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Tapper EB, Chen X, Parikh ND. Testosterone Replacement Reduces Morbidity and Mortality for Most Patients With Cirrhosis. Clin Gastroenterol Hepatol 2025:S1542-3565(25)00200-9. [PMID: 40097035 DOI: 10.1016/j.cgh.2025.02.004] [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: 10/20/2024] [Revised: 01/15/2025] [Accepted: 02/05/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND & AIMS Many men with cirrhosis have low testosterone levels. This is associated with sarcopenia, anemia, and poor quality of life. Data are lacking, however, regarding the clinical impact of testosterone replacement. METHODS We conducted an emulated clinical trial evaluating the impact of testosterone replacement among men who were diagnosed with hypogonadism at the same time as their diagnosis of cirrhosis (new user design). We used nationally representative Medicare data (2008-2020) to examine the risk of death, decompensation events, and fractures in patients who did or did not receive testosterone. We balanced treated and untreated with inverse probability of treatment weighting and evaluated outcomes using an intention-to-treat design. RESULTS A total of 282 patients (7.4%) with testicular hypofunction and cirrhosis received testosterone replacement after diagnosis. Patients started on testosterone spent 28.6% of patient-days on therapy, and patients not started would spend 0.5% of patient-days on therapy (P < .0001). Testosterone use was associated with lower mortality (subdistribution hazard ratio [sHR], 0.92; 95% confidence interval [CI], 0.85-0.99). Testosterone also led to a lower risk of new decompensation events (sHR, 0.92; 95% CI, 0.86-0.99) and especially for ascites requiring paracentesis (sHR, 0.82; 95% CI, 0.76-0.89) and variceal hemorrhage (sHR, 0.67; 95% CI, 0.54-0.85) with less effect on hepatic encephalopathy requiring hospitalization (sHR, 0.92; 95% CI, 0.84-1.01) and fractures (sHR, 0.99; 95% CI, 0.91-1.08) and without increased risk of hepatocellular carcinoma (sHR, 1.09; 95% CI, 0.91-1.3). There was substantial heterogeneity of treatment effect across baseline subgroups. CONCLUSION In our target trial emulation of a nationally representative cohort of older patients with cirrhosis and hypogonadism, testosterone use improved clinical outcomes.
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
| | - Xi Chen
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
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Yang J, Guo G, Yang F, Li C, Wang H, Yang W, Yang Z, Liu Q, Li Q, Sun C. A sex-oriented analysis concerning skeletal muscle quantity and quality and associations to quality of life in hospitalized patients with cirrhosis. Health Qual Life Outcomes 2024; 22:78. [PMID: 39267044 PMCID: PMC11395965 DOI: 10.1186/s12955-024-02295-2] [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: 02/09/2024] [Accepted: 08/29/2024] [Indexed: 09/14/2024] Open
Abstract
BACKGROUND There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities. METHODS Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity. RESULTS The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm2/m2, P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index. CONCLUSIONS Muscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL.
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Affiliation(s)
- Jie Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China
| | - Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
| | - Fang Yang
- Department of Digestive System, Baodi Clinical College of Tianjin Medical University, No.8, Guangchuan Road, Baodi District, Tianjin, 301800, China
| | - Chaoqun Li
- Department of Geriatrics, Tianjin Hexi Hospital, Tianjin, 300202, China
| | - Han Wang
- Department of Health Management, Tianjin Hospital, No. 406 Jiefang South Road, Hexi District, Tianjin, 300211, China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
| | - Ziyi Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
| | - Qing Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China
| | - Qian Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China.
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China.
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Dajti E, Rodrigues SG, Perazza F, Colecchia L, Marasco G, Renzulli M, Barbara G, Azzaroli F, Berzigotti A, Colecchia A, Ravaioli F. Sarcopenia evaluated by EASL/AASLD computed tomography-based criteria predicts mortality in patients with cirrhosis: A systematic review and meta-analysis. JHEP Rep 2024; 6:101113. [PMID: 39035068 PMCID: PMC11259801 DOI: 10.1016/j.jhepr.2024.101113] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/03/2024] [Accepted: 04/24/2024] [Indexed: 07/23/2024] Open
Abstract
Background & Aims Sarcopenia is associated with increased morbidity and mortality in patients with cirrhosis, but its definition in current literature is very heterogeneous. We performed a systematic review and meta-analysis to assess the association between mortality and sarcopenia evaluated by computed tomography (CT) in patients with cirrhosis, both overall and stratified for the criteria used to define sarcopenia. Methods Medline, Embase, Scopus, and Cochrane Library were searched up to January 2023. We included studies assessing sarcopenia presence with CT scans and providing data on the risk of mortality. Adjusted hazard ratios (HRs) and 95% CIs were pooled using a random-effects model. Results Thirty-nine studies comprising 12,827 patients were included in the meta-analysis. The summary prevalence of sarcopenia was 44% (95% CI 38-50%). The presence of sarcopenia (any definition) was an independent predictor of mortality with an adjusted HR of 2.07 (95% CI 1.81-2.36), and the result was consistent in all subgroup analyses. The prognostic role of the EASL/AASLD criteria was confirmed for the first time with an HR of 1.86 (95% CI 1.53-2.26) (n = 14 studies). The cut-offs used to define sarcopenia based on psoas muscle parameters varied among studies, thus, a subgroup analysis was not feasible. There was no substantial heterogeneity for the main estimates and no significant risk of publication bias. Conclusions Sarcopenia on CT is associated with a 2-fold higher risk of mortality in patients with cirrhosis. The cut-offs proposed by EASL/AASLD are prognostically relevant and should be the recommended criteria used to define sarcopenia in clinical practice. Impact and implications Sarcopenia assessed by the reference standard (computed tomography scan) is an independent predictor of mortality in patients with cirrhosis, with a 2-fold increase in the risk of death in all sensitivity analyses. This finding is particularly valid in patients from Europe and North America, and in transplant candidates. Stratifying for the parameters and cut-offs used, we confirmed for the first time the prognostic impact of the definition proposed by EASL/AASLD, supporting their use in clinical practice. Psoas muscle assessment is promising, but data are still limited and too heterogeneous to recommend its routine use at present.
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Affiliation(s)
- Elton Dajti
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Susana G. Rodrigues
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
| | - Federica Perazza
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Luigi Colecchia
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Barbara
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
| | - Antonio Colecchia
- Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Kosuta I, Premkumar M, Reddy KR. Review article: Evaluation and care of the critically ill patient with cirrhosis. Aliment Pharmacol Ther 2024; 59:1489-1509. [PMID: 38693712 DOI: 10.1111/apt.18016] [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] [Received: 01/15/2024] [Revised: 03/21/2024] [Accepted: 04/12/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life-saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver-centric intensive care protocols, to mitigate the high mortality in such patients. AIM Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end-of life care. METHODS We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta-analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care. RESULTS Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource. CONCLUSIONS Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end-of-life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi-disciplinary approach towards critical care management is likely to yield better outcomes.
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Affiliation(s)
- Iva Kosuta
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Chrysavgis L, Adamantou M, Angelousi A, Cholongitas E. The association of testosterone with sarcopenia and frailty in chronic liver disease. Eur J Clin Invest 2024; 54:e14108. [PMID: 37837304 DOI: 10.1111/eci.14108] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/11/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023]
Abstract
BACKGROUND Testosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin-bound, or sex hormone binding globulin (SHBG)-bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic-pituitary-gonadal axis, leading to diminished levels of free testosterone and hypogonadism. METHODS We retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre-cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non-cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients. RESULTS Low testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long-term safety of testosterone use remains an open question. CONCLUSION Low serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver-related outcomes and complications.
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Affiliation(s)
- Lampros Chrysavgis
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Magdalini Adamantou
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Anna Angelousi
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
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Maslennikov R, Alieva A, Poluektova E, Zharikov Y, Suslov A, Letyagina Y, Vasileva E, Levshina A, Kozlov E, Ivashkin V. Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota. World J Gastroenterol 2023; 29:4236-4251. [PMID: 37545638 PMCID: PMC10401661 DOI: 10.3748/wjg.v29.i27.4236] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/25/2023] [Accepted: 06/21/2023] [Indexed: 07/13/2023] Open
Abstract
Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Yana Letyagina
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Ekaterina Vasileva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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7
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Apostolov R, Wong D, Low E, Vaz K, Spurio J, Worland T, Liu D, Chan RK, Gow P, Grossmann M, Sinclair M. Testosterone is lower in men with non-alcoholic fatty liver disease and alcohol-related cirrhosis and is associated with adverse clinical outcomes. Scand J Gastroenterol 2023; 58:1328-1334. [PMID: 37282344 DOI: 10.1080/00365521.2023.2220857] [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: 02/06/2023] [Revised: 05/16/2023] [Accepted: 05/29/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND/AIMS Low serum testosterone is common in cirrhotic men, but the impact of disease aetiology remains uncertain. This study compares serum total testosterone (TT) levels by disease aetiology and assesses its prognostic value. METHODS Single-centre retrospective study of cirrhotic men who had TT levels measured between 2002 and 2020. A cut-off of 12 nmol/L was used to define low TT and 230 pmol/L for calculated free testosterone (cFT). Linear and logistic regression used to adjust for variables known to affect testosterone levels and assess for an association between levels and outcomes. RESULTS Of 766 cirrhotic men, 33.3% had alcohol-related liver disease (ALD) and 11.9% had non-alcoholic fatty liver disease (NAFLD). The median age was 56 years (interquartile range (IQR) 50-61), and the model for end-stage liver disease (MELD) score 14 (IQR 9-20). TT levels were low in 53.3% of patients, (median 11.0 nmol/L; IQR 3.7-19.8) and cFT low in 79.6% (median 122 pmol/L; IQR 48.6-212). Median TT was lower in men with ALD (7.6 nmol/L; IQR 2.1-16.2) and NAFLD (9.8 nmol/L; IQR 2.75-15.6) compared to other aetiologies (11.0 nmol/L; IQR 3.73-19.8) (p < 0.001 for all), which remained true after adjustment for age and MELD score. TT was inversely associated with 12-month mortality or transplant (381 events, p = 0.02) and liver decompensation (345 events, p = 0.004). CONCLUSIONS Low serum testosterone is common in cirrhotic men and is associated with adverse clinical outcomes. TT levels are significantly lower in ALD and NAFLD compared to other disease aetiologies. Further large-scale studies are required to assess the potential benefits of testosterone therapy.
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Affiliation(s)
- Ross Apostolov
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Darren Wong
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Elizabeth Low
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Karl Vaz
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Jessica Spurio
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Thomas Worland
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Dorothy Liu
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | | | - Paul Gow
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Mathis Grossmann
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
- Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia
| | - Marie Sinclair
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
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8
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Liu J, Luo H, Huang L, Wang J. Prevalence of sarcopenia among patients with hepatocellular carcinoma: A systematic review and meta‑analysis. Oncol Lett 2023; 26:283. [PMID: 37274463 PMCID: PMC10236145 DOI: 10.3892/ol.2023.13869] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 04/05/2023] [Indexed: 06/06/2023] Open
Abstract
Sarcopenia is a common condition in patients with hepatocellular carcinoma (HCC). Sarcopenia affects the prognosis of patients with HCC and reduces their quality of life. However, to date, there has been no systematic review and meta-analysis to assess the prevalence of sarcopenia in patients with HCC, to the best of our knowledge. PubMed, Embase, Web of Science and the Cochrane Library were comprehensively screened for relevant literature published from March 2001 to June 2022. A random effect analysis was conducted to pool the incidence rates for each study. Subgroup and meta-regression analyses were used to investigate the latent sources of heterogeneities. The Newcastle-Ottawa Scale was used to estimate the quality of the included studies. The I2 statistic was used to evaluate heterogeneity between studies. In total, 48 studies encompassing 8,959 patients were included in the meta-analysis. The results of the present meta-analysis showed that nearly half (42%) of the patients with HCC had sarcopenia (95% CI, 0.36-0.48). The morbidity of sarcopenia in studies with a high proportion of males (45%) was higher compared with the morbidity observed in studies with a lower proportion of males (37%). In addition, the incidence rate in younger patients (46%) was found to be higher compared with the incidence rate in older patients (39%). In conclusion, the findings in the present systematic review revealed that a large number of patients with HCC suffer from sarcopenia, indicating the necessity of developing screening and intervention measures to improve the outcome in these patients.
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Affiliation(s)
- Jiye Liu
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
- Department of Rehabilitation Medicine, Huludao Central Hospital, Huludao, Liaoning 125000, P.R. China
| | - Hanyong Luo
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
| | - Letian Huang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
| | - Jiahe Wang
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
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DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis. Int J Mol Sci 2023; 24:ijms24065301. [PMID: 36982376 PMCID: PMC10049419 DOI: 10.3390/ijms24065301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/02/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
Dehydroepiandrosterone (DHEA) is an abundant steroid and precursor of sex hormones. During aging, the reduction in DHEA synthesis causes a significant depletion of estrogens and androgens in different organs, such as the ovaries, brain, and liver. Primary Biliary Cholangitis (PBC) is a cholestatic liver disease that begins with immune-mediated bile duct damage, and is followed by liver fibrosis, and finally, cirrhosis. PBC primarily affects postmenopausal women, with an average age of diagnosis of 65 years, but younger women are also affected. Here, we analyzed the levels of DHEA, estradiol (E2), and estriol (E3) in the PBC sera of females at an age of diagnosis under 40 (n = 37) and above 65 (n = 29). Our results indicate that in PBC patients at an age of diagnosis under 40, E2 was significantly lower compared to that in healthy women. In contrast, the levels of DHEA and E3 were in a normal range. Furthermore, ELISA assays revealed that in PBC patients at an age of diagnosis above 65, the levels of DHEA, E2, and E3 significantly declined in comparison to those in younger patients. In addition, flow cytometry analysis showed that the level of IL-8 significantly decreased while the level of TNF-α increased in older PBC patients compared to younger ones. Moreover, we showed for the first time that the sulfonated form of DHEA, DHEA-S, reduces the levels of both pro-inflammatory interleukins, IL-8 and TNF-α, in PBC-like cholangiocytes (H69-miR506), while it diminishes the level of the pro-fibrotic interleukin, IL-13, in hepatocytes (Hep-G2). Finally, we demonstrated that the expression of the pro-fibrotic agent TGF-β significantly increased in both the early (F0–F3) and cirrhotic (F4) stages of PBC, and this elevation was accompanied by higher α-SMA expression.
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Lowe R, Hey P, Sinclair M. The sex-specific prognostic utility of sarcopenia in cirrhosis. J Cachexia Sarcopenia Muscle 2022; 13:2608-2615. [PMID: 35945660 PMCID: PMC9745556 DOI: 10.1002/jcsm.13059] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 06/07/2022] [Accepted: 07/04/2022] [Indexed: 12/15/2022] Open
Abstract
Sarcopenia is an increasingly recognized complication of cirrhosis that is associated with morbidity and mortality. Differences in the prevalence and prognosis of sarcopenia between men and women have been reported in other patient groups, but there is insufficient understanding of how sex impacts the prognostic value of sarcopenia in cirrhosis. A search of MEDLINE and Embase was conducted from earliest entries to April 2021. Studies were included if they examined sex-stratified mortality impact of reduced muscle function or mass in outpatient populations with cirrhosis. We identified 700 studies of which 6 were deemed relevant for inclusion in this narrative review. Studies of interest were heterogeneous, precluding pooling of data and making interpretation of the literature challenging. Muscle mass was assessed in five studies (n = 2566, 1730 men, 836 women) and was reduced in 36-50% of men and 24-43% of women. All five studies found that reduced muscle mass determined by computed tomography, dual-energy X-ray absorptiometry, and bioelectrical impedance analysis was associated with increased mortality in men. Of these, two studies identified a corresponding relationship in women; reduced muscle mass defined by computed tomography was associated with increased mortality [hazard ratio (HR) 2.82, P = 0.001], while increasing muscle mass by bioelectrical impedance analysis likewise conferred a survival benefit (HR 0.45, P = 0.0016). Only one study assessed the relationship of muscle function with sex-stratified mortality (n = 1405, 827 men, 578 women), concluding that reduced muscle function predicted mortality in both men and women (HR 1.65, P < 0.001 and HR 1.54, P < 0.001, respectively). Reduced muscle mass in cirrhosis is consistently associated with mortality in men, but lack of sex-stratification of mortality analyses limits the ability to make strong conclusions about the impact of sarcopenia specifically in women, with even fewer data available for analysing muscle function. Improved understanding of the sex-specific impacts of sarcopenia may help address patient deterioration and mortality while awaiting liver transplantation and allow for early intervention to mitigate mortality risk. Large, multicentre studies with adequate female participation and sex-stratified mortality analyses are warranted.
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Affiliation(s)
- Ryan Lowe
- University of MelbourneMelbourneVictoriaAustralia
- Northern HealthEppingVictoriaAustralia
| | - Penelope Hey
- University of MelbourneMelbourneVictoriaAustralia
- Liver Transplant UnitAustin HealthHeidelbergVictoriaAustralia
| | - Marie Sinclair
- University of MelbourneMelbourneVictoriaAustralia
- Liver Transplant UnitAustin HealthHeidelbergVictoriaAustralia
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11
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Murata K, Kaji K, Nishimura N, Enomoto M, Fujimoto Y, Takeda S, Tsuji Y, Fujinaga Y, Takaya H, Kawaratani H, Namisaki T, Akahane T, Yoshiji H. Rifaximin enhances the L‑carnitine‑mediated preventive effects on skeletal muscle atrophy in cirrhotic rats by modulating the gut‑liver‑muscle axis. Int J Mol Med 2022; 50:101. [PMID: 35686541 PMCID: PMC9242656 DOI: 10.3892/ijmm.2022.5157] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 05/24/2022] [Indexed: 11/05/2022] Open
Abstract
The gut‑liver‑muscle axis is associated with the development of sarcopenia in liver cirrhosis. The present study aimed to illustrate the combined effects of rifaximin and L‑carnitine on skeletal muscle atrophy in cirrhotic rats with steatohepatitis. For this purpose, a total of 344 Fischer rats were fed a choline‑deficient L‑amino acid‑defined (CDAA) diet with the daily oral administration of rifaximin (100 mg/kg) and/or L‑carnitine (200 mg/kg), and measurements of psoas muscle mass index and forelimb grip strength were performed. After feeding for 12 weeks, blood samples, and liver, ileum and gastrocnemius muscle tissues were harvested. The effects of L‑carnitine on rat myocytes were assessed using in vitro assays. Treatment with rifaximin attenuated hyperammonemia and liver fibrosis in the CDAA‑fed rats. Moreover, it improved intestinal permeability with the restoration of tight junction proteins and suppressed the lipopolysaccharide (LPS)‑mediated hepatic macrophage activation and pro‑inflammatory response. In addition, rifaximin prevented skeletal muscle mass atrophy and weakness by decreasing intramuscular myostatin and pro‑inflammatory cytokine levels. Moreover, rifaximin synergistically enhanced the L‑carnitine‑mediated improvement of skeletal muscle wasting by promoting the production of insulin‑like growth factor‑1 and mitochondrial biogenesis, resulting in the inhibition of the ubiquitin‑proteasome system (UPS). The in vitro assays revealed that L‑carnitine directly attenuated the impairment of mitochondrial biogenesis, thereby inhibiting the UPS in rat myocytes that were stimulated with LPS or tumor necrosis factor‑α. On the whole, the present study demonstrates that the combination of rifaximin with L‑carnitine may provide a clinical benefit for liver cirrhosis‑related sarcopenia.
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Affiliation(s)
- Koji Murata
- 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
| | - Soichi Takeda
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan
| | - Yuki Tsuji
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan
| | - Yukihisa Fujinaga
- 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
| | - 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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12
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Hey P, Hoermann R, Gow P, Hanrahan TP, Testro AG, Apostolov R, Sinclair M. Reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients. World J Transplant 2022; 12:120-130. [PMID: 35979539 PMCID: PMC9258268 DOI: 10.5500/wjt.v12.i6.120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 04/24/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation days. Upper limb lean mass (LM) measured by dual-energy X-ray absorptiometry (DEXA) was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for transplantation. AIM To investigate the use of DEXA LM in predicting gender-stratified early post-transplant outcomes. METHODS Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were included. Endpoints included post-transplant mortality and graft failure, bacterial infections, acute cellular rejection (ACR) and intensive care and total hospital length of stay. RESULTS Four hundred and sixty-nine patients met inclusion criteria of which 338 were male (72%). Median age was 55.0 years (interquartile range 47.4, 59.7) and model for end-stage liver disease (MELD) score 16. Median time from assessment to transplantation was 7 mo (3.5, 12). Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant (hazard ratio = 0.42; 95% confidence interval: 0.20-0.89; P = 0.024) in males only. There was a negative correlation between upper limb LM and intensive care (τb = -0.090, P = 0.015) and total hospital length of stay (τb = -0.10, P = 0.0078) in men. In women, neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of stay. Body composition parameters, MELD and age were not associated with 90-d mortality or graft failure in either gender. There were no significant predictors of early ACR. CONCLUSION Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with cirrhosis. DEXA upper limb LM provides a novel measure of muscle wasting that has prognostic value in this cohort. The lack of association in women requires further investigation.
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Affiliation(s)
- Penelope Hey
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | - Rudolf Hoermann
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | - Paul Gow
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | | | - Adam G Testro
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | - Ross Apostolov
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | - Marie Sinclair
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
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13
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Fox R, Stenning K, Slee A, Macnaughtan J, Davies N. Sarcopenia in liver cirrhosis: Prevalence, pathophysiology and therapeutic strategies. Anal Biochem 2022; 647:114581. [PMID: 35134388 DOI: 10.1016/j.ab.2022.114581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 01/31/2022] [Indexed: 11/01/2022]
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Huang Y, Yan D, Zhang H, Lou B, Yan R, Yao Y, Dong M, Yang D, Lv F, Chen Y. Lower testosterone levels predict increasing severity and worse outcomes of hepatitis B virus-related acute-on-chronic liver failure in males. BMC Gastroenterol 2021; 21:457. [PMID: 34872528 PMCID: PMC8650519 DOI: 10.1186/s12876-021-01993-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 10/25/2021] [Indexed: 01/01/2023] Open
Abstract
Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a serious liver disease with pathogenesis remaining unclear. This study aims to investigate the association between testosterone levels, stage (early, middle, or late, categorized according to clinical manifestation), severity scores, and clinical outcomes of HBV-ACLF. Methods This single-center observational study involved 160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB) and 106 healthy controls (HC). Morning blood samples were collected and androgen levels analyzed by chemi-bioluminescent immunoassay. Time to death or liver transplantation within 90 days comprised the primary composite outcome. Results Serum levels of total testosterone (TT), free testosterone index (FTI), dehydroepiandrosterone sulfate and cortisol were significantly lower among HBV-ACLF than CHB and HC, while androstenedione was higher. Low TT, sex hormone binding globulin and FTI were associated with increased stage (of HBV-ACLF, ascites, and hepatic encephalopathy) and severity scores (Model for End-stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-ACLF scores). Low TT (< 142.39 ng/dL) was a risk factor for both the composite outcome and for death alone within 90 days. Multivariate analysis revealed TT to be an independent predictor for the composite outcome (hazard ratio 2.57, 95% CI 1.09–6.02; P = 0.030). Conclusion Low serum testosterone is common among male patients with HBV-ACLF and predictive of increased severity and worse outcome of the disease and may play an important role in the progression of HBV-ACLF.
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Affiliation(s)
- Yandi Huang
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310000, Zhejiang, People's Republic of China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310000, China.,Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Dong Yan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Huafen Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Bin Lou
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310000, Zhejiang, People's Republic of China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310000, China.,Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Ren Yan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Yifan Yao
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310000, Zhejiang, People's Republic of China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310000, China.,Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Minya Dong
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310000, Zhejiang, People's Republic of China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310000, China.,Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Donglei Yang
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310000, Zhejiang, People's Republic of China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310000, China.,Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Feifei Lv
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310000, Zhejiang, People's Republic of China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310000, China.,Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Yu Chen
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310000, Zhejiang, People's Republic of China. .,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310000, China. .,Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310000, China. .,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, China.
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15
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Deng N, Mallepally N, Peng FB, Kanji A, Marcelli M, Hernaez R. Serum testosterone levels and testosterone supplementation in cirrhosis: A systematic review. Liver Int 2021; 41:2358-2370. [PMID: 33966337 DOI: 10.1111/liv.14938] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 04/16/2021] [Accepted: 05/03/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND & AIMS Cirrhosis disrupts the hypothalamic-pituitary-gonadal axis causing low testosterone. Testosterone deficiency is associated with sarcopenia and osteopenia, leading to a state of frailty and worse clinical outcomes, morbidity and mortality. We aimed to conduct a systematic review on the relationship between serum testosterone and laboratory, anthropometric and clinical outcomes in observational and interventional studies in cirrhosis. METHODS PubMed and EMBASE were searched from inception through 27 August 2020 and reviewed independently by two investigators; a third reviewer solved disagreement. A qualitative summary of relevant findings was done. Methodological quality was assessed using the Newcastle Ottawa Scale for non-interventional studies and the Cochrane Risk of Bias for interventional studies. RESULTS Out of 3569 articles, 15 met inclusion criteria with six observational studies of 1267 patients and nine interventional studies of 580 patients. In observational studies, low serum testosterone level was associated with sarcopenia, shorter median time to hepatic decompensation, transplant requirement, higher model for end-stage liver disease (MELD) scores, and death in cirrhotic patients. Nine interventional studies (361 treated with testosterone vs 219 placebo, 1-36 months) showed that testosterone supplementation improved serum testosterone, appendicular mass and bone mineral density. However, no trial reported improvement in liver-related scores, complications, readmission rates or death. CONCLUSIONS Low serum testosterone is associated with increased morbidity and mortality in cirrhosis patients. Testosterone supplementation improved intermediate endpoints, but there was no conclusive data on clinical outcomes. Testosterone supplementation may be a promising strategy to improve frailty and decrease significant clinical complications in cirrhosis.
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Affiliation(s)
- Nanfu Deng
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | | | - Frederick B Peng
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Aleem Kanji
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Section of Diabetes, Metabolism and Endocrinology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Marco Marcelli
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Section of Diabetes, Metabolism and Endocrinology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Ruben Hernaez
- Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.,Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.,Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
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16
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Son SW, Song DS, Chang UI, Yang JM. Definition of Sarcopenia in Chronic Liver Disease. Life (Basel) 2021; 11:349. [PMID: 33923561 PMCID: PMC8074027 DOI: 10.3390/life11040349] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/11/2021] [Accepted: 04/13/2021] [Indexed: 02/07/2023] Open
Abstract
Sarcopenia, which is characterized by decline in muscle mass, muscle strength, and physical performance, is common in patients with chronic liver disease (CLD) and is associated with poor clinical outcomes. Several consensus definitions for community-dwelling elderly people have been proposed, and these recommend the use of various tools and tests to assess muscle properties and performance. These measurement tools have also been applied in patients with CLD and have been useful for predicting prognosis. However, sarcopenia and its diagnostic criteria specific to patients with CLD have not yet been clearly defined. In addition, fluid retention and body composition should be considered when sarcopenia is assessed in patients with CLD. This review aims to introduce definitions of sarcopenia and diagnostic tools used in patients with CLD.
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Affiliation(s)
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (S.W.S.); (U.I.C.); (J.M.Y.)
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17
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Paternostro R, Bardach C, Hofer BS, Scheiner B, Schwabl P, Asenbaum U, Ba‐Ssalamah A, Scharitzer M, Bucscis T, Simbrunner B, Bauer D, Trauner M, Mandorfer M, Reiberger T, Lampichler K. Prognostic impact of sarcopenia in cirrhotic patients stratified by different severity of portal hypertension. Liver Int 2021; 41:799-809. [PMID: 33290614 PMCID: PMC8048669 DOI: 10.1111/liv.14758] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 11/08/2020] [Accepted: 11/25/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Portal hypertension (PH) and sarcopenia are common in patients with advanced chronic liver disease (ACLD). However, the interaction between PH and sarcopenia and their specific and independent impact on prognosis and mortality has yet to be systematically investigated in patients with ACLD. METHODS Consecutive patients with ACLD and hepatic venous pressure gradient (HVPG) ≥10 mm Hg with available CT/MRI imaging were included. Sarcopenia was defined by transversal psoas muscle thickness (TPMT) at <12 mm/m in men and <8 mm/m in women at the level of the third lumbar vertebrae. Hepatic decompensation and mortality was recorded during follow-up. RESULTS Among 203 patients (68% male, age: 55 ± 11, model for end-stage liver disease [MELD]: 12 [9-15]), sarcopenia was observed in 77 (37.9%) and HVPG was ≥20 mm Hg in 98 (48.3%). There was no correlation between TPMT and HVPG (r = .031, P = .66), median HVPG was not different between patients with vs without sarcopenia (P = .211). Sarcopenia was significantly associated with first/further decompensation both in compensated (SHR: 3.05, P = .041) and in decompensated patients (SHR: 1.86, P = .021). Furthermore, sarcopenia (SARC) was a significant predictor of mortality irrespective of HVPG (HVPG < 20-SARC: SHR: 2.25, P = .021; HVPG ≥ 20-SARC: SHR: 3.33, P = .001). On multivariate analysis adjusted for age, HVPG and MELD, sarcopenia was an independent risk factor for mortality (aHR: 1.99, 95% confidence interval: 1.2-3.3, P = .007). CONCLUSION Sarcopenia has a major impact on clinical outcomes both in compensated and in decompensated ACLD patients. The presence of sarcopenia doubled the risk for mortality independently from the severity of PH.
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Affiliation(s)
- Rafael Paternostro
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Constanze Bardach
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Benedikt S. Hofer
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Philipp Schwabl
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Ulrika Asenbaum
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Ahmed Ba‐Ssalamah
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Martina Scharitzer
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Theresa Bucscis
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - David Bauer
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Trauner
- Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Katharina Lampichler
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
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18
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Systematic review and meta-analysis of lean mass and mortality: Rationale and study description. Osteoporos Sarcopenia 2021; 7:S3-S12. [PMID: 33997303 PMCID: PMC8088993 DOI: 10.1016/j.afos.2021.01.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 11/26/2020] [Accepted: 01/26/2021] [Indexed: 01/03/2023] Open
Abstract
Objectives Muscle mass is one of the key components in defining sarcopenia and is known to be important for locomotion and body homeostasis. Lean mass is commonly used as a surrogate of muscle mass and has been shown to be associated with increased mortality. However, the relationship of lean mass with mortality may be affected by different clinical conditions, modalities used, cut-off point to define low or normal lean mass, and even types of cancer among cancer patients. Thus, we aim to perform a comprehensive meta-analysis of lean mass with mortality by considering all these factors. Methods Systematic search was done in PubMed, Cochrane Library and Embase for articles related to lean mass and mortality. Lean mass measured by dual X-ray absorptiometry, bioelectrical impedance analysis, and computerized tomography were included. Results The number of relevant studies has increased continuously since 2002. A total of 188 studies with 98 468 people were included in the meta-analysis. The association of lean mass with mortality was most studied in cancer patients, followed by people with renal diseases, liver diseases, elderly, people with cardiovascular disease, lung diseases, and other diseases. The meta-analysis can be further conducted in subgroups based on measurement modalities, site of measurements, definition of low lean mass adopted, and types of cancer for studies conducted in cancer patients. Conclusions This series of meta-analysis provided insight and evidence on the relationship between lean mass and mortality in all directions, which may be useful for further study and guideline development.
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19
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Abdelbasset WK, Nambi G, Elsayed SH, Moawd SA, Ibrahim AA, Verma A, Tantawy SA, Kamel DM, Saleh AK, Aldhafian OR, Nwihadh NB. Prevalence and Nonpharmacological Interventions for Sarcopenia among Cirrhotic Patients. DISEASE MARKERS 2021; 2021:8866093. [PMID: 33628339 PMCID: PMC7884167 DOI: 10.1155/2021/8866093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 01/24/2021] [Accepted: 01/31/2021] [Indexed: 11/18/2022]
Abstract
Sarcopenia is the most common feature of hepatic cirrhosis characterized by progressive loss of muscle mass and function and increases permanently the mortality and morbidity rates among those patients. The incidence of sarcopenia in cirrhotic patients ranged 40-70% associating with impaired quality of life and augmented rates of infection. Based on these issues, this review is aimed at determining the prevalence and main causes of sarcopenia among cirrhotic patients and recognizing the recent diagnostic and physical treatment modalities that prevent risk factors for sarcopenia in those patients. No ideal modality is currently demonstrated for diagnosing sarcopenia in hepatic diseases, particularly cirrhosis; however, recent studies reported different diagnostic modalities for muscle function in different individuals including handgrip strength, skeletal muscle index, six-min walk test, liver frailty index, short physical performance battery, and radiological assessments for quadriceps and psoas muscles. Exercise training and therapeutic nutrition are strongly recommended for controlling sarcopenia in cirrhotic patients. The exercise program is designed and carried out on a frequent basis within an extensive scheduled time aimed at improving functional performance, aerobic capacity, and healthy conditions. Finally, a combination of exercise training and therapeutic nutrition is powerfully recommended to control sarcopenia in cirrhosis.
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Affiliation(s)
- Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Gopal Nambi
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Shereen H. Elsayed
- Department of Rehabilitation Sciences, Faculty of Health and Rehabilitation Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Samah A. Moawd
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
- Department of Physical Therapy for Cardiovascular/Respiratory Disorders and Geriatrics, Faculty of Physical Therapy, Cairo University, Giza, Egypt
| | - Ahmed A. Ibrahim
- Department of Physical Therapy, College of Applied Medical Sciences, Ha'il University, Hail, Saudi Arabia
| | - Anju Verma
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Sayed A. Tantawy
- Department of Physiotherapy, Centre of Radiation, Oncology and Nuclear Medicine, Cairo University, Giza, Egypt
- Department of Physiotherapy for Integumentary Problems, Faculty of Physical Therapy, Deraya University, Menia, Egypt
| | - Dalia M. Kamel
- Department of Physiotherapy for Women's Health, Faculty of Physical Therapy, Cairo University, Giza, Egypt
| | - Ayman K. Saleh
- Department of Orthopedic Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
- Department of Orthopedic, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Osama R. Aldhafian
- Department of Orthopedic Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Naif Bin Nwihadh
- Department of Orthopedic Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
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20
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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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21
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Sarkar M, Brady CW, Fleckenstein J, Forde KA, Khungar V, Molleston JP, Afshar Y, Terrault NA. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73:318-365. [PMID: 32946672 DOI: 10.1002/hep.31559] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 09/08/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Monika Sarkar
- University of California, San Francisco, San Francisco, CA
| | | | | | | | | | - Jean P Molleston
- Indiana University and Riley Hospital for Children, Indianapolis, IN
| | - Yalda Afshar
- University of California, Los Angeles, Los Angeles, CA
| | - Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, CA
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22
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Puri P, Dhiman RK, Taneja S, Tandon P, Merli M, Anand AC, Arora A, Acharya SK, Benjamin J, Chawla YK, Dadhich S, Duseja A, Eapan C, Goel A, Kalra N, Kapoor D, Kumar A, Madan K, Nagral A, Pandey G, Rao PN, Saigal S, Saraf N, Saraswat VA, Saraya A, Sarin SK, Sharma P, Shalimar, Shukla A, Sidhu SS, Singh N, Singh SP, Srivastava A, Wadhawan M. Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver. J Clin Exp Hepatol 2021; 11:97-143. [PMID: 33679050 PMCID: PMC7897902 DOI: 10.1016/j.jceh.2020.09.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.
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Key Words
- ACLF, acute on chronic liver failure
- ASM, appendicular skeletal muscle mass
- BCAA, branched chain amino acids
- BIA, bioimpedance analysis
- BMD, bone mineral densitometry
- BMI, body mass index
- CLD, chronic liver disease
- CS, corn-starch
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- DEXA, dual-energy X-ray absorptiometry
- EASL, European Association for the Study of the Liver
- ESPEN, European society for Clinical Nutrition and Metabolism
- GSD, glycogen storage disease
- HGS, hand-grip strength
- IBW, ideal body weight
- IEM, inborn error of metabolism
- INASL, Indian National Association for Study of the Liver
- L3, third lumbar
- LFI, Liver Frailty Index
- MCT, medium-chain triglyceride
- MELD, model for end-stage liver disease
- MLD, metabolic liver disease
- MRI, magnetic resonance imaging
- RDA, recommended daily allowance
- REE, NASH
- RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool
- SMI, skeletal muscle index
- Sarcopenia
- TEE, total energy expenditure
- chronic liver disease
- cirrhosis
- malnutrition
- non-alcoholic liver disease, resting energy expenditure
- nutrition
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Radha K. Dhiman
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Puneeta Tandon
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, 00185, Italy
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Anil Arora
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Subrat K. Acharya
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Jaya Benjamin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Yogesh K. Chawla
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Sunil Dadhich
- Department of Gastroenterology SN Medical College, Jodhpur, 342003, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - C.E. Eapan
- Department of Gastroenterology, Christian Medical College, Vellore, 632004, India
| | - Amit Goel
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Naveen Kalra
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad, 500004, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Kaushal Madan
- Max Smart Super Speciality Hospital, New Delhi, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital, Mumbai, 400026, India
| | - Gaurav Pandey
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Padaki N. Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, 500082, India
| | - Sanjiv Saigal
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Vivek A. Saraswat
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | - Sandeep S. Sidhu
- Department of Gastroenterology, SPS Hospital, Ludhiana, 141001, India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, 753007, India
| | - Anshu Srivastava
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases, BL Kapur Memorial Hospital, New Delhi, 110005, India
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23
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Sun S, Xu B, Tan W, Xiang X, Zhou Y, Dan Y, Guo Y, Tan Z, Deng G. Testosterone and Estradiol as Novel Prognostic Indicators for HBV-Related Acute-on-Chronic Liver Failure. Front Med (Lausanne) 2021; 8:729030. [PMID: 34568387 PMCID: PMC8455926 DOI: 10.3389/fmed.2021.729030] [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: 06/22/2021] [Accepted: 08/16/2021] [Indexed: 02/05/2023] Open
Abstract
Background: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality and urgently needs an early warning system with simplicity and high accuracy. Previous studies show that sex hormones play potential roles in the progression of HBV-related liver diseases. Aims: To explore the effect of testosterone and estradiol on the occurrence and prognosis of HBV-ACLF. Methods: A prospective cohort of 300 chronic hepatitis B (CHB) patients was enrolled among which 108 were diagnosed with HBV-ACLF at admission and 20 developed to HBV-ACLF during hospitalization. We compared the level of serum testosterone and estradiol of patients with varied ACLF background, disease severity and cirrhosis conditions and analyzed the predictive ability of short-term prognosis. A novel prognostic model involving testosterone was developed and further validated in the HBV-ACLF group. Results: The baseline estradiol level of HBV-ACLF group was significantly higher while testosterone was lower than that of non-ACLF group. The estradiol level increased while the testosterone level decreased as the number of organ failures increased. Testosterone had high accuracy in predicting the short-term mortality in HBV-ACLF (AUROC = 0.726) and estradiol did better in predicting the occurrence of ACLF during hospitalization (AUROC = 0.695). The novel prognostic model involving testosterone (TATIM model) was proved to have considerable prediction efficiency in HBV-ACLF cohort with or without cirrhosis. Conclusion: Testosterone could be utilized as short-term prognostic indicator for HBV-related ACLF and estradiol can help to predict its occurrence. TATIM model is a novel prognostic model for HBV-related ACLF with simplicity and good performance irrespectively of liver cirrhosis. Clinical Trial Registration Number: This study was based on a sub-cohort from the prospective multicenter cohort (NCT02457637).
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24
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Barbero-Becerra VJ, López-Méndez I, Romo-Araiza A, Visag-Castillo V, Chávez-Tapia NC, Uribe M, Juárez-Hernandez E. Sarcopenia in chronic liver diseases: a translational overview. Expert Rev Gastroenterol Hepatol 2020; 14:355-366. [PMID: 32299261 DOI: 10.1080/17474124.2020.1757427] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Sarcopenia refers to a progressive and generalized muscle mass and strength loss. In liver diseases, it has been related to worse outcomes and high risk of decompensations. AREAS COVERED Sarcopenia is caused by a set of cellular processes in the muscle such as denervation, mitochondrial dysfunction, endotoxemia and inflammation; which are manifested through the alteration of several proteolytic pathways such as lysosomal, proteasomal and caspase systems. In autophagy, myostatin and oxidative stress; such as hyperammonemia, contributes importantly to liver sarcopenia through loss of muscle mass already demonstrated in in vitro and in vivo models. In addition, hormones and the regulation of the intestinal microbiota, influence in a not less important magnitude. In the clinical setting, early identification of sarcopenia has been established as a mandatory item to prevent progression of muscle mass loss; however, diagnostic methods have extreme variation according to methodology, population, etiology and severity of liver disease. Reversing sarcopenia should be an integral therapeutic strategy. EXPERT OPINION Clinical and nutritional interventions should be adapted to liver injury etiology and stage of disease, each of them shares a similar sarcopenia development pathway. There are specific biomarkers that condition or exacerbate loss of skeletal muscle.
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Affiliation(s)
| | - Iván López-Méndez
- Transplants and Hepatology Unit, Medica Sur Clinic & Foundation , Mexico City, Mexico
| | | | - Víctor Visag-Castillo
- Gastroenterology and Obesity Unit, Medica Sur Clinic & Foundation , Mexico City, Mexico
| | - Norberto C Chávez-Tapia
- Translational Research Unit, Medica Sur Clinic & Foundation , Mexico City, Mexico.,Gastroenterology and Obesity Unit, Medica Sur Clinic & Foundation , Mexico City, Mexico
| | - Misael Uribe
- Gastroenterology and Obesity Unit, Medica Sur Clinic & Foundation , Mexico City, Mexico
| | - Eva Juárez-Hernandez
- Translational Research Unit, Medica Sur Clinic & Foundation , Mexico City, Mexico.,Facultad de Ciencias de la Salud, Universidad Anáhuac México , Mexico City, Mexico
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25
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El Sherif O, Dhaliwal A, Newsome PN, Armstrong MJ. Sarcopenia in nonalcoholic fatty liver disease: new challenges for clinical practice. Expert Rev Gastroenterol Hepatol 2020; 14:197-205. [PMID: 32064966 DOI: 10.1080/17474124.2020.1731303] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Sarcopenia is increasingly recognized in patients with nonalcoholic liver disease (NAFLD). Initially recognized as a consequence of advanced liver disease, there is now emerging evidence that sarcopenia may be a novel risk factor for the development of NAFLD, with a role in fibrosis and disease progression.Areas covered: This review examines the epidemiology, pathogenesis, and complex interplay between NAFLD and sarcopenia. Furthermore, the authors discuss the challenges with diagnosis of sarcopenia in the clinic and the evidence-based management of sarcopenia in patients with NAFLD. A MEDLINE and PubMed search was undertaken using the terms; 'sarcopenia,' 'frailty,' 'muscle,' 'obesity,' 'non-alcoholic fatty liver disease,' 'non-alcoholic steatohepatitis', and 'cirrhosis' up to 31 September 2019.Expert opinion: Sarcopenia may be masked by the co-existence of morbid obesity, which is most notable in patients with NAFLD. Sarcopenia is a key indicator of adverse outcomes in patients with cirrhosis, such as hepatic decompensation, poor quality of life and premature mortality. Patients with NAFLD and advanced fibrosis/cirrhosis should undergo anthropometric measures (handgrip strength), dry body mass index, and measures of physical frailty (including muscle function, not just mass) to enable targeted early interventions of nutrition (low fat, 1.5 g/kg/day protein intake, 2-3 hourly food intake) and exercise (combined resistance and aerobic).
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Affiliation(s)
- Omar El Sherif
- Liver Unit, Queen Elizabeth University Hospital Birmingham, UK
| | - Amritpal Dhaliwal
- Liver Unit, Queen Elizabeth University Hospital Birmingham, UK.,National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Philip N Newsome
- Liver Unit, Queen Elizabeth University Hospital Birmingham, UK.,National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Matthew J Armstrong
- Liver Unit, Queen Elizabeth University Hospital Birmingham, UK.,National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
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26
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Paternostro R, Lampichler K, Bardach C, Asenbaum U, Landler C, Bauer D, Mandorfer M, Schwarzer R, Trauner M, Reiberger T, Ferlitsch A. The value of different CT-based methods for diagnosing low muscle mass and predicting mortality in patients with cirrhosis. Liver Int 2019; 39:2374-2385. [PMID: 31421002 PMCID: PMC6899596 DOI: 10.1111/liv.14217] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 06/04/2019] [Accepted: 07/30/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Low muscle mass impacts on morbidity and mortality in cirrhosis. The skeletal-muscle index (SMI) is a well-validated tool to diagnose muscle wasting, but requires specialized radiologic software and expertise. Thus, we compared different Computed tomography (CT)-based evaluation methods for muscle wasting and their prognostic value in cirrhosis. METHODS Consecutive cirrhotic patients included in a prospective registry undergoing abdominal CT scans were analysed. SMI, transversal psoas muscle thickness (TPMT), total psoas volume (TPV) and paraspinal muscle index (PSMI) were measured. Sarcopenia was defined using SMI as a reference method by applying sex-specific cut-offs (males: <52.4 cm2 /m2 ; females: <38.5 cm2 /m2 ). RESULTS One hundred and nine patients (71.6% male) of age 57 ± 11 years, MELD 16 (8-26) and alcoholic liver disease (63.3%) as the main aetiology were included. According to established SMI cut-offs, low muscle mass was present in 69 patients (63.3%) who also presented with higher MELD (17 vs 14 points; P = .025). The following optimal sex-specific cut-offs (men/women) for diagnosing low muscle mass were determined: TPMT: <10.7/ <7.8 mm/m, TPV: <194.9/ <99.2 cm3 and PSMI <26.3/ <20.8 cm2 /m2 . Thirty (27.5%) patients died during a follow-up of 15 (0.3-45.7) months. Univariate competing risks analyses showed a significant risk for mortality according to SMI (aSHR:2.52, 95% CI: 1.03-6.21, P = .043), TPMT (aSHR: 3.87, 95% CI: 1.4-8.09, P = .007) and PSMI (aSHR: 2.7, 95% CI: 1.17-6.23, P = .02), but not TPV (P = .18) derived low muscle mass cut-offs. In multivariate analysis only TPMT (aSHR: 2.82, 95% CI: 1.20-6.67, P = .018) was associated with mortality, SMI (aSHR: 1.93, 95% CI: 0.72-5.16, P = .19) and PSMI (aSHR: 1.93, 95% CI: 0.79-4.75, P = .15) were not. CONCLUSION Low muscle mass was highly prevalent in our cohort of patients with cirrhosis. Gender-specific TPMT, SMI and PSMI cut-offs for low muscle mass can help identify patients with an increased risk for mortality. Importantly, only TPMT emerged as an independent risk factor for mortality in patients with cirrhosis.
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Affiliation(s)
- Rafael Paternostro
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Katharina Lampichler
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Constanze Bardach
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Ulrika Asenbaum
- Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Clara Landler
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - David Bauer
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Remy Schwarzer
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Michael Trauner
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Divison of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Arnulf Ferlitsch
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Department of Medicine IHospital St. John of GodViennaAustria
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27
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Sinclair M. Controversies in Diagnosing Sarcopenia in Cirrhosis-Moving from Research to Clinical Practice. Nutrients 2019; 11:2454. [PMID: 31615103 PMCID: PMC6836123 DOI: 10.3390/nu11102454] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 10/07/2019] [Accepted: 10/10/2019] [Indexed: 02/07/2023] Open
Abstract
Sarcopenia, defined as loss of muscle mass and function, is increasingly recognized as a common consequence of advanced cirrhosis that is associated with adverse clinical outcomes. Despite the recent proliferation in publications pertaining to sarcopenia in end-stage liver disease, there remains no single 'best method' for its diagnosis. The inability to identify a gold standard is common to other specialties, including geriatrics from which many diagnostic tools are derived. Controversies in diagnosis have implications for the accuracy and reproducibility of cohort studies in the field, largely prohibit the introduction of sarcopenia measurement into routine patient care and impede the development of clinical trials to identify appropriate therapies. Difficulties in diagnosis are partly driven by our ongoing limited understanding of the pathophysiology of sarcopenia in cirrhosis, the mechanisms by which it impacts on patient outcomes, the heterogeneity of patient populations, and the accuracy, availability and cost of assessments of muscle mass and function. This review discusses the currently studied diagnostic methods for sarcopenia in cirrhosis, and outlines why reaching a consensus on sarcopenia diagnosis is important and suggests potential ways to improve diagnostic criteria to allow us to translate sarcopenia research into improvements in clinical care.
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Affiliation(s)
- Marie Sinclair
- Department of Medicine, The University of Melbourne, Parkville 3050, Australia.
- Austin Health, Liver Transplant Unit, 145 Studley Road, Heidelberg 3084, Australia.
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28
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Sinclair M, Chapman B, Hoermann R, Angus PW, Testro A, Scodellaro T, Gow PJ. Handgrip Strength Adds More Prognostic Value to the Model for End-Stage Liver Disease Score Than Imaging-Based Measures of Muscle Mass in Men With Cirrhosis. Liver Transpl 2019; 25:1480-1487. [PMID: 31282126 DOI: 10.1002/lt.25598] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 06/18/2019] [Indexed: 12/13/2022]
Abstract
Sarcopenia is associated with mortality in cirrhosis, but there is no gold standard for its diagnosis. The comparative utility of different diagnostic methods is unknown. This single-center observational cohort study followed 145 men referred for liver transplant evaluation between 2005 and 2012. Muscle mass was estimated by handgrip strength, dual energy X-ray absorptiometry (DEXA) lean mass, and single-slice computed tomography (CT) scan at the fourth lumbar vertebra. Recorded outcomes included time to death or liver transplantation. The median (interquartile range [IQR]) age was 54 years (47-59 years), and Model for End-Stage Liver Disease (MELD) score was 17 (14-23). Of 145 men, 56 died with a median (IQR) time to death of 7.44 months (3.48-14.16 months). In total, 79 men underwent transplantation with median (IQR) time to transplant of 7.20 months (3.96-12.84 months). The prevalence of sarcopenia differed between diagnostic modalities with 70.3% using CT muscle mass, 45.9% using handgrip strength, and 38.7% using DEXA. Muscle mass was inversely associated with wait-list mortality for measured CT muscle mass (hazard ratio [HR], 0.94; 95% confidence interval (CI), 0.90-0.98; P = 0.002), DEXA muscle mass (HR, 0.99; 95% CI, 0.99-0.99; P = 0.003), and handgrip strength (HR, 0.94; 95% CI, 0.91-0.98; P = 0.002). These results retained significance independent of the MELD score. In predicting mortality, the MELD-handgrip strength bivariate Cox model was superior to a MELD-CT muscle Cox model (P < 0.001). In conclusion, handgrip strength combined with MELD score was the superior predictive model in this novel study examining 3 commonly employed techniques to diagnose sarcopenia in cirrhosis. Handgrip strength has additional potential clinical benefits because it can be performed serially without the radiation dose, cost, and access issues attributable to CT and DEXA.
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Affiliation(s)
- Marie Sinclair
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Brooke Chapman
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Rudolf Hoermann
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Peter W Angus
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Adam Testro
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Thomas Scodellaro
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Paul J Gow
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
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Vidot H, Kline K, Cheng R, Finegan L, Lin A, Kempler E, Strasser SI, Bowen DG, McCaughan GW, Carey S, Allman-Farinelli M, Shackel NA. The Relationship of Obesity, Nutritional Status and Muscle Wasting in Patients Assessed for Liver Transplantation. Nutrients 2019; 11:E2097. [PMID: 31487854 PMCID: PMC6769900 DOI: 10.3390/nu11092097] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 08/28/2019] [Accepted: 08/30/2019] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Obesity co-exists with malnutrition and muscle atrophy in patients with cirrhosis. Muscle wasting is a feature of sarcopenia, a known determinant of patient outcomes. This is the first description of a relationship between obesity, subjective global assessment (SGA) of nutritional status and muscle wasting in patients with cirrhosis. METHODS The relationship between body mass index (BMI with obesity defined as ≥ 30 kg/m2), nutritional status (assessed by liver-specific subjective global assessment-SGA) and muscle wasting (assessed by corrected total cross-sectional psoas muscle area-cTPA) was analysed in patients with cirrhosis considered for liver transplantation between 1 January 2012 and 31 December 2014. RESULTS There were 205 patients, of whom 70% were males. The mean age was 52 ± 0.7 years and the Model for End-Stage Liver Disease (MELD) score was 16.8 ± 0.5. Overall, 31% of patients were obese and 56% of well-nourished (SGA A) individuals were obese. Muscle wasting was identified in 86% of all patients, irrespective of their nutritional status (A, B, C). All obese males classified as well-nourished (SGA A) were sarcopenic and 62% of obese females classified as SGA A were sarcopenic. Muscle wasting was worse in obese individuals (cTPA 230.9 mm2/m2 ± 12.9, p < 0.0001) and more likely to be associated with hepatic encephalopathy (p = 0.03). Univariate and multivariate analysis demonstrated testosterone deficiency was significantly associated with muscle wasting (p = 0.007) but not obesity (p = 0.8). CONCLUSION Obesity combined with muscle wasting is common in patients with cirrhosis. Muscle wasting is common in well-nourished (SGA A) obese patients. Consequently, all patients assessed for liver transplantation should undergo additional screening for malnutrition and muscle wasting irrespective of BMI.
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Affiliation(s)
- Helen Vidot
- Department Nutrition & Dietetics, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia.
- Liver Injury and Cancer, Centenary Research Institute, The University of Sydney, Sydney, 2006 NSW, Australia.
| | - Katharine Kline
- Sydney Medical School, The University of Sydney, Sydney, 2006 NSW, Australia
| | - Robert Cheng
- Liver Injury and Cancer, Centenary Research Institute, The University of Sydney, Sydney, 2006 NSW, Australia
- A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia
| | - Liam Finegan
- School of Business, The University of Sydney, Sydney, 2006 NSW, Australia
| | - Amelia Lin
- Sydney Medical School, The University of Sydney, Sydney, 2006 NSW, Australia
| | - Elise Kempler
- Sydney Medical School, The University of Sydney, Sydney, 2006 NSW, Australia
| | - Simone I Strasser
- Sydney Medical School, The University of Sydney, Sydney, 2006 NSW, Australia
- A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia
| | - David Geoffrey Bowen
- Liver Injury and Cancer, Centenary Research Institute, The University of Sydney, Sydney, 2006 NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, 2006 NSW, Australia
- A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia
| | - Geoffrey William McCaughan
- Liver Injury and Cancer, Centenary Research Institute, The University of Sydney, Sydney, 2006 NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, 2006 NSW, Australia
- A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia
| | - Sharon Carey
- Department Nutrition & Dietetics, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia
| | - Margaret Allman-Farinelli
- School of Life and Environmental Sciences Charles Perkins Centre, The University of Sydney, Sydney, 2006 NSW, Australia
| | - Nicholas Adam Shackel
- Liver Injury and Cancer, Centenary Research Institute, The University of Sydney, Sydney, 2006 NSW, Australia
- A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia
- Medicine, University of New South Wales, Sydney, 2052 NSW, Australia
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Sinclair M, Hoermann R, Peterson A, Testro A, Angus PW, Hey P, Chapman B, Gow PJ. Use of Dual X-ray Absorptiometry in men with advanced cirrhosis to predict sarcopenia-associated mortality risk. Liver Int 2019; 39:1089-1097. [PMID: 30746903 DOI: 10.1111/liv.14071] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 01/31/2019] [Accepted: 02/02/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Reduced muscle area on CT scan is an independent predictor of mortality in cirrhosis. We examine for the first time the relationship between dual energy x-ray absorptiometry (DEXA) lean mass parameters on outcomes in cirrhotic men awaiting liver transplantation. MATERIALS AND METHODS We retrospectively reviewed DEXA scans performed during transplant assessment between 2001 and 2016. Baseline data including the presence of ascites and MELD score were recorded. DEXA lean mass measures were adjusted for height. The primary outcome was 12-month wait-list mortality. RESULTS Four hundred twenty men with median age 55.4 years [interquartile range 49.2; 59.4] and MELD 16 [12; 20] were studied. Median follow-up was 58.5 [28.8; 109] months. 12-month wait-list mortality was 12.4%. Appendicular lean mass was inversely associated with mortality (HR 0.78 [0.62; 0.98], P = 0.03). Lean mass of arms (HR 0.37 [0.16; 0.83], P = 0.02) rather than legs (HR 0.77 [0.58; 1.03], P = 0.08) was responsible for this association. Upper limb lean mass showed a significant interaction with MELD score in predicting wait-list mortality, particularly within 4 months. Total lean mass was not associated with mortality but increased in conjunction with increasing ascites (OR for ascites 1.20 [1.15; 1.25], P < 0.001 for each unit increase in MELD). CONCLUSION Upper limb lean mass by DEXA is strongly associated with mortality in men awaiting liver transplantation. The superiority of upper limb lean mass probably relates to confounding of lower limb measures by fluid retention. This DEXA parameter represents a novel and reproducible measure of sarcopenia in cirrhosis.
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Affiliation(s)
- Marie Sinclair
- Austin Hospital Liver Transplant Unit, Heidelberg, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Rudolf Hoermann
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Adam Peterson
- Austin Hospital Liver Transplant Unit, Heidelberg, Victoria, Australia
| | - Adam Testro
- Austin Hospital Liver Transplant Unit, Heidelberg, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Peter W Angus
- Austin Hospital Liver Transplant Unit, Heidelberg, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Penelope Hey
- Austin Hospital Liver Transplant Unit, Heidelberg, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Brooke Chapman
- Austin Hospital Liver Transplant Unit, Heidelberg, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- Austin Hospital Liver Transplant Unit, Heidelberg, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
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Chang KV, Chen JD, Wu WT, Huang KC, Han DS. Association of loss of muscle mass with mortality in liver cirrhosis without or before liver transplantation: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e14373. [PMID: 30817561 PMCID: PMC6831322 DOI: 10.1097/md.0000000000014373] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Liver cirrhosis is a risk factor for the loss of muscle mass, which is associated with numerous adverse health outcomes. This meta-analysis aimed to examine whether loss of muscle mass was a predictor of increased mortality in cirrhotic patients without or before liver transplantation. METHODS Without language restriction, PubMed and Embase were searched for articles published from the earliest records to December 2018 investigating the influence of loss of muscle mass on survival of cirrhotic patients. Those who had undergone liver transplantation and had hepatocellular carcinoma were excluded. The main outcome was the hazard ratio (HR) for the association of mortality with loss of muscle mass, and the secondary outcome was the association of loss of muscle mass with Child-Pugh class and death caused by severe infection. RESULTS The meta-analysis included 16 observational studies, comprising 4070 participants. The pooled crude and adjusted HRs for the association of mortality with loss of muscle mass were 2.05 (95% confidence interval [CI], 1.51-2.78) and 2.36 (95% CI, 1.61-3.46). Using Child-Pugh Class A as reference, the odds ratios (ORs) for the association of loss of muscle mass with Child-Pugh Class B and Class C were 1.68 (95% CI, 0.96-2.92) and 1.94 (95% CI, 0.66-5.65). Patients with loss of muscle mass were likely to have infection-related mortality (OR = 3.38, 95% CI, 0.61-18.88) but the association did not reach statistical significance. CONCLUSIONS Loss of muscle mass is associated with mortality in cirrhotic patients without or before liver transplantation. Future studies should be conducted to explore whether exercise and nutritional supplementation can reverse muscle mass loss and improve long-term survival.
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Affiliation(s)
- Ke-Vin Chang
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei
| | - Jin-De Chen
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Gastroenterology, National Taiwan University Hospital, Bei-Hu Branch
| | - Wei-Ting Wu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch
| | - Kuo-Chin Huang
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Family Medicine, National Taiwan University College of Medicine, Taipei
| | - Der-Sheng Han
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei
- Health Science and Wellness Center, National Taiwan University, Taipei, Taiwan
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Paternostro R, Heinisch BB, Reiberger T, Mandorfer M, Bardach C, Lampichler K, Seeland B, Schwarzer R, Trauner M, Peck‐Radosavljevic M, Ferlitsch A. Dysbalanced sex hormone status is an independent predictor of decompensation and mortality in patients with liver cirrhosis. Hepatol Res 2019; 49:201-211. [PMID: 30248213 PMCID: PMC7379971 DOI: 10.1111/hepr.13253] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/13/2018] [Accepted: 09/18/2018] [Indexed: 12/18/2022]
Abstract
AIMS Endocrinological abnormalities, including low testosterone levels, are prevalent in cirrhosis. We assessed sexual hormone status in regard to hemodynamic abnormalities and its impact on hepatic decompensation and survival. METHODS Males with cirrhosis were prospectively included in this study since 2010. Sexual hormones including bioavailable testosterone, total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin as well as Child-Pugh score, Model for End-stage Liver Disease (MELD) score, and hepatic venous pressure gradient were recorded. Sarcopenia was also assessed in patients with available computed tomography scans. Clinical follow-up for hepatic decompensation, liver transplantation, and death was recorded until May 2017. RESULTS One hundred fourteen male cirrhotic patients were included: age 55 ± 9.4 years, MELD 13.5 (range, 7-20.7). Etiologies were alcoholic liver disease in 61(53.5%) patients, viral in 30 (26.3%) patients, and other in 23 (20.2%). Child-Pugh scores were A in 32 (28.1%) patients, B in 48 (42.1%), and C in 34 (29.8%). Levels of bioavailable testosterone and total testosterone decreased with advanced Child-Pugh score (P < 0.001 and P < 0.001) whereas prolactin increased (P = 0.002). Median bioavailable testosterone (0.8 ng/mL [0.1-2] vs. 1.68 ng/mL [0.07-2.65]; P = 0.004) and total testosterone (2.7 ng/mL [0.23-12.34] vs. 7 ng/mL [0.25-10]; P = 0.041) levels were lower in patients with severe portal hypertension (hepatic venous pressure gradient >12 mmHg). Median bioavailable testosterone (0.25 ng/mL [0.07-1.7] vs. 0.97 ng/mL [0.15-2.74)]; P = 0.017) and total testosterone levels (1.28 ng/mL [0.25-7.32] vs. 4.32 ng/mL [0.43-13.47]; P = 0.031) were significantly lower in sarcopenic patients. Median follow-up was 13 months (0.2-75 months) and liver-related events were recorded in 46 patients (40.4%; death, 31 [27.2%]). Low total testosterone was associated with an increased risk for hepatic decompensation and/or death, even after adjusting for Child-Pugh score, MELD, and other relevant factors (Child-Pugh score model: hazard ratio 2.503, 95% confidence interval, 1.214-5.157, P = 0.013; MELD model: hazard ratio 3.065, 95% confidence interval, 1.523-6.169, P = 0.002). CONCLUSION In parallel to increasing severity of cirrhosis, levels of testosterone decline whereas prolactin levels increase. However, low testosterone levels are independently associated with a higher risk for hepatic decompensation and mortality.
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Affiliation(s)
- Rafael Paternostro
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Birgit B. Heinisch
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Constanze Bardach
- Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
| | - Katharina Lampichler
- Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
| | - Berit Seeland
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Remy Schwarzer
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Trauner
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Markus Peck‐Radosavljevic
- Division of Gastroenterology, Hepatology, Endocrinology and NephrologyKlinikum Klagenfurt am WörtherseeKlagenfurtAustria
| | - Arnulf Ferlitsch
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
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Engelmann C, Schob S, Nonnenmacher I, Werlich L, Aehling N, Ullrich S, Kaiser T, Krohn S, Herber A, Sucher R, Bartels M, Surov A, Hasenclever D, Kahn T, Seehofer D, Moche M, Berg T. Loss of paraspinal muscle mass is a gender-specific consequence of cirrhosis that predicts complications and death. Aliment Pharmacol Ther 2018; 48:1271-1281. [PMID: 30417398 DOI: 10.1111/apt.15026] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 09/19/2018] [Accepted: 09/28/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Loss of skeletal muscle mass is a recognised complication with a prognostic impact in patients with cirrhosis. AIM To explore in a retrospective analysis which muscle compartment most reliably predicts the occurrence of cirrhosis-associated complications and if there are gender-related differences. METHODS 795 patients with cirrhosis listed for liver transplantation between 2001 and 2014 met the inclusion and exclusion criteria including an abdominal CT scan (±200). Controls were 109 patients who underwent a CT scan after polytrauma. The paraspinal muscles index (PSMI), the abdominal wall muscles index (AWMI) and its combination skeletal muscle index (SMI) were assessed at L3/L4, normalised to the height (cm2 /m2 ). RESULTS 62.0% of patients with cirrhosis had alcoholic liver disease, and 70.6% were male. As compared to controls, a reduction in PSMI and SMI but not AWMI was associated with high model of end-stage liver disease (MELD) score, high Child-Pugh class, and the presence or history of cirrhosis-associated complications in males but not females. PSMI independently predicted the occurrence of bacterial infections (HR 0.932), spontaneous bacterial peritonitis (HR 0.901), hepatic encephalopathy (HR 0.961), and hepatorenal syndrome (HR 0.946) by multivariate Cox regression analysis in a gender-independent manner. Post-transplant survival was not associated with the PSMI; neither AWMI nor SMI predicted any clinical endpoints. CONCLUSIONS This study links muscle wasting in patients with cirrhosis predominantly to males. However, the presence of a low PSMI mass is a gender-independent predictor of developing cirrhosis-associated complications and death. Scores combining the MELD with muscle parameters should be re-validated by utilizing the PSMI.
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Affiliation(s)
- Cornelius Engelmann
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.,Institute for Liver and Digestive Health, University College London, London, UK
| | - Stefan Schob
- Department for Neuroradiology, University Hospital Leipzig, Leipzig, Germany
| | - Ines Nonnenmacher
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Luise Werlich
- Department for Neuroradiology, University Hospital Leipzig, Leipzig, Germany
| | - Niklas Aehling
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Sebastian Ullrich
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany
| | - Sandra Krohn
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Adam Herber
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Robert Sucher
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Michael Bartels
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany.,HELIOS Park Hospital Leipzig, General-, Visceral- and Vascular Surgery, Leipzig, Germany
| | - Alexey Surov
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Dirk Hasenclever
- IMISE - Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, Germany
| | - Thomas Kahn
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Michael Moche
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany.,Diagnostic and Interventional Radiology, Nuernberg, Germany
| | - Thomas Berg
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
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Abstract
Low plasma testosterone (T) levels correlated with metabolic syndrome, cardiovascular diseases, and increased mortality risk. T exerts a significant effect on the regulation of adipose tissue accumulation, and in the glucose and lipids metabolism. Adipocytes are the primary source of the most important adipokines responsible for inflammation and chronic diseases. This review aims to analyze the possible effect of T on the regulation of the proinflammatory cytokines secretion. A systematic literature search on MEDLINE, Google Scholar, and Cochrane using the combination of the following keywords: “testosterone” with “inflammation,” “cytokines,” “adiponectin, CRP, IL-1B, IL-6, TNFα, leptin” was conducted. Sixteen articles related to the effect of low T level and 18 to the effect of T therapy on proinflammatory cytokine were found. T exerts a significant inhibitory effect on adipose tissue formation and the expression of various adipocytokines, such as leptin, TNF-α, IL-6, IL-1, and is positively correlated with adiponectin level, whereas a low T level is correlated with increased expression of markers of inflammation. Further studies are necessary to investigate the role of T, integrated with weight loss and physical activity, on its action on the mechanisms of production and regulation of proinflammatory cytokines.
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Moctezuma-Velázquez C, Low G, Mourtzakis M, Ma M, Burak KW, Tandon P, Montano-Loza AJ. Association between Low Testosterone Levels and Sarcopenia in Cirrhosis: A Cross-sectional Study. Ann Hepatol 2018; 17:615-623. [PMID: 29893704 DOI: 10.5604/01.3001.0012.0930] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Sarcopenia is an independent predictor of mortality in cirrhosis. Hypogonadism is common in cirrhosis and has been associated with sarcopenia in non-cirrhotic chronic liver disease populations. The aim of this study is to investigate if sarcopenia is associated with low testosterone levels in patients with cirrhosis. MATERIAL AND METHODS This is a retrospective analysis of prospectively collected data of 211 cirrhotic patients undergoing evaluation for liver transplantation. Sarcopenia was defined by computed tomography (CT) scan using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning testosterone levels were obtained in all patients. RESULTS Of the 211 patients, sarcopenia was noted in 94 (45%). Testosterone levels were lower in sarcopenic patients (10.7 ± 1.1 vs. 13.7 ± 1.4 nmol/L, p = 0.03) and hypotestosteronemia was more frequent in them too (34 vs. 16%, p = 0.004). In males, those with sarcopenia had lower testosterone levels (14.6 ± 1.4 vs. 21.9 ± 1.8, p = 0.002), and the corresponding frequency of hypotestosteronemia (42 vs. 19%, p = 0.006) was also higher. There were no significant differences in female patients. There was a weak correlation between L3 SMI and testosterone levels (r 0.37, p < 0.001). On multivariable regression analysis including sex, body mass index (BMI), hypotestosteronemia, MELD and etiology of cirrhosis, only hypotestosteronemia (RR 2.76, p = 0.005) and BMI (RR 0.88, p < 0.001) were independently associated with sarcopenia. CONCLUSION Low testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.
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Affiliation(s)
| | - Gavin Low
- Department of Radiology, University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Marina Mourtzakis
- Department of Rehabilitation Medicine, University of Waterloo, Ontario, Canada
| | - Mang Ma
- Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
| | | | - Puneeta Tandon
- Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
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Song M, Xia L, Liu Q, Sun M, Wang F, Yang C. Sarcopenia in Liver Disease: Current Evidence and Issues to Be sResolved. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1088:413-433. [PMID: 30390263 DOI: 10.1007/978-981-13-1435-3_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Sarcopenia is a common clinical symptom in aging and patients with wasting diseases, characterized by a decreased skeletal muscle mass. As a consequence of lifestyle change, the nonalcoholic fatty liver disease (NAFLD) presents a rising trend. In the past three decades, increasing evidence has proved that sarcopenia is related to NAFLD. In this chapter, we will summarize the emerging evidence of the predictive role of sarcopenia in NAFLD and review the diagnosis value, feasible mechanism, and therapy strategies of sarcopenia in NAFLD. Sarcopenia is a potential risk factor for NAFLD, and targeting sarcopenia can benefit NAFLD to some extent.
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Affiliation(s)
- Meiyi Song
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lu Xia
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Qi Liu
- Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Mengxue Sun
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fei Wang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Changqing Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
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Abstract
With aging and other muscle wasting diseases, men and women undergo similar pathological changes in skeletal muscle: increased inflammation, enhanced oxidative stress, mitochondrial dysfunction, satellite cell senescence, elevated apoptosis and proteasome activity, and suppressed protein synthesis and myocyte regeneration. Decreased food intake and physical activity also indirectly contribute to muscle wasting. Sex hormones also play important roles in maintaining skeletal muscle homeostasis. Testosterone is a potent anabolic factor promoting muscle protein synthesis and muscular regeneration. Estrogens have a protective effect on skeletal muscle by attenuating inflammation; however, the mechanisms of estrogen action in skeletal muscle are less well characterized than those of testosterone. Age- and/or disease-induced alterations in sex hormones are major contributors to muscle wasting. Hence, men and women may respond differently to catabolic conditions because of their hormonal profiles. Here we review the similarities and differences between men and women with common wasting conditions including sarcopenia and cachexia due to cancer, end-stage renal disease/chronic kidney disease, liver disease, chronic heart failure, and chronic obstructive pulmonary disease based on the literature in clinical studies. In addition, the responses in men and women to the commonly used therapeutic agents and their efficacy to improve muscle mass and function are also reviewed.
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Sinclair M, Gow PJ, Grossmann M, Shannon A, Hoermann R, Angus PW. Low serum testosterone is associated with adverse outcome in men with cirrhosis independent of the model for end-stage liver disease score. Liver Transpl 2016; 22:1482-1490. [PMID: 27542090 DOI: 10.1002/lt.24607] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 07/25/2016] [Accepted: 08/02/2016] [Indexed: 12/13/2022]
Abstract
Low serum testosterone has been retrospectively associated with mortality in men on the liver transplant waiting list. The impact of testosterone deficiency on other outcomes has not previously been assessed. We conducted a single center prospective observational study of all men with cirrhosis seen between 2013 and 2014. Baseline data included sex hormone profile, Model for End-Stage Liver Disease (MELD) score, and standard biochemistry. Outcomes were recorded over 12 months including major infection, liver transplantation, and death. Of 268 cirrhotic men, the median MELD score was 10 (interquartile range [IQR], 8-15) and median serum testosterone was 17.4 nmol/L (IQR, 8.9-25.0 nmol/L). During the study period, 32 (12%) men died, 18 (7%) received a liver transplant, and 51 (19%) suffered a major infection. Mortality markedly increased when total testosterone fell below a threshold value of 8.3 nmol/L, and this cutoff was used for further analysis. Testosterone below 8.3 nmol/L was associated with the combined outcome of death or transplantation independently of the MELD score (hazard ratio [HR], 2.36; IQR, 1.16-4.81; P = 0.02) for testosterone (and HR, 1.22; IQR, 1.18-1.27; P < 0.001 for MELD). Low total testosterone was also an independent risk factor for major infection (HR, 3.61; IQR, 1.61-8.06; P < 0.001) and nearly significant for mortality alone (HR, 2.39; IQR, 0.97-5.88; P = 0.057). Low free testosterone (<139 pmol/L) was similarly independently associated with death or transplantation (HR, 2.43; IQR, 1.12-5.29; P = 0.03) and infection (HR, 3.3; IQR, 1.46-7.46; P = 0.004). In conclusion, low testosterone is a novel prognostic marker in men with cirrhosis that is numerically associated with increased mortality or need for transplantation, as well as risk for major infection. Interventional studies of testosterone therapy are required to investigate whether correcting low testosterone can reduce mortality and improve other clinical outcomes. Liver Transplantation 22 1482-1490 2016 AASLD.
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Affiliation(s)
- Marie Sinclair
- Liver Transplant Unit, University of Melbourne, Melbourne, Victoria, Australia.
- Department of Medicine, Gastroenterology and Hepatology, Austin Health, Melbourne, Victoria, Australia.
| | - Paul J Gow
- Liver Transplant Unit, University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Gastroenterology and Hepatology, Austin Health, Melbourne, Victoria, Australia
| | - Mathis Grossmann
- Liver Transplant Unit, University of Melbourne, Melbourne, Victoria, Australia
- Endocrine Unit, Endocrinology, Austin Health, Melbourne, Victoria, Australia
| | - Adam Shannon
- Liver Transplant Unit, University of Melbourne, Melbourne, Victoria, Australia
| | - Rudolf Hoermann
- Liver Transplant Unit, University of Melbourne, Melbourne, Victoria, Australia
| | - Peter W Angus
- Liver Transplant Unit, University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Gastroenterology and Hepatology, Austin Health, Melbourne, Victoria, Australia
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Sinclair M, Grossmann M, Hoermann R, Angus PW, Gow PJ. Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: A randomised controlled trial. J Hepatol 2016; 65:906-913. [PMID: 27312945 DOI: 10.1016/j.jhep.2016.06.007] [Citation(s) in RCA: 181] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 06/02/2016] [Accepted: 06/07/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Low testosterone and sarcopenia are common in men with cirrhosis and both are associated with increased mortality. Whether testosterone therapy in cirrhosis improves muscle mass and other outcomes is unknown. METHODS We conducted a 12-month, double-blinded, placebo-controlled trial of intramuscular testosterone undecanoate in 101 men with established cirrhosis and low serum testosterone (total testosterone <12nmol/L or free testosterone <230pmol/L) in a single tertiary centre. Body composition was assessed using dual-energy X-ray absorptiometry at baseline, 6 and 12months. RESULTS At study completion, appendicular lean mass was significant higher in testosterone-treated subjects, with a mean adjusted difference (MAD) of +1.69kg, (CI +0.40; +2.97kg, p=0.021). Secondary outcomes included a substantially higher total lean mass in the active group (MAD +4.74kg, CI +1.75; +7.74kg, p=0.008), matched by reduced fat mass (MAD -4.34kg, CI -6.65; -2.04, p<0.001). Total bone mass increased (MAD +0.08kg, CI +0.01; +0.15kg, p=0.009) as did bone mineral density at the femoral neck (MAD +0.287points, CI +0.140; +0.434, p<0.001). Haemoglobin was higher with testosterone therapy (MAD +10.2g/L, CI +1.50; +18.9g/L, p=0.041) and percentage glycosylated haemoglobin (HbA1c) lower (MAD -0.35%, CI -0.05; -0.54, p=0.028). Mortality was non-significantly lower in testosterone-treated patients (16% vs. 25.5%, p=0.352). There was no increase in adverse events in testosterone-treated subjects. CONCLUSION Testosterone therapy in men with cirrhosis and low serum testosterone safely increases muscle mass, bone mass and haemoglobin, and reduces fat mass and HbA1c. This is the first evidence-based therapy for sarcopenia in cirrhosis and thus requires larger-scale investigation into its potential impact on mortality. LAY SUMMARY Both low testosterone and muscle wasting are associated with increased risk of death in men with severe liver disease. Administering testosterone to men with liver disease who have low testosterone levels significantly increases their muscle mass. In addition, testosterone has non-muscle beneficial effects which may be able to increase survival in this population. CLINICAL TRIAL NUMBER Australian New Zealand Clinical Trials Registry trial number ACTRN 12614000526673.
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Affiliation(s)
- Marie Sinclair
- The University of Melbourne, Australia; Gastroenterology and Hepatology, Austin Health, Melbourne, Australia.
| | - Mathis Grossmann
- The University of Melbourne, Australia; Endocrinology, Austin Health, Melbourne, Australia
| | | | - Peter W Angus
- The University of Melbourne, Australia; Gastroenterology and Hepatology, Austin Health, Melbourne, Australia
| | - Paul J Gow
- The University of Melbourne, Australia; Gastroenterology and Hepatology, Austin Health, Melbourne, Australia
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