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Zhou H, Gizlenci M, Xiao Y, Martin F, Nakamori K, Zicari EM, Sato Y, Tullius SG. Obesity-associated Inflammation and Alloimmunity. Transplantation 2025; 109:588-596. [PMID: 39192462 PMCID: PMC11868468 DOI: 10.1097/tp.0000000000005183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
Obesity is a worldwide health problem with a rapidly rising incidence. In organ transplantation, increasing numbers of patients with obesity accumulate on waiting lists and undergo surgery. Obesity is in general conceptualized as a chronic inflammatory disease, potentially impacting alloimmune response and graft function. Here, we summarize our current understanding of cellular and molecular mechanisms that control obesity-associated adipose tissue inflammation and provide insights into mechanisms affecting transplant outcomes, emphasizing on the beneficial effects of weight loss on alloimmune responses.
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Affiliation(s)
- Hao Zhou
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
| | - Merih Gizlenci
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Department of General, Visceral, Cancer and Transplant Surgery, University Hospital of Cologne, Cologne, Germany
| | - Yao Xiao
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
| | - Friederike Martin
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Department of Surgery, CVK/CCM, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Keita Nakamori
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Department of Urology, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Elizabeth M. Zicari
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Faculté de Pharmacie, Université Paris Cité, Paris, France
| | - Yuko Sato
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
| | - Stefan G. Tullius
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
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Fadlallah H, El Masri D, Bahmad HF, Abou-Kheir W, El Masri J. Update on the Complications and Management of Liver Cirrhosis. Med Sci (Basel) 2025; 13:13. [PMID: 39982238 PMCID: PMC11843904 DOI: 10.3390/medsci13010013] [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: 01/05/2025] [Revised: 02/01/2025] [Accepted: 02/02/2025] [Indexed: 02/22/2025] Open
Abstract
Liver cirrhosis represents the advanced pathological stage of chronic liver disease, characterized by the progressive destruction and regeneration of the hepatic parenchyma over years, culminating in fibrosis and disruption of the vascular architecture. As a leading global cause of morbidity and mortality, it continues to affect millions worldwide, imposing a substantial burden on healthcare systems. Alcoholic/nonalcoholic fatty liver disease and chronic viral hepatitis infection, hepatitis C (HCV) in particular, remain leading causes of cirrhosis. Despite significant advances in understanding the pathogenesis of cirrhosis, its management is still complex due to the multifaceted complications, including ascites, hepatic encephalopathy, variceal bleeding, and hepatocellular carcinoma, all of which severely compromise the patient outcomes and quality of life. This review aims at filling a critical gap by providing a comprehensive summary of the latest evidence on the complications and management of liver cirrhosis. Evidence-based therapies targeting both the etiologies and complications of cirrhosis are essential for improving outcomes. While liver transplantation is considered a definitive cure, advancements in pharmacological therapies offer promising avenues for halting and potentially reversing disease progression. This review summarizes the latest management strategies for cirrhosis and its associated complications, emphasizing the importance of early intervention and novel therapeutic options for improving outcomes and quality of life in affected individuals.
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Affiliation(s)
- Hiba Fadlallah
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Diala El Masri
- Faculty of Medicine, University of Balamand, Al-Kurah, Tripoli P.O. Box 100, Lebanon;
| | - Hisham F. Bahmad
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA;
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Jad El Masri
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
- Faculty of Medical Sciences, Lebanese University, Beirut 1107-2020, Lebanon
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3
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Burra P, Zanetto A, Schnabl B, Reiberger T, Montano-Loza AJ, Asselta R, Karlsen TH, Tacke F. Hepatic immune regulation and sex disparities. Nat Rev Gastroenterol Hepatol 2024; 21:869-884. [PMID: 39237606 DOI: 10.1038/s41575-024-00974-5] [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] [Accepted: 07/25/2024] [Indexed: 09/07/2024]
Abstract
Chronic liver disease is a major cause of morbidity and mortality worldwide. Epidemiology, clinical phenotype and response to therapies for gastrointestinal and liver diseases are commonly different between women and men due to sex-specific hormonal, genetic and immune-related factors. The hepatic immune system has unique regulatory functions that promote the induction of intrahepatic tolerance, which is key for maintaining liver health and homeostasis. In liver diseases, hepatic immune alterations are increasingly recognized as a main cofactor responsible for the development and progression of chronic liver injury and fibrosis. In this Review, we discuss the basic mechanisms of sex disparity in hepatic immune regulation and how these mechanisms influence and modify the development of autoimmune liver diseases, genetic liver diseases, portal hypertension and inflammation in chronic liver disease. Alterations in gut microbiota and their crosstalk with the hepatic immune system might affect the progression of liver disease in a sex-specific manner, creating potential opportunities for novel diagnostic and therapeutic approaches to be evaluated in clinical trials. Finally, we identify and propose areas for future basic, translational and clinical research that will advance our understanding of sex disparities in hepatic immunity and liver disease.
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Affiliation(s)
- Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy.
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
- Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Rosanna Asselta
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Tom Hemming Karlsen
- Department of Transplantation Medicine, Clinic of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital and University of Oslo, Oslo, Norway
- Research Institute of Internal Medicine, Clinic of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
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O'Regan PW, O'Regan JA, Maher MM, Ryan DJ. The Emerging Role and Clinical Applications of Morphomics in Diagnostic Imaging. Can Assoc Radiol J 2024; 75:793-804. [PMID: 38624049 DOI: 10.1177/08465371241242763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2024] Open
Abstract
Analytic morphomics refers to the accurate measurement of specific biological markers of human body composition in diagnostic medical imaging. The increasing prevalence of disease processes that alter body composition including obesity, cachexia, and sarcopenia has generated interest in specific targeted measurement of these metrics to possibly prevent or reduce negative health outcomes. Typical morphomic measurements include the area and density of muscle, bone, vascular calcification, visceral fat, and subcutaneous fat on a specific validated axial level in the patient's cross-sectional diagnostic imaging. A distinct advantage of these measurements is that they can be made retrospectively and opportunistically with pre-existing datasets. We provide a narrative review of the current state of art in morphomics, but also consider some potential future directions for this exciting field. Imaging based quantitative assessment of body composition has enormous potential across the breadth and scope of modern clinical practice. From risk stratification to treatment planning, and outcome assessment, all can be enhanced with the use of analytic morphomics. Moreover, it is likely that many new opportunities for personalized medicine will emerge as the field evolves. As radiologists, embracing analytic morphomics will enable us to contribute added value in the care of every patient.
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Affiliation(s)
- Patrick W O'Regan
- Department of Radiology, Cork University Hospital, Cork, Ireland
- Department of Radiology, School of Medicine, University College Cork, Cork, Ireland
| | - James A O'Regan
- Department of Medicine, Cork University Hospital, Cork, Ireland
| | - Michael M Maher
- Department of Radiology, Cork University Hospital, Cork, Ireland
- Department of Radiology, School of Medicine, University College Cork, Cork, Ireland
| | - David J Ryan
- Department of Radiology, Cork University Hospital, Cork, Ireland
- Department of Radiology, School of Medicine, University College Cork, Cork, Ireland
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Forsgren MF, Pine S, Harrington CR, Gregory D, Petersson M, Rinella M, Leinhard OD, VanWagner LB. Body composition and muscle composition phenotypes in patients on waitlist and shortly after liver transplant - results from a pilot study. BMC Gastroenterol 2024; 24:356. [PMID: 39385094 PMCID: PMC11462649 DOI: 10.1186/s12876-024-03425-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 09/19/2024] [Indexed: 10/11/2024] Open
Abstract
BACKGROUND Sarcopenia is common in end-stage liver disease and negatively impacts patients awaiting or undergoing liver transplantation (LT). Magnetic resonance imaging (MRI) may be used to measure body composition and sarcopenia. We aimed to evaluate the feasibility of MRI-based LT body composition profiling, describe waitlist body composition, and assess the natural rate of change in body composition while on the waitlist and post-LT. METHODS This prospective pilot study recruited adults listed for LT at an urban, tertiary care facility. Eighteen participants were scanned at time of waitlisting and 15 had follow-up MRIs (waitlist and/or post-LT). An 8-min MRI was used to measure body composition (AMRA® Researcher) including thigh fat-free muscle volume (FFMV) and fat infiltration (MFI), visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissue volumes, and liver fat. A sex- and BMI invariant FFMV z-score (z-FFMV) was calculated, and muscle composition (MC) phenotypes were defined using the muscle assessment score (consisting of the FFMV z-score and sex-adjusted MFI). Rate of body composition change was calculated using mixed-effect modelling and is presented as rate per 30 days. RESULTS At time of waitlisting, 73% of the 18 participants had high MFI and 39% had the adverse MC (low FFMV z-score and high MFI) phenotype. Seven participants received an LT. Post-LT serial MRIs, at a median of 147 days apart within the first 200 days post-LT, demonstrated increased z-FFMV 0.22 SDs/(30 days) (p = 0.002), VAT 0.23 (p < 0.001), and ASAT 0.52 (p = 0.001) L/(30 days), but no change in MFI (p = 0.200) nor liver fat (p = 0.232). CONCLUSION MRI-based body composition profiling is feasible in LT patients and shortly after LT. This can be amended to routine clinical scans and may help in early identification of patients who may benefit from interventions to improve body composition. In addition, body composition changes significantly over time after LT.
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Affiliation(s)
- Mikael F Forsgren
- Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- AMRA Medical AB, Linköping, Sweden
| | - Stewart Pine
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Claire Royalle Harrington
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Dyanna Gregory
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, 5959 Harry Hines Blvd, Suite HP4.420M, Dallas, TX, 75390-8887, USA
| | | | - Mary Rinella
- Department of Medicine, Division of Gastroenterology & Hepatology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - Olof Dahlqvist Leinhard
- Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- AMRA Medical AB, Linköping, Sweden
| | - Lisa B VanWagner
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, 5959 Harry Hines Blvd, Suite HP4.420M, Dallas, TX, 75390-8887, USA.
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Uemura S, Ban D, Esaki M, Nara S, Takamoto T, Mizui T, Shimada K. Risk factor analysis of postoperative pancreatic fistula after distal pancreatectomy with a focus on the peritoneum to portal vein distance on computed tomography. World J Surg 2024; 48:2496-2504. [PMID: 39278820 DOI: 10.1002/wjs.12334] [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: 04/11/2024] [Accepted: 08/21/2024] [Indexed: 09/18/2024]
Abstract
BACKGROUND Postoperative pancreatic fistula (POPF) is a major complication of distal pancreatectomy (DP). Although the visceral fat area (VFA) is a risk factor for POPF in DP, its measurement is complicated. This study aimed to identify a simple marker as a predictive indicator of POPF. METHODS We included 210 patients who underwent resection at our institution between 2020 and 2023. The patients' characteristics, preoperative laboratory data, and radiographic findings (e.g., portal vein distance and VFA) and their association with pancreatic fistula after DP were analyzed. POPF was defined as Grade B or C pancreatic fistula on the basis of the International Study Group of Pancreatic Surgery 2016 consensus. RESULTS POPF developed in 82 (39.0%) patients. Univariate analysis showed that female sex, pancreatic thickness of the cutting line, operative time, blood loss, C-reactive protein (CRP) level on postoperative day (POD) 3, drain amylase level on POD 3, VFA, and the peritoneum to portal vein distance (PPD) were associated with POPF. Receiver operating characteristic curve analysis of PPD showed a higher area under the curve than VFA (cutoff for PPD: 68 mm). Multivariate analysis showed that CRP (odds ratio [OR]: 2.214), drain amylase (OR: 2.875), and PPD (OR: 15.538) were independent risk factors. When we compared the DP fistula risk score and PPD, receiver operating characteristic analysis showed areas under the curve of 0.650 and 0.803, respectively. CONCLUSIONS A PPD of ≥68 mm is a useful risk predictor of POPF. Determining this distance is simple and easily applicable in the clinical setting.
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Affiliation(s)
- Sho Uemura
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Chuo-ku, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Chuo-ku, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Chuo-ku, Japan
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Chuo-ku, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Chuo-ku, Japan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Chuo-ku, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Chuo-ku, Japan
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Gulla A, Jakiunaite I, Juchneviciute I, Dzemyda G. A narrative review: predicting liver transplant graft survival using artificial intelligence modeling. FRONTIERS IN TRANSPLANTATION 2024; 3:1378378. [PMID: 38993758 PMCID: PMC11235265 DOI: 10.3389/frtra.2024.1378378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 04/22/2024] [Indexed: 07/13/2024]
Abstract
Liver transplantation is the only treatment for patients with liver failure. As demand for liver transplantation grows, it remains a challenge to predict the short- and long-term survival of the liver graft. Recently, artificial intelligence models have been used to evaluate the short- and long-term survival of the liver transplant. To make the models more accurate, suitable liver transplantation characteristics must be used as input to train them. In this narrative review, we reviewed studies concerning liver transplantations published in the PubMed, Web of Science, and Cochrane databases between 2017 and 2022. We picked out 17 studies using our selection criteria and analyzed them, evaluating which medical characteristics were used as input for creation of artificial intelligence models. In eight studies, models estimating only short-term liver graft survival were created, while in five of the studies, models for the prediction of only long-term liver graft survival were built. In four of the studies, artificial intelligence algorithms evaluating both the short- and long-term liver graft survival were created. Medical characteristics that were used as input in reviewed studies and had the biggest impact on the accuracy of the model were the recipient's age, recipient's body mass index, creatinine levels in the recipient's serum, recipient's international normalized ratio, diabetes mellitus, and recipient's model of end-stage liver disease score. To conclude, in order to define important liver transplantation characteristics that could be used as an input for artificial intelligence algorithms when predicting liver graft survival, more models need to be created and analyzed, in order to fully support the results of this review.
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Affiliation(s)
- Aiste Gulla
- Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania
| | | | - Ivona Juchneviciute
- Faculty of Mathematics and Informatics, Institute of Data Science and Digital Technologies, Vilnius University, Vilnius, Lithuania
| | - Gintautas Dzemyda
- Faculty of Mathematics and Informatics, Institute of Data Science and Digital Technologies, Vilnius University, Vilnius, Lithuania
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Ha NB, Fan B, Shui AM, Huang CY, Brandman D, Lai JC. CT-quantified sarcopenic visceral obesity is associated with poor transplant waitlist mortality in patients with cirrhosis. Liver Transpl 2023; 29:476-484. [PMID: 36735830 PMCID: PMC10193893 DOI: 10.1097/lvt.0000000000000010] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 10/25/2022] [Indexed: 02/05/2023]
Abstract
Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index <50 cm 2 /m 2 in men and <39 cm 2 /m 2 in women) and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥1.21 in men and ≥0.48 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 44%, 29%, and 13%, respectively. Cumulative incidence of waitlist mortality was higher in patients with SVO compared to patients with sarcopenia without visceral obesity or visceral obesity without sarcopenia at 12 months (40% vs. 21% vs. 12%) (overall logrank p =0.003). In univariable Cox regression, SVO was associated with waitlist mortality (HR: 3.42, 95% CI: 1.58-7.39), which remained significant after adjusting for age, sex, diabetes, ascites, encephalopathy, MELDNa, liver frailty index, and different body compositions (HR: 2.64, 95% CI: 1.11-6.30). SVO was associated with increase waitlist mortality in patients with cirrhosis in the ambulatory setting awaiting liver transplantation. Concurrent loss of skeletal muscle and gain of adipose tissue seen in SVO quantified by CT may be a useful and objective measurement to identify patients at risk for suboptimal pretransplant outcomes.
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Affiliation(s)
- Nghiem B. Ha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Bo Fan
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Amy M. Shui
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Chiung-Yu Huang
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Danielle Brandman
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
- Liver Center, University of California, San Francisco, CA, USA
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Schmeusser BN, Midenberg E, Palacios AR, Ali AA, Patil DH, Higgins M, Nabavizadeh R, Croll B, Williams M, Sheehy J, Zheng B, Narayan VM, Joshi SS, Ogan K, Psutka SP, Bilen MA, Master VA. Low Skeletal Muscle as a Risk Factor for Worse Survival in Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus. Clin Genitourin Cancer 2023:S1558-7673(23)00092-7. [PMID: 37210313 DOI: 10.1016/j.clgc.2023.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 04/11/2023] [Accepted: 04/13/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND Renal cell carcinoma (RCC) with tumor thrombosis often requires nephrectomy and tumor thrombectomy. As an extensive and potentially morbid operation, patient preoperative functional reserve and body composition is an important consideration. Sarcopenia is a risk factor for increased postoperative complications, systemic therapy toxicity, and death solid organ tumors, including RCC. The influence of sarcopenia in RCC patients with tumor thrombus is not well defined. This study evaluates the prognostic ability of sarcopenia regarding surgical outcomes and complications in patients undergoing surgery for RCC with tumor thrombus. METHODS We retrospectively analyzed patients with nonmetastatic RCC and tumor thrombus undergoing radical nephrectomy and tumor thrombectomy. Skeletal muscle index (SMI; cm2/m2) was measured on preoperative CT/MRI. Sarcopenia was defined using body mass index- and sex-stratified thresholds optimally fit via a receiver-operating characteristic analysis for survival. Associations between preoperative sarcopenia and overall (OS), cancer-specific survival (CSS), and 90-day major complications were determined using multivariable analysis. RESULTS 115 patients were analyzed, with median (IQR) age and body mass index of 69 (56-72) and 28.6 kg/m2 (23.6-32.9), respectively. 96 (83.4%) of the cohort had ccRCC. Sarcopenia was associated with shorter median OS (P = .0017) and CSS (P = .0019) in Kaplan-Meier analysis. In multivariable analysis, preoperative sarcopenia was prognostic of shorter OS (HR = 3.38, 95% confidence interval [CI] 1.61-7.09) and CSS (HR = 5.15, 95% CI 1.46-18.18). Notably, 1 unit increases in SMI were associated with improved OS (HR = 0.97, 95% CI 0.94-0.999) but not CSS (HR = 0.95, 95% CI 0.90-1.01). No significant relationship between preoperative sarcopenia and 90-day major surgical complications was observed in this cohort (HR = 2.04, 95% CI 0.65-6.42). CONCLUSION Preoperative sarcopenia was associated with decreased OS and CSS in patients surgically managed for nonmetastatic RCC and VTT, however, was not predictive of 90-day major postoperative complications. Body composition analysis has prognostic utility for patients with nonmetastatic RCC and venous tumor thrombus undergoing surgery.
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Affiliation(s)
| | - Eric Midenberg
- Department of Urology, University of Louisville School of Medicine, Louisville, KY
| | - Arnold R Palacios
- Department of Urology, Creighton University School of Medicine, Omaha, NE
| | - Adil A Ali
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | | | - Michelle Higgins
- Department of Urology, Emory University School of Medicine, Atlanta, GA; The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Reza Nabavizadeh
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Benjamin Croll
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Milton Williams
- Department of Urology, University of Alabama at Birmingham, Birmingham, AL
| | - John Sheehy
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Bill Zheng
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Vikram M Narayan
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Shreyas S Joshi
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Kenneth Ogan
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Sarah P Psutka
- Department of Urology, University of Washington, Seattle, WA; Fred Hutchinson Cancer Center, Seattle, WA
| | - Mehmet A Bilen
- Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia
| | - Viraj A Master
- Department of Urology, Emory University School of Medicine, Atlanta, GA.
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10
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Low adipose tissue index as an indicator of hepatic encephalopathy in cirrhotic patients following transjugular intrahepatic portosystemic shunt. ABDOMINAL RADIOLOGY (NEW YORK) 2023; 48:1454-1467. [PMID: 36735033 DOI: 10.1007/s00261-023-03813-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 01/10/2023] [Accepted: 01/10/2023] [Indexed: 02/04/2023]
Abstract
PURPOSE We aimed to investigate the predictive value of body compositions measured by CT, including skeletal muscle and adipose tissue, for hepatic encephalopathy (HE) in cirrhotic patients following transjugular intrahepatic portosystemic shunt (TIPS). METHODS Patients who underwent TIPS between November 2015 and April 2021 were included in this retrospective study. CT images taken at L3 were quantified for three body composition indexes (cm2/m2), visceral fat area index (VFAI), subcutaneous fat area index (SFAI), and skeletal muscle index (SMI) at baseline. Multivariable logistic regression models were conducted to assess associations between post-TIPS HE and body compositions. Nomograms based on the multivariable logistic regression models were developed and were evaluated from Calibration curves. RESULTS Male patients had greater SMI, whereas SFAI and VFAI were higher in females (p < 0.001 for each). In sex stratified multivariate analyses after adjustment for other confounding variables, VFAI in males (p = 0.033) and SFAI in females (p = 0.003) were significant predictors of post-TIPS HE. Male patients with low VFAI (< 53.52 cm2/m2) (OR 6.44; 95% CI 1.72-23.59; p = 0.006) and female patients with low SFAI (< 70.05 cm2/m2) (OR 10.55; 95% CI 2.36-46.23; p = 0.002) had a higher risk of post-TIPS HE. Risk factors in the nomogram contributing to the male model included age, height, Child-Pugh score, and low VFAI; pre-albumin and low SFAI were contributed to female model. CONCLUSION Body compositions could not only be noninvasively used for nutritional assessment, but also be utilized to predict HE risk of cirrhotic patients after TIPS.
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11
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Ohliger MA. Body Composition at CT and Risk of Future Disease. Radiology 2023; 306:e222162. [PMID: 36165799 PMCID: PMC9885345 DOI: 10.1148/radiol.222162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/08/2022] [Accepted: 09/08/2022] [Indexed: 01/26/2023]
Affiliation(s)
- Michael A. Ohliger
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, 505 Parnassus Ave, San Francisco, CA 94143
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12
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Zhu M, Li H, Yin Y, Ding M, Philips CA, Romeiro FG, Qi X. U-shaped relationship between subcutaneous adipose tissue index and mortality in liver cirrhosis. J Cachexia Sarcopenia Muscle 2023; 14:508-516. [PMID: 36577511 PMCID: PMC9891908 DOI: 10.1002/jcsm.13154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/03/2022] [Accepted: 11/29/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Subcutaneous and visceral adipose tissues are important body components, but their effects on the mortality in patients with liver cirrhosis remain controversial based on the current evidence. METHODS We retrospectively identified 372 eligible patients in whom subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) could be measured by computed tomography images at the third lumbar vertebra. The association of SATI and VATI with the risk of death was evaluated on a continuous scale with restricted cubic spline curves based on Cox proportional hazards models. Cumulative probability of mortality was estimated by Nelson-Aalen cumulative risk curve analyses. Independent predictors of death were evaluated by competing risk analyses after adjusting for age, sex, and model for end-stage liver disease score. RESULTS Majority of patients were male (69.4%) with a mean age of 55.40 ± 10.68 years. SATI had a U-shaped association with mortality (P for non-linearity <0.001). Cutoff values of SATI were 19.7 and 51.8 cm2 /m2 at the points where hazard ratios were just <1.2. SATI was categorized as low (<19.7 cm2 /m2 ), moderate (19.7-51.8 cm2 /m2 ), and high (>51.8 cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate SATI groups (Gray's test, P = 0.052) and high versus moderate SATI groups (Gray's test, P = 0.054). Competing risk analyses demonstrated that low SATI could increase the mortality compared with moderate SATI (subdistribution hazard ratio [sHR] = 1.66, 95% confidence interval [CI]: 0.992-2.78, P = 0.054) and was an independent predictor of death (sHR = 1.86, 95% CI: 1.059-3.28, P = 0.031). Competing risk analyses also demonstrated that high SATI could significantly increase the mortality compared with moderate SATI (sHR = 1.6, 95% CI: 1-2.54, P = 0.049), and was an independent predictor of death (sHR = 2.007, 95% CI: 1.195-3.37, P = 0.0085). VATI had an irregularly shaped association with mortality (P for non-linearity <0.001). Cutoff values of VATI were 9.8 and 40.2 cm2 /m2 at the points where hazard ratios were just <1.2. VATI was categorized as low (<9.8 cm2 /m2 ), moderate (9.8-40.2 cm2 /m2 ), and high (>40.2 cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate VATI groups (Gray's test, P = 0.381) and high versus moderate VATI groups (Gray's test, P = 0.787). Competing risk analyses demonstrated that neither low (sHR = 1.27, 95% CI: 0.599-2.7, P = 0.53) nor high VATI (sHR = 0.848, 95% CI: 0.539-1.34, P = 0.48) was an independent predictor of death compared with moderate VATI. CONCLUSIONS Both excessive deficiency and accumulation of subcutaneous adipose tissues negatively influence the outcomes of cirrhotic patients.
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Affiliation(s)
- Menghua Zhu
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, China.,Postgraduate College, Jinzhou Medical University, Jinzhou, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, China.,Postgraduate College, Jinzhou Medical University, Jinzhou, China.,Postgraduate College, China Medical University, Shenyang, China
| | - Yue Yin
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, China.,Postgraduate College, China Medical University, Shenyang, China
| | - Min Ding
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, China.,Postgraduate College, China Medical University, Shenyang, China
| | - Cyriac Abby Philips
- Department of Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India
| | | | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, China.,Postgraduate College, Jinzhou Medical University, Jinzhou, China.,Postgraduate College, China Medical University, Shenyang, China
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13
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Alqahtan SA, Brown RS. Management and Risks Before, During, and After Liver Transplant in Individuals With Obesity. Gastroenterol Hepatol (N Y) 2023; 19:20-29. [PMID: 36865816 PMCID: PMC9972654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023]
Abstract
Obesity has become a global epidemic, adding to the burden of chronic diseases and disabilities. Metabolic syndrome, especially obesity, is a significant risk factor for nonalcoholic fatty liver disease, which is the most common indication for liver transplant (LT). The prevalence of obesity among the LT population is growing. Obesity increases the necessity of LT by playing a role in the development of nonalcoholic fatty liver disease, decompensated cirrhosis, and hepatocellular carcinoma, and it can also coexist with other diseases requiring LT. Therefore, LT teams must identify key aspects required to manage this high-risk population, but there are currently no defined recommendations for managing obesity in LT candidates. Although body mass index is often used to assess the weight of patients and classify them as overweight or obese, this measure may be inaccurate to use in patients with decompensated cirrhosis, as fluid overload or ascites can significantly add to the weight of patients. Diet and exercise remain the cornerstone of obesity management. Supervised weight loss before LT, without worsening frailty and sarcopenia, may be beneficial in reducing surgical risks and improving long-term LT outcomes. Bariatric surgery is another effective treatment for obesity, with sleeve gastrectomy currently conferring the best outcomes in LT recipients. However, evidence supporting the timing of bariatric surgery is lacking. Long-term patient and graft survival data in individuals with obesity following LT are scarce. Class 3 obesity (body mass index ≥40) further complicates the treatment of this patient population. This article discusses the impact of obesity on the outcome of LT.
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Affiliation(s)
- Saleh A. Alqahtan
- 1Liver Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia,2Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland
| | - Robert S. Brown
- 3Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York
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14
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High visceral adipose tissue area is independently associated with early allograft dysfunction in liver transplantation recipients: a propensity score analysis. Insights Imaging 2022; 13:165. [PMID: 36219263 DOI: 10.1186/s13244-022-01302-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 09/20/2022] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVES To evaluate the association between adipose tissue distribution and early allograft dysfunction (EAD) in liver transplantation (LT) recipients. METHODS A total of 175 patients who received LT from April 2015 to September 2020 were enrolled in this retrospective study. The areas of abdominal adipose tissue and skeletal muscle of all patients were measured based on the preoperative CT images. The appropriate statistical methods including the propensity score-matched (PSM) analysis were performed to identify the association between adipose tissue distribution and EAD. RESULTS Of 175 LT recipients, 55 patients (31.4%) finally developed EAD. The multivariate logistic analysis revealed that preoperative serum albumin (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17-0.70), platelet-lymphocyte ratio (OR 2.35, 95% CI 1.18-4.79), and visceral adipose tissue (VAT) area (OR 3.17, 95% CI 1.56-6.43) were independent associated with EAD. After PSM analysis, VAT area was still significantly associated with EAD (OR 3.95, 95% CI 1.16-13.51). In survival analysis, no significant difference was identified in one-year graft failure (log-rank: p = 0.487), and conversely result was identified in overall survival (OS) (log-rank: p = 0.012; hazard ratio (HR) 4.10, 95% CI 1.27-13.16). CONCLUSIONS LT recipients with high VAT area have higher risk for the occurrence of EAD, and high VAT area might have certain clinical value for predicting the poor OS of patients. For LT candidates with large amount of VAT, the clinicians can take clinical interventions by suggesting physical and nutritional treatments to improve outcomes after LT.
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15
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Ha NB, Montano-Loza AJ, Carey EJ, Lin S, Shui AM, Huang CY, Dunn MA, Lai JC. Sarcopenic visceral obesity is associated with increased post-liver transplant mortality in acutely ill patients with cirrhosis. Am J Transplant 2022; 22:2195-2202. [PMID: 35486028 PMCID: PMC9427718 DOI: 10.1111/ajt.17079] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 03/20/2022] [Accepted: 04/22/2022] [Indexed: 01/25/2023]
Abstract
"Sarcopenic obesity" refers to a condition of low muscle mass in the context of obesity, though may be difficult to assess in patients with cirrhosis who are acutely ill. We aimed to define sarcopenic visceral obesity (SVO) using CT-based skeletal muscle index (SMI) and visceral-to-subcutaneous adipose tissue ratio (VSR) to examine its association with post-transplant mortality. We analyzed 116 adult inpatients with cirrhosis who were urgently listed and transplanted between 1/2005 and 12/2017 at 4 North American transplant centers. SVO was defined as patients with sarcopenia (SMI <50 cm2 /m2 in men and <39 cm2 /m2 in women) and visceral obesity (VSR ≥ 1.54 in men and ≥1.37 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 45%, 42%, and 20%, respectively. Cumulative rates of post-transplant mortality were higher in patients with SVO compared to patients with sarcopenia or visceral obesity alone at 36 months (39% vs. 14% vs. 8%) [logrank p = .01]. In univariable regression, SVO was associated with post-transplant mortality (HR 2.92, 95%CI 1.04-8.23) and remained significant after adjusting for age, sex, diabetes, encephalopathy, hepatocellular carcinoma, and MELD-Na (HR 3.50, 95%CI 1.10-11.15). In conclusion, SVO is associated with increased post-transplant mortality in acutely ill patients with cirrhosis.
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Affiliation(s)
- Nghiem B. Ha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Aldo J. Montano-Loza
- Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Elizabeth J. Carey
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Arizona, Scottsdale, AZ, USA
| | - Shezhang Lin
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Amy M. Shui
- Biostatistics Core, Department of Surgery, University of California, San Francisco, CA, USA
| | - Chiung-Yu Huang
- Biostatistics Core, Department of Surgery, University of California, San Francisco, CA, USA
| | - Michael A. Dunn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
- Liver Center, University of California, San Francisco, CA, USA
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16
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Engelmann C, Aehling NF, Schob S, Nonnenmacher I, Handmann L, Macnaughtan J, Herber A, Surov A, Kaiser T, Denecke T, Jalan R, Seehofer D, Moche M, Berg T. Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis. Hepatol Commun 2022; 6:2198-2209. [PMID: 35420246 PMCID: PMC9315113 DOI: 10.1002/hep4.1946] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 01/24/2022] [Accepted: 02/17/2022] [Indexed: 11/25/2022] Open
Abstract
Cachexia occurs in late stages of liver cirrhosis, and a low-fat mass is potentially associated with poor outcome. This study compared different computed tomography (CT)-derived fat parameters with respect to its prognostic impact on the development of complications and death before and after liver transplantation. Between 2001 and 2014, 612 patients with liver cirrhosis without hepatocellular carcinoma listed for liver transplantation met the inclusion criteria, including abdominal CT scan (±200 days to listing). A total of 109 patients without cirrhosis served as controls. The subcutaneous fat index (SCFI), the paraspinal muscle fat index, and the visceral fat index were assessed at L3/L4 level and normalized to the height (cm2 /m2 ). Data were collected and analyzed retrospectively. Low SCFI was associated with a higher rate of ascites and increased C-reactive protein levels (p < 0.001). In addition, multivariate Cox regression analysis adjusting for sex, age, body mass index (BMI), and Model for End-Stage Liver Disease showed that decreasing SCFI was also associated with an increased risk of cirrhosis-related complications (p = 0.003) and death on the transplant wait list (p = 0.013). Increased paraspinal and visceral fat were not only positively correlated with creatinine levels (p < 0.001), BMI, and metabolic comorbidities (all p < 0.001) before transplantation, but also predictive for 1-year mortality after transplantation. Conclusion: The distribution of body fat is a major determinant for complications and outcome in cirrhosis before and after liver transplantation.
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Affiliation(s)
- Cornelius Engelmann
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany.,Liver Failure GroupInstitute for Liver and Digestive HealthUniversity College LondonRoyal Free CampusLondonUK.,Department of Hepatology and GastroenterologyCampus Virchow-KlinikumCharité-Universitaetsmedizin BerlinBerlinGermany.,522475Berlin Institute of HealthBerlinGermany
| | - Niklas F Aehling
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Stefan Schob
- Department for NeuroradiologyUniversity Hospital LeipzigLeipzigGermany
| | - Ines Nonnenmacher
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Luise Handmann
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Jane Macnaughtan
- Liver Failure GroupInstitute for Liver and Digestive HealthUniversity College LondonRoyal Free CampusLondonUK
| | - Adam Herber
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Alexey Surov
- Department of Diagnostic and Interventional RadiologyUniversity Hospital LeipzigLeipzigGermany
| | - Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular DiagnosticsUniversity Hospital LeipzigLeipzigGermany
| | - Timm Denecke
- Department of Diagnostic and Interventional RadiologyUniversity Hospital LeipzigLeipzigGermany
| | - Rajiv Jalan
- Liver Failure GroupInstitute for Liver and Digestive HealthUniversity College LondonRoyal Free CampusLondonUK
| | - Daniel Seehofer
- Department of VisceralVascularThoracic and Transplant SurgeryUniversity Hospital LeipzigLeipzigGermany
| | - Michael Moche
- Department of Diagnostic and Interventional RadiologyUniversity Hospital LeipzigLeipzigGermany.,Diagnostic and Interventional RadiologyPark Hospital LeipzigLeipzigGermany
| | - Thomas Berg
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
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17
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Esteban JPG, Asgharpour A. Evaluation of liver transplant candidates with non-alcoholic steatohepatitis. Transl Gastroenterol Hepatol 2022; 7:24. [PMID: 35892057 PMCID: PMC9257540 DOI: 10.21037/tgh.2020.03.04] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 02/03/2020] [Indexed: 11/07/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is anticipated to become the leading indication for liver transplantation (LT) in the United States in the near future. LT is indicated in patients with NASH-related cirrhosis who have medically refractory hepatic decompensation, synthetic dysfunction, and hepatocellular carcinoma (HCC) meeting certain criteria. The objective of LT evaluation is to determine which patient will derive the most benefit from LT with the least risk, thus maximizing the societal benefits of a limited resource. LT evaluation is a multidisciplinary undertaking involving several specialists, assessment tools, and diagnostic testing. Although the steps involved in LT evaluation are relatively similar across different liver diseases, patients with NASH-related cirrhosis have unique demographic and clinical features that affect transplant outcomes and influence their LT evaluation. LT candidates with NASH should be assessed for metabolic syndrome and obesity, malnutrition and sarcopenia, frailty, and cardiovascular disease. Interventions that treat cardiometabolic co-morbidities and improve patients' nutrition and functionality should be considered in order to improve patient outcomes in the waitlist and after LT.
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Affiliation(s)
- James Philip G Esteban
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Amon Asgharpour
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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18
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Ha NB, Cho S, Mohamad Y, Kent D, Jun G, Wong R, Swarnakar V, Lin S, Maher JJ, Lai JC. Visceral Adipose Tissue Inflammation and Radiographic Visceral-to-Subcutaneous Adipose Tissue Ratio in Patients with Cirrhosis. Dig Dis Sci 2022; 67:3436-3444. [PMID: 34136974 PMCID: PMC8815298 DOI: 10.1007/s10620-021-07099-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 06/07/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Accumulation of visceral adipose tissue is associated with hepatic inflammation and fibrosis, suggestive of its metabolic and inflammatory properties. We aimed to examine the histologic findings of visceral and subcutaneous adipose tissue and to associate these findings with clinical and radiologic characteristics in patients with cirrhosis. METHODS Included were 55 adults with cirrhosis who underwent liver transplantation from 3/2017-12/2018 and had an abdominal computed tomography (CT) scan within 6 months prior to transplant. Visceral-to-subcutaneous adipose tissue ratio (VSR) was calculated using visceral (VATI) and subcutaneous adipose tissue index (SATI) quantified by CT at the L3-vertebral level and normalized for height (cm2/m2). VAT (greater omentum), SAT (abdominal wall), and skeletal muscle (rectus abdominis) biopsies were collected at transplant. RESULTS Majority of patients had VAT inflammation (71%); only one patient (2%) had SAT inflammation. Patients with VAT inflammation had similar median VATI (42 vs 41 cm2/m2), lower median SATI (64 vs 97 cm2/m2), and higher median VSR (0.63 vs 0.37, p = 0.002) than patients without inflammation. In univariable logistic regression, VSR was associated with VAT inflammation (OR 1.47, 95%CI 1.11-1.96); this association remained significant even after adjusting for age, sex, BMI, HCC, or MELD-Na on bivariable analyses. CONCLUSION In patients with cirrhosis undergoing liver transplantation, histologic VAT inflammation was common, but SAT inflammation was not. Increased VSR was independently associated with VAT inflammation. Given the emerging data demonstrating the prognostic value of VSR, our findings support the value of CT-quantified VSR as a prognostic marker for adverse outcomes in the liver transplant setting.
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Affiliation(s)
- Nghiem B. Ha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Soo‑Jin Cho
- Department of Pathology, University of California, San Francisco, CA, USA
| | - Yara Mohamad
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Dorothea Kent
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Grace Jun
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Randi Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Vivek Swarnakar
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Shezhang Lin
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Jacquelyn J. Maher
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA,Liver Center, University of California, San Francisco, CA, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA,Liver Center, University of California, San Francisco, CA, USA
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19
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Yaseri M, Alipoor E, Seifollahi A, Rouhifard M, Salehi S, Hosseinzadeh-Attar MJ. Association of obesity with mortality and clinical outcomes in children and adolescents with transplantation: A systematic review and meta-analysis. Rev Endocr Metab Disord 2021; 22:847-858. [PMID: 33730228 DOI: 10.1007/s11154-021-09641-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/01/2021] [Indexed: 10/21/2022]
Abstract
Obesity might be associated with mortality and clinical outcomes following transplantation; however, the direction of this relationship has not been well-recognized in youth. The aim of this systematic review and meta-analysis was to investigate the association of obesity with post-transplant mortality and clinical outcomes in children and adolescents. Following a systematic search of observational studies published by December 2018 in PubMed, Scopus, Embase, and Cochrane library, 15 articles with total sample size of 50,498 patients were included in the meta-analysis. The main outcome was mortality and secondary outcomes included acute graft versus host disease (GVHD), acute rejection, and overall graft loss. The pooled data analyses showed significantly higher odds of long term mortality (OR 1.30, 95% CI 1.15-1.48, P < 0.001, I2 = 50.3%), short term mortality (OR 1.79, 95% CI 1.19-2.70, P = 0.005, I2 = 59.6%), and acute GVHD (OR 2.13, 95% CI 1.5-3.02, P < 0.001, I2 = 1.7%) in children with obesity. There were no significant differences between patients with and without obesity in terms of acute rejection (OR 1.07, 95% CI 0.98-1.16, P = 0.132, I2 = 7.5%) or overall graft loss (OR 1.04, 95% CI 0.84-1.28, P = 0.740, I2 = 51.6%). This systematic review and meta-analysis has stated higher post-transplant risk of short and long term mortality and higher risk of acute GVHD in children with obesity compared to those without obesity. Future clinical trials are required to investigate the effect of pre-transplant weight management on post-transplant outcomes to provide insights into the clinical application of these findings. This may in turn lead to establish guidelines for the management of childhood obesity in transplantations.
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Affiliation(s)
- Mehdi Yaseri
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Alipoor
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Atefeh Seifollahi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahtab Rouhifard
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Shiva Salehi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Hosseinzadeh-Attar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
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20
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Lin J, Weir WB, Grenda T, Zhang P, Derstine BA, Enchakalody B, Underhill J, Reddy RM, Chang AC, Wang SC. Analytic Morphomics Are Related to Outcomes After Lung Volume Reduction Surgery. Semin Thorac Cardiovasc Surg 2021; 34:1084-1090. [PMID: 34166813 PMCID: PMC8763534 DOI: 10.1053/j.semtcvs.2021.06.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 06/04/2021] [Indexed: 01/05/2023]
Abstract
:Lung volume reduction surgery continues to have a high morbidity despite National Emphysema Treatment Trial selection criteria. This study evaluated the association between analytic morphomics on chest computed tomography scans and outcomes after lung volume reduction surgery. In a retrospective review of 85 lung volume reduction surgery patients from 1998-2013, dorsal muscle group area, subcutaneous and visceral fat area, and bone mineral density were assessed using analytic morphomics. Lung density was divided into five levels of increasing density (Lung density 1, emphysema; 2, normal lung; 4-5, scarring). Outcomes including survival, hospital length of stay, readmission at 30 days, and pulmonary complications were analyzed using univariate and multivariable techniques. Pulmonary complications developed in 27.1% (23/85). Mortality at 90 days was 9.4% (8/85). On multivariable analysis, lower bone mineral density (Odds ratio 0.61; 95% confidence interval 0.39-0.95) was associated with decreased survival, longer length of stay (0.83; 0.77-0.89), and readmissions (0.39; 0.15-1.00). Higher lung density 5:lung density 2 volume (1.84; 1.05-3.23), possibly due to scarring, was associated with pulmonary complications and longer length of stay (1.32; 1.23-1.41) while lower subcutaneous fat area:height was associated with readmissions which may reflect decreased metabolic reserve (0.35; 0.13-0.93). Patients with signs of frailty including lower bone mineral density may be at increased risk of adverse outcomes including decreased survival after lung volume reduction surgery. The results of this hypothesis-generating study will need to be confirmed in larger, multicenter trials to determine whether analytic morphomics can improve risk stratification and patient selection.
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Affiliation(s)
- Jules Lin
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan..
| | - William B Weir
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Tyler Grenda
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Peng Zhang
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Brian A Derstine
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Binu Enchakalody
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Joshua Underhill
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Rishindra M Reddy
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Andrew C Chang
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Stewart C Wang
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
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21
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Bariatric Surgery in Patients with Cirrhosis: Careful Patient and Surgery-Type Selection Is Key to Improving Outcomes. Obes Surg 2021; 30:3444-3452. [PMID: 32285332 DOI: 10.1007/s11695-020-04583-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE Previous reports suggest an increased mortality in cirrhotic patients undergoing bariatric surgery (BS). With advancements in management of BS, we aim to study the trends, outcomes, and their predictors in patients with cirrhosis undergoing BS. MATERIALS AND METHODS A retrospective study was performed using the National Database from 2008 to 2013. Outcomes of BS in patients with cirrhosis were studied. In-hospital mortality, length of stay, and cost of care were compared between patients with no cirrhosis (NC), compensated cirrhosis (CC), and decompensated cirrhosis (DC). Multivariable logistic regression analysis was performed to study the predictors of mortality. RESULTS Of the 558,017 admissions of patients who underwent BS during the study period, 3086 (0.55%) had CC and 103 (0.02%) had DC. An upward trend of vertical sleeve gastrectomy (VSG) utilization was seen during the study period. On multivariate analysis, mortality in CC was comparable with those in NC (aOR 1.88; CI 0.65-5.46); however, it was higher in DC (aOR 83.8; CI 19.3-363.8). Other predictors of mortality were older age (aOR 1.06; CI 1.04-1.08), male (aOR 2.59; CI 1.76-3.81), Medicare insurance (aOR 1.93; CI 1.24-3.01), lower income (aORs 0.44 to 0.55 for 2nd to 4th income quartile vs. 1st quartile), > 3 Elixhauser Comorbidity Index (aOR 5.30; CI 3.45-8.15), undergoing Roux-en-Y gastric bypass as opposed to VSG (aOR 3.90; CI 1.79-8.48), and centers performing < 50 BS per year (aOR 5.25; CI 3.38-8.15). Length of stay and hospital cost were also significantly higher in patients with cirrhosis as compared with those with NC. CONCLUSION Patients with compensated cirrhosis can be considered for bariatric surgery. However, careful selection of patients, procedure type, and volume of surgical center is integral in improving outcomes and healthcare utilization in patients with cirrhosis undergoing BS.
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Morphometric Changes in Children With Small Bowel Crohn Disease During Induction of Therapy: A Pilot Study. J Pediatr Gastroenterol Nutr 2021; 72:603-609. [PMID: 33264183 DOI: 10.1097/mpg.0000000000003009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Children and adolescents with Crohn disease (CD) commonly gain weight during treatment induction, which is thought to be a marker of better health. Body composition is, however, rarely assessed at diagnosis, and changes during early treatment are not often quantified. Therefore, it is unknown if these gains are truly healthy. We sought to evaluate skeletal muscle changes during initial treatment for CD by using routine imaging. METHODS Single-center prospective study. Pediatric patients diagnosed with small bowel CD underwent serial magnetic resonance enterography (MRE) imaging, laboratory testing, and disease-activity assessment, at diagnosis, 1 and 6 months of treatment. MRE-based cross-sectional morphometry was used to measure psoas muscle cross sectional area (CSA). Psoas CSA z-scores were calculated using normative data. RESULTS We enrolled 30 children (ages 9--17 years). Twenty-eight of 30 (93%) received anti-tumor necrosis factor therapy and 4 required surgical resection. Children with below-average psoas CSA and body mass index (BMI) z-scores at diagnosis were much more likely to fail treatment or undergo surgery by 6 months compared with those with higher z-scores (55% vs 0%; P = 0.001). Children with no activity limitations at diagnosis had significantly larger muscle gains in the first month, compared with those whose activity was limited at diagnosis (P = 0.012). Most patients had higher psoas CSA z-scores by 6 months, and these increases were associated with weight and BMI z-score increases. CONCLUSIONS Skeletal muscle growth contributes to weight gain during treatment induction in most patients with CD. Psoas muscle CSA on diagnostic imaging may have prognostic value in children with CD.
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Ivanics T, Abreu P, De Martin E, Sapisochin G. Changing Trends in Liver Transplantation: Challenges and Solutions. Transplantation 2021; 105:743-756. [PMID: 32910093 DOI: 10.1097/tp.0000000000003454] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Despite improvements in postliver transplant outcomes through refinements in perioperative management and surgical techniques, several changing trends in liver transplantation have presented challenges. Mortality on the waitlist remains high. In the United States, Europe, and the United Kingdom, there is an increasing need for liver transplantation, primarily as a result of increased incidence of nonalcoholic steatohepatitis-related cirrhosis and cancer indications. Meanwhile, donor suitability has decreased, as donors are often older and have more comorbidities. Despite a mismatch between organ need and availability, many organs are discarded. Notwithstanding this, many solutions have been developed to overcome these challenges. Innovative techniques in allograft preservation, viability assessment, and reconditioning have allowed the use of suboptimal organs with adequate results. Refinements in surgical procedures, including live donor liver transplantations, have increased the organ pool and are decreasing the time and mortality on the waitlist. Despite many challenges, a similar number of solutions and prospects are on the horizon. This review seeks to explore the changing trends and challenges in liver transplantation and highlight possible solutions and future directions.
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Affiliation(s)
- Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Phillipe Abreu
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Eleonora De Martin
- APHP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM 1193, Université Paris-Sud, DHU Hepatinov, Villejuif, France
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
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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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Abstract
Obesity is increasing in prevalence in liver transplant candidates and recipients. The rise in liver transplantation for nonalcoholic steatohepatitis reflects this increase. Management of obesity in liver transplant candidates can be challenging due to the presence of decompensated cirrhosis and sarcopenia. Obesity may increase peritransplant morbidity but does not have an impact on long-term post-transplant survival. Bariatric surgery may be a feasible option in select patients before, during, or after liver transplantation. Use of weight loss drugs and/or endoscopic therapies for obesity management ultimately may play a role in liver transplant patients, but more research is needed to determine safety.
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Malamutmann E, Frenzen A, Karadag HI, Emre A, Klein CG, Paul A, Oezcelik A. Inner Abdominal Fat and Psoas Muscle as Predictive Factors for the Outcome After Liver Transplant. EXP CLIN TRANSPLANT 2021; 19:131-136. [PMID: 33455566 DOI: 10.6002/ect.2020.0265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVES We analyzed the nutritional condition of liver transplant recipients and the body mass index, the inner abdominal fat tissue, the outer abdominal fat tissue, the psoas muscle size, and the psoas muscle index of the recipients and evaluated the effects of these factors on patient outcomes after liver transplant. MATERIALS AND METHODS We included recipients of liver transplants from January 2009 to December 2018 who had computed tomography at our center < 3 months before transplant. Preoperative, intraoperative, and postoperative data were evaluated. Outer abdominal fat tissue, inner abdominal fat tissue, and psoas muscle area were measured on the computed tomography abdominal images. We used univariate and multi-variate regression analyses to evaluate the data. RESULTS There were 265 patients; mean age was 54 years (SD, 13 years). The mean value for body mass index, calculated as weight in kilograms divided by height in meters squared, was 25 (SD, 5). The mean score for Model for End-Stage Liver Disease was 17 (SD, 6). All patients underwent orthotopic liver transplant by standard technique. After adjustment for multivariable analysis, the values for psoas muscle size and the psoas muscle index of the recipient were associated as independent factors for postoperative complications and duration of hospital stay. The survival rate at 1 year was 78.5%, and the rate of perioperative mortality was 16.6%. Independent factors associated with survival after liver transplant were inner abdominal fat tissue, etiology, and rate of major postoperative complications. CONCLUSIONS Inner abdominal fat tissue, psoas muscle size, and the psoas muscle index are significantly associated with postoperative complications and/or survival after liver transplant. Our results suggest that these prognostic factors may be useful to optimize the selection of appropriate candidates for liver transplant.
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Affiliation(s)
- Eugen Malamutmann
- From the Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
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Rozenberg D, Orsso CE, Chohan K, Orchanian‐Cheff A, Nourouzpour S, Nicholson JM, Elangeswaran B, Vagaon A, Fidler L, Singer LG, Mathur S. Clinical outcomes associated with computed tomography‐based body composition measures in lung transplantation: a systematic review. Transpl Int 2020; 33:1610-1625. [DOI: 10.1111/tri.13749] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/24/2020] [Accepted: 09/13/2020] [Indexed: 12/16/2022]
Affiliation(s)
- Dmitry Rozenberg
- Department of Medicine University of Toronto Toronto ON Canada
- Lung Transplant Program Respirology Toronto General Hospital Research InstituteUniversity Health Network Toronto ON Canada
| | - Camila E. Orsso
- Department of Agricultural, Food and Nutritional Science University of Alberta Edmonton AB Canada
| | - Karan Chohan
- Department of Medicine University of Toronto Toronto ON Canada
| | - Ani Orchanian‐Cheff
- Library and Information Services University Health Network Toronto ON Canada
| | - Sahar Nourouzpour
- Lung Transplant Program Respirology Toronto General Hospital Research InstituteUniversity Health Network Toronto ON Canada
| | | | - Brenawen Elangeswaran
- Lung Transplant Program Respirology Toronto General Hospital Research InstituteUniversity Health Network Toronto ON Canada
| | - Andrei Vagaon
- Department of Medicine University of Toronto Toronto ON Canada
| | - Lee Fidler
- Department of Medicine University of Toronto Toronto ON Canada
- Respirology Sunnybrook Health Sciences Centre Toronto ON Canada
| | - Lianne G. Singer
- Department of Medicine University of Toronto Toronto ON Canada
- Lung Transplant Program Respirology Toronto General Hospital Research InstituteUniversity Health Network Toronto ON Canada
| | - Sunita Mathur
- Department of Physical Therapy University of Toronto Toronto ON Canada
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Benmassaoud A, Deschenes M, Chen T, Ghali P, Sebastiani G. Optimizing patients with non-alcoholic fatty liver disease pre-transplant. CANADIAN LIVER JOURNAL 2020; 3:237-250. [PMID: 35992526 PMCID: PMC9202706 DOI: 10.3138/canlivj-2019-0025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 11/17/2019] [Indexed: 06/01/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Non-alcoholic steatohepatitis (NASH), which is the progressive counterpart of the disease, is becoming the leading indication for liver transplantation in North America. Owing to the lack of symptoms, NASH is often an incidental diagnosis, resulting in a significant proportion of patients being diagnosed when advanced liver disease has already developed. NAFLD has recently been characterized as the hepatic manifestation of metabolic syndrome. Consequently, it is a multisystem disease that often co-exists with several other conditions, such as obesity, diabetes, cardiovascular diseases, and extra-hepatic malignancy, which have an impact on selection of transplant recipients. The complexity of diagnostic approach, need for multidisciplinary clinical management, and lack of a specific treatment further complicate the picture of this extremely prevalent liver condition. NAFLD patients with advanced liver disease should be considered for early referral to liver transplant clinics for careful metabolic and cardiovascular risk stratification because they have worse survival rates after liver transplantation than other patients with chronic liver disease. Early referral will also facilitate optimization of metabolic comorbidities before proceeding with transplantation. This review provides an overview of strategies to identify patients with advanced NAFLD, with an emphasis on the management of associated comorbidities and optimal timing of pre-transplant evaluation. Other topics that have been shown to affect recipient optimization, such as the role of lifestyle changes and bariatric surgery in the management of obesity, as well as sarcopenia in decompensated NASH-related cirrhosis, are addressed.
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Affiliation(s)
- Amine Benmassaoud
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marc Deschenes
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Tianyan Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Peter Ghali
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Gastroenterology, Department of Medicine, University of Florida, Jacksonville, Florida, USA
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Chronic Viral Illness Service, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
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Automated Measurements of Muscle Mass Using Deep Learning Can Predict Clinical Outcomes in Patients With Liver Disease. Am J Gastroenterol 2020; 115:1210-1216. [PMID: 32467506 PMCID: PMC7415547 DOI: 10.14309/ajg.0000000000000662] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION There is increasing recognition of the central role of muscle mass in predicting clinical outcomes in patients with liver disease. Muscle size can be extracted from computed tomography (CT) scans, but clinical implementation will require increased automation. We hypothesize that we can achieve this by using artificial intelligence. METHODS Using deep convolutional neural networks, we trained an algorithm on the Reference Analytic Morphomics Population (n = 5,268) and validated the automated methodology in an external cohort of adult kidney donors with a noncontrast CT scan (n = 1,655). To test the clinical usefulness, we examined its ability to predict clinical outcomes in a prospectively followed cohort of patients with clinically diagnosed cirrhosis (n = 254). RESULTS Between the manual and automated methodologies, we found excellent inter-rater agreement with an intraclass correlation coefficient of 0.957 (confidence interval 0.953-0.961, P < 0.0001) in the adult kidney donor cohort. The calculated dice similarity coefficient was 0.932 ± 0.042, suggesting excellent spatial overlap between manual and automated methodologies. To assess the clinical usefulness, we examined its ability to predict clinical outcomes in a cirrhosis cohort and found that automated psoas muscle index was independently associated with mortality after adjusting for age, gender, and child's classification (P < 0.001). DISCUSSION We demonstrated that deep learning techniques can allow for automation of muscle measurements on clinical CT scans in a diseased cohort. These automated psoas size measurements were predictive of mortality in patients with cirrhosis showing proof of principal that this methodology may allow for wider implementation in the clinical arena.
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Armenian SH, Iukuridze A, Teh JB, Mascarenhas K, Herrera A, McCune JS, Zain JM, Mostoufi‐Moab S, McCormack S, Slavin TP, Scott JM, Jones LW, Sun C, Forman SJ, Wong FL, Nakamura R. Abnormal body composition is a predictor of adverse outcomes after autologous haematopoietic cell transplantation. J Cachexia Sarcopenia Muscle 2020; 11:962-972. [PMID: 32212263 PMCID: PMC7432567 DOI: 10.1002/jcsm.12570] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/27/2020] [Accepted: 02/25/2020] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non-malignant diseases and may predict outcomes after autologous HCT. METHODS This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non-Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male: <43 cm/m2 [body mass index (BMI) < 25 kg/m2 ] or < 53 cm/m2 [BMI ≥ 25 kg/m2 ] and female: <41 cm/m2 [regardless of BMI]) and obesity [total abdominal adiposity ≥450.0 cm2 (male), ≥396.4 cm2 (female)] were assessed from single-slice abdominal pre-HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30-day unplanned readmission were evaluated based on body composition using multivariable regression analysis, and mortality was evaluated with Kaplan-Meier analysis and Gray's test. RESULTS Median age at HCT was 53.3 years (range, 18.5 to 78.1 years); 26.3% were sarcopenic and an additional 7.8% were sarcopenic obese pre-HCT. Sarcopenic obesity was associated with increased risk of prolonged hospitalization [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.3-9.8], intensive care unit admission (OR = 4.7, 95% CI 1.5-16.1), and unplanned readmission after HCT (OR = 13.6, 95% CI 2.5-62.8). Patients who were sarcopenic obese also had the highest mortality risk at 1 year [hazard ratio (HR): 3.9, 95% CI 1.1-11.0] and 5 years (HR: 2.5, 95% CI 1.1-5.5), compared with patients with normal body composition. Sarcopenia alone, but not obesity alone, was associated with an increased risk of these outcomes, albeit with a lower magnitude of risk than in patients who were sarcopenic obese. CONCLUSIONS Sarcopenic obesity was an important predictor of outcomes in patients undergoing autologous HCT. These findings could inform targeted prevention strategies in patients at highest risk of complications after HCT.
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Affiliation(s)
| | | | | | | | - Alex Herrera
- Department of Hematology and Hematopoietic Cell TransplantationCity of HopeDuarteCAUSA
| | | | - Jasmine M. Zain
- Department of Hematology and Hematopoietic Cell TransplantationCity of HopeDuarteCAUSA
| | - Sogol Mostoufi‐Moab
- Department of PediatricsChildren's Hospital of PhiladelphiaPhiladelphiaPAUSA
| | - Shana McCormack
- Department of PediatricsChildren's Hospital of PhiladelphiaPhiladelphiaPAUSA
| | | | - Jessica M. Scott
- Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkNYUSA
| | - Lee W. Jones
- Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkNYUSA
- Department of MedicineWeill Cornell Medical CenterNew YorkNYUSA
| | - Can‐Lan Sun
- Department of Supportive Care MedicineCity of HopeDuarteCAUSA
| | - Stephen J. Forman
- Department of Hematology and Hematopoietic Cell TransplantationCity of HopeDuarteCAUSA
| | - F. Lennie Wong
- Department of Population SciencesCity of HopeDuarteCAUSA
| | - Ryotaro Nakamura
- Department of Hematology and Hematopoietic Cell TransplantationCity of HopeDuarteCAUSA
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Ebadi M, Bhanji RA, Tandon P, Mazurak V, Baracos VE, Montano-Loza AJ. Review article: prognostic significance of body composition abnormalities in patients with cirrhosis. Aliment Pharmacol Ther 2020; 52:600-618. [PMID: 32621329 DOI: 10.1111/apt.15927] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/17/2020] [Accepted: 06/09/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recent advances in evaluation of body composition show body mass index to be inadequate in differentiating between body compartments in cirrhosis. Given the limitations of body mass index, body composition evaluation using computed tomography has been increasingly used as a non-invasive clinical tool with prognostic value. Another factor influencing prognosis includes sex-specific differences in body composition that are seen in cirrhosis. AIM To review current knowledge regarding the frequency and clinical implications of abnormal body composition features in cirrhosis. METHODS We searched PubMed database and limited the literature search to full-text papers published in English. Studies using inappropriate landmarks or demarcation of body composition components on computed tomography images were eliminated. RESULTS Sarcopenia is a well established factor affecting morbidity and mortality in cirrhosis. Other important body composition components that have been overlooked thus far include subcutaneous adipose tissue and visceral adipose tissue. Female patients with cirrhosis and low subcutaneous adiposity have a higher risk of mortality, whereas male patients with high visceral adiposity have a higher risk of hepatocellular carcinoma and recurrence following liver transplantation. Increased adipose tissue radiodensity has been associated with risk of decompensation and mortality. CONCLUSIONS Further evaluation of body composition abnormalities may help with development of targeted therapeutic strategies and improve outcome in patients with cirrhosis. Moreover, recognition of these abnormalities could improve prioritisation for liver transplantation as our current method based solely on liver function might lead to risk misclassification.
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Affiliation(s)
- Maryam Ebadi
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Rahima A Bhanji
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Puneeta Tandon
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Vera Mazurak
- Division of Human Nutrition, University of Alberta, Edmonton, AB, Canada
| | - Vickie E Baracos
- Department of Oncology, Cross Cancer Institute, Edmonton, AB, Canada
| | - Aldo J Montano-Loza
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
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Abstract
BACKGROUND AND AIM Body composition has emerged as a prognostic factor for end-stage liver disease. We therefore investigated muscle mass, body fat and other clinical-pathological variables as predictors of posttransplant survival. METHODS A total of 368 patients, who underwent orthotopic liver transplantation (OLT) at our institution, were assessed prior to OLT and followed for a median of 9.0 years (range 2.0-10.0 years) after OLT. Psoas, erector spinae and the combined paraspinal muscle area, as well as the corresponding indices normalized by body-height squared, were quantified by a lumbar (L3) cross-sectional computed tomography. In addition, absolute body fat and bone density were estimated by the same computed tomography approach. RESULTS Paraspinal muscle index (PSMI) (hazard ratio 0.955, P = 0.039) and hepatitis C (hazard rati 1.498, P = 0.038) were independently associated with post-OLT mortality. In contrast, body fat and bone density did not significantly affect post-OLT outcome (P > 0.05). The PSMI also predicted one-year posttransplant mortality with a receiver operating characteristics-area under the curve of 0.671 [95% confidence interval (CI) 0.589-0.753, P < 0.001) in male patients and outperformed individual psoas and erector spinae muscle group assessments in this regard. In male patients, a defined PSMI cutoff (<18.41 cm/m) was identified as suitable determinant for sarcopenia and posttransplant one-year mortality. In female OLT-recipients, however, sarcopenia was not predictive for patient survival und a women-specific cutoff could not be derived from this study. CONCLUSIONS Taken together this analysis provides evidence, which PSMI is a relevant marker for muscle mass and that sarcopenia is an independent predictor of early post-OLT survival in male patients.
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Ferguson MK, Mitzman B, Derstine B, Lee SM, Pienta MJ, Wang SC, Lin J. A Morphomic Index Is an Independent Predictor of Survival After Lung Cancer Resection. Ann Thorac Surg 2019; 109:873-878. [PMID: 31862495 DOI: 10.1016/j.athoracsur.2019.10.064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 09/17/2019] [Accepted: 10/18/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Sarcopenia, visceral fat volume, and bone density have been associated with lung cancer survival. We developed a morphomic index based on computed tomographic measurements of these components, and assessed its relationship to survival after lung cancer resection. METHODS Patients who underwent lung cancer resection from 1995 to 2014 were evaluated. A morphomic index (range of 0 to 3) was developed as the sum of the scores for three body components-dorsal muscle area, vertebral trabecular bone density, and visceral fat area-measured at vertebral levels T10 to T12, with a point assigned to each component when in the lowest tercile. The relationship of the morphomic index to overall survival was assessed by the log rank test. Overall survival was assessed using Cox proportional hazards models adjusted for relevant covariates. RESULTS We included 944 patients (451 women; 48%). The mean age was 66.4 ± 10.3 years. Median follow-up was 4.5 years. Median survival was associated with the morphomic index scores on univariate analysis (P < .001). Morphomic index scores of 2 (P = .026) and 3 (P = .004) referenced to score 0 or 1 were independent predictors of survival on Cox regression analysis. CONCLUSIONS A morphomic index is an independent predictor of survival after lung cancer resection. The index may help in calibrating patient expectations and in shared decision making regarding lung cancer surgery.
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Affiliation(s)
- Mark K Ferguson
- Department of Surgery, University of Chicago, Chicago, Illinois.
| | - Brian Mitzman
- Department of Cardiothoracic Surgery, NYU Langone Health, New York, New York
| | - Brian Derstine
- Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Sang Mee Lee
- Department of Public Health Sciences, University of Chicago, Chicago, Illinois
| | - Michael J Pienta
- Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Stewart C Wang
- Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Jules Lin
- Department of Surgery, University of Michigan, Ann Arbor, Michigan
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Tapper EB, Zhang P, Garg R, Nault T, Leary K, Krishnamurthy V, Su GL. Body composition predicts mortality and decompensation in compensated cirrhosis patients: A prospective cohort study. JHEP Rep 2019; 2:100061. [PMID: 32039402 PMCID: PMC7005567 DOI: 10.1016/j.jhepr.2019.11.005] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 10/28/2019] [Accepted: 11/15/2019] [Indexed: 12/13/2022] Open
Abstract
Background & Aims Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. Methods A total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. Results Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p <0.001) as well as visceral and subcutaneous fat density (HR 1.013 and 1.014, respectively, p <0.001). Models utilizing these features outperformed MELD alone for mortality discrimination in both the derivation and validation cohort, particularly for those with compensated cirrhosis (C-statistics of 0.74 vs. 0.58). Using competing risk analysis, we found that subcutaneous fat density was most predictive of decompensation (subdistribution HR 1.018, p = 0.0001). Conclusion The addition of body composition features to predictive models improves the prospective determination of prognosis in patients with cirrhosis, particularly those with compensated disease. Fat density, a novel feature, is associated with the risk of decompensation. Lay summary Am I at high risk of getting sicker and dying? This is the key question on the mind of patients with cirrhosis. The problem is that we have very few tools to help guide our patients, particularly if they have early cirrhosis (without symptoms like confusion or fluid in the belly). We found that how much muscle and fat the patient has and what that muscle or fat looks like on a CT scan provide helpful information. This is important because many patients have CT scans and this information is hiding in plain sight.
Features of body composition can predict clinical outcomes in patients with cirrhosis awaiting liver transplantation. Data are lacking regarding long-term outcomes among patients with compensated disease. We show that features of muscle and fat are associated with decompensation and risk of death across the spectrum of cirrhosis. CT scans obtained for unrelated clinical purposes can be analyzed as a digital risk biomarker for patients with compensated cirrhosis.
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.,Institute for Healthcare Policy and Innovation, Ann Arbor, Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan
| | - Peng Zhang
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Rohan Garg
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Tori Nault
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Kate Leary
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Venkat Krishnamurthy
- Radiology Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan.,Department of Radiology, University of Michigan, Ann Arbor, Michigan
| | - Grace L Su
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan
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Anderson MR, Udupa JK, Edwin E, Diamond JM, Singer JP, Kukreja J, Hays SR, Greenland JR, Ferrante A, Lippel M, Blue T, McBurnie A, Oyster M, Kalman L, Rushefski M, Wu C, Pednekar G, Liu W, Arcasoy S, Sonett J, D'Ovidio F, Bacchetta M, Newell JD, Torigian D, Cantu E, Farber DL, Giles JT, Tong Y, Palmer S, Ware LB, Hancock WW, Christie JD, Lederer DJ. Adipose tissue quantification and primary graft dysfunction after lung transplantation: The Lung Transplant Body Composition study. J Heart Lung Transplant 2019; 38:1246-1256. [PMID: 31474492 PMCID: PMC6883162 DOI: 10.1016/j.healun.2019.08.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 07/30/2019] [Accepted: 08/05/2019] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Obesity is associated with an increased risk of primary graft dysfunction (PGD) after lung transplantation. The contribution of specific adipose tissue depots is unknown. METHODS We performed a prospective cohort study of adult lung transplant recipients at 4 U.S. transplant centers. We measured cross-sectional areas of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on chest and abdominal computed tomography (CT) scans and indexed each measurement to height.2 We used logistic regression to examine the associations of adipose indices and adipose classes with grade 3 PGD at 48 or 72 hours, and Cox proportional hazards models to examine survival. We used latent class analyses to identify the patterns of adipose distribution. We examined the associations of adipose indices with plasma biomarkers of obesity and PGD. RESULTS A total of 262 and 117 subjects had available chest CT scans and underwent protocol abdominal CT scans, respectively. In the adjusted models, a greater abdominal SAT index was associated with an increased risk of PGD (odds ratio 1.9, 95% CI 1.02-3.4, p = 0.04) but not with survival time. VAT indices were not associated with PGD risk or survival time. A greater abdominal SAT index correlated with greater pre- and post-transplant leptin (r = 0.61, p < 0.001, and r = 0.44, p < 0.001), pre-transplant IL-1RA (r = 0.25, p = 0.04), and post-transplant ICAM-1 (r = 0.25, p = 0.04). We identified 3 latent patterns of adiposity. The class defined by high thoracic and abdominal SAT had the greatest risk of PGD. CONCLUSIONS Subcutaneous, but not visceral, adiposity is associated with an increased risk of PGD after lung transplantation.
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Affiliation(s)
- Michaela R Anderson
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Jayaram K Udupa
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ethan Edwin
- Columbia Institute of Human Nutrition, Columbia University Medical Center, New York, New York
| | - Joshua M Diamond
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jonathan P Singer
- Department of Medicine University of California at San Francisco, San Francisco, California
| | - Jasleen Kukreja
- Department of Surgery, University of California at San Francisco, San Francisco, California
| | - Steven R Hays
- Department of Medicine University of California at San Francisco, San Francisco, California
| | - John R Greenland
- Department of Medicine University of California at San Francisco, San Francisco, California
| | - Anthony Ferrante
- Columbia Institute of Human Nutrition, Columbia University Medical Center, New York, New York
| | - Matthew Lippel
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Tatiana Blue
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Amika McBurnie
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Michelle Oyster
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Laurel Kalman
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Melanie Rushefski
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Caiyun Wu
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Gargi Pednekar
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Wen Liu
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Selim Arcasoy
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Joshua Sonett
- Department of Surgery, Columbia University Medical Center, New York, New York
| | - Frank D'Ovidio
- Department of Surgery, Columbia University Medical Center, New York, New York
| | - Matthew Bacchetta
- Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - John D Newell
- Department of Radiology, University of Iowa, Iowa City, Iowa
| | - Drew Torigian
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Edward Cantu
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Donna L Farber
- Department of Surgery, University of California at San Francisco, San Francisco, California; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York; Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York
| | - Jon T Giles
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Yubing Tong
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Scott Palmer
- Department of Medicine, Duke University & Duke Clinical Research Institute, Durham, North Carolina
| | - Lorraine B Ware
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Wayne W Hancock
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jason D Christie
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - David J Lederer
- Department of Medicine, Columbia University Medical Center, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, New York.
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Zhang W, Huang R, Wang Y, Rao H, Wei L, Su GL, Lok AS. Fat Accumulation, Liver Fibrosis, and Metabolic Abnormalities in Chinese Patients With Moderate/Severe Versus Mild Hepatic Steatosis. Hepatol Commun 2019; 3:1585-1597. [PMID: 31832569 PMCID: PMC6887912 DOI: 10.1002/hep4.1435] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022] Open
Abstract
Several drugs in development for nonalcoholic fatty liver disease (NAFLD) aim to decrease the amount of fat in the liver. We compared quantity and quality of fat in subcutaneous, visceral and muscle compartments, liver fibrosis, and prevalence of metabolic abnormalities between Chinese patients with moderate/severe hepatic steatosis versus those with mild hepatic steatosis. NAFLD patients were prospectively recruited from Peking University People's Hospital in Beijing, China. All patients had baseline body composition measurements using computed tomography and analytic morphomics, clinical evaluation, labs and Fibroscan® controlled attenuation parameter and liver stiffness measurement. Moderate/severe hepatic steatosis was defined as computed tomography liver attenuation of 40 Hounsfield units or less. Calorie intake and physical activity were based on self-report. A total of 160 NAFLD patients were included (46% men, median age 47 years): 50% had normal body mass index (BMI), 24% were diabetic, and 56% had metabolic syndrome (MS). Fifty-three (33%) had moderate/severe steatosis, of whom 19 (35.8%) had normal BMI, and the rest had mild steatosis. Patients who had moderate/severe steatosis had significantly higher BMI, waist circumference, aminotransferases, controlled attenuation parameter, liver stiffness measurement, and prevalence of MS compared to those with mild steatosis. They also had larger visceral fat area, subcutaneous fat area, and low density dorsal muscle area. In addition, their calorie intake was higher and time spent on recreation activities was shorter. Conclusion: NAFLD patients with moderate/severe steatosis, including those with normal BMI, had higher prevalence of MS and more fat in visceral, subcutaneous, and muscle compartments than those with mild steatosis. They also had more advanced liver disease. Strategies to decrease hepatic fat may benefit both liver and metabolic diseases.
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Affiliation(s)
- Wei Zhang
- Peking University Hepatology InstitutePeking University People's HospitalBeijingChina
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMI
- National Center for International Cooperation on Translational and Clinical ResearchPeking University Health Sciences CenterBeijingChina
| | - Rui Huang
- Peking University Hepatology InstitutePeking University People's HospitalBeijingChina
- National Center for International Cooperation on Translational and Clinical ResearchPeking University Health Sciences CenterBeijingChina
| | - Yi Wang
- Department of RadiologyPeking University People's HospitalBeijingChina
- National Center for International Cooperation on Translational and Clinical ResearchPeking University Health Sciences CenterBeijingChina
| | - Huiying Rao
- Peking University Hepatology InstitutePeking University People's HospitalBeijingChina
- National Center for International Cooperation on Translational and Clinical ResearchPeking University Health Sciences CenterBeijingChina
| | - Lai Wei
- Peking University Hepatology InstitutePeking University People's HospitalBeijingChina
- National Center for International Cooperation on Translational and Clinical ResearchPeking University Health Sciences CenterBeijingChina
| | - Grace L. Su
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMI
- GI SectionVA Ann Arbor Healthcare SystemAnn ArborMI
| | - Anna S. Lok
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMI
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Obesity in the Liver Transplant Setting. Nutrients 2019; 11:nu11112552. [PMID: 31652761 PMCID: PMC6893648 DOI: 10.3390/nu11112552] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 09/23/2019] [Accepted: 09/25/2019] [Indexed: 12/12/2022] Open
Abstract
The obesity epidemic has resulted in an increased prevalence of obesity in liver transplant (LT) candidates and in non-alcoholic fatty liver disease (NAFLD) becoming the fastest growing indication for LT. LT teams will be dealing with obesity in the coming years, and it is necessary for them to recognize some key aspects surrounding the LT in obese patients. Obesity by itself should not be considered a contraindication for LT, but it should make LT teams pay special attention to cardiovascular risk assessment, in order to properly select candidates for LT. Obese patients may be at increased risk of perioperative respiratory and infectious complications, and it is necessary to establish preventive strategies. Data on patient and graft survival after LT are controversial and scarce, especially for long-term outcomes, but morbid obesity may adversely affect these outcomes, particularly in NAFLD. The backbone of obesity treatment should be diet and exercise, whilst being careful not to precipitate or worsen frailty and sarcopenia. Bariatric surgery is an alternative for treatment of obesity, and the ideal timing regarding LT is still unknown. Sleeve gastrectomy is probably the procedure that has the best evidence in LT because it offers a good balance between safety and efficacy.
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Kamo N, Kaido T, Hamaguchi Y, Okumura S, Kobayashi A, Shirai H, Yao S, Yagi S, Uemoto S. Impact of sarcopenic obesity on outcomes in patients undergoing living donor liver transplantation. Clin Nutr 2019; 38:2202-2209. [DOI: 10.1016/j.clnu.2018.09.019] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 09/11/2018] [Accepted: 09/12/2018] [Indexed: 12/17/2022]
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Ahn JC, Sundaram V. Obesity and Liver Decompensation. Clin Liver Dis (Hoboken) 2019; 14:12-15. [PMID: 31391930 PMCID: PMC6677014 DOI: 10.1002/cld.807] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 01/08/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Joseph C. Ahn
- Department of Internal MedicineCedars‐Sinai Medical CenterLos AngelesCA
| | - Vinay Sundaram
- Division of Gastroenterology and Comprehensive Transplant CenterCedars‐Sinai Medical CenterLos AngelesCA
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Visceral Obesity and Open Passive Drainage Increase the Risk of Pancreatic Fistula Following Distal Pancreatectomy. J Gastrointest Surg 2019; 23:1414-1424. [PMID: 30120668 DOI: 10.1007/s11605-018-3878-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Accepted: 07/10/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND The predictive risk factors of clinically relevant pancreatic fistula (CR-PF) following distal pancreatectomy (DP) remain to be identified. METHODS This is a retrospective cohort analysis of a single-institution database of patients undergoing DP, taking into account usual demographic, operative, and pathologic variables and visceral fat area (VFA), total muscle area (TMA), and surface muscle index (SMI) measured on preoperative CT scan. The primary end point was CR-PF. All variables associated with a p value < 0.05 on univariate analysis were included in a logistic regression model for multivariate analysis. RESULTS From 2012 to 2016, 208 patients operated by 4 pancreatic surgeons underwent DP including 32 (15%) who developed CR-PF. Risk factors of CR-PF on univariate analysis were: BMI ≥ 25 kg/m2 (p = 0.050), VFA ≥ 92 cm2 (p = 0.006), laparotomy (p = 0.023), main pancreatic duct dilatation (p = 0.035), open passive drainage (versus closed suction drainage) (p = 0.001), and blood loss ≥ 225 ml (p = 0.001). Sarcopenia did not influence the risk of CR-PF (p = 0.076). On multivariate analysis, VFA ≥ 92 cm2 (OR 3.14; IC 95% (1.18-8.31), p = 0.022), blood loss ≥ 225 ml (OR: 2.72; IC 95% (1.06-6.96), p = 0.037), and open passive drainage (OR 3.72; IC 95% (1.40-9.87) p = 0.008) were three independent predictive factors of CR-PF. A CR-PF risk score was developed, predicting a 0% risk of CR-PF when no risk factors were present and a 39% risk when the 3 risk factors were present. CONCLUSIONS Visceral obesity, blood loss ≥ 225 ml and open passive drainage significantly increase the risk of CR-PF following DP.
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Shi Y, Huang B, Deng R, Ma Y. The Association of obesity with vascular complications after liver transplantation. BMC Gastroenterol 2019; 19:39. [PMID: 30845923 PMCID: PMC6407261 DOI: 10.1186/s12876-019-0954-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 02/19/2019] [Indexed: 12/14/2022] Open
Abstract
Background Because of the growing number of obese patients undergoing liver transplantation (LT), it is important to investigate the impact of obesity on post-transplant outcomes. Vascular complications are rare, but serious causes of morbidity and mortality after LT. It is not known if pre-transplant obesity is associated with an increased incidence of post-LT vascular complications. Methods Medline, Embase, and Cochrane Library databases were searched in September 2017. The primary outcome was the impact of obesity on the vascular complication rate in adult LT recipients. Survival and biliary complications rates were also analyzed. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare pooled data between groups with a body mass index (BMI) ≥ 30 kg/m2 and < 30 kg/m2. Results Six retrospective cohort studies with a total of 987 patients with a BMI ≥ 30 kg/m2 (high BMI group) and 2911 patients with a BMI < 3 0 kg/m2 (control group) were included in the analysis. All studies had Newcastle-Ottawa Scale scores ≥4. The vascular complication rates were similar between the high BMI group and control group (RR = 1.13, 95% CI: 0.87–1.47, P = 0.27), as were the patient survival, graft survival, and biliary complication rates. In subgroup analysis, there was no difference in the vascular complication rates between BMI ≥ 35 vs. BMI < 25 kg/m2; BMI 30–35 vs. BMI 18–25 kg/m2; BMI ≥ 30 vs. BMI 18–25 kg/m2; and BMI ≥ 35 vs. BMI < 35 kg/m2. No difference was found in subgroup analysis when BMI was adjusted for ascites. However, recipients whose primary disease was alcoholic liver disease, those with a BMI ≥ 30 kg/m2 had higher incidence of vascular complications than those with a BMI < 30 kg/m2 (RR = 1.55, 95% CI: 1.07–2.25, P = 0.02) . Conclusions BMI does not affect incidence of vascular complications after LT. High pre-transplant BMI is not a risk factor for patient survival and biliary complications after LT. Electronic supplementary material The online version of this article (10.1186/s12876-019-0954-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yi Shi
- Department of Organ Transplantation, First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, China
| | - Bingsong Huang
- Department of Organ Transplantation, First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, China
| | - Ronghai Deng
- Department of Organ Transplantation, First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, China.
| | - Yi Ma
- Department of Organ Transplantation, First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, China.
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Bhanji RA, Takahashi N, Moynagh MR, Narayanan P, Angirekula M, Mara KC, Dierkhising RA, Watt KD. The evolution and impact of sarcopenia pre- and post-liver transplantation. Aliment Pharmacol Ther 2019; 49:807-813. [PMID: 30714184 DOI: 10.1111/apt.15161] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Revised: 10/10/2018] [Accepted: 01/02/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Sarcopenia is associated with both increased wait-list mortality and mortality following liver transplantation. AIMS To determine the course of sarcopenia from transplant evaluation until 1 year post-transplant, and its implications on hospitalisation and mortality following liver transplantation. METHODS Two hundred and ninety-three transplant recipients from 2002 to 2006 had pre-transplant CT scans analysed at the third lumbar region for sarcopenia, myosteatosis and abdominal visceral fat content. Half the recipients had post-transplant CT scan for interpretation (161/293). RESULTS Sarcopenia was present in 146/293 (50%) of the patients pre-transplant. There was a significant decrease in muscle mass (loss 2.0 ± 4.9 cm2 /m2 ; P < 0.001), and an increase in myosteatosis while awaiting liver transplantation. There was no significant change in abdominal visceral fat. For every 1 cm2 /m2 decrease in muscle mass there was an increase in post-transplant length of stay by 0.36 days (P = 0.005). Post-transplant, 98/161 (61%) of patients with CT imaging had sarcopenia (25 de novo and 73 persistent), with continued increase in myosteatosis, lower Hounsfield units (-5.0 [IQR -8.6 to 0.1]; P < 0.001) and an increase in abdominal visceral fat (4.9 [IQR -4.4 to 15.6] cm2 /m2 ; P < 0.001). There was no statistically significant difference in 1-year mortality in patients with de novo sarcopenia compared to patients with sarcopenia both pre- and post-transplant (HR 1.88; P = 0.088). CONCLUSIONS Sarcopenia progresses up to 1 year following liver transplantation and is associated with an increase in post-transplant length of stay.
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Affiliation(s)
- Rahima A Bhanji
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Praveena Narayanan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Mounika Angirekula
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Kristin C Mara
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Ross A Dierkhising
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Abstract
PURPOSE OF REVIEW Sarcopenia is highly prevalent in end-stage liver disease (ESLD) patients and has been linked to poor outcomes on the wait list and post-transplantation. This current perspectives article reviews the ongoing challenges to define sarcopenia in ESLD patients, describes associations of sarcopenia with wait-list and post-transplantation outcomes, and provides summarized data on efforts to prevent and treat sarcopenia through novel interventions. RECENT FINDINGS Supervised exercise programs improve muscle strength, but muscle mass outcomes are limited by short study follow-up times. Branched chain amino acid supplementation may ameliorate sarcopenia in ESLD patients, but studies limited by low participant numbers and confounding. Myostatin inhibition shown to improve sarcopenia in elderly, frail patients; further study needed in ESLD patients. Correction of low testosterone improves sarcopenia in male ESLD patients. SUMMARY Recent literature supports sarcopenia as an independent risk factor for poor outcomes in ESLD patients. Ongoing study is limited by poor standardization of sarcopenia definition and relevant muscle-mass cutoffs. Supervised exercise programs should be encouraged for all ESLD patients. More advanced therapies require further clinical investigation before their widespread use.
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Affiliation(s)
- John Montgomery
- Department of Surgery, University of Michigan Health System, Ann Arbor, MI
| | - Michael Englesbe
- Department of Surgery, University of Michigan Health System, Ann Arbor, MI
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Schiavo L, Busetto L, Cesaretti M, Zelber-Sagi S, Deutsch L, Iannelli A. Nutritional issues in patients with obesity and cirrhosis. World J Gastroenterol 2018; 24:3330-3346. [PMID: 30122874 PMCID: PMC6092576 DOI: 10.3748/wjg.v24.i30.3330] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/15/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.
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Affiliation(s)
- Luigi Schiavo
- Department of Translational Medical Science, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
- IX Division of General Surgery, Vascular Surgery and Applied Biotechnology, Naples University Policlinic, Naples 80131, Italy
| | - Luca Busetto
- Department of Medicine, University of Padua, Padua 35128, Italy
- Center for the Study and the Integrated Management of Obesity, University Hospital of Padua, Padua 35128, Italy
| | - Manuela Cesaretti
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, AP-HP, Clichy 92110, France
- Department of Nanophysics, Italian Institute of Technology, Genova 16163, Italy
| | - Shira Zelber-Sagi
- School of Public Health, University of Haifa, Haifa 3498838, Israel
- Department of Gastroenterology and Liver disease, Tel Aviv Medical Center, 62431, Tel-Aviv 62431, Israel
| | - Liat Deutsch
- Department of Gastroenterology and Liver disease, Tel Aviv Medical Center, 62431, Tel-Aviv 62431, Israel
- The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 62431, Israel
| | - Antonio Iannelli
- Digestive Unit, Archet 2 Hospital, University Hospital of Nice, F-06202, Nice, France; Inserm, U1065, Team 8 “Hepatic complications of obesity”, Nice F-06204, France
- University of Nice Sophia-Antipolis, Nice F-06107, France
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Pienta MJ, Zhang P, Derstine BA, Enchakalody B, Weir WB, Grenda T, Goulson R, Reddy RM, Chang AC, Wang SC, Lin J. Analytic Morphomics Predict Outcomes After Lung Transplantation. Ann Thorac Surg 2017; 105:399-405. [PMID: 29198627 DOI: 10.1016/j.athoracsur.2017.08.049] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 07/18/2017] [Accepted: 08/24/2017] [Indexed: 01/10/2023]
Abstract
BACKGROUND The purpose of this study was to identify morphomic factors on standard, pretransplantation computed tomography (CT) scans associated with outcomes after lung transplantation. METHODS A retrospective review of 200 patients undergoing lung transplantation at a single institution from 2003 to 2014 was performed. CT scans obtained within 1 year before transplantation underwent morphomic analysis. Morphomic characteristics included lung, dorsal muscle group, bone, and subcutaneous and visceral fat area and density. Patient data were gathered from institutional and United Network for Organ Sharing databases. Outcomes, including initial ventilator support greater than 48 hours, length of stay, and survival, were evaluated using univariate and multivariable analyses. RESULTS On multivariable Cox regression, subcutaneous fat/total body area (hazard ratio [HR] 0.60, p = 0.001), lung density 3 volume (HR 0.67, p = 0.013), and creatinine (HR 4.37, p = 0.010) were independent predictors of survival. Initial ventilator support more than 48 hours was associated with decreased vertebral body to linea alba distance (odds ratio [OR] 0.49, p = 0.002) and Zubrod score 4 (OR 14.0, p < 0.001). Increased bone mineral density (p < 0.001) and increased cross-sectional body area (p < 0.001) were associated with decreased length of stay, whereas supplemental oxygen (p < 0.001), bilateral transplantation (p = 0.002), cardiopulmonary bypass (p < 0.001), and Zubrod score 3 (p < 0.001) or 4 (p = 0.040) were associated with increased length of stay. CONCLUSIONS Morphomic factors associated with lower metabolic reserve and frailty, including decreased subcutaneous fat, bone density, and body dimensions were independent predictors of survival, prolonged ventilation, and increased length of stay. Analytic morphomics using pretransplantation CT scans may improve recipient selection and risk stratification.
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Affiliation(s)
- Michael J Pienta
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Peng Zhang
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Brian A Derstine
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Binu Enchakalody
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - William B Weir
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Tyler Grenda
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Rebecca Goulson
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Rishindra M Reddy
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Andrew C Chang
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Stewart C Wang
- Division of Acute Care Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Jules Lin
- Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
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Safwan M, Collins KM, Abouljoud MS, Salgia R. Outcome of liver transplantation in patients with prior bariatric surgery. Liver Transpl 2017; 23:1415-1421. [PMID: 28752920 DOI: 10.1002/lt.24832] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 07/23/2017] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease is becoming the leading cause of disease resulting in liver transplantation (LT). As a result of this trend, more LT candidates are presenting with prior history of bariatric surgery (BS). Over the last decade, 960 patients underwent LT at our institution; 11 (1.1%) had prior BS. The most common type of BS was Roux-en-Y gastric bypass (n = 9) with 1 sleeve gastrectomy and 1 jejunoileal bypass. A total of 9 patients underwent LT alone, and 2 underwent simultaneous liver-kidney transplantation. The most common indication for LT was nonalcoholic steatohepatitis (n = 10) with 5 having additional diagnosis of alcoholic liver disease. The 30-day reoperation rate was 36.4% (n = 4); indications were bile duct repair (n = 3) and wound repair (n = 1). In the first 6 months after LT, biliary complications were seen in 54.5% (n = 6) of the patients. Both patient and graft survival rates at 1 and 2 years were 81.8% (n = 9) and 72.7% (n = 8), respectively. A total of 8 patients (72.7%) had indications for liver biopsy after LT; significant macrovesicular steatosis was found in 2 (18.2%). In patients with a history of alcohol consumption, 2 (40.0%) relapsed after LT. Two patients (18.2%) had a history of diet-controlled diabetes before LT; 1 of these patients became insulin dependent after LT. Mean body mass index (BMI) at LT was 31.0 ± 5.7 kg/m2 . Mean BMI at 1, 6, and 12 months after LT was 28.3 ± 5.8, 28.0 ± 3.2, and 31.0 ± 6.6 kg/m2 , respectively. Mean preoperative albumin was 2.6 ± 0.6 mg/dL. Patients showed improvement in albumin after LT, with mean albumin of 2.7 ± 0.6 and 3.2 ± 0.5 mg/dL at 1 and 3 months, respectively. The liver profile was stable after LT, with mean aspartate aminotransferase of 32.9 ± 18.4 and 26.6 ± 19.8 IU/L and alanine aminotransferase of 28.0 ± 17.5 and 30.2 ± 17.0 IU/L at 6 and 12 months, respectively. In conclusion, outcomes of LT patients with prior BS are comparable with other transplant recipients with regards to patient and graft survival and post-LT complication rates. Liver Transplantation 23 1415-1421 2017 AASLD.
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Affiliation(s)
| | | | | | - Reena Salgia
- Department of Gastroenterology, Henry Ford Hospital, Detroit, MI
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Abstract
Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.
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Impact of Skeletal Muscle Mass Index, Intramuscular Adipose Tissue Content, and Visceral to Subcutaneous Adipose Tissue Area Ratio on Early Mortality of Living Donor Liver Transplantation. Transplantation 2017; 101:565-574. [PMID: 27926595 DOI: 10.1097/tp.0000000000001587] [Citation(s) in RCA: 101] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Skeletal muscle depletion has been shown to be an independent risk factor for poor survival in various diseases. However, in surgery, the significance of other body components including visceral and subcutaneous adipose tissue remains unclear. METHODS This retrospective study included 250 adult patients undergoing living donor liver transplantation (LDLT) between January 2008 and April 2015. Using preoperative plain computed tomography imaging at the third lumbar vertebra level, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by the skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral to subcutaneous adipose tissue area ratio (VSR), respectively. The cutoff values of these parameters were determined for men and women separately using the data of 657 healthy donors for LDLT between 2005 and 2016. Impact of these parameters on outcomes after LDLT was analyzed. RESULTS VSR was significantly correlated with patient age (P = 0.041), neutrophil-lymphocyte ratio (P < 0.001), body mass index (P < 0.001), and SMI (P = 0.001). The overall survival probability was significantly lower in patients with low SMI (P < 0.001), high IMAC (P < 0.001), and high VSR (P < 0.001) than in each respective normal group. On multivariate analysis, low SMI (hazard ratio [HR], 2.367, P = 0.002), high IMAC (HR, 2.096, P = 0.004), and high VSR (HR, 2.213, P = 0.003) were identified as independent risk factors for death after LDLT. CONCLUSIONS Preoperative visceral adiposity, as well as low muscularity, was closely involved with posttransplant mortality.
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Bamgbola O. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Ther Adv Endocrinol Metab 2016; 7:110-27. [PMID: 27293540 PMCID: PMC4892400 DOI: 10.1177/2042018816641580] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Among other factors, sophistication of immunosuppressive (IS) regimen accounts for the remarkable success attained in the short- and medium-term solid organ transplant (SOT) survival. The use of steroids, mycophenolate mofetil and calcineurin inhibitors (CNI) have led to annual renal graft survival rates exceeding 90% in the last six decades. On the other hand, attrition rates of the allograft beyond the first year have remained unchanged. In addition, there is a persistent high cardiovascular (CV) mortality rate among transplant recipients with functioning grafts. These shortcomings are in part due to the metabolic effects of steroids, CNI and sirolimus (SRL), all of which are implicated in hypertension, new onset diabetes after transplant (NODAT), and dyslipidemia. In a bid to reduce the required amount of harmful maintenance agents, T-cell-depleting antibodies are increasingly used for induction therapy. The downsides to their use are greater incidence of opportunistic viral infections and malignancy. On the other hand, inadequate immunosuppression causes recurrent rejection episodes and therefore early-onset chronic allograft dysfunction. In addition to the adverse metabolic effects of the steroid rescue needed in these settings, the generated proinflammatory milieu may promote accelerated atherosclerotic disorders, thus setting up a vicious cycle. The recent availability of newer agent, belatacept holds a promise in reducing the incidence of metabolic disorders and hopefully its long-term CV consequences. Although therapeutic drug monitoring as applied to CNI may be helpful, pharmacodynamic tools are needed to promote a customized selection of IS agents that offer the most benefit to an individual without jeopardizing the allograft survival.
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Affiliation(s)
- Oluwatoyin Bamgbola
- State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203-2098, USA
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