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Li Y, Wu YT, Wu H. Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions. World J Gastroenterol 2025; 31:103512. [PMID: 40309228 PMCID: PMC12038546 DOI: 10.3748/wjg.v31.i15.103512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 03/04/2025] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.
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Affiliation(s)
- Ying Li
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Tong Wu
- Chongqing Medical University-University of Leicester Joint Institute, Chongqing Medical University, Chongqing 400016, China
| | - Hao Wu
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Miwa T, Tsuruoka M, Ueda H, Abe T, Inada H, Yukawa-Muto Y, Ohara M, Arai T, Tamai Y, Isoda H, Tadokoro T, Hanai T, Ito T, Tamaki N, Sakamaki A, Aoki Y, Tada F, Yoshio S, Takahashi H, Morishita A, Ishikawa T, Inoue J, Suda G, Ogawa C, Atsukawa M, Hiraoka A, Kuroda H, Namisaki T, Honda T, Kawaguchi T, Tanaka Y, Terai S, Ikegami T, Yoshiji H, Iwasa M, Shimizu M. Current management and future perspectives of covert hepatic encephalopathy in Japan: a nationwide survey. J Gastroenterol 2025:10.1007/s00535-025-02232-0. [PMID: 40053108 DOI: 10.1007/s00535-025-02232-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 02/16/2025] [Indexed: 04/20/2025]
Abstract
BACKGROUND Covert hepatic encephalopathy (CHE) leads to devastating outcomes in patients with cirrhosis. This study aims to elucidate the current management and future perspectives of CHE in Japan. METHODS A questionnaire-based cross-sectional study was conducted among physicians involved in managing cirrhosis in Japan. The primary aim was to elucidate the real-world management of CHE, including testing and treatment. Factors influencing the implementation of CHE testing were analyzed using a logistic regression model. Limitations and future perspectives for improving the management of CHE were also evaluated. RESULTS Of 511 physicians surveyed, 93.9% recognized CHE as a significant problem, and 86.9% agreed that it should be tested. Overall, 62.8% of physicians tested for CHE, whereas 37.2% did not. Multivariable analysis identified institutional factors and certifying board as significant determinants of CHE test implementation. The Stroop (68.2%) and neuropsychiatric tests (57.5%) were the most commonly used methods of identifying CHE. Among those who tested for CHE, 87.7% treated CHE; the most common treatments were lactulose (81.5%), rifaximin (76.3%), and branched-chain amino acids (70.4%). Among non-testers, the primary barrier was the time requirement for testing. Proposals to encourage CHE testing included the development of simple tests and integration of multidisciplinary teams. CONCLUSIONS Most physicians involved in cirrhosis care in Japan recognize CHE as a significant problem that warrants testing. However, testing for CHE remains limited by institutional factors and physician specialties. Time requirements for CHE testing are the primary barrier, and simple tests and multidisciplinary teams are recommended to enhance CHE management.
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Affiliation(s)
- Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
| | - Mio Tsuruoka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, 980-8574, Japan
| | - Hajime Ueda
- Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-Machi, Inashiki-Gun, Ibaraki, 300-3095, Japan
| | - Tamami Abe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-Cho, Shiwa-Gun, Yahaba, Iwate, 028-3694, Japan
| | - Hiroki Inada
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto University, 1-1-1, Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Yoshimi Yukawa-Muto
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-Shi, Hokkaido, 060-8638, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan
| | - Yasuyuki Tamai
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan
| | - Hiroshi Isoda
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu, Kagawa, 761-0793, Japan
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa, Nagoya, 466-8550, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1Kyonan-Cho, Musashino-Shi, Tokyo, 180-8610, Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-Ku, Niigata, 951-8510, Japan
| | - Yoshihiko Aoki
- Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, 272-8516, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-Cho, Matsuyama, Ehime, 790-0024, Japan
| | - Sachiyo Yoshio
- Department of Human Immunology and Translational Research, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu, Kagawa, 761-0793, Japan
| | - Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube-Yamaguchi, 7558505, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, 980-8574, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-Shi, Hokkaido, 060-8638, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, 4-1-3 Bancho, Takamatsu City, Kagawa Prefecture, 760-0017, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-Cho, Matsuyama, Ehime, 790-0024, Japan
| | - Hidekatsu Kuroda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-Cho, Shiwa-Gun, Yahaba, Iwate, 028-3694, Japan
| | - Tadashi Namisaki
- Department of Gastroenterology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa, Nagoya, 466-8550, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, 830-0011, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto University, 1-1-1, Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-Ku, Niigata, 951-8510, Japan
| | - Tadashi Ikegami
- Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-Machi, Inashiki-Gun, Ibaraki, 300-3095, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
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Sobhrakhshankhah E, Farahmand M, Hasan Rashedi M, Shahinfar H, Shab-Bidar S, Dinari S, Doustmohammadian A. Efficacy of different nutrition interventions on sarcopenia in patients with cirrhosis: a systematic review and network meta-analysis. BMC Nutr 2025; 11:39. [PMID: 39940017 DOI: 10.1186/s40795-025-01028-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 02/05/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND & AIMS Sarcopenia, characterized by the loss of muscle mass and strength, is a significant concern in cirrhotic patients. Nutritional interventions have been explored for its management, but the comparative efficacy of these interventions remains unclear. This study synthesizes current evidence to evaluate the effectiveness of nutritional interventions for sarcopenia in cirrhosis. METHODS Data sources included Scopus, PubMed, Web of Science Core Collection, and Cochrane Library up to Dec 2024. Eligible trials compared different nutritional interventions against control diets, placebos, or each other. A Bayesian network meta-analysis was performed to combine direct and indirect evidence. Effect sizes were calculated as mean differences (MD) with 95% confidence intervals (CIs). Intervention rankings were assessed using P-score, and evidence quality was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS A total of 14 randomized controlled trials (RCTs) involving 1,437 patients met the inclusion criteria. For improving muscle mass (MAMC), post-paracentesis intravenous nutritional support combined with an oral nutritional protocol (Treat A) showed the greatest effect compared to high-calorie, high-protein diets (HCHP) (MD: 2.78 cm, 95% CI: 1.15 to 4.40, low certainty), and oral nutritional protocol (Treat B) (MD of 3.41 cm, 95% CI: 2.12, 4.69). For muscle strength, the HINT diet (MD: 8.01 kg, 95% CI: 7.64 to 8.37, low certainty) and the HCHP (MD: 5 kg, 95% CI: 3.90 to 6.10, low certainty) were more effective than control diets. HCHP also demonstrated greater handgrip improvement than the HINT diet (MD: 3.00 kg, 95% CI: 1.84, 4.16; low certainty evidence). BCAA combined with vitamin D (2000 IU once a day) significantly improved skeletal muscle index (SMI) compared to both BCAA (MD: 0.72 kg/m2, 95% CI: 0.11 to 1.34; low certainty evidence) and placebo (MD: 0.25 kg/m2, 95% CI: -0.05 to 0.05; very low certainty evidence). BCAA supplementation effectively improved handgrip strength compared to placebo (MD: 2.36 kg, 95% CI: 1.85, 2.88; low certainty evidence). CONCLUSIONS Post-paracentesis intravenous nutritional support combined with an oral nutritional protocol effectively improves muscle mass, while high-calorie, high-protein diets enhance handgrip strength. BCAA supplementation alone or with vitamin D has been shown to effectively enhance muscle strength and muscle mass. However, these findings should be interpreted cautiously due to low evidence certainty.
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Affiliation(s)
- Elham Sobhrakhshankhah
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Farahmand
- Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Minoo Hasan Rashedi
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Shahinfar
- Nutritional Health Research Center, School of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Sakineh Shab-Bidar
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Saghar Dinari
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Internal Medicine, School of Medicine, Firoozgar General Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Azam Doustmohammadian
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Yokobori S, Yatabe T, Kondo Y, Ajimi Y, Araki M, Chihara N, Nagayama M, Samkamoto T. Intravenous branched-chain amino acid administration for the acute treatment of hepatic encephalopathy: a systematic review and meta-analysis. J Intensive Care 2025; 13:2. [PMID: 39780295 PMCID: PMC11716518 DOI: 10.1186/s40560-024-00771-x] [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: 09/25/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a severe complication of acute hepatic failure requiring urgent critical care management. Branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine have been investigated as potential treatments to improve outcomes in patients with acute HE. However, the effectiveness of BCAA administration during the acute phase remains unclear. This study aimed to evaluate the effect of intravenous BCAA (IV-BCAA) treatment on clinical outcomes in patients with acute HE by systematically reviewing and analyzing randomized controlled trials (RCTs). METHODS We conducted a comprehensive literature search of MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI), a Japanese database for medical literature. We included RCTs involving adult patients with acute HE who received IV-BCAA or placebo during the acute phase after admission (< 7 days). Two reviewers independently screened the citations and extracted data. The primary "critical" outcomes were mortality from any cause and improvement in disturbance of consciousness. The secondary "important" outcome included the incidence of complications such as nausea and diarrhea. Risk ratios (RRs) were calculated using random effects models with inverse variance weighting. RESULTS Among the 2073 screened records, four met the criteria for quantitative analysis. The analysis included 219 patients: 109 received IV-BCAA, and 110 received placebo. Improvement in the disturbance of consciousness and mortality were not significantly different between the two groups (RR, 1.26; 95% confidence interval [CI], 0.96-1.66; RR, 0.90; 95% CI 0.70-1.16, respectively). Following IV-BCAA administration, the absolute differences of improvement in the disturbance of consciousness and mortality were 118 more per 1000 (95% CI 18 fewer-300 more) and 55 fewer per 1000 (95% CI 165 fewer-88 more), respectively. No significant differences were observed in the incidence of nausea or diarrhea between the two groups. CONCLUSIONS Our meta-analysis demonstrates that all outcomes were not significantly different between IV-BCAA treatment and placebo for acute HE. Further RCTs are required to better understand IV-BCAA treatment potential in patients with HE.
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Affiliation(s)
- Shoji Yokobori
- Department of Emergency and Critical Care Medicine, Nippon Medical School, Bunkyo-Ku, Tokyo, 113-8603, Japan.
| | - Tomoaki Yatabe
- Emergency Department, Nishichita General Hospital, Tokai-Shi, Aichi, 477-8522, Japan
| | - Yutaka Kondo
- Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Yasuhiko Ajimi
- Department of Emergency Medicine, Teikyo University School of Medicine, Itabashi-Ku, Tokyo, 173-8605, Japan
| | - Manabu Araki
- Department of Neurology, Kawakita General Hospital, Tokyo, 166-8588, Japan
| | - Norio Chihara
- Division of Neurology, Kobe University Hospital, 7-5-2, Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan
| | - Masao Nagayama
- Departments of Neurology, Critical Care Medicine, and the Center for Preventive Medicine, International University of Health and Welfare Narita Hospital, Narita, Chiba, 286-8520, Japan
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Abuelazm M, Fares A, Elhady MM, Amin AM, Khan U, Gowaily I, Jaber F. Branched-Chain Amino Acid Supplements for Sarcopenia in Liver Cirrhosis: A Systematic Review and Meta-analysis. J Clin Exp Hepatol 2025; 15:102417. [PMID: 39834601 PMCID: PMC11742309 DOI: 10.1016/j.jceh.2024.102417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 09/23/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Sarcopenia, a key aspect of malnutrition in liver cirrhosis (LC), affects 30-70% of LC patients. Given the inconsistent results from RCTs on branched-chain amino acids (BCAAs) for treating sarcopenia in LC, we conducted a systematic review and meta-analysis to assess the efficacy and safety of BCAAs for sarcopenia management in LC patients. METHODS A systematic review and meta-analysis synthesizing evidence from RCTs obtained from PubMed, Embase, Cochrane, Scopus, and Web of Science from inception to April 2024. We used the fixed-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42024542761. RESULTS Five RCTs with 434 patients were included. BCAAs were significantly associated with decreased liver frailty index change (MD: -0.14 with 95% CI [-0.28, -0.01], P = 0.03). However, there was no significant difference between BCAAs and the control group regarding hand grip strength change (MD: 0.98 with 95% CI [-0.45, 2.41], P = 0.18). Also, BCAAs were associated with increased body mass index (BMI) change (MD: 0.99 with 95% CI [0.16, 1.82], P = 0.02) and increased QoL (standardized mean difference : 0.27 with 95% CI [0.03, 0.52], P = 0.03). However, there was no significant difference between BCAAs and the control group in model for end-stage liver disease (MELD) score change (MD: 0.65 with 95% CI [-1.20, 2.50], P = 0.49), skeletal muscle index change (MD: 0.21 with 95% CI [-0.23, 0.65], P = 0.35), and gait speed change (MD: 0.10 with 95% CI [-0.15, 0.34], P = 0.43). CONCLUSION BCAA supplementation in cirrhotic patients with sarcopenia reduced the liver frailty index, increased BMI and QoL, but did not affect handgrip strength, skeletal muscle index, gait speed, or MELD score. Outcome heterogeneity and study bias were noted, highlighting the need for further RCTs to confirm these results.
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Affiliation(s)
| | - Ahmed Fares
- Internal Medicine Department, Tufts Medical Center, Boston, USA
| | | | | | - Ubaid Khan
- Department of Medicine, University of Maryland School of Medicine, USA
| | | | - Fouad Jaber
- Department of Gastroenterology and hepatology, Baylor College of Medicine, Houston, TX, USA
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Hanai T, Nishimura K, Unome S, Miwa T, Nakahata Y, Imai K, Suetsugu A, Takai K, Shimizu M. Nutritional counseling improves mortality and prevents hepatic encephalopathy in patients with alcohol-associated liver disease. Hepatol Res 2024; 54:1089-1098. [PMID: 38683882 DOI: 10.1111/hepr.14053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 04/02/2024] [Accepted: 04/12/2024] [Indexed: 05/02/2024]
Abstract
AIM Nutritional counseling improves malnutrition, which determines the prognosis of patients with chronic liver disease. In this study, we investigated the effects of nutritional counseling on mortality and the risk of overt hepatic encephalopathy (HE) in patients with alcohol-associated liver disease. METHODS In this retrospective cohort study, we included 211 patients with alcohol-associated liver disease who visited Gifu University Hospital between August 2008 and June 2023. Patients were classified into two groups according to the frequency of nutritional counseling by a registered dietitian. The primary outcomes were all-cause mortality and overt HE. Propensity score matching analysis was performed to adjust for potential confounders. RESULTS Among the patients (median age 67 years; 88% men; and median Model for End-Stage Liver Disease score, 9), 86 (39%) were in the high-frequency (≥2) nutritional counseling group. The high-frequency group had a significantly higher survival rate (46% vs. 25%) and a lower incidence of overt HE (16% vs. 27%) at 5 years than the low-frequency group. Nutritional counseling was associated with a reduced risk of mortality (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.36-0.63) and overt HE (HR 0.64; 95% CI 0.42-0.99), independent of hepatocellular carcinoma and liver function reserve. After propensity score matching, nutritional counseling was still associated with a reduced risk of mortality (HR 0.34; 95% CI 0.19-0.59) and overt HE (HR 0.31; 95% CI 0.11-0.87). CONCLUSIONS Nutritional counseling effectively improves mortality and prevents overt HE in patients with alcohol-associated liver disease, thereby proving essential for the management of these patients.
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Affiliation(s)
- Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Kayoko Nishimura
- Center for Nutrition Support and Infection Control, Gifu University Hospital, Gifu, Japan
| | - Shinji Unome
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Takao Miwa
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuki Nakahata
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Kenji Imai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Atsushi Suetsugu
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Koji Takai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
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Dunn W, Herrmann SD, Montgomery RN, Hastert M, Honas JJ, Rachman J, Donnelly JE, Steger FL. Optimizing muscle preservation during weight loss in patients with cirrhosis: A pilot study comparing continuous energy restriction to alternate-day modified fasting for weight loss in patients with obesity and non-alcoholic cirrhosis of the liver. Obes Sci Pract 2024; 10:e70016. [PMID: 39450267 PMCID: PMC11500757 DOI: 10.1002/osp4.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/10/2024] [Accepted: 10/03/2024] [Indexed: 10/26/2024] Open
Abstract
Introduction Obesity is associated with increased morbidity in patients with advanced liver disease, but it is particularly challenging for these patients to preserve skeletal muscle mass during weight loss and accelerating sarcopenia is a concern. Alternate-day modified fasting (ADMF) may be particularly effective for weight loss in patients with concomitant cirrhosis and obesity due to preservation of fat-free mass (FFM). Methods A weight loss program featuring either ADMF or a continuous low-calorie diet (LCD) was evaluated in a 24-week randomized clinical trial in 20 adult patients with Child-Pugh Class A cirrhosis and obesity. Participants were randomized to either ADMF (n = 11) or LCD (n = 9). Both groups received a remotely delivered exercise program. Body composition, sarcopenia measures, and functional outcomes were assessed pre-post. Results Thirteen participants completed the intervention (Age = 57 ± 10; BMI = 37.7 ± 5.8 kg/m2). The median body weight lost in ADMF was 13.7 ± 4.8 kg (13.9% of initial body weight), while LCD lost 9.9 ± 6.9 kg (10.7% of initial body weight). Total body fat percentage decreased in both groups (ADMF: -4.1 ± 4.0%; LCD = -2.8 ± 1.4%). Fat-free mass accounted for 34 ± 20% of total weight loss in ADMF and 38 ± 10% in LCD. Functional measures, such as timed chair stands, improved in both groups. Conclusion This pilot study demonstrates the feasibility of the ADMF and LCD interventions to produce significant weight loss while improving body composition in patients with cirrhosis and obesity. Further research is needed to validate these findings in larger cohorts and to assess changes in muscle quality and visceral fat. Trial Registration ClinicalTrials.gov Identifier: NCT05367596.
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Affiliation(s)
- Winston Dunn
- Division of Gastroenterology, Hepatology and Motility, Diabetes, and Clinical PharmacologyDepartment of Internal MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Stephen D. Herrmann
- Division of Physical Activity and Weight ManagementDepartment of Internal MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Robert N. Montgomery
- Department of Biostatistics and Data Science, Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Mary Hastert
- Division of Physical Activity and Weight ManagementDepartment of Internal MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Jeffery J. Honas
- Division of Physical Activity and Weight ManagementDepartment of Internal MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Jessica Rachman
- Division of Gastroenterology, Hepatology and Motility, Diabetes, and Clinical PharmacologyDepartment of Internal MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Joseph E. Donnelly
- Division of Physical Activity and Weight ManagementDepartment of Internal MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Felicia L. Steger
- Division of Endocrinology, Diabetes, and Clinical Pharmacology, Department of Internal MedicineDepartment of Dietetics and NutritionUniversity of Kansas Medical CenterKansas CityKansasUSA
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8
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Maharshi S, Sharma BC. Prophylaxis of hepatic encephalopathy: current and future drug targets. Hepatol Int 2024; 18:1096-1109. [PMID: 38492132 DOI: 10.1007/s12072-024-10647-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 01/18/2024] [Indexed: 03/18/2024]
Abstract
Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.
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Affiliation(s)
- Sudhir Maharshi
- Department of Gastroenterology, SMS Medical College and Hospitals, Jaipur, India
| | - Barjesh Chander Sharma
- Department of Gastroenterology, G.B. Pant Hospital, Room No. 201, Academic Block, New Delhi, 110002, India.
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9
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Reichelt S, Merle U, Klauss M, Kahlert C, Lurje G, Mehrabi A, Czigany Z. Shining a spotlight on sarcopenia and myosteatosis in liver disease and liver transplantation: Potentially modifiable risk factors with major clinical impact. Liver Int 2024; 44:1483-1512. [PMID: 38554051 DOI: 10.1111/liv.15917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 03/07/2024] [Accepted: 03/17/2024] [Indexed: 04/01/2024]
Abstract
Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.
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Affiliation(s)
- Sophie Reichelt
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital of Bonn, Bonn, Germany
| | - Uta Merle
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Miriam Klauss
- Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christoph Kahlert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Georg Lurje
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Zoltan Czigany
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
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10
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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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11
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Singh J, Ibrahim B, Han SH. Nontraditional Treatment of Hepatic Encephalopathy. Clin Liver Dis 2024; 28:297-315. [PMID: 38548441 DOI: 10.1016/j.cld.2024.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
The pathophysiology of hepatic encephalopathy (HE) is complex, with hyperammonemia playing a central role in its development. Traditional therapies for HE have targeted ammonia and include medications such as lactulose and rifaximin. Although these agents are considered standard of care, nontraditional treatments seek to affect other factors in the pathogenesis of HE. Finally, procedural therapies include albumin dialysis, shunt closure, and the ultimate cure for HE, which is liver transplant. The treatments discussed provide alternative options for patients who have failed standard of care. However, more high-quality studies are needed to routinely recommend many of these agents.
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Affiliation(s)
- Jasleen Singh
- Department of Medicine, University of California at Los Angeles; Los Angeles, CA, USA.
| | - Brittney Ibrahim
- Department of Surgery, University of California at Los Angeles; Los Angeles, CA, USA
| | - Steven-Huy Han
- Department of Medicine, University of California at Los Angeles; Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles; Los Angeles, CA, USA
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12
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Cruz C, Prado CM, Gillis C, Martindale R, Bémeur C, Lai JC, Tandon P. Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant. Hepatology 2024:01515467-990000000-00825. [PMID: 38546288 PMCID: PMC11828479 DOI: 10.1097/hep.0000000000000818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 01/20/2024] [Indexed: 04/21/2024]
Abstract
Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."
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Affiliation(s)
- Christofer Cruz
- Department of Medicine, Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Carla M. Prado
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Chelsia Gillis
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
- Departments of Anesthesia & Surgery, McGill University, Montreal, Quebec, Canada
| | - Robert Martindale
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, California, USA
| | - Chantal Bémeur
- Department of Nutrition, Université de Montréal, Montreal, Quebec, Canada
| | - Jennifer C. Lai
- Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA
| | - Puneeta Tandon
- Department of Medicine, Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
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13
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Kibble H, Shawcross DL. The assessment and management of cirrhotic patients with encephalopathy. United European Gastroenterol J 2024; 12:187-193. [PMID: 38180440 PMCID: PMC10954429 DOI: 10.1002/ueg2.12530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 11/24/2023] [Indexed: 01/06/2024] Open
Abstract
Hepatic encephalopathy (HE) is a debilitating complication associated with both acute and chronic liver injury. It is associated with a greater risk of death than any other significant hepatic decompensation event. It manifests as a wide spectrum of neuropsychological abnormalities ranging from subtle impairments in higher cognitive function, to confusion and coma. The pathophysiological role of ammonia in the development of HE is well known, but there is increasing recognition that the gut microbiome, gut-derived systemic inflammation and development of infection can serve as drivers of HE in patients with cirrhosis. The development of HE portents to the severity of cirrhosis and the prognosis is poor without liver transplantation. A referral for liver transplantation should therefore be considered early in those who are eligible. This review covers the pragmatic assessment of HE in patients with cirrhosis, as well as the current evidence base for the best practice management of HE in such patients.
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Affiliation(s)
- H Kibble
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Debbie L Shawcross
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
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14
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de Felice I, Ridola L, Riggio O, Faccioli J, Nardelli S, Gioia S. Transjugular Intrahepatic Portosystemic Shunt Placement: Effects on Nutritional Status in Cirrhotic Patients. J Clin Med 2023; 12:7029. [PMID: 38002642 PMCID: PMC10672441 DOI: 10.3390/jcm12227029] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 10/27/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
Malnutrition is a tangible complication of cirrhosis with portal hypertension with a prevalence of up to 50%. In particular, sarcopenia and myosteatosis, defined as the alteration in muscle quantity and quality, have a negative impact on the main complications of liver disease and are associated with higher mortality in patients with cirrhosis. Recently, alterations in adipose tissue have also been described in cirrhotic patients and they seem to influence the course of liver disease. Several pieces of evidence indicate that a transjugular intrahepatic portosystemic shunt (TIPS), placed for the treatment of refractory portal hypertension, can lead to a modification of body composition consisting in the improvement of the skeletal muscle index, myosteatosis, and an increase in subcutaneous fat. These modifications of the nutritional status, even more pronounced in sarcopenic patients before TIPS, have been associated with an amelioration of cognitive impairment after TIPS as well as with an increase in the survival rate. The aim of this paper is to provide an overview of the effects of TIPS placement on nutritional status in cirrhosis focusing on its pathophysiological mechanisms and its relationship with liver-related outcomes.
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Affiliation(s)
| | | | | | | | | | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (I.d.F.); (L.R.); (O.R.); (J.F.); (S.N.)
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15
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Colosimo S, Bertoli S, Saffioti F. Use of Branched-Chain Amino Acids as a Potential Treatment for Improving Nutrition-Related Outcomes in Advanced Chronic Liver Disease. Nutrients 2023; 15:4190. [PMID: 37836474 PMCID: PMC10574343 DOI: 10.3390/nu15194190] [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: 09/02/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 10/15/2023] Open
Abstract
Advanced chronic liver disease (ACLD) represents a complex and multifactorial clinical entity characterized by liver dysfunction and associated complications. In recent years, the significance of nutritional status in ACLD prognosis has gained considerable attention. This review article delves into the multifactorial pathogenesis of malnutrition in ACLD and its profound consequences for health outcomes. We explore the clinical implications of secondary sarcopenia in ACLD and highlight the critical relevance of frailty in both decompensated and compensated ACLD. A specific focus of this review revolves around branched-chain amino acids (BCAAs) and their pivotal role in managing liver disease. We dissect the intricate relationship between low Fischer's ratio and BCAA metabolism in ACLD, shedding light on the molecular mechanisms involved. Furthermore, we critically evaluate the existing evidence regarding the effects of BCAA supplementation on outcomes in ACLD patients, examining their potential to ameliorate the nutritional deficiencies and associated complications in this population.
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Affiliation(s)
- Santo Colosimo
- School of Nutrition Science, University of Milan, 20133 Milan, Italy
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, 20133 Milan, Italy
| | - Simona Bertoli
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, 20133 Milan, Italy
- Laboratory of Clinical Studies on Obesity, Istituto Auxologico Italiano IRCCS, 20145 Milan, Italy
| | - Francesca Saffioti
- Oxford Liver Unit, Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK;
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16
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Jamioł-Milc D, Gudan A, Kaźmierczak-Siedlecka K, Hołowko-Ziółek J, Maciejewska-Markiewicz D, Janda-Milczarek K, Stachowska E. Nutritional Support for Liver Diseases. Nutrients 2023; 15:3640. [PMID: 37630830 PMCID: PMC10459677 DOI: 10.3390/nu15163640] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/16/2023] [Accepted: 08/17/2023] [Indexed: 08/27/2023] Open
Abstract
The liver is a key organ that is responsible for the metabolism of proteins, fats, and carbohydrates and the absorption and storage of micronutrients. Unfortunately, the prevalence of chronic liver diseases at various stages of advancement in the world population is significant. Due to the physiological function of the liver, its dysfunction can lead to malnutrition and sarcopenia, and the patient's nutritional status is an important prognostic factor. This review discusses key issues related to the diet therapy of patients with chronic liver diseases, as well as those qualified for liver transplantation and in the postoperative period.
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Affiliation(s)
- Dominika Jamioł-Milc
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | - Anna Gudan
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | - Karolina Kaźmierczak-Siedlecka
- Department of Medical Laboratory Diagnostics—Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, 80-211 Gdansk, Poland
| | - Joanna Hołowko-Ziółek
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | | | - Katarzyna Janda-Milczarek
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
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17
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Swansson WD, Anderson BM, Yeoh SW, Lewis DJ. Management of minimal and overt hepatic encephalopathy with branched-chain amino acids: a review of the evidence. Eur J Gastroenterol Hepatol 2023; 35:812-821. [PMID: 37395232 DOI: 10.1097/meg.0000000000002595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
Hepatic encephalopathy (HE) is a challenging complication of liver disease that is associated with substantial morbidity and mortality. Branched-chain amino acid (BCAA) supplementation in the management of HE is a debated topic. This narrative review aims to provide an up-to-date review of the topic and includes studies featuring patients with hepatocellular carcinoma. A review of the literature was performed using the online databases MEDLINE and EMBASE for studies between 2002 and December 2022. Keywords 'branched-chain amino acids', 'liver cirrhosis' and 'hepatic encephalopathy' were used. Studies were assessed for inclusion and exclusion criteria. Of 1045 citations, 8 studies met the inclusion criteria. The main outcomes reported for HE was changed in minimal HE (MHE) (n = 4) and/or incidence of overt HE (OHE) (n = 7). Two of the 4 studies reporting on MHE had improvement in psychometric testing in the BCAA group, but there was no change in the incidence of OHE in any of the 7 papers in the BCAA group. There were few adverse effects of BCAA supplementation. This review found weak evidence for BCAA supplementation for MHE, and no evidence for BCAAs for OHE. However, given the relative paucity and methodological heterogeneity of the current research, there is scope for future studies to examine the effects of varying timing, dosage, and frequency of BCAAs on outcomes such as HE. Importantly, research is also needed to examine BCAAs in conjunction with standard therapies for HE such as rifaximin and/or lactulose.
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Affiliation(s)
| | | | - Sern Wei Yeoh
- Melbourne Medical School, The University of Melbourne
- Department of Gastroenterology, Northern Health, Melbourne, VIC, Australia
| | - Diana J Lewis
- Melbourne Medical School, The University of Melbourne
- Department of Gastroenterology, Northern Health, Melbourne, VIC, Australia
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18
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Marrone G, Serra A, Miele L, Biolato M, Liguori A, Grieco A, Gasbarrini A. Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis: Evidence and uncertainties. World J Gastroenterol 2023; 29:2905-2915. [PMID: 37274800 PMCID: PMC10237095 DOI: 10.3748/wjg.v29.i19.2905] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/24/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023] Open
Abstract
Liver cirrhosis is commonly associated with nutritional alterations, reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis. Nutritional disturbances are associated with a worse prognosis and increased risk of complication. Serum levels of branched-chain amino acids (BCAAs) are decreased in patients with liver cirrhosis. The imbalance of amino acids levels has been suggested to be associated with the development of complications, such as hepatic encephalopathy and sarcopenia, and to affect the clinical presentation and prognosis of these patients. Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis, but uncertainties remain about the real efficacy, the best route of administration, and dosage.
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Affiliation(s)
- Giuseppe Marrone
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Amato Serra
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Miele
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Marco Biolato
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Liguori
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Grieco
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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19
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Nardelli S, Gioia S, Faccioli J, Riggio O, Ridola L. Hepatic encephalopathy - recent advances in treatment and diagnosis. Expert Rev Gastroenterol Hepatol 2023; 17:225-235. [PMID: 36843291 DOI: 10.1080/17474124.2023.2183386] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2023]
Abstract
INTRODUCTION Hepatic encephalopathy (HE) is a peculiar kind of brain dysfunction typical of liver cirrhosis characterized by nonspecific neurological and psychiatric manifestations. HE ranges from minimal hepatic encephalopathy (MHE) to the most severe form characterized by alteration of consciousness or coma (overt HE, OHE). Once the diagnosis of OHE is made, every effort to identify and correct the precipitating cause is essential for the resolution of symptoms. Clinical studies that assessed the prevalence and incidence of any type of HE (MHE and OHE) in patients affected by cirrhosis were included in this review. No language, publication date, or publication status restrictions were imposed. The studies were identified by searching electronic databases (PubMed and SCOPUS). AREAS COVERED The most widely empirical pharmacological approach consists of non-absorbable antibiotics (rifaximin) and non-absorbable disaccharides (lactulose, lactitol per os and per enemas). Other agents (including branched-chain amino acids, probiotics, other antibiotics, or intravenous L-ornithine L-aspartate) are available, but the evidence supporting their efficacy remains under debate. EXPERT OPINION Gray areas and future needs remain the therapeutic approach to MHE and issues in the design of therapeutic studies for HE which have been extensively discussed in this review.
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Affiliation(s)
- Silvia Nardelli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Jessica Faccioli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
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20
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Abstract
Hepatic encephalopathy (HE) is brain dysfunction secondary to liver insufficiency or portosystemic shunting. HE is a major burden on patients and caregivers, impairs quality of life and is associated with higher mortality. Overt HE is a clinical diagnosis while Covert HE, needs specialized diagnostic strategies. Mainstay of treatment of HE is nonabsorbable disaccharides such as lactulose as well as rifaximin; however, investigational therapies are discussed in this review. Better tools are needed to prognosticate which patients will go on to develop HE but microbiome and metabolomic-driven strategies are promising. Here we review methods to prevent the HE development and admissions.
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21
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Sarcopenia and Frailty in Cirrhosis. Med Clin North Am 2023; 107:589-604. [PMID: 37001955 DOI: 10.1016/j.mcna.2022.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Sarcopenia and frailty are frequent in cirrhosis, and both contribute to increased morbidity and mortality. The complex pathogenesis of sarcopenia in cirrhosis is mainly determined by hyperammonemia and malnutrition. Sarcopenia/frailty screening and reevaluation should be undertaken in all cirrhotic patients. Frailty tests are useful in the ambulatory setting, whereas the computed tomography scan is the diagnostic gold standard for sarcopenia. To manage sarcopenia/frailty, a multidisciplinary team should develop a personalized comprehensive care plan that includes patient education, protein/calorie intake goals, late evening meals, exercise programs, and micronutrient replenishment. In selected patients, branched-chain amino acid and testosterone supplements may also be beneficial.
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22
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Yu L, Paski SC, Dodge J, Bambha K, Biggins SW, Ioannou GN. Effect of dietary branched chain amino acids on liver related mortality: Results from a large cohort of North American patients with advanced HCV infection. PLoS One 2023; 18:e0284739. [PMID: 37098004 PMCID: PMC10128927 DOI: 10.1371/journal.pone.0284739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 04/06/2023] [Indexed: 04/26/2023] Open
Abstract
Branched chain amino acids (BCAA) supplementation may reduce the incidence of liver failure and hepatocellular carcinoma in patients with cirrhosis. We aimed to determine whether long-term dietary intake of BCAA is associated with liver-related mortality in a well-characterized cohort of North American patients with advanced fibrosis or compensated cirrhosis. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. The analysis included 656 patients who completed two Food Frequency Questionnaires. The primary exposure was BCAA intake measured in grams (g) per 1000 kilocalories (kcal) of energy intake (range 3.0-34.8 g/1000 kcal). During a median follow-up of 5.0 years, the incidence of liver-related death or transplantation was not significantly different among the four quartiles of BCAA intake before and after adjustment of confounders (AHR 1.02, 95% CI 0.81-1.27, P-value for trend = 0.89). There remains no association when BCAA was modeled as a ratio of BCAA to total protein intake or as absolute BCAA intake. Finally, BCAA intake was not associated with the risk of hepatocellular carcinoma, encephalopathy or clinical hepatic decompensation. We concluded that dietary BCAA intake was not associated with liver-related outcomes in HCV-infected patients with advanced fibrosis or compensated cirrhosis. The precise effect of BCAA in patients with liver disease warrants further study.
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Affiliation(s)
- Lei Yu
- Division of Gastroenterology, University of Washington, Seattle, Washington, United States of America
| | - Shirley C Paski
- Division of Gastroenterology, Cedar Sinai School of Medicine, Los Angeles, California, United States of America
| | - Jennifer Dodge
- Department of Surgery, Division of Transplant Surgery, University of California San Francisco, San Francisco, California, United States of America
| | - Kiran Bambha
- Division of Gastroenterology, University of Washington, Seattle, Washington, United States of America
| | - Scott W Biggins
- Division of Gastroenterology, University of Washington, Seattle, Washington, United States of America
| | - George N Ioannou
- Division of Gastroenterology, University of Washington, Seattle, Washington, United States of America
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington, United States of America
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23
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Kumar R, Prakash SS, Priyadarshi RN, Anand U. Sarcopenia in Chronic Liver Disease: A Metabolic Perspective. J Clin Transl Hepatol 2022; 10:1213-1222. [PMID: 36381104 PMCID: PMC9634780 DOI: 10.14218/jcth.2022.00239] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/14/2022] [Accepted: 07/19/2022] [Indexed: 12/04/2022] Open
Abstract
Sarcopenia, a condition of low muscle mass, quality, and strength, is commonly found in patients with chronic liver disease (CLD) and is associated with adverse clinical outcomes including reduction in quality of life, increased mortality, and complications. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover wherein changes in various metabolic factors such as hyperammonemia, amino acid deprivation, hormonal imbalance, gut dysbiosis, insulin resistance, chronic inflammation, etc. have important roles. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α-ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Skeletal muscle is a major organ of insulin-induced glucose metabolism, and sarcopenia is closely linked to insulin resistance and metabolic syndrome. Patients with liver cirrhosis are in a hypermetabolic state that is associated with catabolism and depletion of amino acids, particularly branched-chain amino acids. Sarcopenia can have significant implications for nonalcoholic fatty liver disease, the most common form of CLD worldwide, because of the close link between metabolic syndrome and sarcopenia. This review discusses the potential metabolic derangement as a cause or effect of sarcopenia in CLD, as well as interorgan crosstalk, which that might help identifying a novel therapeutic strategies.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Sabbu Surya Prakash
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | | | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna, India
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24
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Du JY, Shu L, Zhou YT, Zhang L. Branched-chain amino acids supplementation has beneficial effects on the progression of liver cirrhosis: A meta-analysis. World J Clin Cases 2022; 10:10984-10996. [PMID: 36338230 PMCID: PMC9631141 DOI: 10.12998/wjcc.v10.i30.10984] [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: 07/18/2022] [Revised: 08/19/2022] [Accepted: 09/19/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Liver cirrhosis (LC) is currently the 11th most common cause of death and 15th cause of morbidity globally. The treatment of LC is mainly aimed at etiological intervention, lifestyle intervention, prevention and treatment of complications and nutritional treatment. Nutritional treatment of LC mainly includes increasing dietary intake, food intake time and branched-chain amino acids (BCAAs). Despite the recommendation of BCAAs in some guidelines, adverse effects have been reported in studies so the efficacy and safety of BCAAs remain controversial. Currently, BCAAs have been widely used in chronic liver disease, while the summary of the effect of BCAAs on long-term prognosis is rare.
AIM To determine the effects of BCAAs in patients with LC.
METHODS The PubMed, Cochrane Library, Embase and Web of Science databases were searched. The retrieval deadline was 1 October 2021 and there were no language restrictions set in the retrieval. The study was performed in strict accordance with the inclusion and exclusion criteria. Nine studies were finally included. The primary outcome was complications of LC. The secondary outcomes were nutritional status and liver function. This meta-analysis used the Review Manager, version 5 statistical package (Cochrane Collaboration, Oxford, England) for analysis.
RESULTS The analysis included nine studies that consisted of 1080 patients (554 in the BCAA groups and 526 in the control groups). The nine studies were randomized control trials (RCTs). The quality of the studies was assessed using the risk of bias method recommended by the Cochrane Collaboration. BCAAs reduced the rate of complications in LC patients [Risk ratio: 0.70, 95% confidence interval (CI): 0.56-0.88, P = 0.002] and improved patients’ albumin levels [std mean difference SMD: 0.26, 95%CI: 0.12-0.40, P = 0.0002]. Meanwhile, BCAAs significantly ameliorated the levels of alanine transaminase (SMD: -2.03, 95%CI: -2.52 to -1.53, P < 0.00001) and aspartate aminotransferase (SMD: -1.8, 95%CI: -2.14 to -1.46, P < 0.00001). Meanwhile, glucose in the LC was significantly increased in BCAA-treated patients (MD: 13.04, 95%CI: 6.81-19.89, P = 0.0002).
CONCLUSION BCAAs reduce the incidence of complications in patients with LC and ameliorate nutritional status.
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Affiliation(s)
- Jia-Yu Du
- School of Clinical Medicine, Chengdu Medical College, Chengdu 610000, Sichuan Province, China
| | - Liu Shu
- Department of Neuroscience, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, China
| | - Yu-Tian Zhou
- Department of Geriatrics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610000, Sichuan Province, China
| | - Li Zhang
- Department of Geriatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
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25
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Montagnese S, Rautou PE, Romero-Gómez M, Larsen FS, Shawcross DL, Thabut D, Vilstrup H, Weissenborn K. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol 2022; 77:807-824. [PMID: 35724930 DOI: 10.1016/j.jhep.2022.06.001] [Citation(s) in RCA: 178] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/01/2022] [Indexed: 12/12/2022]
Abstract
The EASL Clinical Practice Guidelines (CPGs) on the management of hepatic encephalopathy (HE) present evidence-based answers to a set of relevant questions (where possible, formulated in PICO [patient/population, intervention, comparison and outcomes] format) on the definition, diagnosis, differential diagnosis and treatment of HE. The document does not cover the pathophysiology of HE and does not cover all available treatment options. The methods through which it was developed and any information relevant to its interpretation are also provided.
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26
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Johnston HE, Takefala TG, Kelly JT, Keating SE, Coombes JS, Macdonald GA, Hickman IJ, Mayr HL. The Effect of Diet and Exercise Interventions on Body Composition in Liver Cirrhosis: A Systematic Review. Nutrients 2022; 14:nu14163365. [PMID: 36014871 PMCID: PMC9414099 DOI: 10.3390/nu14163365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 12/01/2022] Open
Abstract
Alterations in body composition, in particular sarcopenia and sarcopenic obesity, are complications of liver cirrhosis associated with adverse outcomes. This systematic review aimed to evaluate the effect of diet and/or exercise interventions on body composition (muscle or fat) in adults with cirrhosis. Five databases were searched from inception to November 2021. Controlled trials of diet and/or exercise reporting at least one body composition measure were included. Single-arm interventions were included if guideline-recommended measures were used (computed tomography/magnetic resonance imaging, dual-energy X-ray absorptiometry, bioelectrical impedance analysis, or ultrasound). A total of 22 controlled trials and 5 single-arm interventions were included. Study quality varied (moderate to high risk of bias), mainly due to lack of blinding. Generally, sample sizes were small (n = 6–120). Only one study targeted weight loss in an overweight population. When guideline-recommended measures of body composition were used, the largest improvements occurred with combined diet and exercise interventions. These mostly employed high protein diets with aerobic and or resistance exercises for at least 8 weeks. Benefits were also observed with supplementary branched-chain amino acids. While body composition in cirrhosis may improve with diet and exercise prescription, suitably powered RCTs of combined interventions, targeting overweight/obese populations, and using guideline-recommended body composition measures are needed to clarify if sarcopenia/sarcopenic obesity is modifiable in patients with cirrhosis.
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Affiliation(s)
- Heidi E. Johnston
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Correspondence: ; Tel.: +61-7-3176-7938
| | - Tahnie G. Takefala
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
| | - Jaimon T. Kelly
- Centre for Online Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Centre for Health Services Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Shelley E. Keating
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Jeff S. Coombes
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Graeme A. Macdonald
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
| | - Ingrid J. Hickman
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Hannah L. Mayr
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Centre for Functioning and Health Research, Metro South Health, Brisbane, QLD 4102, Australia
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD 4226, Australia
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27
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Lee HA, Chang Y, Sung PS, Yoon EL, Lee HW, Yoo JJ, Lee YS, An J, Song DS, Cho YY, Kim SU, Kim YJ. Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases. Clin Mol Hepatol 2022; 28:425-472. [PMID: 35850495 PMCID: PMC9293616 DOI: 10.3350/cmh.2022.0186] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 06/29/2022] [Indexed: 11/05/2022] Open
Abstract
The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non-antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4'-dimethoxy-5,6,5',6'-dimethylenedixoybiphenyl-2,2'-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non-antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.
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Affiliation(s)
- Han Ah Lee
- Departments of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Pil Soo Sung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eileen L. Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Youn Cho
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Mohta S, Anand A, Sharma S, Qamar S, Agarwal S, Gunjan D, Singh N, Madhusudhan KS, Pandey RM, Saraya A. Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia. Hepatol Int 2022; 16:680-690. [PMID: 35469091 PMCID: PMC9037580 DOI: 10.1007/s12072-022-10334-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 03/21/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND The role of branched-chain amino acids (BCAA) in improving muscle mass in cirrhosis is presently debatable. AIMS To evaluate the role of BCAA in improving muscle mass in a double-blind randomized placebo-controlled trial in patients with cirrhosis having sarcopenia. METHODS Consecutive patients with cirrhosis with Child-Pugh score < 10 and sarcopenia were randomized to receive either 12 g/day of BCAA orally or a placebo (1:1) for 6 months in addition to a home-based exercise program (30 min/day), dietary counselling and standard medical therapy. Sarcopenia was defined according to gender-specific axial skeletal muscle index (SMI) cut-offs. The primary endpoint was a change in muscle mass based on CT scan (SMI) after 6 months of supplementation. RESULTS Sixty patients [mean age 41.6 ± 9.9 years; males (66.6%) of predominantly viral (40%) and alcohol-related (31.7%) cirrhosis] were randomized. Baseline clinical and demographic characters were similar except MELD score (10.2 ± 2.8 vs. 12.2 ± 3.5, p = 0.02) and calorie intake (1838.1 kcal ± 631.5 vs. 2217.5 kcal ± 707.3, p = 0.03), both being higher in the placebo arm. After adjusting for both baseline confounders, baseline SMI and protein intake, the change in SMI at 6 months was similar in both groups [mean adjusted difference (MAD) + 0.84, CI - 2.9; + 1.2, p = 0.42] by intention-to-treat analysis. The secondary outcomes including change in handgrip strength (p = 0.65), 6-m gait speed (p = 0.20), 6-min walk distance (p = 0.39) were similar in both arms. Four patients had minor adverse events in each arm. CONCLUSION Addition of BCAA to exercise, dietary counselling and standard medical therapy did not improve muscle mass in patients with cirrhosis having sarcopenia. (CTRI/2019/05/019269). TRIAL REGISTRATION NUMBER CTRI/2019/05/019269 (Clinical Trials Registry of India).
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Affiliation(s)
- Srikant Mohta
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Abhinav Anand
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Sumaira Qamar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Samagra Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
| | | | - Ravindra Mohan Pandey
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029 India
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Konstantis G, Pourzitaki C, Chourdakis M, Kitsikidou E, Germanidis G. Efficacy of branched chain amino acids supplementation in liver cirrhosis: A systematic review and meta-analysis. Clin Nutr 2022; 41:1171-1190. [PMID: 35500317 DOI: 10.1016/j.clnu.2022.03.027] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/23/2022] [Accepted: 03/21/2022] [Indexed: 11/30/2022]
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30
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Kroupina K, Bémeur C, Rose CF. Amino acids, ammonia, and hepatic encephalopathy. Anal Biochem 2022; 649:114696. [PMID: 35500655 DOI: 10.1016/j.ab.2022.114696] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 03/30/2022] [Accepted: 04/21/2022] [Indexed: 11/30/2022]
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Nardelli S, Gioia S, Ridola L, Carlin M, Cioffi AD, Merli M, Spagnoli A, Riggio O. Risk of falls in patients with cirrhosis evaluated by timed up and go test: Does muscle or brain matter more? Dig Liver Dis 2022; 54:371-377. [PMID: 34233863 DOI: 10.1016/j.dld.2021.06.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/20/2021] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Minimal hepatic encephalopathy (MHE) is considered a risk factor for falls in patients with liver cirrhosis. However, MHE is prevalent in patients with muscle alterations (sarcopenia and myosteatosis) probably due to the role of muscle in ammonia handling. AIM To assess the respective role of muscle alterations and MHE on the risk of falls in cirrhotic patients. METHODS Fifty cirrhotics were studied for MHE detection by using Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT). CT scan was used to quantify the skeletal muscle index (SMI) and muscle attenuation, as a measure of myosteatosis. The risk of falls was evaluated by the Timed Up&Go test (TUG). The occurrence of falls during follow up was also detected. RESULTS 32 patients (64%) had an abnormal TUG (< 14 s). In the group with TUG ≥ 14 s, MHE (72vs31%, p<0.005) and myosteatosis (94vs50%, p = 0.002) were significantly more frequent than in patients with TUG<14 s. At multivariate the variables independently associated to TUG ≥ 14 s were myosteatosis, MHE and chronic beta-blockers use. During a mean follow-up of 25±16.9 months, 12 patients fell; the percentage of falls was significantly higher in patients with TUG ≥ 14 s (50%vs9%, p = 0.001) as well as in patients with myosteatosis (33%vs6%, p = 0.03), but similar in patients with or without MHE (35%vs15%, NS). CONCLUSION In cirrhotic patients both muscle alterations and cognitive impairment, as well as chronic beta-blockers use, are associated to the risk of falls.
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Affiliation(s)
- Silvia Nardelli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome 00185, Italy.
| | - Stefania Gioia
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome 00185, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome 00185, Italy
| | - Michele Carlin
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome 00185, Italy
| | - Antonio Davide Cioffi
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome 00185, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome 00185, Italy
| | - Alessandra Spagnoli
- Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome 00185, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome 00185, Italy
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Ismaiel A, Bucsa C, Farcas A, Leucuta DC, Popa SL, Dumitrascu DL. Effects of Branched-Chain Amino Acids on Parameters Evaluating Sarcopenia in Liver Cirrhosis: Systematic Review and Meta-Analysis. Front Nutr 2022; 9:749969. [PMID: 35155535 PMCID: PMC8828569 DOI: 10.3389/fnut.2022.749969] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 01/03/2022] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION Sarcopenia is a major element of malnutrition in liver cirrhosis (LC) and is present in 30-70% of this population, being associated with a poor overall prognosis due to related complications such as hepatic encephalopathy, ascites, and portal hypertension. This systematic review and meta-analysis aimed to evaluate the effects of branched-chain amino acids (BCAA) supplementation on several parameters used to assess sarcopenia in LC. MATERIALS AND METHODS A comprehensive systematic electronic search was performed in PubMed, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov databases using predefined keywords. We included full articles that satisfied the inclusion and exclusion criteria. Quality assessment of included studies was conducted using Cochrane Collaboration's tool and NHLBI quality assessment tools for interventional and observational studies, respectively. The principal summary outcome was the mean difference (MD) in the evaluated parameters. We performed a pre- and post-intervention analysis and comparison between two intervention groups (BCAA vs. controls) of the evaluated parameters when applicable. RESULTS A total of 12 studies involving 1,225 subjects were included in our qualitative synthesis and five in our quantitative synthesis. At baseline vs. post-intervention assessment, subjects receiving BCAA supplementation were found to have a significant improvement in skeletal muscle index (SMI) (-0.347 [95% CI -0.628-0.067; p-value 0.015]) and mid-arm muscle circumference (MAMC) (-1.273 [95% CI (-2.251-0.294; p-value 0.011]). However, no improvements were reported in handgrip (-0.616 [95% CI -2.818-1.586; p-value 0.584]) and triceps subcutaneous fat (1.10 [95% CI -0.814-3.014; p-value 0.263]). CONCLUSION Following BCAA supplementation, several parameters used to evaluate sarcopenia in LC patients were found to be improved, including SMI and MAMC. Nevertheless, no improvements were seen in handgrip and triceps subcutaneous fat. Results should be interpreted with caution due to the limited methodological quality of the included studies.
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Affiliation(s)
- Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Camelia Bucsa
- Drug Information Research Center, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Andreea Farcas
- Drug Information Research Center, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Daniel-Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Stefan-Lucian Popa
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Dan L. Dumitrascu
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Yu B, Wang J. The efficacy of parenteral nutrition (PN) and enteral nutrition (EN) supports in cirrhosis: A systematic review and network meta-analysis. Medicine (Baltimore) 2022; 101:e28618. [PMID: 35060537 PMCID: PMC8772655 DOI: 10.1097/md.0000000000028618] [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: 09/29/2020] [Accepted: 12/30/2021] [Indexed: 01/05/2023] Open
Abstract
IMPORTANCE Multiple nutritional therapies are currently available for patients with liver cirrhosis, yet many interventions have not been compared head-to-head within randomized clinical trials. OBJECTIVE To evaluate the improvement of nutritional indicators and liver function indexes of liver cirrhosis treated with different nutrition intervention. DATA SOURCE We searched PubMed, Embase. com and Cochrane Library database from construction to April 3, 2020. After eliminating the duplicated or overlapping reports, 6 studies were included. We performed a Bayesian network meta-analysis by Stata 12.0 and GeMTC 0.14.3 in order to compare different nutritional interventions with consistency model. STUDY SELECTION Randomized clinical trials comparing 2 or more therapies in patients with cirrhosis were evaluated. Six randomized clinical trials met the selection criteria. DATA EXTRACTION AND SYNTHESIS Two investigators independently reviewed the full manuscripts of eligible studies and extracted information into an electronic database: patients' characteristics study design, interventions, the number of events of interest in each group. MAIN OUTCOMES AND MEASURES Body mass index, Child-Pugh score, model for end-stage liver disease score, total bilirubin, alanine transaminase, aspartate transaminase, total protein, Triceps skinfold, Midarm Muscle Circumference, Fischer ratio, overall survival. RESULTS There are 6 studies enrolling a total of 1148 patients who received different nutrition supports including parenteral nutrition (PN), enteral nutrition (EN), EN (without branched-chain amino acids), EN + intestinal probiotics, PN + EN, late evening snacks (LES), EN + LES, noLES. The direct comparisons showed that the effect of EN was better than EN (without branched-chain amino acids); EN + intestinal probiotics was better than EN and PN; PN + EN was better than them alone; EN + LES was better than LES and EN; LES was better than noLES. Although the difference of indirect comparisons between the included regimens was not statistically significant, the results showed that EN + intestinal probiotics appeared to be superior to PN + EN. While LES and EN + LES seemed to rank behind them and the difference between them was extremely small. CONCLUSION AND RELEVANCE Available evidence suggests that EN + intestinal probiotics appear to be the most effective strategy for patients with cirrhosis compared with other interventions.
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Affiliation(s)
- Bin Yu
- Department of Pharmacy, Mianyang Central Hospital, Mianyang, Sichuan, China
| | - Jiting Wang
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
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Takeda S, Kaji K, Nishimura N, Enomoto M, Fujimoto Y, Murata K, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Yoshiji H. Angiotensin Receptor Blockers Potentiate the Protective Effect of Branched-Chain Amino Acids on Skeletal Muscle Atrophy in Cirrhotic Rats. Mol Nutr Food Res 2021; 65:e2100526. [PMID: 34687151 DOI: 10.1002/mnfr.202100526] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 10/11/2021] [Indexed: 12/11/2022]
Abstract
SCOPE This study investigated the combined effect of the angiotensin II (AT-II) receptor blocker losartan and branched-chain amino acids (BCAAs) on skeletal muscle atrophy in rats with cirrhosis and steatohepatitis. METHOD AND RESULTS Fischer 344 rats are fed a choline-deficient l-amino acid-defined (CDAA) diet for 12 weeks and treated with oral losartan (30 mg kg-1 day-1 ) and/or BCAAs (Aminoleban EN, 2500 mg kg-1 day-1 ). Treatment with losartan and BCAAs attenuated hepatic inflammation and fibrosis and improved skeletal muscle atrophy and strength in CDAA-fed rats. Both agents reduced intramuscular myostatin and pro-inflammatory cytokine levels, resulting in inhibition of the ubiquitin-proteasome system (UPS) through interference with the SMAD and nuclear factor-kappa B pathways, respectively. Losartan also augmented the BCAA-mediated increase of skeletal muscle mass by promoting insulin growth factor-I production and mitochondrial biogenesis. Moreover, losartan decreased the intramuscular expression of transcription factor EB (TFEB), a transcriptional inducer of E3 ubiquitin ligase regulated by AT-II. In vitro assays illustrated that losartan promoted mitochondrial biogenesis and reduced TFEB expression in AT-II-stimulated rat myocytes, thereby potentiating the inhibitory effects of BCAAs on the UPS and caspase-3 cleavage. CONCLUSION These results indicate that this regimen could serve as a novel treatment for patients with sarcopenia and liver cirrhosis.
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Affiliation(s)
- Soichi Takeda
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Kosuke Kaji
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Norihisa Nishimura
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Masahide Enomoto
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Yuki Fujimoto
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Koji Murata
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Hiroaki Takaya
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Hideto Kawaratani
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Kei Moriya
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Tadashi Namisaki
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Takemi Akahane
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, 634-8521, Japan
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Hong MK, Liu HH, Chen GH, Zhu JQ, Zheng SY, Zhao D, Diao J, Jia H, Zhang DD, Chen SX, Gao L, Li J. Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:3259238. [PMID: 34721757 PMCID: PMC8553473 DOI: 10.1155/2021/3259238] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/22/2021] [Accepted: 09/11/2021] [Indexed: 12/03/2022]
Abstract
Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.
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Affiliation(s)
- Mu-keng Hong
- Department of Rheumatic & TCM Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medical, Southern Medical University, Guangzhou, China
| | - Hai-hua Liu
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Gui-hong Chen
- Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medical, Southern Medical University, Guangzhou, China
| | - Jun-qing Zhu
- Department of Rheumatic & TCM Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Song-yuan Zheng
- Department of Rheumatic & TCM Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Di Zhao
- Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medical, Southern Medical University, Guangzhou, China
| | - Jianxing Diao
- Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medical, Southern Medical University, Guangzhou, China
| | - Hui Jia
- Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medical, Southern Medical University, Guangzhou, China
| | - Ding-ding Zhang
- Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medical, Southern Medical University, Guangzhou, China
| | - Shi-xian Chen
- Department of Rheumatic & TCM Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lei Gao
- Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medical, Southern Medical University, Guangzhou, China
| | - Juan Li
- Department of Rheumatic & TCM Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Seifert LL, Schindler P, Schoster M, Weller JF, Wilms C, Schmidt HH, Maschmeier M, Masthoff M, Köhler M, Heinzow H, Wildgruber M. Recurrence of Hepatic Encephalopathy after TIPS: Effective Prophylaxis with Combination of Lactulose and Rifaximin. J Clin Med 2021; 10:jcm10204763. [PMID: 34682886 PMCID: PMC8537523 DOI: 10.3390/jcm10204763] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/26/2021] [Accepted: 10/13/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. METHODS N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). RESULTS Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). CONCLUSIONS Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.
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Affiliation(s)
- Leon Louis Seifert
- Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Infectiology, University Hospital Muenster, 48149 Muenster, Germany; (L.L.S.); (M.S.); (C.W.); (H.H.S.); (M.M.); (H.H.)
| | - Philipp Schindler
- Clinic for Radiology, University Hospital Muenster, 48149 Muenster, Germany; (P.S.); (M.M.); (M.K.)
| | - Martin Schoster
- Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Infectiology, University Hospital Muenster, 48149 Muenster, Germany; (L.L.S.); (M.S.); (C.W.); (H.H.S.); (M.M.); (H.H.)
| | - Jan Frederic Weller
- Department of Hematology, University Hospital Tuebingen, 72076 Tuebingen, Germany;
| | - Christian Wilms
- Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Infectiology, University Hospital Muenster, 48149 Muenster, Germany; (L.L.S.); (M.S.); (C.W.); (H.H.S.); (M.M.); (H.H.)
| | - Hartmut H. Schmidt
- Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Infectiology, University Hospital Muenster, 48149 Muenster, Germany; (L.L.S.); (M.S.); (C.W.); (H.H.S.); (M.M.); (H.H.)
- Department of Gastroenterology and Hepatology, University Hospital Duisburg-Essen, 45147 Essen, Germany
| | - Miriam Maschmeier
- Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Infectiology, University Hospital Muenster, 48149 Muenster, Germany; (L.L.S.); (M.S.); (C.W.); (H.H.S.); (M.M.); (H.H.)
- Department of Medicine I, Krankenhaus der Barmherzigen Brüder, 54292 Trier, Germany
| | - Max Masthoff
- Clinic for Radiology, University Hospital Muenster, 48149 Muenster, Germany; (P.S.); (M.M.); (M.K.)
| | - Michael Köhler
- Clinic for Radiology, University Hospital Muenster, 48149 Muenster, Germany; (P.S.); (M.M.); (M.K.)
| | - Hauke Heinzow
- Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Infectiology, University Hospital Muenster, 48149 Muenster, Germany; (L.L.S.); (M.S.); (C.W.); (H.H.S.); (M.M.); (H.H.)
- Department of Medicine I, Krankenhaus der Barmherzigen Brüder, 54292 Trier, Germany
| | - Moritz Wildgruber
- Clinic for Radiology, University Hospital Muenster, 48149 Muenster, Germany; (P.S.); (M.M.); (M.K.)
- Department of Radiology, University Hospital LMU Munich, 81377 Munich, Germany
- Correspondence:
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Vargas-Mendoza N, García-Machorro J, Angeles-Valencia M, Martínez-Archundia M, Madrigal-Santillán EO, Morales-González Á, Anguiano-Robledo L, Morales-González JA. Liver disorders in COVID-19, nutritional approaches and the use of phytochemicals. World J Gastroenterol 2021; 27:5630-5665. [PMID: 34629792 PMCID: PMC8473593 DOI: 10.3748/wjg.v27.i34.5630] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/19/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a "cytokine storm" and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.
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Affiliation(s)
- Nancy Vargas-Mendoza
- Laboratorio de Medicina de Conservacion, Instituto Politécnico Nacional, México 11340, Mexico
| | - Jazmín García-Machorro
- Laboratorio de Medicina de Conservacion, Instituto Politécnico Nacional, México 11340, Mexico
| | | | - Marlet Martínez-Archundia
- Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotécnológica, Instituto Politécnico Nacional, México 11340, Mexico
| | | | | | | | - José A Morales-González
- Laboratorio Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México 11340, Mexico
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Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol 2021; 56:593-619. [PMID: 34231046 PMCID: PMC8280040 DOI: 10.1007/s00535-021-01788-x] [Citation(s) in RCA: 189] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Department of Gastroenterology, Nara Medical University, Shijo-cho 840, Kashihara, Nara, 634-8522, Japan.
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuaki Chayama
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tetsuo Takehara
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res 2021; 51:725-749. [PMID: 34231046 DOI: 10.1111/hepr.13678] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 05/26/2021] [Indexed: 12/14/2022]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan.,Department of Gastroenterology, Nara Medical University, Nara, Japan
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
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Moran S, López-Sánchez M, Milke-García MDP, Rodríguez-Leal G. Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis. World J Gastroenterol 2021; 27:3050-3063. [PMID: 34168407 PMCID: PMC8192295 DOI: 10.3748/wjg.v27.i22.3050] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/01/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.
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Affiliation(s)
- Segundo Moran
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
| | - Marlene López-Sánchez
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
| | | | - Gustavo Rodríguez-Leal
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
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Chang C, Huang CH, Tseng HJ, Yang FC, Chien RN. Real-World Experience of the One-Year Efficacy of Rifaximin Add-On to Lactulose Is Superior to Lactulose Alone in Patients with Cirrhosis Complicated with Recurrent Hepatic Encephalopathy in Taiwan. J Pers Med 2021; 11:478. [PMID: 34071787 PMCID: PMC8226737 DOI: 10.3390/jpm11060478] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 05/21/2021] [Accepted: 05/21/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE), a neuropsychiatric complication of decompensated cirrhosis, is associated with high mortality and high risk of recurrence. Rifaximin add-on to lactulose for 3 to 6 months is recommended for the prevention of recurrent episodes of HE after the second episode. However, whether the combination for more than 6 months is superior to lactulose alone in the maintenance of HE remission is less evident. Therefore, the aim of this study is to evaluate the one-year efficacy of rifaximin add-on to lactulose for the maintenance of HE remission in Taiwan. METHODS We conducted a real-world single-center retrospective cohort study to compare the long-term efficacy of rifaximin add-on to lactulose (group R + L) versus lactulose alone (group L, control group). Furthermore, the treatment efficacy before and after rifaximin add-on to lactulose was also analyzed. The primary endpoint of our study was time to first HE recurrence (Conn score ≥ 2). All patients were followed up every three months until death, and censored at one year if still alive. RESULTS AND CONCLUSIONS 12 patients were enrolled in group R + L. Another 31 patients were stratified into group L. Sex, comorbidity, ammonia level, and ascites grade were matched while age, HE grade, and model for end-stage liver disease (MELD) score were adjusted in the multivariable logistic regression model. Compared with group L, significant improvement in the maintenance of HE remission and decreased episodes and days of HE-related hospitalizations were demonstrated in group R + L. The serum ammonia levels were significantly lower at the 3rd and 6th month in group 1. Concerning changes before and after rifaximin add-on in group R + L, mini-mental status examination (MMSE), episodes of hospitalization, and variceal bleeding also improved at 6 and 12 months. Days of hospitalization, serum ammonia levels also improved at 6th month. Except for concern over price, no patients discontinued rifaximin due to adverse events or complications. The above results provide evidence for the one-year use of rifaximin add-on to lactulose in reducing HE recurrence and HE-related hospitalization for patients with decompensated cirrhosis.
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Affiliation(s)
- Ching Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
| | - Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
- College of Medicine, Chang-Gung University, Taoyuan 33305, Taiwan
| | - Hsiao-Jung Tseng
- Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan;
| | - Fang-Chen Yang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
- College of Medicine, Chang-Gung University, Taoyuan 33305, Taiwan
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Cañamares-Orbis P, Bernal-Monterde V, Sierra-Gabarda O, Casas-Deza D, Garcia-Rayado G, Cortes L, Lué A. Impact of Liver and Pancreas Diseases on Nutritional Status. Nutrients 2021; 13:1650. [PMID: 34068295 PMCID: PMC8153270 DOI: 10.3390/nu13051650] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/02/2021] [Accepted: 05/11/2021] [Indexed: 12/12/2022] Open
Abstract
Liver and pancreatic diseases have significant consequences on nutritional status, with direct effects on clinical outcomes, survival, and quality of life. Maintaining and preserving an adequate nutritional status is crucial and should be one of the goals of patients with liver or pancreatic disease. Thus, the nutritional status of such patients should be systematically assessed at follow-up. Recently, great progress has been made in this direction, and the relevant pathophysiological mechanisms have been better established. While the spectrum of these diseases is wide, and the mechanisms of the onset of malnutrition are numerous and interrelated, clinical and nutritional manifestations are common. The main consequences include an impaired dietary intake, altered macro and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, and osteopathy. In this review, we summarize the factors contributing to malnutrition, and the effects on nutritional status and clinical outcomes of liver and pancreatic diseases. We explain the current knowledge on how to assess malnutrition and the efficacy of nutritional interventions in these settings.
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Affiliation(s)
- Pablo Cañamares-Orbis
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge, 22004 Huesca, Spain;
| | - Vanesa Bernal-Monterde
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain; (V.B.-M.); (O.S.-G.); (D.C.-D.)
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
| | - Olivia Sierra-Gabarda
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain; (V.B.-M.); (O.S.-G.); (D.C.-D.)
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
| | - Diego Casas-Deza
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain; (V.B.-M.); (O.S.-G.); (D.C.-D.)
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
| | - Guillermo Garcia-Rayado
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
- Service of Digestive Diseases, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
| | - Luis Cortes
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
- Service of Digestive Diseases, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
| | - Alberto Lué
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge, 22004 Huesca, Spain;
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Eriksen CS, Kimer N, Suetta C, Møller S. Arm lean mass determined by dual-energy X-ray absorptiometry is superior to characterize skeletal muscle and predict sarcopenia-related mortality in cirrhosis. Am J Physiol Gastrointest Liver Physiol 2021; 320:G729-G740. [PMID: 33729006 DOI: 10.1152/ajpgi.00478.2020] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Sarcopenia worsens survival in patients with advanced liver disease including cirrhosis. In this study, we aimed to characterize skeletal muscle status by dual-energy X-ray absorptiometry (DXA) in patients with cirrhosis and examine the association between different skeletal muscle compartments and mortality. We included 231 men and 84 women (Child A, B, and C) with cirrhosis and 315 healthy matched controls (231 men and 84 women). Body composition was assessed with DXA. Appendicular skeletal muscle index (ASMI), arms index (AI), and legs index (LI) were calculated by normalizing lean mass to height squared. Low ASMI was defined as ASMI < 7.0 kg/m2 in men and <5.5 kg/m2 in women. Biochemical and hemodynamic data were recorded for cirrhotic patients and mortality data retrieved from registers. Low ASMI was more prevalent in both men (49%) and women (43%) with cirrhosis compared with healthy men (8%) and women (5%) (P < 0.001). ASMI and LI were lowest in Child B, whereas AI decreased gradually with advancing Child class. ASMI was inversely associated with mortality in men [HR = 0.74 (0.59-0.93), P < 0.01], and this was mainly driven by AI [HR = 0.37 (0.18-0.71), P < 0.01]. AI showed closer association than ASMI or LI to both the severity of liver disease and to mortality, which may be due to increasing prevalence of leg edema with disease progression in this population. Determination of arm lean mass may add information on survival in patients with cirrhosis.NEW & NOTEWORTHY Sarcopenia increases mortality in patients with end-stage liver disease. We show that arm lean mass determined by dual-energy X-ray absorptiometry is a better marker than the traditional appendicular skeletal muscle mass when predicting sarcopenia-related mortality in patients with cirrhosis of different severity. The findings add to the dispute about the optimal method for repeated assessments of skeletal muscle status in patients with cirrhosis and may have implications for clinical decision making.
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Affiliation(s)
- Christian Skou Eriksen
- Center of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre University Hospital, Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Hvidovre University Hospital, Copenhagen, Denmark
| | - Charlotte Suetta
- Geriatric Research Unit, Department of Geriatrics and Palliative Medicine, Bispebjerg and Frederiksberg University Hospitals, Copenhagen, Denmark.,Geriatric Research Unit, Department of Medicine, Herlev and Gentofte University Hospitals, Copenhagen, Denmark.,Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Center of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre University Hospital, Copenhagen, Denmark
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Kim Y. Emerging Treatment Options for Sarcopenia in Chronic Liver Disease. Life (Basel) 2021; 11:life11030250. [PMID: 33803020 PMCID: PMC8002763 DOI: 10.3390/life11030250] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/13/2021] [Accepted: 03/15/2021] [Indexed: 12/17/2022] Open
Abstract
Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition.
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Affiliation(s)
- Yun Kim
- Hanyang Medicine-Engineering-Bio Collaborative & Comprehensive Center for Drug Development, Hanyang University, Seoul 04763, Korea
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Recommendations and guidance on nutritional supplementation in the liver transplant setting. Transplantation 2021; 105:2528-2537. [PMID: 33724244 DOI: 10.1097/tp.0000000000003736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Malnutrition is a frequent complication in patients with cirrhosis and liver transplant (LT) candidates. It is highly related to sarcopenia, and their implications in morbidity and mortality go beyond the waiting list period throughout the post-LT. However, there are no specific interventions defined by guidelines, regarding the kind or the timing of the nutritional intervention to improve LT outcomes. Results from studies developed in the LT setting and evaluating their impact on the LT candidates or recipients are discussed in this review, and new research lines are presented.
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Traub J, Reiss L, Aliwa B, Stadlbauer V. Malnutrition in Patients with Liver Cirrhosis. Nutrients 2021; 13:540. [PMID: 33562292 PMCID: PMC7915767 DOI: 10.3390/nu13020540] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 02/04/2021] [Accepted: 02/04/2021] [Indexed: 12/13/2022] Open
Abstract
Liver cirrhosis is an increasing public health threat worldwide. Malnutrition is a serious complication of cirrhosis and is associated with worse outcomes. With this review, we aim to describe the prevalence of malnutrition, pathophysiological mechanisms, diagnostic tools and therapeutic targets to treat malnutrition. Malnutrition is frequently underdiagnosed and occurs-depending on the screening methods used and patient populations studied-in 5-92% of patients. Decreased energy and protein intake, inflammation, malabsorption, altered nutrient metabolism, hypermetabolism, hormonal disturbances and gut microbiome dysbiosis can contribute to malnutrition. The stepwise diagnostic approach includes a rapid prescreen, the use of a specific screening tool, such as the Royal Free Hospital Nutritional Prioritizing Tool and a nutritional assessment by dieticians. General dietary measures-especially the timing of meals-oral nutritional supplements, micronutrient supplementation and the role of amino acids are discussed. In summary malnutrition in cirrhosis is common and needs more attention by health care professionals involved in the care of patients with cirrhosis. Screening and assessment for malnutrition should be carried out regularly in cirrhotic patients, ideally by a multidisciplinary team. Further research is needed to better clarify pathogenic mechanisms such as the role of the gut-liver-axis and to develop targeted therapeutic strategies.
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Affiliation(s)
- Julia Traub
- Department of Clinical Medical Nutrition, University Hospital Graz, 8036 Graz, Austria; (J.T.); (L.R.)
| | - Lisa Reiss
- Department of Clinical Medical Nutrition, University Hospital Graz, 8036 Graz, Austria; (J.T.); (L.R.)
| | - Benard Aliwa
- Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria;
| | - Vanessa Stadlbauer
- Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria;
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Hey P, Gow P, Testro AG, Apostolov R, Chapman B, Sinclair M. Nutraceuticals for the treatment of sarcopenia in chronic liver disease. Clin Nutr ESPEN 2021; 41:13-22. [PMID: 33487256 DOI: 10.1016/j.clnesp.2020.11.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 11/30/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Sarcopenia, defined as loss of muscle mass, strength and function, is associated with adverse clinical outcomes in patients with cirrhosis. Despite improved understanding of the multifaceted pathogenesis, there are few established therapies to treat or prevent muscle loss in this population. This narrative review examines the available literature investigating the role of nutraceuticals for the prevention or treatment of muscle wasting in chronic liver disease. METHODS A comprehensive search or Medline and PubMED databases was conducted. Reference lists were screened to identify additional articles. RESULTS A number of nutritional supplements and vitamins target the specific metabolic derangements that contribute to sarcopenia in cirrhosis including altered amino acid metabolism, hyperammonaemia and inflammation. Branched chain amino acid (BCAA) supplementation has proposed anabolic effects through dual pathways of enhanced ammonia clearance and stimulation of muscle protein synthesis. l-carnitine also has multimodal effects on muscle and shows promise as a therapy for muscle loss through anti-inflammatory, antioxidant and ammonia lowering properties. Other nutraceuticals including l-ornithine l-aspartate, omega-3 polyunsaturated fatty acids and zinc and vitamin D supplementation, may similarly have positive effects on muscle homeostasis, however further evidence to support their use in cirrhotic populations is required. CONCLUSION Nutraceuticals offer a promising and likely safe adjunct to standard care for sarcopenia in cirrhosis. While there is most evidence to support the use of BCAA and l-carnitine supplementation, further well-designed clinical trials are needed to elucidate their efficacy as a therapy for muscle loss in this population.
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Affiliation(s)
- Penelope Hey
- Liver Transplant Unit, Austin Health, 145 Studley Rd, Heidelberg, Victoria, Australia; The University of Melbourne, Parkville, Victoria, Australia.
| | - Paul Gow
- Liver Transplant Unit, Austin Health, 145 Studley Rd, Heidelberg, Victoria, Australia; The University of Melbourne, Parkville, Victoria, Australia.
| | - Adam G Testro
- Liver Transplant Unit, Austin Health, 145 Studley Rd, Heidelberg, Victoria, Australia; The University of Melbourne, Parkville, Victoria, Australia.
| | - Ross Apostolov
- Liver Transplant Unit, Austin Health, 145 Studley Rd, Heidelberg, Victoria, Australia; The University of Melbourne, Parkville, Victoria, Australia.
| | - Brooke Chapman
- The University of Melbourne, Parkville, Victoria, Australia; Department of Nutrition and Dietetics, Austin Health, 145 Studley Rd, Heidelberg, Victoria, Australia.
| | - Marie Sinclair
- Liver Transplant Unit, Austin Health, 145 Studley Rd, Heidelberg, Victoria, Australia; The University of Melbourne, Parkville, Victoria, Australia.
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Dos Santos ALS, Anastácio LR. The impact of L-branched-chain amino acids and L-leucine on malnutrition, sarcopenia, and other outcomes in patients with chronic liver disease. Expert Rev Gastroenterol Hepatol 2021; 15:181-194. [PMID: 32993404 DOI: 10.1080/17474124.2021.1829470] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Metabolic and hormonal disorders resulting from chronic liver diseases culminate in increased proteolysis and decreased protein synthesis, which contributes to the development and progression of malnutrition and, consequently, sarcopenia. Nutritional management of sarcopenia in liver cirrhosis is a continuously evolving field and data on essential amino acid supplementation in chronic liver diseases is scarce. AREAS COVERED This review encompasses the current literature on oral amino acids supplementation in patients with chronic liver disease or patients with liver cirrhosis to try to elucidate the possible effects of L-branched-chain amino acids and isolated L-leucine as a therapeutic approach to malnutrition and sarcopenia. EXPERT COMMENTARY To ensure an optimal nutritional status and to reduce sarcopenia, it is necessary to assess nutritional status in all patients with liver cirrhosis and to apply nutritional interventions accordingly. The supply of calories, proteins, and essential amino acids is necessary for the maintenance of muscle mass and function. Although supplementation of L-branched-chain amino acids plays an important role in liver disease, L-leucine has been described as the main amino acid involved in protein turnover, reducing proteolysis, and stimulating protein synthesis.
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Affiliation(s)
- Ana Luiza Soares Dos Santos
- Food Science Post-Graduation Program, Pharmacy School, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil
| | - Lucilene Rezende Anastácio
- Food Science Post-Graduation Program, Pharmacy School, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil
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Abstract
Greater than half of patients with decompensated liver disease suffer from frailty and/or sarcopenia, which can lead to increased pre- and post-liver transplant morbidity and mortality. Although frailty and sarcopenia can impact patients with end-stage liver disease in similar ways, they are unique clinical entities with differing underlying etiologies. Early assessment and identification of frailty and sarcopenia in patients is critical to guide clinical decision-making regarding transplantation and to implement nutritional and exercise-based treatment regiments. Nonetheless, accurate diagnosis and, in particular, predicting patients that will develop frailty and/or sarcopenia remains challenging, and the success of clinical interventions is limited.
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Kabbani AR, Tergast TL, Manns MP, Maasoumy B. [Treatment strategies for acute-on-chronic liver failure]. Med Klin Intensivmed Notfmed 2021; 116:3-16. [PMID: 31463674 PMCID: PMC7095250 DOI: 10.1007/s00063-019-00613-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 07/17/2019] [Accepted: 07/31/2019] [Indexed: 12/15/2022]
Abstract
Acute-on-chronic liver failure (ACLF) is a newly defined syndrome in patients with liver cirrhosis characterized by acute hepatic decompensation (jaundice, ascites, hepatic encephalopathy, bacterial infection and gastrointestinal bleeding), single or multiple organ failure and a high mortality (>15% within 28 days). The affected organ systems include not only the liver but also the circulation, lungs, kidneys, brain and/or coagulation. Pathophysiologically decisive is an uncontrolled inflammation that is induced by specific triggers and on the basis of previously (possibly not diagnosed) compensated as well as already decompensated liver cirrhosis leads to a severe systemic clinical syndrome, ACLF. The course during the first 72 h is decisive for the prognosis. In addition to treatment of the respective organ or system failure, the underlying triggers should be quickly identified and if necessary specifically treated. Often, however, these cannot (no longer) be determined with any certainty, in particular recent alcohol consumption as well as bacterial and viral infections play an important role. A specific treatment for the ACLF is (currently) not established. Some experimental approaches are currently being tested, including administration of granulocyte colony-stimulating factor (GCSF). Additionally, suitable patients should be presented to a liver transplantation center in a timely manner.
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Affiliation(s)
| | | | | | - B Maasoumy
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625, Hannover, Deutschland.
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