Duke University, Durham, North Carolina
| | - Rafal P. Witek
- Department of Medicine, Duke University, Durham, North Carolina
| | | | - Liu Yang
- Department of Medicine, Duke University, Durham, North Carolina
| | | | - Richard J. Milton
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - Ian N. Hines
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - Richard A. Rippe
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | | | | | - Anna Mae Diehl
- Department of Medicine, Duke University, Durham, North Carolina
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18
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O'Brien A, Williams R. Nutrition in end-stage liver disease: principles and practice. Gastroenterology 2008; 134:1729-40. [PMID: 18471550 DOI: 10.1053/j.gastro.2008.02.001] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2007] [Revised: 01/25/2008] [Accepted: 02/01/2008] [Indexed: 02/07/2023]
Affiliation(s)
- Alastair O'Brien
- Institute of Hepatology, Royal Free and University College Medical School, University College London, London, England. a.o'
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19
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Koretz RL. Do Data Support Nutrition Support? Part I: Intravenous Nutrition. ACTA ACUST UNITED AC 2007; 107:988-96; quiz 998. [PMID: 17524720 DOI: 10.1016/j.jada.2007.03.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2006] [Indexed: 11/29/2022]
Abstract
Intravenous (parenteral) nutrition has been advocated widely as adjunctive care in patients with a variety of underlying diseases. However, the enthusiasm for this therapeutic intervention was based largely on expert opinion. Because the best way to assess the efficacy of any treatment is to test it in a randomized controlled trial, this review will focus on data that was derived from such studies. Using established search strategies, randomized controlled trials were sought that compared one of two forms of intravenous nutrition: parenteral nutrition (nitrogen and >or=10 kcal/kg/day of non-protein calories for >or=5 days) or protein-sparing therapy (nitrogen and fewer non-protein calories) with no type of artificial nutrition beyond regular food and/or standard (5%) dextrose. The randomized controlled trials were stratified by the underlying disease state. The clinical outcomes of interest were mortality, morbidity (total/infectious complications), and/or duration of hospitalization. More than 100 randomized controlled trials failed for the most part to demonstrate that intravenous nutrition had any effect on clinical outcome. There were a few exceptions. In patients undergoing attempted curative surgery for upper gastrointestinal cancer, the use of preoperative parenteral nutrition seemed to reduce the incidence of major postoperative complications. However, this benefit was only found in low-quality randomized controlled trials. Findings conflict regarding the use of parenteral nutrition in patients with acute pancreatitis or undergoing bone marrow transplantation. Parenteral nutrition was harmful when provided to patients undergoing radiation or chemotherapy for cancer. Although no randomized controlled trials exist, it is assumed that parenteral nutrition is useful in patients with an inadequate gastrointestinal tract ("short gut"). Thus, for the most part, randomized controlled trials comparing intravenous nutrition to no artificial nutrition have not shown that this medical intervention is of benefit.
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Affiliation(s)
- Ronald L Koretz
- Department of Medicine, Olive View UCLA Medical Center, Sylmar, CA 91342, USA.
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20
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Abstract
Alcoholic hepatitis is a serious liver disease that may lead to cirrhosis and carcinoma, and the short-term mortality rate is fairly high in severe patients. Various strategies have been tested over the decades and none has shown any consistent benefit but the corticosteroids. Until now hepatic transplantation is the best solution to the patients with severe alcoholic hepatitis, but the timing and indications for transplantation are still problematic. Recent advances in the understanding of alcoholic hepatitis, including the roles of hepatocyte apoptosis, oxidative stress and cytokines, have provided a new opportunity to discover specific therapies for alcoholic hepatitis.
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21
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Abstract
The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis.
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Affiliation(s)
- Catherine Rongey
- Robert Wood Johnson Clinical Scholars Program, University of California at Los Angeles, 911 Broxton Avenue, Los Angeles, CA 90024, USA.
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22
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Abstract
Cirrhosis and its sequelae are responsible for close to 2% of all causes of death in the United States. Some studies have suggested that the costs of liver disease may account for as much as 1% of all health care spending, with alcohol-related liver disease (ALD) representing a major portion. It accounts for between 40% to 50% of all deaths due to cirrhosis, with an accompanying rate of progression of up to 60% in patients with pure alcoholic fatty liver over 10 years, and a 5-year survival rate as low as 35% if patients continue to drink. A subset of patients with ALD will develop an acute, virulent form of injury, acute alcoholic hepatitis, which has a substantially worse prognosis. Despite enormous progress in understanding the physiology of this disease, much remains unknown, and therefore, a consensus regarding effective therapy for ALD is lacking. Conventional therapy is still based largely on abstinence from alcohol, as well as general supportive and symptomatic care. Unfortunately, hepatocellular damage may progress despite these measures. Multiple treatment interventions for both the short- and long-term morbidity and mortality of this disease have been proposed, but strong disagreement exists among experts regarding the value of any of the proposed specific therapeutic interventions.
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Affiliation(s)
- Robert S O'Shea
- Department of Gastroenterology and Hepatology A30, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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23
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Affiliation(s)
- Stephen F Stewart
- Centre for Liver Research, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
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24
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Abstract
Chronic alcohol consumption may lead to primary and secondary malnutrition. In particular, protein energy malnutrition not only aggravates alcoholic liver disease but also correlates with impaired liver function and increased mortality. Therefore, in these patients, adequate nutritional support should be implemented in order to improve their prognosis. Clinical trials addressing this issue have shown that nutritional therapy either enterally or parenterally improves various aspects of malnutrition, and there is increasing evidence that it may also improve survival. Therefore, malnourished alcoholics should be administered a diet rich in carbohydrate- and protein-derived calories preferentially via the oral or enteral route. Micronutrient deficiencies typically encountered in alcoholics, such as for thiamine and folate, require specific supplementation. Patients with hepatic encephalopathy may be treated with branched-chain amino acids in order to achieve a positive nitrogen balance. Fatty liver represents the early stage of alcoholic liver disease, which is usually reversible with abstinence. Metadoxine appears to improve fatty liver but confirmatory studies are necessary. S-adenosyl-L-methionine may be helpful for patients with severe alcoholic liver damage, since various mechanisms of alcohol-related hepatotoxicity are counteracted with this essential methyl group donor, while a recent large trial showed that the use of polyenylphosphatidylcholine is of limited efficacy.
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Affiliation(s)
- F Stickel
- Department of Medicine I, University of Erlangen-Nuremberg, Germany
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25
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Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev 2003:CD001939. [PMID: 12804416 DOI: 10.1002/14651858.cd001939] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy. OBJECTIVES To evaluate the beneficial and harmful effects of BCAA for patients with hepatic encephalopathy. SEARCH STRATEGY We identified trials through The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), (Issue 3, 2002), MEDLINE (1966-2002/09) and EMBASE (1980-2002/05), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies. SELECTION CRITERIA Randomised trials comparing BCAA with any kind of control therapy for hepatic encephalopathy were included, regardless of blinding, language, or publication status. DATA COLLECTION AND ANALYSIS Trial inclusion and data extraction were made independently by two reviewers. Our primary outcome was improvement of hepatic encephalopathy. Statistical heterogeneity was tested using random effects and fixed effect models. Binary outcomes are reported as risk ratios (RR) based on a random effects model. MAIN RESULTS Eleven randomised trials (556 patients) assessing BCAA versus carbohydrates, neomycin/lactulose, or isonitrogenous control were included. The median number of patients in each trial was 55 (range 22 to 75). Follow-up after treatment was reported in four trials (median 17 days (range 6 to 30 days)). Compared to the control regimens, BCAA significantly increased the number of patients improving from hepatic encephalopathy at the end of treatment (risk ratio (RR) 1.31, 95% confidence interval (CI) 1.04 to 1.66, nine trials). We found no evidence of an effect of BCAA on survival (RR 1.06, 95% CI 0.98 to 1.14, eight trials) or adverse events (RR 0.97, 95% CI 0.41 to 2.31, three trials). Sensitivity analyses indicated that methodological quality had significant impact on the results. We found no evidence of an effect of BCAA on improvement of hepatic encephalopathy in trials with adequate generation of the allocation sequence (RR 1.01, 95% CI 0.84 to 1.23, three trials), adequate allocation concealment (RR 1.09, 95% CI 0.89 to 1.33, five trials), or adequate double-blinding (RR 1.20, 95% CI 0.83 to 1.73, three trials). REVIEWER'S CONCLUSIONS We did not find convincing evidence that BCAA had a significant beneficial effect on patients with hepatic encephalopathy. The trials performed in this field were small with short follow-up and most had low methodological quality.
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Affiliation(s)
- B Als-Nielsen
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, H:S Rigshospitalet, Dep. 7102, Blegdamsvej 9, Copenhagen, Denmark.
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26
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Abstract
In the past year, some relevant papers related to the diagnosis of malnutrition and its pathogenesis in cirrhosis have been published. The value of anthropometrics in the nutritional assessment of end-stage cirrhotic patients has been reinforced. Also, the role of bioelectrical impedance analysis in these patients has been redefined. Several papers have investigated the relationship between leptin and malnutrition in chronic liver disease, particularly the role of alcoholism in hyperleptinaemia, and the importance of protein-bound leptin in these patients. In other papers, the impact of both undernutrition and obesity on the outcome of liver transplantation has been investigated. Two randomized, controlled trials on enteral nutrition in liver disease have been published in this period. One of them deals with a clinical situation (i.e. severe alcoholic hepatitis) associated with a high mortality rate, whereas the second is the first controlled trial in the field of preoperative nutrition in liver transplantation. Finally, some papers provide further arguments in the dilemma of which route of nutrition (enteral or parenteral) is better in cirrhosis.
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Affiliation(s)
- E Cabré
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
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27
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Abstract
This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics Committee. The paper was approved by the Committee on September 13, 2001, and by the AGA Governing Board on May 18, 2001.
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Affiliation(s)
- R L Koretz
- Olive View-UCLA Medical Center Sylmar, California, USA
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28
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Cabré E, Rodríguez-Iglesias P, Caballería J, Quer JC, Sánchez-Lombraña JL, Parés A, Papo M, Planas R, Gassull MA. Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Hepatology 2000; 32:36-42. [PMID: 10869286 DOI: 10.1053/jhep.2000.8627] [Citation(s) in RCA: 213] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Steroids are recommended in severe alcohol-induced hepatitis, but some data suggest that artificial nutrition could also be effective. We conducted a randomized trial comparing the short- and long-term effects of total enteral nutrition or steroids in these patients. A total of 71 patients (80% cirrhotic) were randomized to receive 40 mg/d prednisolone (n = 36) or enteral tube feeding (2,000 kcal/d) for 28 days (n = 35), and were followed for 1 year or until death. Side effects of treatment occurred in 5 patients on steroids and 10 on enteral nutrition (not significant). Eight enterally fed patients were prematurely withdrawn from the trial. Mortality during treatment was similar in both groups (9 of 36 vs. 11 of 35, intention-to-treat) but occurred earlier with enteral feeding (median 7 vs. 23 days; P =.025). Mortality during follow-up was higher with steroids (10 of 27 vs. 2 of 24 intention-to-treat; P =. 04). Seven steroid patients died within the first 1.5 months of follow-up. In contrast to total enteral nutrition (TEN), infections accounted for 9 of 10 follow-up deaths in the steroid group. In conclusion, enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis, although death occurs earlier with enteral nutrition. However, steroid therapy is associated with a higher mortality rate in the immediate weeks after treatment, mainly because of infections. A possible synergistic effect of both treatments should be investigated.
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Abstract
Hepatic changes resulting from the regular ingestion of alcohol are many and include fat infiltration, alcoholic hepatitis, and cirrhosis. Only 10% to 15% of chronic alcoholics develop liver disease. Women are more susceptible. An area of considerable importance is the high prevalence of concomitant infection with hepatitis C virus in chronic alcoholics. Patients who have hepatitis C and alcohol-induced liver injury are much more likely to develop progressive liver disease and cirrhosis. Corticosteroid therapy has proven useful in the treatment of patients with severe acute alcoholic hepatitis.
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Affiliation(s)
- W C Maddrey
- Department of Internal Medicine, University of Texas Medical Center at Dallas, Dallas, Texas, USA
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30
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Cabré E, Gassull MA. Assistance nutritionnelle des hépatopathies aiguës : hépatite alcoolique et cirrhose. NUTR CLIN METAB 1999. [DOI: 10.1016/s0985-0562(99)80052-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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McCullough AJ, O'Connor JF. Alcoholic liver disease: proposed recommendations for the American College of Gastroenterology. Am J Gastroenterol 1998; 93:2022-36. [PMID: 9820369 DOI: 10.1111/j.1572-0241.1998.00587.x] [Citation(s) in RCA: 159] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The objective of this work was to develop practice guidelines for the management of alcoholic liver disease. METHOD A computerized search using the Medline Data Base from 1966-July 1997 was performed with the search headings; alcohol, alcoholic hepatitis, alcoholic liver disease, liver transplant, diagnosis, epidemiology, human, and English only. All randomized controlled trials, case-control studies, and meta-analyses were read in depth. A manual search was also done using references from each retrieved report, review articles, editorials, postgraduate course syllabi, and textbooks. In the subsequent review, evidence was evaluated using a hierarchical scale with randomized, controlled trials given the most importance. Abstracts presented at national meetings were included only when unique data were obtained from those studies.
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Affiliation(s)
- A J McCullough
- Center of Nutrition and Metabolism, Metro Health Medical Center, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA
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32
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Affiliation(s)
- J Kondrup
- Department of Hepatology, Medical Department A, Rigshospitalet, Denmark
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33
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Plauth M, Merli M, Kondrup J, Weimann A, Ferenci P, Müller MJ. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr 1997; 16:43-55. [PMID: 16844569 DOI: 10.1016/s0261-5614(97)80022-2] [Citation(s) in RCA: 234] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- M Plauth
- IV. Medizinische Klinik, Klinikum Charitéder Humboldt Universität, D-10098 Berlin, Germany
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34
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Nielsen K, Kondrup J, Martinsen L, Døssing H, Larsson B, Stilling B, Jensen MG. Long-term oral refeeding of patients with cirrhosis of the liver. Br J Nutr 1995; 74:557-67. [PMID: 7577893 DOI: 10.1079/bjn19950158] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
A previous study has shown that malnourished, clinically stable patients with liver cirrhosis are in protein and energy balance at their spontaneous dietary intake and that an improvement in nutritional status cannot be anticipated at this intake (Nielsen et al. 1993). In the present study we examined to what extent oral intake could be increased by nutritional support, and to what extent dietary protein would be retained with increased intake. The techniques used for balance studies were also validated since this information is not available for patients with liver cirrhosis. Fifteen malnourished patients with alcoholic liver cirrhosis were given increasing amounts of a balanced ordinary diet for 38 (SE 3) d. Intakes of protein and energy were recorded by weighing servings and leftovers on food trays. Protein intake was calculated from food tables. Total N disposal was calculated after measurement of urinary N excretion, and protein balance was calculated from the N balance. A validation study of protein balance in a subgroup of patients (analysis of N in food by the duplicate portion technique, correction for incomplete recovery of urine by measurement of urinary para-aminobenzoic acid (PABA) after administration of PABA tablets, and measurement of faecal N) did not change protein balance values. Protein intake increased from 1.0 (SE 0.1) g/kg per d to 1.8 (SE 0.1) g/kg per d. With increasing protein intake, 84 (SE 8)% of the increase in intake was retained. The rate of protein retention was not saturated at the intakes obtained in this study. Protein intolerance was only encountered in one patient. Available evidence indicates that the requirement for achieving N balance is increased in these patients but protein retention is highly efficient with increased intake. Protein retention is dependent on energy balance. Energy intake was calculated from food tables and total energy expenditure was calculated by the factorial method. A validation study was performed in a subgroup of patients. The energy contents of food sampled by the duplicate portion technique, and of urine and faeces were measured by bomb calorimetry. Resting energy expenditure (REE) was measured by indirect calorimetry before and at the end of the study, and O2 uptake during bicycle exercise was measured before and at the end of the study. The measured intake of metabolizable energy was on average 13% lower than the value given in food tables. Calculated energy expenditure was not changed by the validation study.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- K Nielsen
- Department of Medicine A-2152, Rigshospitalet, Denmark
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35
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Mendenhall CL, Moritz TE, Roselle GA, Morgan TR, Nemchausky BA, Tamburro CH, Schiff ER, McClain CJ, Marsano LS, Allen JI. Protein energy malnutrition in severe alcoholic hepatitis: diagnosis and response to treatment. The VA Cooperative Study Group #275. JPEN J Parenter Enteral Nutr 1995; 19:258-65. [PMID: 8523623 DOI: 10.1177/0148607195019004258] [Citation(s) in RCA: 113] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Active nutrition therapy and the anabolic steroid oxandrolone (OX), in selected patients with severe alcoholic hepatitis, significantly improved liver status and survival. We report here on the changes in their nutritional parameters. METHODS Protein energy malnutrition (PEM) was evaluated and expressed as percent of low normal in 271 patients initially, at 1 month and at 3 months. Active therapy consisted of OX plus a high caloric food supplement vs a matching placebo and a low calorie supplement. RESULTS PEM was present in every patient; mean PEM score 60% of low normal. Most of the parameters improved significantly from baseline on standard care; the largest improvement seen in visceral proteins, the smallest in fat stores (skinfold thickness). Total PEM score significantly correlated with 6 month mortality (p = .0012). Using logistic regression analysis, creatinine height index, hand grip strength and total peripheral blood lymphocytes were the best risk factors for survival. When CD lymphocyte subsets replaced total lymphocyte counts in the equation, CD8 levels became a significant risk factor (p = .004). Active treatment produced significant risk factor (p = .004). Active treatment produced significant improvements in those parameters related to total body and muscle mass (ie, mid arm muscle area, p = .02; creatinine height index, p = .03; percent ideal body weight, p = .04). CONCLUSION Deterioration in nutritional parameters is a significant risk factor for survival in severe patients with alcoholic hepatitis. This deterioration is reversible with standard hospital care. Active therapy further improves creatinine height index, mid arm muscle area and total lymphocyte counts. Hence, these later parameters appear to be the best indicators for follow-up assessments.
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Affiliation(s)
- C L Mendenhall
- Department of Veterans Affairs Medical Centers: Cincinnati, Ohio 45220, USA
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Szende B, Timár F, Hargitai B. Olive oil decreases liver damage in rats caused by carbon tetrachloride (CCl4). EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY : OFFICIAL JOURNAL OF THE GESELLSCHAFT FUR TOXIKOLOGISCHE PATHOLOGIE 1994; 46:355-9. [PMID: 7894247 DOI: 10.1016/s0940-2993(11)80116-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Oral carbon tetrachloride (CCl4) poisoning of the liver of male F-344 rats was modified by dissolving CCl4 in various oils (sunflower, corn, fish and olive). After 8 weeks of CCl4 treatment (3 x 0.2 ml/kg body weight every other day, dissolved in aliquots of 0.5 ml of each types of oil) the rats were sacrificed and the ratio of connective tissue in the liver was determined by morphometry after picrosirius staining. The percentage of collagen fibres increased in all CCl4-treated groups compared to the controls. This increase was almost the same (6-8%) in the case of CCl4 dissolved in sunflower, corn or fish oil, but when olive oil was applied as a solvent, the collagen ratio was only 2-4 percent. On the bases of this finding olive oil is considered as less harmful to the liver in acute CCl4 poisoning than other oils.
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Affiliation(s)
- B Szende
- I. Institute of Pathology and Experimental Cancer Research Semmelweis University of Medicine Budapest, Hungary
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Affiliation(s)
- D J Nompleggi
- Department of Medicine, Surgery, Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester 01655
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Ramond MJ, Rueff B, Benhamou JP. Medical treatment for alcoholic liver disease. BAILLIERE'S CLINICAL GASTROENTEROLOGY 1993; 7:697-716. [PMID: 8219407 DOI: 10.1016/0950-3528(93)90009-h] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
The most effective treatment for alcoholic liver disease is abstinence from alcohol and it is the only treatment for patients with alcoholic fatty liver. Although many empirical therapeutic agents have been studied in the short-term and long-term treatment of alcoholic hepatitis, results have been mainly inconclusive. To date, only corticosteroids have proved to decrease the short-term mortality rate of patients with severe forms of acute alcoholic hepatitis. Corticosteroids are not beneficial to the majority of patients with mild or moderate forms of acute alcoholic hepatitis; such patients improve with abstinence from alcohol and general supportive measures and do not need a specific short-term treatment. Most long-term trials have only showed that most patients with alcoholic liver disease were neither abstinent nor compliant, and that long-term survival was strongly correlated to abstinence from alcohol. In one study, propylthiouracil decreased the long-term mortality rate of compliant patients with severe alcoholic liver disease who reduced their alcohol intake; however, further clinical trials are needed before propylthiouracil can be recommended. In another study, colchicine decreased the long-term mortality rate of cirrhotic patients, 45% of whom had alcoholic cirrhosis. Results were highly significant, and the need for further clinical trials of colchicine in the long-term treatment of alcoholic and non-alcoholic cirrhosis is imperative. Enteral nutrition should also be studied in severely malnourished cirrhotic patients, since it was shown to decrease the short-term mortality rate of such patients in a recent study.
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Nielsen K, Kondrup J, Martinsen L, Stilling B, Wikman B. Nutritional assessment and adequacy of dietary intake in hospitalized patients with alcoholic liver cirrhosis. Br J Nutr 1993; 69:665-79. [PMID: 8329343 DOI: 10.1079/bjn19930068] [Citation(s) in RCA: 74] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Nutritional assessment and adequacy of spontaneous dietary intake was evaluated in thirty-seven clinically stable hospitalized patients with alcoholic liver cirrhosis. About two-thirds of the patients had ascites or oedema, or both, and, therefore, body weight could not be used for assessment of nutritional status. Lean body mass (LBM; measured by three consecutive 24 h creatinine excretions) was 62 (range 40-95)% of reference values, mid-arm-muscle area (MAMA) was 70 (range 43-115)% and triceps skinfold (TSF) was 45 (range 20-113)% of reference values (all median values). In patients without ascites or oedema, or both, there was a rectilinear correlation between body weight and LBM and between body weight and MAMA (r 0.93 and 0.85 respectively). In patients with ascites or oedema, or both, the correlation between body weight and LBM was poor as could be expected. We suggest that LBM is a useful measure of nutritional status when body weight is unreliable because of ascites or oedema, or both. Energy balance for the group was calculated from energy intake recorded by a 24 h dietary recall and energy expenditure calculated by the factorial method. Median intake was 102 (range 34-176)% of expenditure. N loss was calculated from the average of three 24 h urea excretions. Protein intake was calculated from the 24 h dietary recall. The N balance was positive in the patients as a group (median intake was 120 (range 26-183)% of output). The most malnourished patients tended to have the most positive N balance which was due to a significantly lower N excretion. The protein requirement for N balance was 0.83 (SE 0.05) g/kg per d and only at an intake above 1.20 g/kg per d were all patients in positive N balance. The median intakes of thiamin, folacin, vitamin D, vitamin E, Mg, and Zn were judged to be insufficient. It is concluded that impaired nutritional status is common among patients with liver cirrhosis, even in a stable clinical condition. It is suggested that nutritional status in these patients is evaluated by dietary recalls, in combination with measurement of body weight in patients without ascites or oedema, or both, or in combination with determination of LBM by three 24 h creatinine excretions in patients with ascites or oedema, or both. Criteria for selection of patients that might benefit from nutritional therapy are discussed.
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Affiliation(s)
- K Nielsen
- Medical Department A, Rigshospitalet, Copenhagen, Denmark
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Mendenhall CL, Moritz TE, Roselle GA, Morgan TR, Nemchausky BA, Tamburro CH, Schiff ER, McClain CJ, Marsano LS, Allen JI. A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study. Hepatology 1993; 17:564-76. [PMID: 8477961 DOI: 10.1002/hep.1840170407] [Citation(s) in RCA: 228] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A Veterans Affairs cooperative study involving 273 male patients was performed to evaluate efficacy of oxandrolone in combination with an enteral food supplement in severe alcoholic hepatitis. All patients had some degree of protein calorie malnutrition. On an intention-to-treat basis, only minimal changes in mortality were observed. However, in patients with moderate malnutrition mortality on active treatment at 1 mo was 9.4% compared with 20.9% in patients receiving placebo. This beneficial effect was maintained so that after 6 mo on active treatment 79.7% of patients were still alive, compared with 62.7% of placebo-treated patients (p = 0.037). Improvements in both the severity of the liver injury (p = 0.03) and malnutrition (p = 0.05) also occurred. No significant improvement was observed with severe malnutrition. To better determine the effect on therapeutic efficacy, we compared results with those from a nearly identical population (cooperative study 119) treated with oxandrolone but not given the food supplement. Patients were stratified according to their caloric intake (greater than 2,500 kcal/day was considered adequate to supply energy needs and promote anabolism). For patients with moderate malnutrition and adequate caloric intake, oxandrolone treatment reduced 6-mo mortality (4% active treatment vs. 28% placebo [p = 0.002]). For patients with moderate malnutrition and inadequate calorie intake, oxandrolone had no effect on mortality (30% active treatment vs. 33% placebo). In cases of severe malnutrition, oxandrolone had no effect on survival. However, adequate caloric intake was associated with 19% mortality, whereas patients with inadequate intake exhibited 51% mortality (p = 0.0001). These results indicate that nutritional status should be evaluated in patients with alcoholic hepatitis. When malnutrition is present, vigorous nutrition therapy should be provided, and in patients with moderate malnutrition oxandrolone should be added to the regimen.
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Affiliation(s)
- C L Mendenhall
- Department of Veterans Affairs Medical Center, Cincinnati, Ohio 45220
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Affiliation(s)
- T R Morgan
- Gastroenterology Section, VA Medical Center, Long Beach, California 90822
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Abstract
The biochemistry of alcohol liver disease as it relates to clinical medicine and experimental alcohol liver disease is presented. Clinical features are emphasized in the diagnosis of alcohol liver disease, particularly as it relates to staging the disease and predictors of prognosis. Currently, it is true that the biochemical diagnosis of alcohol liver disease is at best very limited in terms of the sensitivity tests and specificity of the test. It is particularly difficult to detect alcohol liver disease biochemically in the early stages when steatohepatitis is not severe. Consequently, 50% of the patients have already developed cirrhosis at the time they are diagnosed clinically. In this review indicators of malnutrition are emphasized because they have the strongest implications regarding survival during the acute hospitalization stage of the disease. They are also the best indicators of response to therapy during the recovery phase. With respect to experimental work on the pathogenesis of alcohol liver disease, it appears that necrosis is due to the inability to increase blood flow to compensate for increased oxygen utilization. The hypothesis that mitochondrial damage is the cause of liver cell damage is regarded as less important in the pathogenesis of necrosis. The shift in the redox state during alcohol metabolism accounts for the fatty change noted in the central lobular area of the liver in animals fed alcohol. Apparently, there is strong experimental evidence that highly reactive intermediates are important in the pathogenesis of liver damage due to the induction of the isozyme cytochrome P450 IIE1 by alcohol ingestion. This mechanism is enhanced by a diet high in polyunsaturated fatty acids.
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Affiliation(s)
- S W French
- Department of Pathology, Harbor-UCLA Medical Center, Torrance
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Kearns PJ, Young H, Garcia G, Blaschke T, O'Hanlon G, Rinki M, Sucher K, Gregory P. Accelerated improvement of alcoholic liver disease with enteral nutrition. Gastroenterology 1992; 102:200-5. [PMID: 1727754 DOI: 10.1016/0016-5085(92)91801-a] [Citation(s) in RCA: 162] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
This prospective study compared the effects of tube-fed nutrition with those of a regular diet in alcoholic liver disease. The high prevalence of malnutrition in patients with alcoholic liver disease requires clarification of the benefits of aggressive nutritional support. Patients were randomly assigned a regular diet without or with tube-fed supplementation, delivering 1.5 g/kg protein and 167 kJ/kg daily. Comparisons of encephalopathy, antipyrine clearance, metabolic rate, and biochemical parameters were performed weekly for 4 weeks. Sixteen patients receiving enteral supplementation had antipyrine half-life (50% vs. 3% reduction), serum bilirubin (25% vs. 0% reduction), and median encephalopathy scores that improved more rapidly than those of controls. Initially, 15 controls did not consume adequate calories to meet measured resting energy expenditure. Aggressive nutritional intervention accelerated improvement in alcoholic liver disease. Adverse effects did not offset the demonstrated benefits of a 2-cal/mL, casein-based tube-fed supplement. These findings support the use of standard, casein-based solutions in the treatment of alcoholic liver disease and as the control condition for future studies.
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Affiliation(s)
- P J Kearns
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, California
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Maddrey WC. Alcoholic hepatitis: pathogenesis and approaches to treatment. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1990; 175:118-30. [PMID: 2237274 DOI: 10.3109/00365529009093136] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Alcoholic hepatitis is a necrotizing, often inflammatory, process that is an important precursor to the development of cirrhosis. Acetaldehyde, which is derived from alcohol by the action of alcohol dehydrogenase, is apparently the most important factor leading to alcohol-induced liver injury. Other factors of importance in determining the appearance and rate of progression of liver diseases in patients who are chronic alcoholics include sex, nutritional status, and various immunologic reactions. In addition, there is an incompletely understood genetic predisposition to the development of alcoholic hepatitis. Several histologic features found in patients with alcoholic hepatitis have been evaluated in efforts to determine which are of prognostic value. The predominance of the alcohol-induced injury in zone III of the hepatic lobule; deposition of collagen, IgA, and fibronectin in the space of Disse; defenestration of endothelial cells; and transformation of lipocytes and myofibroblasts to fibroblasts have been investigated. Prolongation of the prothrombin time and marked elevation of serum bilirubin levels are indicators of a subgroup of patients with alcoholic hepatitis who have a poor prognosis, especially if there is also evidence of hepatic encephalopathy. Supportive care and abstinence from alcohol are the foundations of therapy. Corticosteroid therapy appears to decrease the number of early deaths in patients with severe alcoholic hepatitis. Other experimental approaches to therapy include the use of propylthiouracil, anabolic-androgenic steroids, and insulin and glucagon.
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Affiliation(s)
- W C Maddrey
- University of Texas Southwestern Medical Center, Dallas 75235
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