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Wunderle C, Ciobanu C, Ritz J, Tribolet P, Neyer P, Bernasconi L, Stanga Z, Mueller B, Schuetz P. Association of leucine and other branched chain amino acids with clinical outcomes in malnourished inpatients: a secondary analysis of the randomized clinical trial EFFORT. Eur J Clin Nutr 2025; 79:42-49. [PMID: 39245679 DOI: 10.1038/s41430-024-01507-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND The essential branched-chain amino acids leucine, isoleucine and valine are considered anabolic and stimulate protein synthesis in the muscles as well in the liver. They also promote muscle recovery and contribute to glucose homeostasis. Recent studies in critically ill patients have demonstrated that depletion of plasma leucine is associated with increased mortality, but data in the non-critical care setting is lacking. METHODS This secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), investigated the impact of leucine, isoleucine, and valine metabolism on clinical outcomes. The primary endpoint was 180-day all-cause mortality. RESULTS Among 238 polymorbid patients with available metabolite measurements, low serum leucin levels were associated with a doubled risk of 180-day all-cause mortality in a fully adjusted regression model (adjusted HR 2.20 [95% CI 1.46-3.30], p < 0.001). There was also an association with mortality for isoleucine (1.56 [95% CI 1.03-2.35], p = 0.035) and valine (1.69 [95% CI 1.13-2.53], p = 0.011). When comparing effects of nutritional support on mortality in patients with high and low levels of leucine, there was no evidence of significant differences in effectiveness of the intervention. The same was true for isoleucine and valine. CONCLUSION Our data suggest that depletion of leucine, isoleucine, and valine among malnourished polymorbid patients is associated with increases in long-term mortality. However, patients with low metabolite levels did not show a pronounced benefit from nutritional support. Further research should focus on the clinical effects of nutritional support in patients with depleted stores of essential branched-chain amino acids. CLINICAL TRIAL REGISTRATION clinicaltrials.gov as NCT02517476 (registered 7 August 2015).
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Affiliation(s)
- Carla Wunderle
- Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland
| | - Claudia Ciobanu
- Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
| | - Jacqueline Ritz
- Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
| | - Pascal Tribolet
- Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland
- Department of Health Professions, Bern University of Applied Sciences, Bern, Switzerland
- Department of Nutritional Sciences and Research Platform Active Ageing, University of Vienna, Vienna, Austria
| | - Peter Neyer
- Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland
| | - Luca Bernasconi
- Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland
| | - Zeno Stanga
- Division of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Beat Mueller
- Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
| | - Philipp Schuetz
- Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
- Medical Faculty of the University of Basel, Basel, Switzerland.
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Li XQ, Liang Y, Huang CF, Li SN, Cheng L, You C, Liu YX, Wang T. Advancements in nutritional diagnosis and support strategies during the perioperative period for patients with liver cancer. World J Gastrointest Surg 2024; 16:2409-2425. [PMID: 39220056 PMCID: PMC11362955 DOI: 10.4240/wjgs.v16.i8.2409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/27/2024] [Accepted: 06/24/2024] [Indexed: 08/16/2024] Open
Abstract
Liver cancer represents a grave hepatic condition and constitutes a significant global health concern. Surgical resection remains the principal therapeutic modality for liver cancer. Nevertheless, perioperative malnutrition exerts a notable impact on patients with liver cancer, emerging as an independent risk factor for disease mortality and adverse outcomes. Hence, precise nutritional diagnosis and timely nutritional support hold the potential to enhance therapeutic efficacy and quality of life for liver cancer patients. This study represents a meticulous foray into the literature, extracting data from PubMed, Web of Science, and EMBASE databases, with a focus on the past 5 years. It scrutinizes the impact of malnutrition on patients undergoing liver cancer surgery, the etiological underpinnings of malnutrition within this patient cohort, the critical assessment of perioperative nutritional status, and the strategic approaches to nutritional support. Utilizing rigorous inclusion and exclusion criteria, the amassed scholarly works are meticulously synthesized, methodically organized, and categorically elaborated upon. Ultimately, the authors propose the incorporation of a multidisciplinary nutrition management team during the perioperative period, comprising nutritionists, pharmacists, physicians, nurses, psychologists, and rehabilitation therapists, among other specialized professionals. Together, they collaborate to devise and implement personalized nutritional support plans, monitor patients' nutritional status, and make necessary adjustments as required. Through comprehensive management and intervention, improvements in the nutritional status of liver cancer patients can be achieved, thereby enhancing surgical success rates and facilitating postoperative recovery. It is believed that this manuscript will offer valuable insights to advance the nutritional management during the perioperative phase of liver cancer, aiding in ameliorating patients' nutritional status and treatment outcomes.
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Affiliation(s)
- Xiao-Qin Li
- Department of Hepatobiliary Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Yun Liang
- Department of Paediatric Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Chen-Feng Huang
- Department of Cardiovascular Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510632, Guangdong Province, China
| | - Sui-Ning Li
- Department of Cardiovascular Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510632, Guangdong Province, China
| | - Lei Cheng
- Department of Hepatobiliary Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Chuan You
- Department of Hepatobiliary Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Yao-Xia Liu
- Department of Geriatric Endocrinology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan Province, China
| | - Tao Wang
- Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, Sichuan Province, China
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Zhang Y, Zhan L, Zhang L, Shi Q, Li L. Branched-Chain Amino Acids in Liver Diseases: Complexity and Controversy. Nutrients 2024; 16:1875. [PMID: 38931228 PMCID: PMC11206364 DOI: 10.3390/nu16121875] [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: 05/09/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular signaling. The liver is a crucial site for BCAA metabolism, linking the changes in BCAA homeostasis with the pathogenesis of a variety of liver diseases and their complications. Peripheral circulating BCAA levels show complex trends in different liver diseases. This review delineates the alterations of BCAAs in conditions including non-alcoholic fatty liver disease, hepatocellular carcinoma, cirrhosis, hepatic encephalopathy, hepatitis C virus infection, and acute liver failure, as well as the potential mechanisms underlying these changes. A significant amount of clinical research has utilized BCAA supplements in the treatment of patients with cirrhosis and liver cancer. However, the efficacy of BCAA supplementation in clinical practice remains uncertain and controversial due to the heterogeneity of studies. This review delves into the complicated relationship between BCAAs and liver diseases and tries to untangle what role BCAAs play in the occurrence, development, and outcomes of liver diseases.
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Affiliation(s)
- Yaqi Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
| | - Luqi Zhan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
| | - Lingjian Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
- Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310024, China
| | - Qingmiao Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
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Biselli M, Reggidori N, Iavarone M, Renzulli M, Lani L, Granito A, Piscaglia F, Lorenzini S, Alimenti E, Vara G, Caraceni P, Sangiovanni A, Marignani M, Gigante E, Brandi N, Gramenzi A, Trevisani F. Impact of Sarcopenia on the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib. Cancers (Basel) 2024; 16:1080. [PMID: 38539416 PMCID: PMC10968777 DOI: 10.3390/cancers16061080] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 02/29/2024] [Accepted: 03/05/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND AND AIMS Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. METHODS A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. RESULTS Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment.
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Affiliation(s)
- Maurizio Biselli
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Nicola Reggidori
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, 48018 Faenza, Italy
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (M.I.); (E.A.); (A.S.)
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.R.); (G.V.); (N.B.)
| | - Lorenzo Lani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Alessandro Granito
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Stefania Lorenzini
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
| | - Eleonora Alimenti
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (M.I.); (E.A.); (A.S.)
| | - Giulio Vara
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.R.); (G.V.); (N.B.)
| | - Paolo Caraceni
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (M.I.); (E.A.); (A.S.)
| | - Massimo Marignani
- Division of Gastroenterology and Hepatology, Ospedale Regina Apostolorum, 00041 Albano Laziale, Italy;
| | - Elia Gigante
- Service d’Hépato-Gastroentérologie et de Cancérologie Digestive, Hôpital Robert Debré, Université Reims-Champagne-Ardenne, 51092 Reims, France;
| | - Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.R.); (G.V.); (N.B.)
| | - Annagiulia Gramenzi
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
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Yap KY, Chi H, Ng S, Ng DHL, Shelat VG. Effect of perioperative branched chain amino acids supplementation in liver cancer patients undergoing surgical intervention: A systematic review. World J Gastrointest Surg 2023; 15:2596-2618. [PMID: 38111761 PMCID: PMC10725538 DOI: 10.4240/wjgs.v15.i11.2596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/15/2023] [Accepted: 10/23/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Branched chain amino acid (BCAA) supplementation has been associated with favourable outcomes in liver malignancies requiring definitive resection or liver transplantation. Currently, there are no updated systematic reviews evaluating the efficacy of perioperative BCAA supplementation in patients undergoing surgery for liver cancer. AIM To evaluate the efficacy of perioperative BCAA supplementation in patients undergoing surgery for liver cancer. METHODS A systematic review of randomized control trials and observational studies was conducted on PubMed, Embase, Cochrane Library, Scopus, and Web of Science to evaluate the effect of perioperative BCAA supplementation compared to standard in-hospital diet, in liver cancer patients undergoing surgery. Clinical outcomes were extracted, and a meta-analysis was performed on relevant outcomes. RESULTS 16 studies including 1389 patients were included. Perioperative BCAA administration was associated with reduced postoperative infection [risk ratio (RR) = 0.58 95% confidence intervals (CI): 0.39 to 0.84, P = 0.005] and ascites [RR = 0.57 (95%CI: 0.38 to 0.85), P = 0.005]. There was also a reduction in length of hospital stay (LOS) [weighted mean difference (WMD) = -3.03 d (95%CI: -5.49 to -0.57), P = 0.02] and increase in body weight [WMD = 1.98 kg (95%CI: 0.35 to 3.61, P = 0.02]. No significant differences were found in mortality, cancer recurrence and overall survival. No significant safety concerns were identified. CONCLUSION Perioperative BCAA administration is efficacious in reducing postoperative infection, ascites, LOS, and increases body weight in liver cancer patients undergoing surgical resection.
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Affiliation(s)
- Kwan Yi Yap
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - HongHui Chi
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Sherryl Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Doris HL Ng
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore
| | - Vishal G Shelat
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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Teymoori F, Ahmadirad H, Jahromi MK, Mokhtari E, Farhadnejad H, Mohammadzadeh M, Babrpanjeh M, Shahrokhtabar T, Jamshidi S, Mirmiran P. Serum branched amino acids and the risk of all-cause mortality: a meta-analysis and systematic review. Amino Acids 2023; 55:1475-1486. [PMID: 37725184 DOI: 10.1007/s00726-023-03329-7] [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: 06/28/2023] [Accepted: 08/29/2023] [Indexed: 09/21/2023]
Abstract
Recently, the serum levels of branched-chain amino acids (BCAAs) have been considered as an indicator to evaluate health status and predict chronic diseases risk. This systematic review and meta-analysis aimed to assess the relationship between Serum BCAAs and the risk of all-cause mortality. We carried out a comprehensive and systematic search in various important databases, including PubMed, Scopus, and Web of Science databases to find the relevant studies published up to October 2022 with no language, design, or time limitation. We extracted the reported hazard ratio (HR) with 95% confidence interval (CI) and odds ratio (OR) with 95%CI in cohorts and case-control studies, respectively, and computed the log HR or OR and its standard error. Then, we used the random-effects model with inverse variance weighting method for the present meta-analysis, to calculate the pooled effect size. Ten observational studies, including nine cohort studies and one case-control study, were included in the present meta-analysis. The number of participants ranges from 53 to 26,711, with an age range of 18-99 years. During 6 months to 24 years of follow-up, 3599 deaths were ascertained. The pooled results indicated that there was no significant association between serum BCAAs (RR: 1.17; 95% CI 0.85-1.60), isoleucine (RR: 1.41; 95%CI 0.92-2.17), leucine (RR: 1.13; 95% CI 0.94-1.36), and valine (RR: 1.02; 95%CI 0.86-1.22) and all-cause mortality. Also, there was significant heterogeneity between studies for serum BCAAs (I2 = 74.1% and P-heterogeneity = 0.021), isoleucine (I2 = 89.4% and P-heterogeneity < 0.001), leucine (I2 = 87.8% and P-heterogeneity < 0.001), and valine (I2 = 86.6% and P-heterogeneity < 0.001). Our results suggested that the serum BCAAs and its components, including isoleucine, leucine, and valine, were not associated with the risk of all-cause mortality.
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Affiliation(s)
- Farshad Teymoori
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hamid Ahmadirad
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Kazemi Jahromi
- Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Ebrahim Mokhtari
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Community Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Farhadnejad
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Milad Mohammadzadeh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Babrpanjeh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tahere Shahrokhtabar
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sanaz Jamshidi
- Imam Ali Hospital, Shiraz University of Medical Sciences, Kazerun, Iran.
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Kristian YY, Cahyanur R, Wulandari Y, Sinaga W, Lukito W, Prasetyawaty F, Lestari W. Correlation between branched-chain amino acids intake and total lymphocyte count in head and neck cancer patients: a cross-sectional study. BMC Nutr 2023; 9:86. [PMID: 37452428 PMCID: PMC10347797 DOI: 10.1186/s40795-023-00746-5] [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: 04/12/2023] [Accepted: 07/10/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND Cellular immunity as reflected by total lymphocyte count (TLC) has been proven to be related to overall survival rate cancer patients. Lymphocyte proliferation is regulated, to some extent, by nutritional factor. Branched chain amino acid (BCAA) is documented as one of numerous nutrients that play important role in lymphocyte proliferation through its effect on protein synthesis and DNA replication. Many studies describe the correlation between BCAA and TLC in hepatic cancer patients. This study emphasized the observation of that links in head and neck cancer patients. METHODS Eighty-five subjects were included in final analysis, aged 18-75, mostly male, with head and neck cancer who had not received treatment participated in this cross-sectional study at the Dr. Cipto Mangunkusumo General Hospital's radiation and medical haematology oncology clinic. The BCAAs intake was assessed using a semi-quantitative food frequency questionnaire. Flow cytometry method was used to quantify TLC. RESULTS Overall, the subjects' nutritional status mostly was considered normal, with the median intake of 1505 (800-3040) kcal/day of energy and mean of 73.96 ± 23.39 g/day of protein. Moreover, subjects' average BCAA intake was 10.92 ± 0.48 g/day. Meanwhile, 17.6% of subjects were found to have low TLC level. From thorough analysis, we did not find a strong correlation between BCAA level and TLC (r = 0.235, p = 0.056). CONCLUSION In participants with head and neck cancer who had not received chemoradiotherapy, there is no correlation between BCAA intake and TLC. The contribution of non-BCAA amino acids from dietary sources to lymphocyte proliferation requires further investigation. TRIAL REGISTRATION Retrospectively registered, with clinical trial number NCT05226065 on February 7th 2022.
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Affiliation(s)
- Yosua Yan Kristian
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia.
| | - Rahmat Cahyanur
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Yohannessa Wulandari
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Wina Sinaga
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Widjaja Lukito
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Findy Prasetyawaty
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Wiji Lestari
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
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Sideris GA, Tsaramanidis S, Vyllioti AT, Njuguna N. The Role of Branched-Chain Amino Acid Supplementation in Combination with Locoregional Treatments for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:926. [PMID: 36765884 PMCID: PMC9913329 DOI: 10.3390/cancers15030926] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/30/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Branched-chain amino acid (BCAA) supplementation has been linked with favorable outcomes in patients undergoing surgical or palliative treatments for hepatocellular carcinoma (HCC). To date, there has been no systematic review investigating the value of BCAA supplementation in HCC patients undergoing locoregional therapies. MATERIALS AND METHODS A systematic search of the literature was performed across five databases/registries using a detailed search algorithm according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was conducted on March 23, 2022. RESULTS Sixteen studies with a total of 1594 patients were analyzed. Most patients were male (64.6%) with a mean age of 68.2 ± 4.1 years, Child-Pugh score A (67.9%) and stage II disease (40.0%). Locoregional therapy consisted of radiofrequency ablation, transarterial chemoembolization or hepatic artery infusion chemotherapy. BCAA supplementation was in the form of BCAA granules or BCAA-enriched nutrient. Most studies reported improved albumin levels, non-protein respiratory quotient and quality of life in the BCAA group. Results pertaining to other outcomes including overall survival, recurrence rate, and Child-Pugh score were variable. Meta-analysis showed significantly higher levels of post-treatment serum albumin in the BCAA group (SMD = 0.54, 95% CI 0.20-0.87) but no significant differences in mortality rate (RR = 0.81, 95% CI: 0.65-1.02) and AST (SMD = -0.13, 95% CI: -0.43-0.18). CONCLUSION BCAA supplementation is associated with higher post-treatment albumin levels. There are currently not sufficient data to support additional benefits. Further studies are needed to elucidate their value.
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Affiliation(s)
- Georgios A. Sideris
- Baystate Medical Center, Department of Radiology, University of Massachusetts Medical School, Springfield, MA 01199, USA
- Radiology Working Group, Society of Junior Doctors, 11527 Athens, Greece
| | - Savvas Tsaramanidis
- Radiology Working Group, Society of Junior Doctors, 11527 Athens, Greece
- Department of Surgery, Ippokrateio General Hospital of Thessaloniki, Aristotle University of Thessaloniki School of Medicine, 54642 Thessaloniki, Greece
| | | | - Njogu Njuguna
- Baystate Medical Center, Department of Radiology, University of Massachusetts Medical School, Springfield, MA 01199, USA
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9
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Lee HY, Sim BC, Nga HT, Moon JS, Tian J, Linh NT, Ju SH, Choi DW, Setoyama D, Yi HS. Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves' Disease. Endocrinol Metab (Seoul) 2022; 37:891-900. [PMID: 36604959 PMCID: PMC9816501 DOI: 10.3803/enm.2022.1590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 11/28/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGRUOUND An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment. METHODS Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data. RESULTS Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways. CONCLUSION In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.
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Affiliation(s)
- Ho Yeop Lee
- Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
| | - Byeong Chang Sim
- Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
| | - Ha Thi Nga
- Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
| | - Ji Sun Moon
- Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea
| | - Jingwen Tian
- Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
| | - Nguyen Thi Linh
- Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
| | - Sang Hyeon Ju
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Dong Wook Choi
- Department of Biochemistry, Chungnam National University College of Natural Sciences, Daejeon, Korea
| | - Daiki Setoyama
- Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan
- Corresponding authors: Hyon-Seung Yi. Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea Tel: +82-42-280-6994, Fax: +82-42-280-7995, E-mail:
| | - Hyon-Seung Yi
- Laboratory of Endocrinology and Immune System, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
- Daiki Setoyama. Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Fukuoka 812-8582, Japan Tel: +81-92-642-5752, Fax: +81-92-642-5752, E-mail:
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10
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Manjunatha N, Ganduri V, Rajasekaran K, Duraiyarasan S, Adefuye M. Transarterial Chemoembolization and Unresectable Hepatocellular Carcinoma: A Narrative Review. Cureus 2022; 14:e28439. [PMID: 36176866 PMCID: PMC9509692 DOI: 10.7759/cureus.28439] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor, and even with the breakthrough in preventive strategies, and new diagnostic and treatment modalities, incidence and fatality rates continue to climb. Patients with HCC are most commonly diagnosed in the later stage, where the disease has already advanced, making it impossible to undertake potentially curative surgery. Transarterial chemoembolization (TACE) is a locoregional therapy regarded as a first-line treatment in patients with intermediate-stage HCC (Barcelona clinical liver cancer {BCLC}-B). TACE is a minimally invasive and non-surgical procedure that combines local chemotherapeutic drug administration with embolization to treat HCC. It helps limit tumor growth, preserve liver function, and increase overall and progression-free survival in patients with intermediate-stage HCC. This article has reviewed the efficacy, survival, limitations, and overall benefit of TACE in patients with unresectable HCC. This article has also discussed the effectiveness of TACE for neoadjuvant chemoembolization and the use of TACE with combination therapies.
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Affiliation(s)
- Nisha Manjunatha
- Research, Our Lady of Fatima University College of Medicine, Metro Manila, PHL
| | | | | | | | - Mayowa Adefuye
- Research, University of Ibadan College of Medicine, Ibadan, NGA
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11
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Salas S, Cottet V, Dossus L, Fassier P, Ginhac J, Latino-Martel P, Romieu I, Schneider S, Srour B, Touillaud M, Touvier M, Ancellin R. Nutritional Factors during and after Cancer: Impacts on Survival and Quality of Life. Nutrients 2022; 14:2958. [PMID: 35889914 PMCID: PMC9323157 DOI: 10.3390/nu14142958] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/12/2022] [Accepted: 07/13/2022] [Indexed: 02/04/2023] Open
Abstract
The French National Cancer Institute conducted a collective expertise study with researchers and clinical experts from the French Network for Nutrition And Cancer Research (NACRe Network). The objective was to update the state of knowledge on the impacts of nutritional factors on clinical endpoints during or after cancer. Data from 150 meta-analyses, pooled analyses or intervention trials and 93 cohort studies were examined; they concerned 8 nutritional factors, 6 clinical events and 20 cancer locations. This report shows that some nutritional factors have impacts on mortality and on the risks of recurrence or second primary cancer in cancer patients. Therefore, high-risk nutritional conditions can be encountered for certain cancer sites: from the diagnosis and throughout the health care pathways, weight loss (lung and esophageal cancers), malnutrition (lung, esophageal, colorectal, pancreatic, gastric and liver cancers), weight gain (colorectal, breast and kidney cancers) and alcohol consumption (upper aerodigestive cancers) should be monitored; and after cancer treatments, excess weight should be detected (colorectal, breast and kidney cancers). These situations require nutritional assessments, and even support or management by health care professionals, in the context of tertiary prevention. This report also highlights some limitations regarding the existing literature and some needs for future research.
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Affiliation(s)
- Sébastien Salas
- AP-HM, Timone Hospital, Aix Marseille University, 13000 Marseille, France;
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
| | - Vanessa Cottet
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- INSERM UMR1231/CIC 1432, University Hospital, LabEx LipSTIC ANR-11-LABX-0021, University of Burgundy-Franche-Comté, 21000 Dijon, France
| | - Laure Dossus
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- International Agency for Research on Cancer, 69000 Lyon, France
| | - Philippine Fassier
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- Gustave Roussy Institute, 94800 Villejuif, France
| | - Julie Ginhac
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Nord University, INSERM, INRAE, CNAM, Epidemiology and Statistics Research Centre (CRESS), University of Paris, 93022 Bobigny, France
| | - Paule Latino-Martel
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Nord University, INSERM, INRAE, CNAM, Epidemiology and Statistics Research Centre (CRESS), University of Paris, 93022 Bobigny, France
| | - Isabelle Romieu
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- International Agency for Research on Cancer, 69000 Lyon, France
| | - Stéphane Schneider
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- University Hospital, University of Côte d’Azur, 06000 Nice, France
| | - Bernard Srour
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Nord University, INSERM, INRAE, CNAM, Epidemiology and Statistics Research Centre (CRESS), University of Paris, 93022 Bobigny, France
| | - Marina Touillaud
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- Léon-Bérard Cancer Centre, UA8 Inserm, 69000 Lyon, France
| | - Mathilde Touvier
- The French Network for Nutrition and Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France; (L.D.); (P.F.); (J.G.); (P.L.-M.); (I.R.); (S.S.); (B.S.); (M.T.); (M.T.)
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Nord University, INSERM, INRAE, CNAM, Epidemiology and Statistics Research Centre (CRESS), University of Paris, 93022 Bobigny, France
| | - Raphaëlle Ancellin
- The French National Cancer Institute (INCa), 92012 Boulogne-Billancourt, France;
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12
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An amino acid-defined diet impairs tumour growth in mice by promoting endoplasmic reticulum stress and mTOR inhibition. Mol Metab 2022; 60:101478. [PMID: 35367410 PMCID: PMC9014392 DOI: 10.1016/j.molmet.2022.101478] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/10/2022] [Accepted: 03/17/2022] [Indexed: 12/17/2022] Open
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Dong D, Shi JY, Shang X, Liu B, Xu WL, Cui GZ, Wang NY. Prognostic significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib: A retrospective analysis. Medicine (Baltimore) 2022; 101:e28680. [PMID: 35119010 PMCID: PMC8812594 DOI: 10.1097/md.0000000000028680] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 01/04/2022] [Indexed: 02/07/2023] Open
Abstract
Our study investigated the correlation between sarcopenia and clinical outcomes in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. We retrospectively evaluated 40 consecutive patients with unresectable HCC receiving lenvatinib between November 2018 and May 2020 at the First Hospital of Jilin University. Skeletal muscle mass was measured before treatment initiation. Prognostic significance was assessed with univariate and multivariate Cox proportional hazards models. Overall survival (OS) and progression-free survival (PFS) were evaluated for patients with and without sarcopenia. Sarcopenia was present in 23/40 patients (57.5%). After a median follow-up of 9.2 months, patients with sarcopenia had significantly worse OS and PFS compared with those without sarcopenia (OS: 8.4 months [m] vs 14.7 m, P = .02; PFS: 4.2 m vs 9.0 m, P = .04). Multivariate Cox proportional hazards models identified presence of sarcopenia as an independent risk factor for shorter OS (hazard ratio [HR], 0.257; 95% confidence interval [CI], 0.083-0.794; P = .02). In subgroup analysis, sarcopenia was associated with worse survival than non-sarcopenic patients, irrespective of age, Barcelona clinic liver cancer stage, or albumin-bilirubin grade. Our results show sarcopenia may be a predictor of poor prognosis in patients with HCC receiving lenvatinib. Management of sarcopenia is a vital factor for improving survival outcomes in patients with HCC.
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Affiliation(s)
- Dong Dong
- Department of Radiology, First Hospital of Jilin University, Changchun, China
| | - Jin-Yu Shi
- Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Xiao Shang
- Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Bo Liu
- Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Wei-Ling Xu
- Department of Radiology, First Hospital of Jilin University, Changchun, China
| | - Guo-Zhen Cui
- Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Nan-Ya Wang
- Cancer Center, First Hospital of Jilin University, Changchun, China
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Bai GH, Tsai MC, Tsai HW, Chang CC, Hou WH. Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis. Eur J Nutr 2021; 61:637-651. [PMID: 34705076 DOI: 10.1007/s00394-021-02710-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 10/13/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE According to criteria recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), we analyzed the effects of branched-chain amino acid (BCAA)-rich supplements on muscle strength, muscle mass, and physical performance in older people. METHODS We searched PubMed, Embase, Cochrane Library, and CINAHL from inception until March 2021. Randomized controlled trials that examined the effect of BCAA-rich supplements on older people were included. Random-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were stratified by participant and supplementation characteristics. Meta-regression analyses were performed to examine the effect of continuous variables. RESULTS Thirty-five studies were included in this meta-analysis. Quality assessment revealed that 14 of 35 RCTs had some potential bias. The overall standardized mean difference (SMD) in muscle strength, muscle mass, and physical performance between the supplement and control groups was 0.35 (95% CI = [0.15, 0.55], P = 0.0007), 0.25 (95% CI = [0.10, 0.40], P = 0.0008), and 0.29 (95% CI = [0.00, 0.57], P = 0.05), respectively. Subgroup analysis revealed that essential amino acid supplementation improved handgrip strength more significantly than whey protein supplementation in older people. Meta-regression analysis revealed a significant linear relationship between improvements in handgrip strength and body mass index. CONCLUSIONS BCAA-rich supplementation by older people may have beneficial effects on muscle mass and strength. However, the included studies had high heterogeneity, and the results must be interpreted with caution. PROSPERO REGISTRATION NUMBER CRD42020206674.
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Affiliation(s)
- Geng-Hao Bai
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
- Center of Evidence-Based Medicine, Department of Education, Taipei Medical University Hospital, 252 Wu-Xing Street, Taipei, Taiwan, ROC
| | - Meng-Chen Tsai
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
- Center of Evidence-Based Medicine, Department of Education, Taipei Medical University Hospital, 252 Wu-Xing Street, Taipei, Taiwan, ROC
| | - Han-Wei Tsai
- Center of Evidence-Based Medicine, Department of Education, Taipei Medical University Hospital, 252 Wu-Xing Street, Taipei, Taiwan, ROC
- Master Program in Long-Term Care and School of Gerontology Health Management, College of Nursing, Taipei Medical University, Taipei, Taiwan, ROC
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Wen-Hsuan Hou
- Center of Evidence-Based Medicine, Department of Education, Taipei Medical University Hospital, 252 Wu-Xing Street, Taipei, Taiwan, ROC.
- Master Program in Long-Term Care and School of Gerontology Health Management, College of Nursing, Taipei Medical University, Taipei, Taiwan, ROC.
- Department of Geriatric Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC.
- Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei, Taiwan, ROC.
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Effects of Branched-chain Amino Acids on Nutritional Metabolism and Pharmacoeconomics in Patients with Severe Abdominal Trauma. Curr Med Sci 2021; 41:894-900. [PMID: 34652627 DOI: 10.1007/s11596-021-2424-0] [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: 08/16/2020] [Accepted: 06/13/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To observe the influences of branched-chain amino acids (BCAAs) on nutrition metabolism and prognosis of patients with severe abdominal trauma; at the same time, to analyze and evaluate the pharmacoeconomics of it. METHODS A total of 75 severe abdominal trauma patients were recruited from June 2016 to December 2017 and randomly divided into control group and observation group. After surgery and basic treatment, parenteral nutrition support therapy with iso-nitrogen and iso-calorie of both groups was administered. Meanwhile, an equivalent of 8.5% (18AA-II) and 10% (20AA) compound AA injection was administrated to the control and observation groups, respectively. The nitrogen balance, serum protein level and plasma amino spectrum of the patients were observed before and after treatment. Besides, the hospital stay, survival rate, complications, adverse reactions and hospitalization costs were also compared. RESULTS After a 7-day course treatment, the nitrogen balance level of the two groups was significantly improved, but no significant difference was found between them. In addition, the serum protein level and plasma amino spectrum of the two groups was generally improved when compared to before treatment. Compared with the control group, the level of albumin and transferrin in the observation group was improved significantly after treatment, while no difference in plasma amino spectrum was found between the two groups. Moreover, the cost analysis showed remarkably reduced hospitalization costs in the observation group. CONCLUSION To a certain degree, BCAAs could improve the nutritional metabolism and prognosis of patients with severe abdominal trauma, and have good cost-effectiveness.
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Ancellin R, Cottet V, Dossus L, Fassier P, Gaillot de Saintignon J, Ginhac J, Romieu I, Salas S, Schneider S, Srour B, Touillaud M, Touvier M, Latino-Martel P. [Impact of nutritional factors during and after cancer]. Bull Cancer 2021; 108:455-464. [PMID: 33836862 DOI: 10.1016/j.bulcan.2021.03.001] [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: 02/02/2021] [Accepted: 03/07/2021] [Indexed: 02/07/2023]
Abstract
Nutritional factors (diet, weight, alcohol, physical activity) are identified as factors having an impact on the onset of several cancer sites. Less abundant scientific data also underline their impact on the tumor progression. A review of the scientific literature was carried out by a group of experts established by the French National Cancer Institute (INCa) to better document the influence of nutritional factors during and after cancer on outcomes such as overall mortality, cancer specific mortality, recurrence, second primary cancers and quality of life. This analysis of the literature completes messages of reduction of alcohol consumption, prevention of undernutrition or excess weight and adherence to dietary recommendations, avoiding the use of dietary supplements, fasting or restrictive diets and strengthens messages promoting the practice of physical activity and the fight against sedentary lifestyle.
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Affiliation(s)
- Raphaëlle Ancellin
- Institut national du cancer, 52, avenue André-Morizet, 92100 Boulogne-Billancourt, France.
| | - Vanessa Cottet
- CHU de Dijon, université de Bourgogne-Franche-Comté, Inserm UMR1231 & CIC1432, 7, boulevard Jeanne-d'Arc, 21079 Dijon, France
| | - Laure Dossus
- Centre international de recherche sur le cancer (CIRC), 150, cours Albert-Thomas, 69008 Lyon, France
| | | | | | - Julie Ginhac
- Cellule de coordination, domaine de Vilvert, réseau national alimentation cancer recherche (Réseau NACRe), 78350 Jouy-en-Josas, France
| | - Isabelle Romieu
- Center for Research on Population Health, National Institute of Public Health, Mexico, Mexique; Emory University, Hubert Department of Global Health, Atlanta, Georgia, États-Unis
| | - Sébastien Salas
- CHU de Timone, 264, rue Saint-Pierre, 13005 Marseille, France
| | - Stéphane Schneider
- Université Côte d'Azur, CHU de Nice, Hôpital de l'Archet, 151, route de Saint-Antoine, 06200 Nice, France
| | - Bernard Srour
- Cellule de coordination, domaine de Vilvert, réseau national alimentation cancer recherche (Réseau NACRe), 78350 Jouy-en-Josas, France; Université Sorbonne Paris Nord, université de Paris (CRESS), Inrae U1125, Cnam, équipe de recherche en épidémiologie nutritionnelle (EREN), centre de recherche en épidémiologie et statistiques, Inserm U1153, 74, rue Marcel-Cachin, 93017 Bobigny, France
| | - Marina Touillaud
- Centre Léon-Bérard, Inserm UA8 « Radiations : défense, santé et environnement », 28, rue Laennec, 69008 Lyon, France
| | - Mathilde Touvier
- Université Sorbonne Paris Nord, université de Paris (CRESS), Inrae U1125, Cnam, équipe de recherche en épidémiologie nutritionnelle (EREN), centre de recherche en épidémiologie et statistiques, Inserm U1153, 74, rue Marcel-Cachin, 93017 Bobigny, France
| | - Paule Latino-Martel
- Cellule de coordination, domaine de Vilvert, réseau national alimentation cancer recherche (Réseau NACRe), 78350 Jouy-en-Josas, France
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Vuille-Lessard É, Lange N, Riebensahm C, Dufour JF, Berzigotti A. Dietary Interventions in Liver Diseases: Focus on MAFLD and Cirrhosis. ACTA ACUST UNITED AC 2021. [DOI: 10.1007/s11901-021-00563-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Abstract
Purpose of Review
Dietary interventions (DI) aimed at improving overweight and metabolic abnormalities in metabolic dysfunction-associated fatty liver disease (MAFLD) and at reducing malnutrition and sarcopenia in cirrhosis should become part of routine care in hepatology. This review focuses on recent advances in this field.
Recent Findings
In patients with MAFLD, a gradual reduction, respectively, of 7–10% of body weight if overweight or of 3–5% if lean, obtained by moderately reducing caloric intake, is effective to improve liver disease. Intermittent energy restriction might be an alternative to continuous energy restriction with higher adherence. Qualitative dietary adjustments should include increased intake of unprocessed foods including fruits and vegetables, whole grains, fiber, and unsaturated fatty acids (FAs), for example, through a Mediterranean diet. Refined carbohydrates (CHOs), saturated FA (SFAs), red meat, and processed meat should be limited. DI studies in HIV-infected subjects with MAFLD are very limited, and this is a field for future research. In patients with cirrhosis, DI should aim at correcting malnutrition and improving skeletal muscle mass. Daily diet contents should aim at achieving 30–35 kcal/kg of body weight, including 1.2–1.5 g/kg proteins, and oral or enteral supplementation might be used in patients unable to achieve these targets. In some studies, branched-chain amino acids (BCAAs) proved to be effective in improving muscle mass and were associated with a lower risk of hepatic encephalopathy. Obesity requires adjustment of the above-mentioned targets, and its management is challenging. Studies looking at the efficacy of DI recommended by the existing guidelines on clinical endpoints are a field for future research.
Summary
Dietary interventions are able to improve MAFLD and show potential to reduce complications in liver disease. Despite its key importance, there are many barriers limiting the implementation of DI in patients with chronic liver disease. Patients’ empowerment is crucial and should be the focus of specific educational programs. In addition, liver clinics would benefit from multidisciplinary teams involving experts in nutrition, physical exercise, primary care physicians, and psychologists when needed.
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Ibrahim ES, Houseni M. Oral nutritional supplements (ONSs) for cirrhotic patients undergoing liver resection assessed by ultrasound measurement of rectus femoris and anterior tibialis muscles thickness. Randomized clinical trial. Saudi J Anaesth 2021; 15:116-122. [PMID: 34188627 PMCID: PMC8191260 DOI: 10.4103/sja.sja_923_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 09/27/2020] [Accepted: 10/02/2020] [Indexed: 11/26/2022] Open
Abstract
PURPOSE We evaluated the effects of postoperative administration of (ONSs) on the liver function and the outcome of cirrhotic patients using ultrasound (US) assessment of rectus femoris (RF) and anterior tibialis (AT) muscles. PATIENTS AND METHODS Forty-three malnourished adult hepatic patients who underwent major liver resections were recruited in this study. In the conventional diet (CD) group, the patients took water at postoperative day (POD) 0 and routine soft diet starting from POD1. In the ONS group, a commercially elemental diet was started from POD1 for 7 days postoperatively, with a target endpoint of 35-40 kcal/kg and 1.2-1.5 g/kg of protein per day. US assessment of the RF and AT muscles was done preoperatively and at POD3 and 7, including anterior-posterior (AP) diameter, lateral-lateral (LL) diameter, and cross-sectional area (CSA). Muscles' echogenicity was defined by the Heckmatt scale. The outcome of the patients was also recorded. RESULTS Consumption of ONS preserved the measured RF and AT characteristics (AP and LL diameters and CSA) in the ONS group at POD3 and 7 compared to the CD group. Heckmatt scale was significantly increased at POD3 and 7 in the CD group compared to the ONS group. Both total protein and albumin levels at POD3 and 7 were significantly lower in the CD group compared to the ONS group [P = (0.02, 0.03) and (0.05, 0.04), respectively]. Serum phosphate was significantly lower at POD7 in the ONS group than the CD group (p = 0.04). There were significant decreases in the ICU stay and time of passing flatus (h) in the ONS group comparing with the CD group (P = 0.045 and P = 0.00, respectively). CONCLUSIONS ONS maintains muscle mass and echogenicity of RF and AT along with better liver function and intestinal function recovery.
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Affiliation(s)
- Eman S. Ibrahim
- Department of Anaesthesia and ICU, Liver Institute, Menoufia University, Shebeen Elkom, Egypt
| | - Mohamed Houseni
- Department of Radiology, Liver Institute, Menoufia University, Shebeen Elkom, Egypt
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Simon TG, Chan AT. Lifestyle and Environmental Approaches for the Primary Prevention of Hepatocellular Carcinoma. Clin Liver Dis 2020; 24:549-576. [PMID: 33012445 PMCID: PMC7536356 DOI: 10.1016/j.cld.2020.06.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Patients with chronic liver disease are at increased risk of developing hepatocellular carcinoma (HCC). Most patients diagnosed with HCC have limited treatment options and a poor overall prognosis, with a 5-year survival less than 15%. Preventing the development of HCC represents the most important strategy. However, current guidelines lack specific recommendations for primary prevention. Lifestyle factors may be central in the pathogenesis of HCC, and primary prevention strategies focused on lifestyle modification could represent an important approach to the prevention of HCC. Both experimental and epidemiologic studies have identified promising chemopreventive agents for the primary prevention of HCC.
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Affiliation(s)
- Tracey G. Simon
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA
| | - Andrew T. Chan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA,Broad Institute, Boston MA,Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston MA
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20
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Ardito F, Lai Q, Rinninella E, Mimmo A, Vellone M, Panettieri E, Adducci E, Cintoni M, Mele MC, Gasbarrini A, Giuliante F. The impact of personalized nutritional support on postoperative outcome within the enhanced recovery after surgery (ERAS) program for liver resections: results from the NutriCatt protocol. Updates Surg 2020; 72:681-691. [PMID: 32410162 DOI: 10.1007/s13304-020-00787-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 05/02/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Malnutrition in liver surgery is correlated with higher postoperative complications and longer length of hospital stay (LOHS), the same items that ERAS programs try to optimize. However, to date, standardized dietary protocols have not been defined within ERAS programs. Aim of this study was to evaluate the impact on LOHS and postoperative complications, of a personalized nutritional protocol (NutriCatt) with diet and oral branched-chain amino acid (BCAA) supplementation, adopted within the ERAS program. METHODS 1960 consecutive liver resections were performed from January 2000 to September 2018. EXCLUSION CRITERIA perihilar cholangiocarcinoma, simultaneous colorectal and liver resections. Four groups for analysis: resections before 2009 (1st period); from 2009 to 2016 (2nd period, including laparoscopic resections); between 2016 and September 2017 (ERAS); after September 2017 (ERAS + NutriCatt). RESULTS LOHS declined (p < 0.0001), from a median of 10 days (1st period) to 8, 7 and 6 in 2nd period, ERAS and ERAS + NutriCatt groups, respectively. At multivariable analysis for risk of LOHS > 8 days, the 2nd period, ERAS and ERAS + NutriCatt groups showed a protective effect. These results were confirmed for both minor and major resections. LOHS was significantly lower in ERAS + Nutricatt group than in ERAS group, without increasing risk of postoperative complications, although the rate of laparoscopic resections was similar in these two groups and complexity of liver resections was significantly higher in the last period. CONCLUSIONS Adoption of a personalized nutritional protocol with BCAA supplementation within the ERAS program for liver resections was a safe and effective approach that may impact on reducing the LOHS.
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Affiliation(s)
- Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy.
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Emanuele Rinninella
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Clinical Nutrition Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
| | - Antonio Mimmo
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
| | - Maria Vellone
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Elena Panettieri
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
| | - Enrica Adducci
- Department of Anesthesiology and Intensive Care, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Marco Cintoni
- Clinical Nutrition Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
| | - Maria Cristina Mele
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Clinical Nutrition Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Internal Medicine and Gastroenterology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
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Kumada T, Toyoda H, Tada T, Yasuda S, Tanaka J. Changes in Background Liver Function in Patients with Hepatocellular Carcinoma over 30 Years: Comparison of Child-Pugh Classification and Albumin Bilirubin Grade. Liver Cancer 2020; 9:518-528. [PMID: 33083278 PMCID: PMC7548913 DOI: 10.1159/000507933] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 04/11/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Background liver function in patients with hepatocellular carcinoma (HCC) has improved remarkably with advances in various treatments. Recently, the Child-Pugh classification (CPC) system has been recognized as limited in its ability to assess patients with good hepatic reserve. We compared the albumin-bilirubin (ALBI) grade, which is suitable for a more detailed evaluation of patients with good liver function, with CPC over a 30-year period. METHODS A total of 2,347 patients were analyzed. Patients were stratified by year of diagnosis into 6 groups: Group A (1990-1994, n = 376), Group B (1995-1999, n = 434), Group C (2000-2004, n = 438), Group D (2005-2009, n = 444), Group E (2010-2014, n = 392), and Group F (2015-2018, n = 263). We compared ALBI grade and CPC across the groups. RESULTS The prevalence of patients with CPC A at diagnosis increased throughout the study period, reaching nearly 80% in Groups E and F (p < 0.001). By contrast, the percentage of patients with ALBI grade 1 disease remained approximately 50% in Groups E and F (p < 0.001). Modified ALBI (mALBI) grade 2a corresponds to patients with CPC A who have poor hepatic function. There were significant survival differences between patients with mALBI grade 1 versus 2a, 1 versus 2b, and 2a versus 2b disease, respectively (p < 0.0001), in patients with CPC A. CONCLUSIONS CPC is not suitable for assessing patients with recently diagnosed HCC and good remnant hepatic function. In such patients with HCC, the prognosis can be stratified by ALBI grade rather than CPC.
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Affiliation(s)
- Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Tedesco L, Rossi F, Ragni M, Ruocco C, Brunetti D, Carruba MO, Torrente Y, Valerio A, Nisoli E. A Special Amino-Acid Formula Tailored to Boosting Cell Respiration Prevents Mitochondrial Dysfunction and Oxidative Stress Caused by Doxorubicin in Mouse Cardiomyocytes. Nutrients 2020; 12:nu12020282. [PMID: 31973180 PMCID: PMC7071384 DOI: 10.3390/nu12020282] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 12/23/2019] [Accepted: 01/02/2020] [Indexed: 12/24/2022] Open
Abstract
Anthracycline anticancer drugs, such as doxorubicin (DOX), can induce cardiotoxicity supposed to be related to mitochondrial damage. We have recently demonstrated that a branched-chain amino acid (BCAA)-enriched mixture (BCAAem), supplemented with drinking water to middle-aged mice, was able to promote mitochondrial biogenesis in cardiac and skeletal muscle. To maximally favor and increase oxidative metabolism and mitochondrial function, here we tested a new original formula, composed of essential amino acids, tricarboxylic acid cycle precursors and co-factors (named α5), in HL-1 cardiomyocytes and mice treated with DOX. We measured mitochondrial biogenesis, oxidative stress, and BCAA catabolic pathway. Moreover, the molecular relevance of endothelial nitric oxide synthase (eNOS) and mechanistic/mammalian target of rapamycin complex 1 (mTORC1) was studied in both cardiac tissue and HL-1 cardiomyocytes. Finally, the role of Krüppel-like factor 15 (KLF15), a critical transcriptional regulator of BCAA oxidation and eNOS-mTORC1 signal, was investigated. Our results demonstrate that the α5 mixture prevents the DOX-dependent mitochondrial damage and oxidative stress better than the previous BCAAem, implying a KLF15/eNOS/mTORC1 signaling axis. These results could be relevant for the prevention of cardiotoxicity in the DOX-treated patients.
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Affiliation(s)
- Laura Tedesco
- Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
| | - Fabio Rossi
- Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
| | - Maurizio Ragni
- Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
| | - Chiara Ruocco
- Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
| | - Dario Brunetti
- Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
| | - Michele O. Carruba
- Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
| | - Yvan Torrente
- Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, 20122 Milan, Italy
| | - Alessandra Valerio
- Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy
- Correspondence: (A.V.); (E.N.); Tel.: +39-030-3717504 (A.V.); +39-02-50316956 (E.N.); Fax: +39-030-3717529 (A.V.); +39-02-50317118 (E.N.)
| | - Enzo Nisoli
- Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
- Correspondence: (A.V.); (E.N.); Tel.: +39-030-3717504 (A.V.); +39-02-50316956 (E.N.); Fax: +39-030-3717529 (A.V.); +39-02-50317118 (E.N.)
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Lu SD, Li L, Liang XM, Chen W, Chen FL, Fan LL, Ahir BK, Zhang WG, Zhong JH. Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy. Expert Rev Gastroenterol Hepatol 2019; 13:1077-1088. [PMID: 31648568 DOI: 10.1080/17474124.2019.1684898] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
Introduction: The 5-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection or local ablation is up to 70%. Adjuvant therapies to prevent HCC recurrence have been reported but are not currently recommended by EASL or AASLD guidelines. This review examined evidence from randomized controlled trials, meta-analyses and systematic reviews on the safety and efficacy of adjuvant therapies and chemotherapies in HCC patients after resection or local ablation.Areas covered: PubMed was searched through 15 June 2019. Available evidence was assessed based on the GRADE system.Expert commentary: Transarterial chemoembolization is the best adjuvant therapy for HCC patients at high risk of recurrence, antiviral therapy with nucleoside analogs is effective for preventing recurrence of HBV-related HCC, and interferon-α is effective for preventing recurrence of HCV-related HCC. Further studies are needed to clarify the efficacy of adjuvant immune checkpoint inhibitors. Adjuvant sorafenib appears to offer negligible clinical benefit and high risk of adverse effects.
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Affiliation(s)
- Shi-Dong Lu
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lin Li
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xin-Min Liang
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Wu Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Fu-Li Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Lang-Lin Fan
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Bhavesh K Ahir
- Section of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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Loosen SH, Schulze-Hagen M, Bruners P, Tacke F, Trautwein C, Kuhl C, Luedde T, Roderburg C. Sarcopenia Is a Negative Prognostic Factor in Patients Undergoing Transarterial Chemoembolization (TACE) for Hepatic Malignancies. Cancers (Basel) 2019; 11:E1503. [PMID: 31597337 PMCID: PMC6827165 DOI: 10.3390/cancers11101503] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 10/04/2019] [Accepted: 10/07/2019] [Indexed: 12/12/2022] Open
Abstract
: Background and Aims: While transarterial chemoembolization (TACE) represents a standard of therapy for intermediate-stage hepatocellular carcinoma (HCC) and is also routinely performed in patients with liver metastases, it is still debated which patients represent the ideal candidates for TACE therapy in terms of overall survival. Sarcopenia, the degenerative loss of skeletal muscle mass and strength, has been associated with an adverse outcome for various malignancies, but its role in the context of TACE has largely remained unknown. Here, we evaluated the role of sarcopenia on the outcome of patients undergoing TACE for primary and secondary liver cancer. METHODS The patients' psoas muscle size was measured on axial computed tomography (CT) scans and normalized for the patients' height squared. This value was referred to as the psoas muscle index (PMI). The PMI was correlated with clinical and laboratory markers. RESULTS While pre-interventional sarcopenia had no impact on the direct tumor response to TACE, sarcopenic patients with a pre-interventional PMI below our ideal cut-off value of 13.39 mm/m2 had a significantly impaired long-term outcome with a median overall survival of 491 days compared to 1291 days for patients with a high PMI. This finding was confirmed by uni- and multivariate Cox-regression analyses. Moreover, a progressive rapid decline in muscle mass after TACE was a predictor for an unfavorable prognosis. CONCLUSION Our data suggest that sarcopenia represents a previously unrecognized prognostic factor for patients undergoing TACE therapy which might yield important information on the patients' post-interventional outcome and should therefore be implemented into clinical stratification algorithms.
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Affiliation(s)
- Sven H Loosen
- Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
| | - Maximilian Schulze-Hagen
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
| | - Philipp Bruners
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
| | - Frank Tacke
- Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Augustenburger Platz 1, 10117 Berlin, Germany.
| | - Christian Trautwein
- Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
| | - Christiane Kuhl
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
| | - Tom Luedde
- Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
- Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
| | - Christoph Roderburg
- Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Augustenburger Platz 1, 10117 Berlin, Germany.
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Chen CJ, Wang LC, Kuo HT, Fang YC, Lee HF. Significant effects of late evening snack on liver functions in patients with liver cirrhosis: A meta-analysis of randomized controlled trials. J Gastroenterol Hepatol 2019; 34:1143-1152. [PMID: 30883904 DOI: 10.1111/jgh.14665] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Revised: 02/09/2019] [Accepted: 03/12/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Reducing post-absorptive (fasting) phase by eating late evening snacks (LESs) is a potential intervention to improve substrate utilization and reverse sarcopenia. This study analyzed the results of published randomized controlled trials and controlled clinical trials to evaluate the effects of LES on liver function of patients with cirrhosis. METHODS A meta-analysis was conducted. The search strategy included electronic database searches, and 300 articles were searched. Eight of these articles provided qualified data for pooling and analysis. Outcomes assessments included serum albumin, total bilirubin, alanine aminotransferase, prothrombin time, and aspartate aminotransferase, complications of cirrhosis, severity of liver disease, and blood glucose levels. RESULTS Our analysis included eight studies comprising 341 patients (167 in LES groups and 174 in control groups). The results showed that LES intervention helped to maintain liver reserves. These eight studies demonstrated that LES intervention had significant effects for liver biochemical parameters on albumin, ammonia, and prothrombin time, with respective effect sizes of 0.233, -0.425, and -0.589; liver enzymes include aspartate aminotransferase and alanine aminotransferase, with respective effect sizes of -0.320 and -0.284. Studies on clinical signs of liver dysfunction showed lower occurrence rates of ascites and hepatic encephalopathy than in the control group. LES had no significant effect on Child-Pugh score. CONCLUSIONS The overall results of the meta-analysis indicated that having LES can improve liver function reserve for patients with liver cirrhosis, with or without hepatocellular carcinoma. LES is a promising intervention for reversing anabolic resistance and the sarcopenia of cirrhosis, resulting in an improved quality of life for patients with cirrhosis.
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Affiliation(s)
- Chen-Ju Chen
- Department of Nursing, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Liang-Chao Wang
- Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepato-gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.,Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Yu-Chiung Fang
- Department of Nursing, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Huan-Fang Lee
- Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Boyd GW, Drew M, Ward S, Baird M, Connaboy C, Graham SM. The effect of the branched-chain amino acids on the in-vitro activity of bovine intestinal alkaline phosphatase. Appl Physiol Nutr Metab 2019; 44:632-636. [DOI: 10.1139/apnm-2018-0449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Branched-chain amino acids (BCAA) are used as nutritional support for patients with a range of conditions including liver cirrhosis and in-born errors of amino acid metabolism, and they are commonly used “sports” or exercise supplements. The effects of the BCAA on the in-vitro activity of calf intestinal alkaline phosphatase (EC. 3.1.3.1) were studied. All three BCAA were found to be uncompetitive inhibitors of the enzyme with L-leucine being the most potent ([Formula: see text] = 24.9 mmol/L) and L-valine, the least potent ([Formula: see text] = 37 mmol/L). Mixed BCAA are able to act in combination to inhibit the enzyme. Given the important role of intestinal alkaline phosphatase in gut homeostasis, these findings have potential implications for those taking high levels of BCAA as supplements.
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Affiliation(s)
- Gary William Boyd
- School of Science and Sport, University of the West of Scotland, Paisley, PA1 2BE, UK
| | - Marion Drew
- School of Science and Sport, University of the West of Scotland, Paisley, PA1 2BE, UK
| | - Shannon Ward
- School of Science and Sport, University of the West of Scotland, Paisley, PA1 2BE, UK
| | - Marianne Baird
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, EH11 4BN, UK
| | - Christopher Connaboy
- School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Scott Murray Graham
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, EH11 4BN, UK
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Valenzuela PL, Morales JS, Emanuele E, Pareja-Galeano H, Lucia A. Supplements with purported effects on muscle mass and strength. Eur J Nutr 2019; 58:2983-3008. [PMID: 30604177 DOI: 10.1007/s00394-018-1882-z] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 12/13/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Several supplements are purported to promote muscle hypertrophy and strength gains in healthy subjects, or to prevent muscle wasting in atrophying situations (e.g., ageing or disuse periods). However, their effectiveness remains unclear. METHODS This review summarizes the available evidence on the beneficial impacts of several popular supplements on muscle mass or strength. RESULTS Among the supplements tested, nitrate and caffeine returned sufficient evidence supporting their acute beneficial effects on muscle strength, whereas the long-term consumption of creatine, protein and polyunsaturated fatty acids seems to consistently increase or preserve muscle mass and strength (evidence level A). On the other hand, mixed or unclear evidence was found for several popular supplements including branched-chain amino acids, adenosine triphosphate, citrulline, β-Hydroxy-β-methylbutyrate, minerals, most vitamins, phosphatidic acid or arginine (evidence level B), weak or scarce evidence was found for conjugated linoleic acid, glutamine, resveratrol, tribulus terrestris or ursolic acid (evidence level C), and no evidence was found for other supplements such as ornithine or α-ketoglutarate (evidence D). Of note, although most supplements appear to be safe when consumed at typical doses, some adverse events have been reported for some of them (e.g., caffeine, vitamins, α-ketoglutarate, tribulus terrestris, arginine) after large intakes, and there is insufficient evidence to determine the safety of many frequently used supplements (e.g., ornithine, conjugated linoleic acid, ursolic acid). CONCLUSION In summary, despite their popularity, there is little evidence supporting the use of most supplements, and some of them have been even proven ineffective or potentially associated with adverse effects.
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Affiliation(s)
- Pedro L Valenzuela
- Department of Sport and Health, Spanish Agency for Health Protection in Sport (AEPSAD), Madrid, Spain.,Physiology Unit. Systems Biology Department, University of Alcalá, Madrid, Spain
| | - Javier S Morales
- Faculty of Sport Sciences, Universidad Europea De Madrid, Villaviciosa De Odón, 28670, Madrid, Spain
| | | | - Helios Pareja-Galeano
- Faculty of Sport Sciences, Universidad Europea De Madrid, Villaviciosa De Odón, 28670, Madrid, Spain. .,Research Institute of the Hospital 12 De Octubre (i+12), Madrid, Spain.
| | - Alejandro Lucia
- Faculty of Sport Sciences, Universidad Europea De Madrid, Villaviciosa De Odón, 28670, Madrid, Spain.,Research Institute of the Hospital 12 De Octubre (i+12), Madrid, Spain
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28
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Zhenyukh O, González-Amor M, Rodrigues-Diez RR, Esteban V, Ruiz-Ortega M, Salaices M, Mas S, Briones AM, Egido J. Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation. J Cell Mol Med 2018; 22:4948-4962. [PMID: 30063118 PMCID: PMC6156282 DOI: 10.1111/jcmm.13759] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 06/08/2018] [Indexed: 12/12/2022] Open
Abstract
Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA‐induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.
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Affiliation(s)
- Olha Zhenyukh
- Renal, Vascular and Diabetes Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
| | - Maria González-Amor
- Department of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, IdiPaz, Spain.,Ciber de Enfermedades Cardiovasculares, Madrid, Spain
| | - Raul R Rodrigues-Diez
- Renal, Vascular and Diabetes Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
| | - Vanesa Esteban
- Laboratory of Immunoallergy, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain
| | - Marta Ruiz-Ortega
- Renal, Vascular and Diabetes Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
| | - Mercedes Salaices
- Department of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, IdiPaz, Spain.,Ciber de Enfermedades Cardiovasculares, Madrid, Spain
| | - Sebastian Mas
- Renal, Vascular and Diabetes Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.,Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
| | - Ana M Briones
- Department of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, IdiPaz, Spain.,Ciber de Enfermedades Cardiovasculares, Madrid, Spain
| | - Jesus Egido
- Renal, Vascular and Diabetes Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.,Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
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29
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Kobayashi T, Kawai H, Nakano O, Abe S, Kamimura H, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, Terai S. Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intra-arterial therapies. BMC Cancer 2018; 18:756. [PMID: 30041616 PMCID: PMC6056944 DOI: 10.1186/s12885-018-4673-2] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 07/18/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The impact of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) who receive transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, remains unclear. We investigated the prognostic value of skeletal muscle loss (SML) stratified by cutoffs for sarcopenia and rate of change in skeletal muscle mass over 6 months. METHODS We retrospectively evaluated 102 patients with HCC treated with transcatheter intra-arterial therapies between 2005 and 2015. Computed tomography images of the third lumbar vertebra (L3) were analyzed to obtain the skeletal muscle area normalized for the height squared, defined as the skeletal muscle index at L3 (L3 SMI), before and 6 months after treatment. Low or high SMI was defined using cutoff values of 42 cm2/m2 in men and 38 cm2/m2 in women. The rate of change in skeletal muscle mass (ΔL3 SMI) over 6 months was calculated. Overall survival (OS) was compared in groups classified by baseline L3 SMI and ΔL3 SMI; prognostic significance was assessed with univariate and multivariate analyses, using Cox proportional hazards models. RESULTS OS did not differ significantly between groups with low (n = 31) and high (n = 71) SMI at baseline (P = 0.172), but OS was significantly poorer in patients with SML (n = 41), defined as ΔL3 SMI < - 4.6% over 6 months than in those without SML (n = 61, P = 0.018). On multivariate analysis, SML (hazard ratio [HR], 1.675; 95% confidence interval [CI], 1.031-2.721; P = 0.037), serum alpha-fetoprotein ≥20 ng/mL (HR, 2.550; 95% CI, 1.440-4.515; P = 0.001), and maximum tumor diameter ≥ 30 mm (HR, 1.925; 95% CI, 1.166-3.179; P = 0.010) were independent predictors of poor OS. Baseline L3 SMI was not significantly associated with OS (HR, 1.405; 95% CI, 0.861-2.293; P = 0.174). CONCLUSIONS ΔL3 SMI was an independent prognostic factor in patients with HCC treated with transcatheter intra-arterial therapies. Further study is required to reveal whether prevention of skeletal muscle depletion might be a new therapeutic strategy to contribute to improved clinical outcomes in patients with HCC.
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Affiliation(s)
- Takamasa Kobayashi
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Oki Nakano
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Satoshi Abe
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
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30
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Holeček M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab (Lond) 2018; 15:33. [PMID: 29755574 PMCID: PMC5934885 DOI: 10.1186/s12986-018-0271-1] [Citation(s) in RCA: 460] [Impact Index Per Article: 65.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 04/18/2018] [Indexed: 02/07/2023] Open
Abstract
Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness. In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs. Enhanced consumption of BCAA for ammonia detoxification to glutamine in muscles is the cause of decreased BCAA levels in liver cirrhosis and urea cycle disorders. Increased BCKD activity is responsible for enhanced oxidation of BCAA in chronic renal failure, trauma, burn, sepsis, cancer, phenylbutyrate-treated subjects, and during exercise. Decreased BCKD activity is the main cause of increased BCAA levels and BCKAs in maple syrup urine disease, and plays a role in increased BCAA levels in diabetes type 2 and obesity. Increased BCAA concentrations during brief starvation and type 1 diabetes are explained by amination of BCKAs in visceral tissues and decreased uptake of BCAA by muscles. The studies indicate beneficial effects of BCAAs and BCKAs in therapy of chronic renal failure. New therapeutic strategies should be developed to enhance effectiveness and avoid adverse effects of BCAA on ammonia production in subjects with liver cirrhosis and urea cycle disorders. Further studies are needed to elucidate the effects of BCAA supplementation in burn, trauma, sepsis, cancer and exercise. Whether increased BCAA levels only markers are or also contribute to insulin resistance should be known before the decision is taken regarding their suitability in obese subjects and patients with type 2 diabetes. It is concluded that alterations in BCAA metabolism have been found common in a number of disease states and careful studies are needed to elucidate their therapeutic effectiveness in most indications.
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Affiliation(s)
- Milan Holeček
- Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic
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31
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Ocaña-Mondragón A, Mata-Marín JA, Uriarte-López M, Bekker-Méndez C, Alcalá-Martínez E, Ribas-Aparicio RM, Uribe-Noguéz LA, Rodríguez-Galindo DM, Martínez-Rodríguez MDLL. Effect of branched-chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients. Biomed Rep 2017; 8:85-90. [PMID: 29399341 DOI: 10.3892/br.2017.1012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Accepted: 10/19/2017] [Indexed: 12/23/2022] Open
Abstract
The incidence rate of insulin resistance (IR) in patients with chronic hepatitis C (CHC) is high. Recently, branched-chain amino acids (BCAA) have been shown to attenuate IR in CHC patients; however, their effect on patient quality of life remains unclear. Therefore, the aim of the current prospective study was to determine the effects of BCAA supplement on IR and health-related quality of life (HR-QoL) in patients with CHC. In the study, 20 non-diabetic patients with CHC, who were non-responders to peginterferon-α and ribavirin, were recruited. Patients took a BCAA supplement once a day (30 g, after a minimum 10-h overnight fast) for 3 months. Serum levels of glucose, insulin, albumin, triglycerides and cholesterol were measured at 0 and 3 months. Additionally, IR was measured using the Homeostasis Model Assessment-IR, HR-QoL was assessed using the 36-item Short Form Health Survey and viral load was measured by reverse transcription polymerase chain reaction using Taqman probes. The Wilcoxon signed-rank test was used to determine statistical significance. The results indicated that 70% of the subjects were positive for IR, which decreased to 50% by the end of the study; furthermore, 85% of the subjects demonstrated some level of improvement. Overall, the BCAA treatment significantly decreased IR (P=0.006) and augmented serum albumin concentration (P=0.008) compared with basal values. Additionally, by the end of the treatment, viral load and triglycerides levels had decreased, though these results were not significant (P=0.084 and P=0.080, respectively). BCAA treatment also improved HR-QoL regarding role limitations due to physical health problems (P=0.017), role limitations due to emotional problems (P=0.026) and social function (P=0.008). In conclusion, BCAA supplementation reduced IR and improved HR-QoL in patients with CHC. These findings support the application of IR therapy as a possible therapeutic strategy for hepatitis C infection.
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Affiliation(s)
- Alicia Ocaña-Mondragón
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - José Antonio Mata-Marín
- Unidad Médica de Alta Especialidad, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - Mario Uriarte-López
- Departamento de Investigación y Desarrollo, AYDSA Aminas y Derivados S.A. de C.V., Mexico City 06400, Mexico
| | - Carolina Bekker-Méndez
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - Enrique Alcalá-Martínez
- Unidad Médica de Alta Especialidad, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - Rosa María Ribas-Aparicio
- Departamento de Microbiología, Programa en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Luis Antonio Uribe-Noguéz
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico.,Departamento de Microbiología, Programa en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Dulce María Rodríguez-Galindo
- Departamento de Psicología Clínica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - María de La Luz Martínez-Rodríguez
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
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32
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Ishikawa T, Imai M, Ko M, Sato H, Nozawa Y, Sano T, Iwanaga A, Seki K, Honma T, Yoshida T. Evaluation of the branched-chain amino acid-to-tyrosine ratio prior to treatment as a prognostic predictor in patients with liver cirrhosis. Oncotarget 2017; 8:79480-79490. [PMID: 29108327 PMCID: PMC5668060 DOI: 10.18632/oncotarget.18447] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 05/29/2017] [Indexed: 01/07/2023] Open
Abstract
This study evaluated whether the branched-chain amino acid-to-tyrosine ratio (BTR) is a prognostic predictive factor in patients with liver cirrhosis by determining the relationship of the BTR with event-free survival in a retrospective, observational cohort study. The medical records of patients with liver cirrhosis who visited our institution from February 2000 to May 2012 were examined. Events due to liver cirrhosis were defined as death, worsening of esophageal and/or gastric varices, hepatocellular carcinoma, and liver failure. The primary endpoint was the period from the date of BTR measurement until the first onset of these events. Event-free survival was compared between patients with BTR ≥ 4 and BTR < 4. Relationships between the BTR and other factors predicting prognosis were also examined. Event-free survival was evaluated in patients with and without branched-chain amino acid supplementation using propensity score matching. Significantly longer event-free survival was found in liver cirrhosis patients with BTR ≥ 4 (n = 425) compared with those with BTR < 4 (n = 105), and the BTR was associated with liver cirrhosis events. The BTR showed significant relationships with other predictive factors evaluated. In subcohorts matched by propensity score, branched-chain amino acid supplementation significantly improved event-free survival in patients with BTR <4. The BTR is clinically useful for predicting prognosis in liver cirrhosis patients. BCAA supplementation may be beneficial in those with BTR < 4.
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Affiliation(s)
- Toru Ishikawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Michitaka Imai
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Masayoshi Ko
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Hiroki Sato
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Yujiro Nozawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Tomoe Sano
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Akito Iwanaga
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Keiichi Seki
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Terasu Honma
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
| | - Toshiaki Yoshida
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
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Rinninella E, Cerrito L, Spinelli I, Cintoni M, Mele MC, Pompili M, Gasbarrini A. Chemotherapy for Hepatocellular Carcinoma: Current Evidence and Future Perspectives. J Clin Transl Hepatol 2017; 5:235-248. [PMID: 28936405 PMCID: PMC5606970 DOI: 10.14218/jcth.2017.00002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 04/29/2017] [Accepted: 04/29/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatocarcinogenesis is a multistep process, heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis. Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways. As hepatocellular carcinoma has higher arterial vascularization than normal liver, this could be a good target for novel molecular therapies. Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor. The importance of this drug lies not only in the modest gain of patients' survival, but in having opened a roadmap towards the development of new molecules and targets. Unfortunately, after the introduction of sorafenib, during the last years, a wide number of clinical trials on antiangiogenic therapies failed in achieving significant results. However, many of these trials are still ongoing and promise to improve overall survival and progression-free survival. A recent clinical trial has proven regorafenib effective in patients showing tumor progression under sorafenib, thus opening new interesting therapeutic perspectives. Many other expectations have been borne from the discovery of the immune checkpoint blockade, already known in other solid malignancies. Furthermore, a potential role in hepatocellular carcinoma therapy may derive from the use of branched-chain amino acids and of nutritional support. This review analyses the biomolecular pathways of hepatocellular carcinoma and the ongoing studies, the actual evidence and the future perspectives concerning drug therapy in this open field.
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Affiliation(s)
- Emanuele Rinninella
- Internal Medicine and Gastroenterology Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
- Clinical Nutrition Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
| | - Lucia Cerrito
- Internal Medicine and Gastroenterology Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
| | - Irene Spinelli
- Internal Medicine and Gastroenterology Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
| | - Marco Cintoni
- Clinical Nutrition Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
| | - Maria Cristina Mele
- Clinical Nutrition Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Unit, Gastroenterology Area, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy
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Khedr NF, Khedr EG. Branched chain amino acids supplementation modulates TGF-β1/Smad signaling pathway and interleukins in CCl4-induced liver fibrosis. Fundam Clin Pharmacol 2017; 31:534-545. [PMID: 28544244 DOI: 10.1111/fcp.12297] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Revised: 05/13/2017] [Accepted: 05/19/2017] [Indexed: 12/19/2022]
Affiliation(s)
- Naglaa F. Khedr
- Faculty of Pharmacy; Tanta University; Postal number: 31527 Tanta Egypt
| | - Eman G. Khedr
- Faculty of Pharmacy; Tanta University; Postal number: 31527 Tanta Egypt
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35
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Terashima T, Yamashita T, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S. Beneficial Effect of Maintaining Hepatic Reserve during Chemotherapy on the Outcomes of Patients with Hepatocellular Carcinoma. Liver Cancer 2017; 6. [PMID: 28626734 PMCID: PMC5473075 DOI: 10.1159/000472262] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Hepatocellular carcinoma (HCC) usually develops in chronically damaged liver. We investigated hepatic reserves during chemotherapy of patients with advanced HCC and compensated liver function to evaluate the effect on patients' outcomes of maintaining hepatic reserve after chemotherapy. We retrospectively reviewed the medical records of 190 patients with Child-Pugh A with advanced HCC who were treated with sorafenib or hepatic arterial infusion chemotherapy (HAIC). We investigated the Child-Pugh score and albumin-bilirubin grade for hepatic reserve, and evaluated the effect of the change in Child-Pugh scores on patients' outcomes. Subjects were treated with sorafenib (n = 59) or HAIC (n = 131). Of patients with Child-Pugh data, 66.7% maintained or improved their Child-Pugh score after 4 weeks. Treatment with HAIC was the only factor that significantly contributed to maintaining Child-Pugh scores after 4 weeks. The overall survival of patients with a higher Child-Pugh score after 4 weeks was shorter than that of patients whose Child-Pugh classification was unchanged. Multivariate analysis demonstrated that an increased Child-Pugh score after 4 weeks was one of the independent unfavorable prognostic factors. The change of hepatic reserve as a function of albumin-bilirubin grade did not significantly correlate with patients' outcomes. Maintaining the Child-Pugh score during chemotherapy benefits the outcomes of patients with advanced HCC, even those with sufficient hepatic reserve.
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Affiliation(s)
- Takeshi Terashima
- Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan,Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Tatsuya Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan,*Tatsuya Yamashita, MD, PhD, Department of Gastroenterology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawashi, Ishikawa 920-8641 (Japan), E-Mail
| | - Kuniaki Arai
- Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan
| | - Kazunori Kawaguchi
- Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan
| | - Kazuya Kitamura
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Taro Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Yoshio Sakai
- Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan
| | - Eishiro Mizukoshi
- Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan
| | - Masao Honda
- Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan
| | - Shuichi Kaneko
- Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan
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Colagrande S, Inghilesi AL, Aburas S, Taliani GG, Nardi C, Marra F. Challenges of advanced hepatocellular carcinoma. World J Gastroenterol 2016; 22:7645-7659. [PMID: 27678348 PMCID: PMC5016365 DOI: 10.3748/wjg.v22.i34.7645] [Citation(s) in RCA: 128] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 07/06/2016] [Accepted: 08/08/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.
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Abstract
BACKGROUND Hepatocellular carcinoma (HCC) significantly contributes to the global burden of cancer. Liver cancer is the third most frequent cause of cancer-related death with HCC representing more than 90% of primary liver cancers. The majority of patients are not only affected by the malignant disease but do also suffer from chronic liver disease. Therefore, several factors impact on the prognosis of patients with HCC, including tumor-related factors, liver function and patient-related factors such as performance status and other comorbidities. The nutritional status is of high significance for the patients' performance status, the tolerance of tumor-targeting therapy and the prognosis of cancer of any type and is specially referenced in HCC. This overview is on current concepts on the role of nutritional factors in hepatocarcinogenesis and the role of nutrition in patients affected by HCC. SUMMARY Nutritional status and composition of diet are relevant factors related to the risk of HCC. They also have an important role concerning the prognosis of patients with HCC. Besides risk factors, several macro- and micronutrient components have been found to be inversely correlated with the risk of HCC. To prevent disease progression to liver cirrhosis or HCC in patients with nonalcoholic steatohepatitis, it is crucial to optimize the metabolic state. KEY MESSAGE AND PRACTICAL IMPLICATION Evidence from well-designed prospective interventional trials with the aim to reduce the HCC incidence or to prolong survival in patients with HCC based on nutritional modification is still to be generated.
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Affiliation(s)
- Kerstin Schütte
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Christian Schulz
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
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