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Gu C, Dong L, Chai L, Tong Z, Gao F, Ageno W, Romeiro FG, Qi X. Risk of Coronary Artery Disease in Patients with Liver Cirrhosis: A Systematic Review and Meta-analysis. J Clin Transl Hepatol 2025; 13:93-104. [PMID: 39917469 PMCID: PMC11797818 DOI: 10.14218/jcth.2024.00226] [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: 07/04/2024] [Revised: 10/18/2024] [Accepted: 10/31/2024] [Indexed: 02/09/2025] Open
Abstract
Background and Aims Coronary artery disease (CAD) is increasingly observed in patients with liver cirrhosis. However, data on the incidence and prevalence of CAD in cirrhotic patients are heterogeneous, and the association remains uncertain. In this study, we aimed to conduct a systematic review and meta-analysis to address these issues. Methods PubMed, EMBASE, and Cochrane Library databases were searched. Incidence, prevalence, and factors associated with CAD were pooled using a random-effects model. Risk ratio (RR) and odds ratio (OR), with their 95% confidence interval (CI), were calculated to evaluate differences in CAD incidence and prevalence between patients with and without liver cirrhosis. Results Fifty-one studies were included. The pooled incidences of CAD, acute coronary syndromes, and myocardial infarction (MI) were 2.28%, 2.02%, and 1.80%, respectively. Liver cirrhosis was not significantly associated with CAD incidence (RR = 0.77; 95% CI = 0.46-1.28) or MI (RR = 0.87; 95% CI = 0.49-1.57). The pooled prevalence of CAD, acute coronary syndromes, and MI was 18.87%, 12.54%, and 6.12%, respectively. Liver cirrhosis was not significantly associated with CAD prevalence (OR = 1.29; 95% CI = 0.83-2.01) or MI (OR = 0.58; 95% CI = 0.28-1.22). Non-alcoholic steatohepatitis, hepatitis C virus, advanced age, male sex, diabetes mellitus, hypertension, hyperlipidemia, smoking history, and family history of CAD were significantly associated with CAD in cirrhotic patients. Conclusions CAD is common in cirrhotic patients, but cirrhosis itself may not be associated with an increased CAD risk. In addition to traditional risk factors, non-alcoholic steatohepatitis and hepatitis C virus infection are also associated with CAD presence in cirrhotic patients.
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Affiliation(s)
- Chunru Gu
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the China Medical University), Shenyang, Liaoning, China
| | - Liyan Dong
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the China Medical University), Shenyang, Liaoning, China
| | - Lu Chai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the China Medical University), Shenyang, Liaoning, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Zhenhua Tong
- Section of Medical Service, General Hospital of Northern Theater Command (Teaching Hospital of the China Medical University), Shenyang, Liaoning, China
| | - Fangbo Gao
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the China Medical University), Shenyang, Liaoning, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | | | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the China Medical University), Shenyang, Liaoning, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
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Wei J, Hui W, Fang Y, Jia H, Yang Y, Zhang T, Wu H, Su B, Jiang T. The prevalence of nonalcoholic fatty liver disease in people living with HIV: a systematic review and meta-analysis. BMC Infect Dis 2025; 25:239. [PMID: 40108499 PMCID: PMC11921747 DOI: 10.1186/s12879-025-10455-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 01/07/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Owing to long-term antiretroviral therapy (ART), the incidence of non-HIV-related chronic diseases is increasing, and liver disease is the leading cause of increased AIDS mortality. Moreover, the prevalence of NAFLD and liver fibrosis has been reported to vary widely across regions and studies. There is no precise description of the trend and characteristics of NAFLD in PLWH. Here, we aimed to explore the prevalence and outcomes of NAFLD in people living with HIV (PLWH). METHODS The PubMed, Web of Science, Embase, and Cochrane Library databases were searched on August 15, 2023, for studies that evaluated the prevalence of NAFLD or liver fibrosis among PLWH. The meta-synthesized effects of NAFLD and liver fibrosis were the primary outcomes, and potential moderators were the secondary outcomes. The meta-analysis of the combined event rate (ER) and random effects was conducted on the basis of the number of individuals with NAFLD, the number of individuals with liver fibrosis, and the total sample size. RESULTS Of the 3520 studies identified, 41 studies were eligible for the meta-analysis. The results revealed that the combined ERs of NAFLD and liver fibrosis were 0.38 (95% CI: 0.33-0.43, p < 0.01) and 0.25 (95% CI: 0.18-0.32, p < 0.01), respectively. CONCLUSIONS This meta-analysis provided empirical evidence that the prevalence of NAFLD and liver fibrosis in PLWH is greater than that in the general population, which requires sufficient attention. In the HIV population, noninvasive imaging to monitor NAFLD changes should be strengthened, and a high TG level might be an early predictive indicator for HIV-associated fatty liver disease; however, large-scale prospective clinical research data are still needed for further validation and evaluation.
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Affiliation(s)
- Jiaqi Wei
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Wei Hui
- Beijing Youan Hospital, Telemedicine and Connected Health Center, Capital Medical University, Beijing, 100069, China
| | - Yuan Fang
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Han Jia
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Yu Yang
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Tong Zhang
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Hao Wu
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Bin Su
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
| | - Taiyi Jiang
- Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
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Sato-Espinoza K, Chotiprasidhi P, Liza E, Placido-Damian Z, Diaz-Ferrer J. Evolution of liver transplantation in the metabolic dysfunction-associated steatotic liver disease era: Tracking impact through time. World J Transplant 2024; 14:98718. [PMID: 39697455 PMCID: PMC11438936 DOI: 10.5500/wjt.v14.i4.98718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/19/2024] [Accepted: 08/23/2024] [Indexed: 09/20/2024] Open
Abstract
Liver transplantation (LT) for metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally due to rising rates of obesity and metabolic syndrome, posing significant challenges. MASLD patients typically present with advanced age, higher body mass index (BMI), and metabolic comorbidities such as diabetes, hypertension, and dyslipidemia. Comprehensive pre-transplant evaluations are crucial for assessing surgical risks and preparing patients for transplantation. MASLD patients with higher BMI may experience longer operative times, potentially affecting intraoperative outcomes. In the months following LT, MASLD recipients face persistent challenges, including a higher incidence of metabolic syndrome and cardiovascular events compared to non-MASLD recipients. However, survival rates at 1-, 3-, and 5-years post-LT do not markedly differ from other etiologies, indicating comparable surgical outcomes. Optimizing outcomes in MASLD patients undergoing LT demands a multidisciplinary approach from pre-transplant assessment to post-transplant care. Strategies must address metabolic comorbidities, manage cardiovascular health, and monitor steatosis recurrence, which can be exacerbated by obesity and diabetes. This approach aims to mitigate long-term graft complications and mortality risks, ultimately enhancing transplant success and patient well-being. Continued research is essential to refine these approaches and meet the evolving challenges posed by MASLD as a leading indication for LT worldwide.
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Affiliation(s)
- Karina Sato-Espinoza
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55902, United States
| | - Perapa Chotiprasidhi
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55902, United States
| | - Estefanía Liza
- Hepatology Service, Department of Digestive Diseases, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
| | - Zuly Placido-Damian
- Hepatology Service, Department of Digestive Diseases, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
| | - Javier Diaz-Ferrer
- Hepatology Service, Department of Digestive Diseases, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
- Medicine Faculty, Universidad San Martin de Porres, Lima 02002, Peru
- Gastroenterology Service, Clinica Internacional, Lima 02002, Peru
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Alnimer L, Arellano D, Brombosz E, Noureddin M. Metabolic issues in patients with metabolic dysfunction-associated steatohepatitis (MASH) and their impact on MASH recurrence following liver transplantation: A narrative review. Liver Transpl 2024:01445473-990000000-00524. [PMID: 39621112 DOI: 10.1097/lvt.0000000000000544] [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] [Received: 05/16/2024] [Accepted: 11/12/2024] [Indexed: 01/03/2025]
Abstract
Decompensated cirrhosis secondary to metabolic dysfunction-associated steatohepatitis (MASH) is not only a common indication for liver transplant (LT) but is becoming the leading cause of LT in postmenopausal women in the United States. Given the different complex mechanisms involved in the occurrence of MASH, it is being recognized as the hepatic manifestation of the metabolic syndrome. There are multiple metabolic issues associated with MASH, including obesity, DMT2, cardiovascular disease, and chronic kidney disease, which need to be addressed in the pretransplant and posttransplant setting for better patient outcomes. Recurrence of MASH following LT can occur due to many reasons including reversal of the catabolic state seen in cirrhosis, improvement in appetite, and the effect of certain post-LT medications on the graft; however, managing recurrence can be challenging and thus urges addressing these issues before transplant, in addition to recognizing, and treating them in the posttransplant setting. In this review, we discuss the various metabolic issues that face patients with MASH and the medical and surgical management options available to improve outcomes and reduce chances of recurrence.
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Affiliation(s)
- Lynna Alnimer
- Department of Medicine, Division of Gastroenterology, Ascension Providence Hospital, College of Human Medicine, Michigan State University, Southfield, Michigan, USA
| | - Diego Arellano
- Department of Medicine, Houston Methodist Hospital, Houston Research Institute, Houston, Texas, USA
| | | | - Mazen Noureddin
- Department of Medicine, Houston Liver Institute, Houston Research Institute, Houston, Texas, USA
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Harinstein ME, Gandolfo C, Gruttadauria S, Accardo C, Crespo G, VanWagner LB, Humar A. Cardiovascular disease assessment and management in liver transplantation. Eur Heart J 2024; 45:4399-4413. [PMID: 39152050 DOI: 10.1093/eurheartj/ehae502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 04/21/2024] [Accepted: 07/25/2024] [Indexed: 08/19/2024] Open
Abstract
The prevalence and mortality related to end-stage liver disease (ESLD) continue to rise globally. Liver transplant (LT) recipients continue to be older and have inherently more comorbidities. Among these, cardiac disease is one of the three main causes of morbidity and mortality after LT. Several reasons exist including the high prevalence of associated risk factors, which can also be attributed to the rise in the proportion of patients undergoing LT for metabolic dysfunction-associated steatohepatitis (MASH). Additionally, as people age, the prevalence of now treatable cardiac conditions, including coronary artery disease (CAD), cardiomyopathies, significant valvular heart disease, pulmonary hypertension, and arrhythmias rises, making the need to treat these conditions critical to optimize outcomes. There is an emerging body of literature regarding CAD screening in patients with ESLD, however, there is a paucity of strong evidence to support the guidance regarding the management of cardiac conditions in the pre-LT and perioperative settings. This has resulted in significant variations in assessment strategies and clinical management of cardiac disease in LT candidates between transplant centres, which impacts LT candidacy based on a transplant centre's risk tolerance and comfort level for caring for patients with concomitant cardiac disease. Performing a comprehensive assessment and understanding the potential approaches to the management of ESLD patients with cardiac conditions may increase the acceptance of patients, who appear too complex, but rather require extra evaluation and may be reasonable candidates for LT. The unique physiology of ESLD can profoundly influence preoperative assessment, perioperative management, and outcomes associated with underlying cardiac pathology, and requires a thoughtful multidisciplinary approach. The strategies proposed in this manuscript attempt to review the latest expert experience and opinions and provide guidance to practicing clinicians who assess and treat patients being considered for LT. These topics also highlight the gaps that exist in the comprehensive care of LT patients and the need for future investigations in this field.
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Affiliation(s)
- Matthew E Harinstein
- Division of Cardiology, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Caterina Gandolfo
- Unit of Interventional Cardiology, Department of Cardiothoracic Surgery, UPMC IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Salvatore Gruttadauria
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, UPMC IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy
| | - Caterina Accardo
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, UPMC IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Gonzalo Crespo
- Liver Transplant Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Lisa B VanWagner
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Abhinav Humar
- Division of Transplantation, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Mallet M, Silaghi CA, Sultanik P, Conti F, Rudler M, Ratziu V, Thabut D, Pais R. Current challenges and future perspectives in treating patients with NAFLD-related cirrhosis. Hepatology 2024; 80:1270-1290. [PMID: 37183906 DOI: 10.1097/hep.0000000000000456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023]
Abstract
Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.
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Affiliation(s)
- Maxime Mallet
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, Roumanie
| | - Philippe Sultanik
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Filomena Conti
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
| | - Marika Rudler
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Vlad Ratziu
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- INSERM UMRS 1138 CRC, Paris, France
| | - Dominique Thabut
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
| | - Raluca Pais
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024; 81:492-542. [PMID: 38851997 DOI: 10.1016/j.jhep.2024.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 06/10/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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Elzein SM, Brombosz EW, Kodali S. Cardiac abnormalities pre- and post-liver transplantation for metabolic dysfunction-associated steatohepatitis – Evidence and special considerations. JOURNAL OF LIVER TRANSPLANTATION 2024; 15:100228. [DOI: 10.1016/j.liver.2024.100228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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Choudhury A, Singh SP, Desmukh A, Sahoo B, Eslam M. Post-Liver Transplant Metabolic Syndrome. J Clin Exp Hepatol 2024; 14:101368. [PMID: 38523736 PMCID: PMC10960134 DOI: 10.1016/j.jceh.2024.101368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 02/14/2024] [Indexed: 03/26/2024] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is the second most frequent cause of liver transplantation following alcoholic liver disease. With longer follow-up and increased survival rates, the occurrence rate of the metabolic syndrome is increasing with time among liver transplant recipients. Reappearances of non-alcoholic fatty liver disease after transplantation, both as recurring cases and new instances, are prevalent; nonetheless, the recurrence of fibrosis is minimal. Recognizing populations at elevated risk and enhancing the management of metabolic-related conditions are crucial for maintaining a healthy transplanted organ, particularly considering the prolonged utilization of immunosuppressive treatments. Furthermore, NASH-related cirrhosis patients who had transplant are at a greater risk of cardiovascular, renal events and increased incidence of cancer, necessitating a unique care strategy. This review discusses post-transplant metabolic syndrome, risk factors, pathogenesis, diagnosis, prevention strategy, recurrent and de novo NAFLD and customized immunosuppression.
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Affiliation(s)
- Ashok Choudhury
- Dept of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Satender P. Singh
- Dept of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akhil Desmukh
- Dept of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bishnupriya Sahoo
- Associate Professor of Pediatrics, Consultant Pediatric Gastroenterology, Hepatology and Liver Transplant, SGT University, Gurugram, Haryana, India
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia
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Savino A, Loglio A, Neri F, Camagni S, Pasulo L, Lucà MG, Trevisan R, Fagiuoli S, Viganò M. Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) after Liver Transplantation: A Narrative Review of an Emerging Issue. J Clin Med 2024; 13:3871. [PMID: 38999436 PMCID: PMC11242808 DOI: 10.3390/jcm13133871] [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: 05/30/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 07/14/2024] Open
Abstract
The development of steatotic liver disease after liver transplant (LT) is widely described, and epidemiological data have revealed an increased incidence in recent times. Its evolution runs from simple steatosis to steatohepatitis and, in a small proportion of patients, to significant fibrosis and cirrhosis. Apparently, post-LT steatotic disease has no impact on the recipient's overall survival; however, a higher cardiovascular and malignancy burden has been reported. Many donors' and recipients' risk factors have been associated with this occurrence, although the recipient-related ones seem of greater impact. Particularly, pre- and post-LT metabolic alterations are strictly associated with steatotic graft disease, sharing common pathophysiologic mechanisms that converge on insulin resistance. Other relevant risk factors include genetic variants, sex, age, baseline liver diseases, and immunosuppressive drugs. Diagnostic evaluation relies on liver biopsy, although non-invasive methods are being increasingly used to detect and monitor both steatosis and fibrosis stages. Management requires a multifaceted approach focusing on lifestyle modifications, the optimization of immunosuppressive therapy, and the management of metabolic complications. This review aims to synthesize the current knowledge of post-LT steatotic liver disease, focusing on the recent definition of metabolic-dysfunction-associated steatotic liver disease (MASLD) and its metabolic and multisystemic concerns.
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Affiliation(s)
- Alberto Savino
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; (A.S.); (S.F.)
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
| | - Alessandro Loglio
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; (A.S.); (S.F.)
| | - Flavia Neri
- Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Stefania Camagni
- Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Luisa Pasulo
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; (A.S.); (S.F.)
| | - Maria Grazia Lucà
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; (A.S.); (S.F.)
| | - Roberto Trevisan
- Endocrine and Diabetology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Department of Medicine and Surgery, University of Milano Bicocca, 20126 Milan, Italy
| | - Stefano Fagiuoli
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; (A.S.); (S.F.)
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
| | - Mauro Viganò
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; (A.S.); (S.F.)
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
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EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obes Facts 2024; 17:374-444. [PMID: 38852583 PMCID: PMC11299976 DOI: 10.1159/000539371] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/15/2024] [Indexed: 06/11/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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12
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Vogel AS, Roediger R, von Ahrens D, Fortune BE, Schwartz JM, Frager S, Chacko KR, Tow CY. The Impact of Metabolic Health and Obesity on Liver Transplant Candidates and Recipients. Life (Basel) 2024; 14:685. [PMID: 38929668 PMCID: PMC11204519 DOI: 10.3390/life14060685] [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: 03/18/2024] [Revised: 04/12/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Poor metabolic health and obesity have significant impacts on the outcomes of patients suffering from chronic liver disease, particularly those with metabolic dysfunction-associated steatotic liver disease. Patients with such comorbidities who require liver transplant evaluation for advancing liver disease or liver failure require special consideration due to increased risk of cardiovascular disease, renal dysfunction, sarcopenic obesity, and cancer. Those who have had a history of prior bariatric surgery pose specific anatomical constraints and may also be at increased risk of alcohol use disorder. Pre-operative risk assessment as well as strict control of metabolic risk factors are essential to reduce intra-operative and post-liver transplant complications. As immunosuppressive therapy exacerbates metabolic dysfunction and risk for cancer, post-liver transplant care must focus on balancing the need to prevent rejection and the impact of progressive metabolic dysfunction in this unique, but growing, patient population.
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Affiliation(s)
| | | | | | | | | | | | | | - Clara Y. Tow
- Correspondence: ; Tel.: +1-888-795-4837; Fax: +1-602-563-8224
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13
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Sanyal AJ, Husain M, Diab C, Mangla KK, Shoeb A, Lingvay I, Tapper EB. Cardiovascular disease in patients with metabolic dysfunction-associated steatohepatitis compared with metabolic dysfunction-associated steatotic liver disease and other liver diseases: A systematic review. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 41:100386. [PMID: 38623572 PMCID: PMC11016929 DOI: 10.1016/j.ahjo.2024.100386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 03/14/2024] [Accepted: 03/14/2024] [Indexed: 04/17/2024]
Abstract
The burden of cardiovascular disease (CVD) in patients with metabolic dysfunction-associated steatohepatitis (MASH) is poorly characterized, particularly vs other liver diseases including metabolic dysfunction-associated steatotic liver disease (MASLD). To identify available evidence, Embase, MEDLINE, and Cochrane database searches (main search: 2011-September 6, 2021; additional ad hoc search [MEDLINE only]: September 7, 2021-February 15, 2023), plus manual searches (2019-September 2021), were performed. Studies reporting CVD outcomes (angina, coronary artery disease [CAD], heart failure, myocardial infarction, peripheral artery disease, stroke, venous thromboembolic disease, and CV mortality) in adults with histologically confirmed MASH and MASLD or other liver diseases were identified, with studies of MASLD without confirmed MASH excluded. Of 8732 studies, 21 were included. An increased incidence or prevalence of CVD in patients with MASH vs other conditions was reported in 12 studies; odds ratios (OR), where reported, ranged from 3.12 (95 % CI: 1.33-5.32) to 4.12 (95 % CI: 1.91-8.90). The risk of CAD was increased in people with MASH in 6 of 7 studies, while the risk of stroke was increased in 6 of 6 studies, and heart failure in 2 of 4 studies. Three of 6 studies provided evidence of increased CVD-related mortality in patients with MASH vs those without. In conclusion, this literature review suggests that CVD is prevalent in patients with MASH and may contribute to increased mortality. Accordingly, cardiovascular risk factors should be aggressively managed in this population. Whether the CVD burden in patients with MASH is a direct consequence of MASH itself requires further study.
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Affiliation(s)
- Arun J. Sanyal
- Department of Internal Medicine, Medical College of Virginia, Richmond, VA, USA
| | - Mansoor Husain
- Ted Rogers Centre for Heart Research, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | | | | | | | - Ildiko Lingvay
- Department of Internal Medicine/Endocrinology and Peter O'Donnel Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MA, USA
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14
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Müller M, Grasshoff C. [The Role of the Anaesthesiologist in Liver Transplantation - Preoperative Evaluation]. Anasthesiol Intensivmed Notfallmed Schmerzther 2024; 59:283-295. [PMID: 38759684 DOI: 10.1055/a-2152-7350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2024]
Abstract
Preoperative evaluation prior to listing for orthotopic liver transplantation (LT) requires a careful multidisciplinary approach with specialized teams including surgeons, hepatologists and anesthesiologists in order to improve short- and long-term clinical outcomes. Due to inadequate supply of donor organs and changing demographics, patients listed for LT have become older, sicker and share more comorbidities. As cardiovascular events are the leading cause for early mortality precise evaluation of risk factors is mandatory. This review focuses on the detection and management of coronary artery disease, cirrhotic cardiomyopathy, portopulmonary hypertension and hepatopulmonary syndrome in patients awaiting LT. Further insights are being given into scoring systems, patients with Acute-on-chronic-liver-failure (ACLF), frailty, NASH cirrhosis and into psychologic evaluation of patients with substance abuse.
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15
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Soldera J, Corso LL, Rech MM, Ballotin VR, Bigarella LG, Tomé F, Moraes N, Balbinot RS, Rodriguez S, Brandão ABDM, Hochhegger B. Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model: A cohort study. World J Hepatol 2024; 16:193-210. [PMID: 38495288 PMCID: PMC10941741 DOI: 10.4254/wjh.v16.i2.193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/27/2023] [Accepted: 02/04/2024] [Indexed: 02/27/2024] Open
Abstract
BACKGROUND Liver transplant (LT) patients have become older and sicker. The rate of post-LT major adverse cardiovascular events (MACE) has increased, and this in turn raises 30-d post-LT mortality. Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients. AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort. METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center. We developed a predictive model for post-LT MACE (defined as a composite outcome of stroke, new-onset heart failure, severe arrhythmia, and myocardial infarction) using the extreme gradient boosting (XGBoost) machine learning model. We addressed missing data (below 20%) for relevant variables using the k-nearest neighbor imputation method, calculating the mean from the ten nearest neighbors for each case. The modeling dataset included 83 features, encompassing patient and laboratory data, cirrhosis complications, and pre-LT cardiac assessments. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC). We also employed Shapley additive explanations (SHAP) to interpret feature impacts. The dataset was split into training (75%) and testing (25%) sets. Calibration was evaluated using the Brier score. We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting. Scikit-learn and SHAP in Python 3 were used for all analyses. The supplementary material includes code for model development and a user-friendly online MACE prediction calculator. RESULTS Of the 537 included patients, 23 (4.46%) developed in-hospital MACE, with a mean age at transplantation of 52.9 years. The majority, 66.1%, were male. The XGBoost model achieved an impressive AUROC of 0.89 during the training stage. This model exhibited accuracy, precision, recall, and F1-score values of 0.84, 0.85, 0.80, and 0.79, respectively. Calibration, as assessed by the Brier score, indicated excellent model calibration with a score of 0.07. Furthermore, SHAP values highlighted the significance of certain variables in predicting postoperative MACE, with negative noninvasive cardiac stress testing, use of nonselective beta-blockers, direct bilirubin levels, blood type O, and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level. These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE, making it a valuable tool for clinical practice. CONCLUSION Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE, using both cardiovascular and hepatic variables. The model demonstrated impressive performance, aligning with literature findings, and exhibited excellent calibration. Notably, our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data, reinforcing the model's value as a reliable tool for predicting post-LT MACE in clinical practice.
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Affiliation(s)
- Jonathan Soldera
- Post Graduate Program at Acute Medicine and Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
- Postgraduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil.
| | - Leandro Luis Corso
- Department of Engineering, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Brazil
| | - Matheus Machado Rech
- School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Brazil
| | | | | | - Fernanda Tomé
- Department of Engineering, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Brazil
| | - Nathalia Moraes
- Department of Engineering, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Brazil
| | | | - Santiago Rodriguez
- Postgraduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil
| | - Ajacio Bandeira de Mello Brandão
- Postgraduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil
| | - Bruno Hochhegger
- Postgraduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil
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16
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Widmer J, Eden J, Abbassi F, Angelico R, Rössler F, Müllhaupt B, Dutkowski P, Bueter M, Schlegel A. How best to combine liver transplantation and bariatric surgery?-Results from a global, web-based survey. Liver Int 2024; 44:566-576. [PMID: 38082500 DOI: 10.1111/liv.15791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/20/2023] [Accepted: 10/31/2023] [Indexed: 01/31/2024]
Abstract
BACKGROUND AND AIMS Obesity is a growing healthcare challenge worldwide and a significant risk factor for liver failure as seen with non-alcoholic steatohepatitis (NASH). Combining metabolic-bariatric surgery (MBS) with liver transplantation (LT) appears as attractive strategy to treat both, the underlying liver disease and obesity. However, there is an ongoing debate on best timing and patient selection. This survey was designed to explore the current treatment practice for patients with NASH and obesity worldwide. METHODS A web-based survey was conducted in 2022 among bariatric and LT surgeons, and hepatologists from Europe, North and South America and Asia. RESULTS The survey completion rate was 74% (145/196). The average respondents were 41-50 years (38%), male (82.1%) and had >20 years of clinical experience (42.1%). Centres with a high LT-caseload for NASH were mainly located in the USA and United Kingdom. Almost 30% have already performed a combination of LT with MBS and 49% plan to do it. A majority of bariatric surgeons prefer MBS before LT (77.2%), whereas most of LT surgeons (52%) would perform MBS during LT. Most respondents (n = 114; 80%) favour sleeve gastrectomy over other bariatric techniques. One third (n = 42; 29.4%) has an established protocol regarding MBS for LT candidates. CONCLUSION The most experienced centres doing LT for NASH are in the USA and United Kingdom with growing awareness worldwide. Overall, a combination of MBS and LT has already been performed by a third of respondents. Sleeve gastrectomy is the bariatric technique of choice-preferably performed either before or during LT.
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Affiliation(s)
- Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
| | - Fariba Abbassi
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
| | - Roberta Angelico
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Fabian Rössler
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
| | - Beat Müllhaupt
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
| | - Marco Bueter
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
- Department of Surgery, Spital Männedorf, Männedorf, Switzerland
| | - Andrea Schlegel
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
- Transplantation Center, Digestive Disease and Surgery Institute and Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, Milan, Italy
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17
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Ferretti S, Barreyro FJ. Worldwide Increasing Prevalence of Non-alcoholic Steatohepatitis as an Indication of Liver Transplantation: Epidemiological View and Implications. CURRENT HEPATOLOGY REPORTS 2024; 23:193-203. [DOI: 10.1007/s11901-023-00628-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/18/2023] [Indexed: 01/05/2025]
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18
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Møller S, Wiese S, Barløse M, Hove JD. How non-alcoholic fatty liver disease and cirrhosis affect the heart. Hepatol Int 2023; 17:1333-1349. [PMID: 37770804 DOI: 10.1007/s12072-023-10590-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 08/29/2023] [Indexed: 09/30/2023]
Abstract
Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field.
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Affiliation(s)
- Søren Møller
- Department Clinical Physiology and Nuclear Medicine 260, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Copenhagen University Hospital, Kettegaards alle 30, 2650, Hvidovre, Denmark.
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Signe Wiese
- Gastro Unit, Medical Division, Hvidovre Hospital, Hvidovre, Denmark
| | - Mads Barløse
- Department Clinical Physiology and Nuclear Medicine 260, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Copenhagen University Hospital, Kettegaards alle 30, 2650, Hvidovre, Denmark
| | - Jens D Hove
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Cardiology, Hvidovre Hospital, Hvidovre, Denmark
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19
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Paklar N, Mijic M, Filipec-Kanizaj T. The Outcomes of Liver Transplantation in Severe Metabolic Dysfunction-Associated Steatotic Liver Disease Patients. Biomedicines 2023; 11:3096. [PMID: 38002096 PMCID: PMC10669065 DOI: 10.3390/biomedicines11113096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 11/16/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
The increasing prevalence of diabetes mellitus, obesity, and metabolic syndrome in the population can lead to metabolic dysfunction-associated steatohepatitis (MASH) and metabolic dysfunction-associated steatotic liver disease (MASLD). In Western industrialized countries, this has become a major problem with significant socioeconomic impacts. MASH is now a leading cause of liver transplantation (LT), especially in developed countries. However, the post-transplant outcomes of such patients are a major concern, and published data are limited and extremely variable. In this article, we discuss graft and patient survival after LT, complications, the recurrence of MASH, and MASH appearing de novo after transplantation. Recent studies suggest that patients with MASH have slightly worse short-term survival, potentially due to increased cardiovascular mortality. However, most studies found that longer-term outcomes for patients undergoing LT for MASH are similar or even better than those for other indications. Hepatocellular carcinoma due to MASH cirrhosis also has similar or even better outcomes after LT than other etiologies. In conclusion, we suggest questions and topics that require further research to enhance healthcare for this growing patient population.
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Affiliation(s)
- Natasa Paklar
- Department of Anesthesiology, Reanimatology and Intensive Care, University Hospital Merkur, 10000 Zagreb, Croatia
| | - Maja Mijic
- Department of Gastroenterology, University Hospital Merkur, 10000 Zagreb, Croatia
| | - Tajana Filipec-Kanizaj
- Department of Gastroenterology, University Hospital Merkur, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
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20
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Hashim A, Maraey A, Elzanaty A, Zordok M, Elsharnoby H, Khalil M, Al Wahadneh O, Siragy H. Nonalcoholic Fatty Liver Disease Predicts Acute Kidney Injury Readmission in Heart Failure Hospitalizations: A Nationwide Analysis. Curr Probl Cardiol 2023; 48:101816. [PMID: 37211306 DOI: 10.1016/j.cpcardiol.2023.101816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 05/13/2023] [Indexed: 05/23/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has been associated with the progression of chronic kidney disease. However, limited data is available on its impact on acute kidney injury (AKI) in heart failure(HF) patients. All primary adult HF admissions from the national readmission database of 2016-2019 were identified. Admissions from July to December of each year were excluded to allow 6 months of follow-up. Patients were stratified according to the presence of NAFLD. Complex multivariate cox regression was used to adjust for confounders and calculate the adjusted hazard ratio. A total of 420,893 weighted patients admitted with HF were included in our cohort, of whom 780 had a secondary diagnosis of NAFLD. Patients with NAFLD were younger, more likely to be female, and had higher rates of obesity and diabetes mellitus. Both groups had similar rates of chronic kidney disease irrespective of the stage. NAFLD was associated with an increased risk of 6-month readmission with AKI (26.8% vs 16.6%, adjusted hazard ratio:1.44, 95% CI [1.14-1.82], P = 0.003). The mean time to AKI readmission was 150 ± 44 days. NAFLD was associated with a shorter mean time to readmission (145 ± 45 vs 155 ± 42 days, β = -10 days, P = 0.044). Our study from a national database suggests that NAFLD is an independent predictor of 6-months readmission with AKI in patients admitted with HF. Further research is warranted to validate these findings.
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Affiliation(s)
- Ahmed Hashim
- Ain Shams University, Faculty of Medicine, Cairo, Egypt
| | - Ahmed Maraey
- Department of Internal Medicine, Carle Foundation Hospital, Urbana, IL.
| | - Ahmed Elzanaty
- Department of Cardiovascular Medicine, University of Toledo, Toledo, OH
| | - Magdi Zordok
- Department of Internal Medicine, Catholic Medical Center, Manchester, NH
| | - Hadeer Elsharnoby
- Department of Internal Medicine, Carle Foundation Hospital, Urbana, IL
| | - Mahmoud Khalil
- Department of Internal Medicine, Lincoln Medical Center, Bronx, NY
| | - Omar Al Wahadneh
- Department of Internal Medicine, Carle Foundation Hospital, Urbana, IL
| | - Helmy Siragy
- Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA
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21
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Polyzos SA, Chrysavgis L, Vachliotis ID, Chartampilas E, Cholongitas E. Nonalcoholic fatty liver disease and hepatocellular carcinoma:Insights in epidemiology, pathogenesis, imaging, prevention and therapy. Semin Cancer Biol 2023; 93:20-35. [PMID: 37149203 DOI: 10.1016/j.semcancer.2023.04.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 04/23/2023] [Accepted: 04/27/2023] [Indexed: 05/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is estimated to be the third leading cause of cancer-related mortality and is characterized by low survival rates. Nonalcoholic fatty liver disease (NAFLD) is emerging as a leading cause of HCC, whose rates are increasing, owing to the increasing prevalence of NAFLD. The pathogenesis of NAFLD-associated HCC is multifactorial: insulin resistance, obesity, diabetes and the low-grade hepatic inflammation, which characterizes NAFLD, seem to play key roles in the development and progression of HCC. The diagnosis of NAFLD-associated HCC is based on imaging in the presence of liver cirrhosis, preferably computerized tomography or magnetic resonance imaging, but liver biopsy for histological confirmation is usually required in the absence of liver cirrhosis. Some preventive measures have been recommended for NAFLD-associated HCC, including weight loss, cessation of even moderate alcohol drinking and smoking, as well as the use of metformin, statins and aspirin. However, these preventive measures are mainly based on observational studies, thus they need validation in trials of different design before introducing in clinical practice. The treatment of NAFLD should be tailored on an individual basis and should be ideally determined by a multidisciplinary team. In the last two decades, new medications, including tyrosine kinase inhibitors and immune checkpoints inhibitors, have improved the survival of patients with advanced HCC, but trials specifically designed for patients with NAFLD-associated HCC are scarce. The aim of this review was to overview evidence on the epidemiology and pathophysiology of NAFLD-associated HCC, then to comment on imaging tools for its appropriate screening and diagnosis, and finally to critically summarize the currently available options for its prevention and treatment.
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Affiliation(s)
- Stergios A Polyzos
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Lampros Chrysavgis
- First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, Athens, Greece
| | - Ilias D Vachliotis
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Evangelos Chartampilas
- Department of Radiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, Athens, Greece
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22
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Samuel S, Abulawi A, Malik R. Hepatitis C and Nonalcoholic Steatohepatitis in the 21st Century: Impact on Liver Disease and Liver Transplantation. GASTROENTEROLOGY INSIGHTS 2023; 14:249-270. [DOI: 10.3390/gastroent14030018] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Hepatitis C infection is a leading etiology of hepatic dysfunction and a major indication for liver transplantation due to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease (NAFLD) and, specifically, its subtype nonalcoholic steatohepatitis (NASH) is a rising cause of liver disease. It is predicted to surpass hepatitis C as a leading indication for transplant. The introduction of direct-acting antivirals (DAAs) decreased the prevalence of chronic hepatitis C infections, but the obesity epidemic and metabolic syndrome have increased the prevalence of NASH. Weight loss and dietary modifications are recommended NASH therapies, but unlike for hepatitis C, federally approved agents are lacking and currently under investigation. Clinical trials face many barriers in NASH treatment because of the difficulty of diagnosis and a lack of standardized and accurate clinical and histologic responses. Mortality and morbidity in NASH are heightened because of the presence of multiple comorbidities including cardiovascular disease, diabetes, and renal dysfunction. A liver transplant may be indicated, but a thorough screening of candidates, including a comprehensive cardiovascular assessment, is essential to ensuring successful outcomes pre- and post-transplant. Therapeutic agents for NASH are warranted before it becomes a significant and leading cause of morbidity and mortality worldwide.
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Affiliation(s)
- Sonia Samuel
- Division of Gastroenterology & Hepatology, Albany Medical Center, 47 New Scotland Ave, Albany, NY 12208, USA
| | - Ahmad Abulawi
- Division of Gastroenterology & Hepatology, Albany Medical Center, 47 New Scotland Ave, Albany, NY 12208, USA
| | - Raza Malik
- Division of Gastroenterology & Hepatology, Albany Medical Center, 47 New Scotland Ave, Albany, NY 12208, USA
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23
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Harrington CR, Levy P, Cabrera E, Gao J, Gregory DL, Padilla C, Crespo G, VanWagner LB. Evolution of pretransplant cardiac risk factor burden and major adverse cardiovascular events in liver transplant recipients over time. Liver Transpl 2023; 29:581-590. [PMID: 36724875 PMCID: PMC10192050 DOI: 10.1097/lvt.0000000000000013] [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: 05/11/2022] [Accepted: 10/26/2022] [Indexed: 02/03/2023]
Abstract
Major adverse cardiovascular events (MACEs) are the leading cause of early (<1 y) complications after liver transplantation (LT). NASH, the leading indication for waitlisting for LT, is associated with high cardiac risk factor burden. The contemporary prevalence and temporal trends in pretransplant cardiac risk factor burden and post-LT MACE among LT recipients (LTRs) with and without NASH are unknown. The aim of this study was to evaluate (1) the evolution of post-LT cardiac risk factors in LTRs over time and (2) post-LT MACE over time, stratified by NASH status. This is a retrospective cohort of 1775 adult LTRs at a single transplant center (2003-2020). MACE was defined as death or hospitalization from myocardial infarction, revascularization, stroke, heart failure during the first post-LT year. Between 2003 and 2020, there was a significant increase in pre-LT NASH ( ptrend <0.05). There was also a significant increase in pre-LT obesity, atherosclerotic cardiovascular (CV) disease, and older age (≥65 y old) ( ptrend <0.05 for all). There was no significant change in the proportion of LTRs with diabetes, chronic kidney disease, or heart failure. Unexpectedly, there were no changes in the rate of post-LT MACE over the study period (-0.1% per year, ptrend =0.44). The lack of change in MACE despite an increase in CV risk factor prevalence may reflect advancement in the identification and management of CV risk factors in LTRs. With projected continued increase in cardiac risk burden and the proportion of patients transplanted for NASH, it is critical for LT programs to develop and implement quality improvement efforts to optimize CV care in LTRs.
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Affiliation(s)
- Claire R Harrington
- Division of GI and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Paul Levy
- Division of GI and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Elizabeth Cabrera
- Division of GI and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jing Gao
- Division of GI and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Dyanna L Gregory
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Cynthia Padilla
- Division of GI and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Gonzalo Crespo
- Hepatology and Liver Transplant Unit, Hospital Clinic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Lisa B VanWagner
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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24
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Vanlerberghe BTK, van Malenstein H, Sainz-Bariga M, Jochmans I, Cassiman D, Monbaliu D, van der Merwe S, Pirenne J, Nevens F, Verbeek J. Utility and prognostic value of diagnosing MAFLD in patients undergoing liver transplantation for alcohol-related liver disease. Clin Transplant 2023:e14965. [PMID: 36940254 DOI: 10.1111/ctr.14965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 02/12/2023] [Accepted: 02/26/2023] [Indexed: 03/22/2023]
Abstract
BACKGROUND Recently, the term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace non-alcoholic fatty liver disease (NAFLD). This concept enables diagnosing liver disease associated with metabolic dysfunction in patients with alcohol-related liver disease (ALD), a main indication for liver transplantation (LTx). We assessed MAFLD prevalence in ALD patients undergoing LTx and its prognostic value on post-LTx outcomes. METHODS We retrospectively analyzed all ALD patients transplanted at our center between 1990 and August 2020. MAFLD was diagnosed based on the presence or history of hepatic steatosis and a BMI > 25 or type II diabetes or ≥ 2 metabolic risk abnormalities at LTx. Overall survival and risk factors for recurrent liver and cardiovascular events were analyzed by Cox regression. RESULTS Of the 371 included patients transplanted for ALD, 255 (68.7%) had concomitant MAFLD at LTx. Median follow-up post-LTx was 72 months (IQR: 34.50-122). Patients with ALD-MAFLD were older at LTx (p = .001), more often male (p < .001) and more frequently had hepatocellular carcinoma (p < .001). No differences in perioperative mortality and overall survival were found. ALD-MAFLD patients had an increased risk of recurrent hepatic steatosis, irrespective of alcohol relapse, but no superimposed risk of cardiovascular events. CONCLUSIONS The co-presence of MAFLD at LTx for ALD is associated with a distinct patient profile and is an independent risk factor for recurrent hepatic steatosis. The use of MAFLD criteria in ALD patients might increase awareness and treatment of specific hepatic and systemic metabolic abnormalities before and after LTx.
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Affiliation(s)
- Benedict T K Vanlerberghe
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), University Maastricht, Maastricht, the Netherlands
| | - Hannah van Malenstein
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Mauricio Sainz-Bariga
- Transplantation Research Group, Department of Microbiology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, University of Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Ina Jochmans
- Transplantation Research Group, Department of Microbiology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, University of Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - David Cassiman
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Transplantation Research Group, Department of Microbiology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, University of Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Schalk van der Merwe
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Transplantation Research Group, Department of Microbiology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, University of Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Jef Verbeek
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
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25
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Battistella S, D'Arcangelo F, Grasso M, Zanetto A, Gambato M, Germani G, Senzolo M, Russo FP, Burra P. Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management. Clin Mol Hepatol 2023; 29:S286-S301. [PMID: 36577425 PMCID: PMC10029965 DOI: 10.3350/cmh.2022.0392] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 12/22/2022] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the fastest growing indication to liver transplantation (LT) in Western Countries, both for end stage liver disease and hepatocellular carcinoma. NAFLD/non-alcoholic steatohepatitis (NASH) is often expression of a systemic metabolic syndrome; therefore, NAFLD/NASH patients require a multidisciplinary approach for a proper pre-surgical evaluation, which is important to achieve a post-transplant outcome comparable to that of other indications to LT. NAFLD/NASH patients are also at higher risk of post-transplant cardiovascular events, diabetes, dyslipidemia, obesity, renal impairment and recurrent NASH. Lifestyle modifications, included diet and physical activity, are key to improve survival and quality of life after transplantation. A tailored immunosuppressive regimen may be proposed in selected patients. Development of new drugs for the treatment of recurrent NASH is awaited.
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Affiliation(s)
- Sara Battistella
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Francesca D'Arcangelo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Marco Grasso
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Giacomo Germani
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
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26
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Yong JN, Lim WH, Ng CH, Tan DJH, Xiao J, Tay PWL, Lin SY, Syn N, Chew N, Nah B, Dan YY, Huang DQ, Tan EXX, Sanyal AJ, Noureddin M, Siddiqui MS, Muthiah MD. Outcomes of Nonalcoholic Steatohepatitis After Liver Transplantation: An Updated Meta-Analysis and Systematic Review. Clin Gastroenterol Hepatol 2023; 21:45-54.e6. [PMID: 34801743 DOI: 10.1016/j.cgh.2021.11.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/05/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic steatohepatitis (NASH) is the fastest growing indication of liver transplantation (LT) and is projected to be the leading cause of LT in the near future. The systemic pathogenesis of NASH increases risks of adverse clinical outcomes in patients with NASH receiving LT. Thus, this study aimed to conduct a time-dependent survival analysis between LT recipients with and without NASH using hazard ratios. METHODS A search was conducted on Medline and Embase databases for articles relating to LT outcomes for NASH recipients. A survival analysis was conducted of hazard ratios using the DerSimonian and Laird random-effects model with meta-regression. To account for censoring, survival data were reconstructed from published Kaplan-Meier curves and pooled to derive more accurate hazard estimates and all-cause mortality in NASH patients after LT. Pairwise meta-analysis was conducted to analyze secondary outcomes. RESULTS Fifteen studies involving 119,327 LT recipients were included in our analysis with a prevalence of NASH of 20.2% (95% CI, 12.9-30.2). The pooled 1-year, 5-year, and 10-year all-cause mortality in NASH patients after LT were 12.5%, 24.4%, and 37.9%, respectively. Overall survival was comparable between LT recipients for NASH vs non-NASH (hazard ratio, 0.910; 95% CI, 0.760 to 1.10; P = .34). Meta-regression showed that a higher model for end-stage liver disease score was associated with significantly worse overall survival in NASH compared with non-NASH after LT (95% CI, -0.0856 to -0.0181; P = .0026). CONCLUSIONS This study shows that patients undergoing LT for NASH cirrhosis have comparable complication rates, overall survival, and graft survival compared with non-NASH patients, although close monitoring may be indicated for those with higher model for end-stage liver disease scores.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Nicholas Chew
- Department of Cardiology, National University Heart Centre
| | - Benjamin Nah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Yock Young Dan
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Centre, Los Angeles, California
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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27
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Preexisting Coronary Artery Disease in Liver Transplant Candidates: Risk Factor or Risk Marker? Transplantation 2022; 107:824-826. [PMID: 36372929 DOI: 10.1097/tp.0000000000004403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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28
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Outcomes of Liver Transplantation in Patients with Preexisting Coronary Artery Disease. Transplantation 2022; 107:933-940. [PMID: 36397734 DOI: 10.1097/tp.0000000000004402] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.
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29
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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30
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Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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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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32
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Tapper EB, Fleming C, Rendon A, Fernandes J, Johansen P, Augusto M, Nair S. The Burden of Nonalcoholic Steatohepatitis: A Systematic Review of Epidemiology Studies. GASTRO HEP ADVANCES 2022; 1:1049-1087. [PMID: 39131247 PMCID: PMC11307414 DOI: 10.1016/j.gastha.2022.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 06/30/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Nonalcoholic steatohepatitis (NASH) is associated with increased mortality and risk of complications but is often asymptomatic and under-recognized. A systematic review of NASH epidemiology was conducted to provide information on the burden of NASH and highlight important evidence gaps for future research. Methods Medline, EMBASE, and Cochrane Library databases were searched for English-language publications published from 2010 to January 2022 that reported on natural history, risk factors, comorbidities, and complications of a NASH population or subpopulation. Results Overall, 173 publications were included. NASH was shown to have a variable disease course and high prevalence of comorbid disease. Although many patients progressed to cirrhosis and end-stage liver disease, disease regression or resolution was reported in up to half of patients in some studies. Reported risk factors for disease progression or resolution included levels of (or changes in) serum fibrosis markers, liver enzymes, and platelets. The presence of NASH increased the risk of liver cirrhosis and other serious diseases such as hepatocellular carcinoma, colorectal cancer, chronic kidney disease, and cardiovascular disease. In 2017, NASH was responsible for ∼118,000 cirrhosis deaths globally, and an increasing proportion of patients are receiving liver transplantation for NASH in Europe and the United States. Consolidation of data was hampered by heterogeneity across the studies in terms of patient populations, follow-up time, and outcomes measured. Conclusion NASH is associated with significant morbidity and mortality, an increased risk of comorbidities, and imposes an increasing burden among liver transplantation recipients. Longer studies with harmonized study criteria are required to better understand the impact of NASH on patient outcomes.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Adriana Rendon
- Global Medical Affairs, Novo Nordisk A/S, Søborg, Denmark
| | - João Fernandes
- Payer Evidence Generation, Novo Nordisk A/S, Søborg, Denmark
| | - Pierre Johansen
- Novo Nordisk Denmark A/S, Region North & West Europe, Ørestad, Denmark
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33
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Zhou GP, Jiang YZ, Sun LY, Zhu ZJ. Clinical evidence of outcomes following liver transplantation in patients with nonalcoholic steatohepatitis: An updated meta-analysis and systematic review. Int J Surg 2022; 104:106752. [PMID: 35803515 DOI: 10.1016/j.ijsu.2022.106752] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/18/2022] [Accepted: 06/20/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Nonalcoholic steatohepatitis (NASH) is a dramatically growing indication for liver transplantation (LT) worldwide and the posttransplant outcomes of NASH patients are currently under intensive investigation. This quantitative meta-analysis aimed to update the clinical evidence on outcomes of transplanted patients with NASH. METHODS We performed a systematic review and meta-analysis of studies (published up to September 15, 2021) that focused on LT outcomes for NASH versus non-NASH patients. Random-effect meta-analysis was conducted to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on crucial baseline clinical characteristics and leave-one-out sensitivity analyses were conducted to assess the robustness of the pooled results. Meta-regression was used to evaluate study-level demographic, clinical, and biochemical characteristics to identify potential confounders affecting patient survival. RESULTS Twenty-two non-randomized comparative studies with 1,538 NASH and 6,014 non-NASH patients were included. 1- (OR, 0.94; 95% CI, 0.77-1.14), 3- (OR, 0.82; 95% CI, 1.00-1.22), and 5- (OR, 1.05; 95% CI, 0.84-1.31) year patient survival was equivalent between NASH and non-NASH recipients. NASH patients were associated with similar cardiovascular mortality (OR, 1.36; 95% CI, 0.89-2.09) and retransplantation rates (OR, 0.69; 95% CI, 1.03-1.53), lower graft failure-related mortality (OR, 0.11; 95% CI, 0.29-0.74), but higher sepsis-related mortality (OR, 1.53; 95% CI, 1.13-2.06). Meta-regression revealed that a higher proportion of patients with hepatocellular carcinoma (HCC) were associated with significantly superior overall patient survival at 1 (P = 0.044), 3 (P = 0.035) and 5 (P = 0.049) years after LT in NASH compared with non-NASH. CONCLUSIONS This study shows no difference in posttransplant survival between NASH and non-NASH patients. Carefully selected patients with NASH-related HCC may benefit from LT. NASH recipients should be managed with caution posttransplant, especially regarding the potentially high risk of sepsis-related death.
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Affiliation(s)
- Guang-Peng Zhou
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China
| | - Yi-Zhou Jiang
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China
| | - Li-Ying Sun
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China.
| | - Zhi-Jun Zhu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China.
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Kaya E, Yilmaz Y. Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver. J Clin Transl Hepatol 2022; 10:329-338. [PMID: 35528971 PMCID: PMC9039705 DOI: 10.14218/jcth.2021.00178] [Citation(s) in RCA: 96] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 08/19/2021] [Accepted: 09/17/2021] [Indexed: 02/05/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of extrahepatic manifestations, such as obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cognitive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malignancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is parallel to the severity of NAFLD. In clinical practice, awareness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corresponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.
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Affiliation(s)
- Eda Kaya
- Department of Internal Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
- Liver Research Unit, Institute of Gastroenterology, Marmara University, Istanbul, Turkey
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Han S, Park J, Hong SH, Park CS, Choi J, Chae MS. Cardiovascular manifestation of end-stage liver disease and perioperative echocardiography for liver transplantation: anesthesiologist’s view. Anesth Pain Med (Seoul) 2022; 17:132-144. [PMID: 35538654 PMCID: PMC9091670 DOI: 10.17085/apm.22132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 03/30/2022] [Indexed: 11/19/2022] Open
Abstract
Liver transplantation (LT) is the curative therapy for decompensated cirrhosis. However, anesthesiologists can find it challenging to manage patients undergoing LT due to the underlying pathologic conditions of patients with end-stage liver disease and the high invasiveness of the procedure, which is frequently accompanied by massive blood loss. Echocardiography is a non-invasive or semi-invasive imaging tool that provides real-time information about the structural and functional status of the heart and is considered to be able to improve outcomes by enabling accurate and detailed assessments. This article reviews the pathophysiologic changes of the heart accompanied by cirrhosis that mainly affect hemodynamics. We also present a comparative review of the diagnostic criteria for cirrhotic cardiomyopathy published by the World Congress of Gastroenterology in 2005 and the Cirrhotic Cardiomyopathy Consortium in 2019. This article discusses the conditions that could affect hemodynamic stability and postoperative outcomes, such as coronary artery disease, left ventricular outflow tract obstruction, portopulmonary hypertension, hepatopulmonary syndrome, pericardial effusion, cardiac tamponade, patent foramen ovale, and ascites. Finally, we cover a number of intraoperative factors that should be considered, including intraoperative blood loss, rapid reaccumulation of ascites, manipulation of the inferior vena cava, post-reperfusion syndrome, and adverse effects of excessive fluid infusion and transfusion. This article aimed to summarize the cardiovascular manifestations of cirrhosis that can affect hemodynamics and can be evaluated using perioperative echocardiography. We hope that this article will provide information about the hemodynamic characteristics of LT recipients and stimulate more active use of perioperative echocardiography.
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Affiliation(s)
- Sangbin Han
- Department of Emergency Medicine, Cheongyang Health Center County Hospital, Cheongyang, Korea
| | - Jaesik Park
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sang Hyun Hong
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Soo Park
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jongho Choi
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min Suk Chae
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Corresponding author Min Suk Chae, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: 82-2-2258-6150 Fax: 82-2-537-1951 E-mail:
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McCarthy KJ, Motta-Calderon D, Estrada-Roman A, Cajiao KM, Curry MP, Bonder A, Anagnostopoulos AM, Gavin M. Introduction of a standardized protocol for cardiac risk assessment in candidates for liver transplant - A retrospective cohort analysis. Ann Hepatol 2022; 27:100582. [PMID: 34808392 DOI: 10.1016/j.aohep.2021.100582] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/27/2021] [Accepted: 10/11/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Recommendations on non-invasive imaging to assess pre-operative cardiac risk among liver transplant candidates vary amongst societal guidelines and individual institutional practices. In 2018, a standardized pre-transplant coronary evaluation protocol was established at Beth Israel Deaconess Medical Center, Boston MA, to ensure appropriate and consistent pre-operative testing was performed. METHODS All patients who underwent liver transplant evaluation between January 1st, 2016 and December 31st, 2019, were retrospectively analyzed and divided into three cohorts; before the introduction of the protocol (prior to 2018), initial protocol favoring invasive coronary angiography (ICA) (2018), and amended protocol favoring coronary computed tomography angiography (CCTA) (post-2018). We described clinical characteristics, candidacy for transplant, and cardiovascular complications during follow-up. As an unadjusted exploratory analysis, the Cochran-Armitage Exact Trend Test was used to examine univariate differences across time. RESULTS A total of 462 patients underwent liver transplant evaluation during the study period. Among these, 218 (47.2%) patients underwent stress test, 50 (10.8%) underwent CCTA, and 68 (14.8%) underwent ICA. Across the three time periods, there was an increase in the proportion of CCTAs performed (3%, 6.3%, and 26.3% respectively; p <0.001) and proportion of patients diagnosed with obstructive CAD using CCTA (0%, 30%, and 51.4% respectively; p = 0.04). There was no significant difference in post-transplant cardiac complications among patients evaluated before 2018, during 2018, and after 2018 (5.9% vs. 5.6 vs. 6.0%; p=1.0). CONCLUSION Our findings suggest it is reasonable to shift practice to a less invasive approach utilizing CCTA or nuclear stress testing when assessing liver transplant candidates at increased cardiovascular risk.
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Affiliation(s)
- Killian J McCarthy
- Division of Cardiology, Beth Israel Deaconess Medical Center, Boston MA, United States
| | - Daniel Motta-Calderon
- Division of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | | | - Karen M Cajiao
- Division of Medicine, St. Mary's Hospital, Waterbury, CT, United States
| | - Michael P Curry
- Division of Hepatology, Beth Israel Deaconess Medical Center, Boston, MA, United States
| | - Alan Bonder
- Division of Hepatology, Beth Israel Deaconess Medical Center, Boston, MA, United States
| | | | - Michael Gavin
- Division of Cardiology, Beth Israel Deaconess Medical Center, Boston MA, United States.
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Louissaint J, Fortune BE. Blood Pressure Variability in Liver Transplant Recipients: The Who, What, When, and How. Liver Transpl 2022; 28:549-551. [PMID: 35092162 DOI: 10.1002/lt.26414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 01/20/2022] [Indexed: 01/13/2023]
Affiliation(s)
- Jeremy Louissaint
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY
| | - Brett E Fortune
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY
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38
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Altieri MH, Liu H, Lee SS. Cardiovascular events after liver transplantation: MACE hurts. Rev Cardiovasc Med 2022; 23:91. [PMID: 35345258 DOI: 10.31083/j.rcm2303091] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/17/2021] [Accepted: 01/04/2022] [Indexed: 01/04/2025] Open
Abstract
The curative therapy for patients with end-stage liver disease is liver transplantation. However, liver transplantation challenges the cardiovascular system, and is associated with major adverse cardiovascular events (MACE). Immediately after implantation of the liver graft, changes in cardiac preload and afterload increase the cardiac workload. Longer-term postoperatively, a more sedentary lifestyle and enhanced appetite increase obesity and body mass index. Immunosuppressants may also affect the cardiovascular system. All these factors that liver recipients encounter impact the function of the cardiovascular system. Cardiac events are the third-leading cause of death in liver recipients. This review describes the pertinent factors that predispose to development of MACE after liver transplantation, and how to predict these cardiovascular events in the post-transplant period. We review the roles of metabolic syndrome, renal dysfunction, non-alcoholic fatty liver disease, diagnostic tests such as imaging and biomarkers, and parameters such as systolic and diastolic dysfunction, and QT interval prolongation in cardiovascular events. We summarize the current literature on scoring systems to predict cardiovascular events.
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Affiliation(s)
- Mario H Altieri
- Division of Gastroenterology, Hepatology and Nutrition, CHU, 14000 Caen, France
| | - Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
| | - Samuel S Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
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Levitsky J, Kandpal M, Guo K, Kleiboeker S, Sinha R, Abecassis M. Donor-derived cell-free DNA levels predict graft injury in liver transplant recipients. Am J Transplant 2022; 22:532-540. [PMID: 34510731 DOI: 10.1111/ajt.16835] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 08/15/2021] [Accepted: 09/02/2021] [Indexed: 01/25/2023]
Abstract
Donor-derived cell-free DNA (dd-cfDNA) has been evaluated as a rejection marker in organ transplantation. This study sought to assess the utility of dd-cfDNA to diagnose graft injury in liver transplant recipients (LTR) and as a predictive biomarker prior to different causes of graft dysfunction. Plasma from single and multicenter LTR cohorts was analyzed for dd-cfDNA. Phenotypes of treated biopsy-proven acute rejection (AR, N = 57), normal function (TX, N = 94), and acute dysfunction no rejection (ADNR; N = 68) were divided into training and test sets. In the training set, dd-cfDNA was significantly different between AR versus TX (AUC 0.95, 5.3% cutoff) and AR versus ADNR (AUC 0.71, 20.4% cutoff). Using these cutoffs in the test set, the accuracy and NPV were 87% and 100% (AR vs. TX) and 66.7% and 87.8% (AR vs. ADNR). Blood samples collected serially from LTR demonstrated incremental elevations in dd-cfDNA prior to the onset of graft dysfunction (AR > ADNR), but not in TX. Dd-cfDNA also decreased following treatment of rejection. In conclusion, the serial elevation of dd-cfDNA identifies pre-clinical graft injury in the context of normal liver function tests and is greatest in rejection. This biomarker may help detect early signs of graft injury and rejection to inform LTR management strategies.
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Affiliation(s)
- Josh Levitsky
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Manoj Kandpal
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Kexin Guo
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | - Rohita Sinha
- Eurofins Viracor Clinical Diagnostics, Lee's Summit, Missouri
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Foerster F, Gairing SJ, Müller L, Galle PR. NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options. J Hepatol 2022; 76:446-457. [PMID: 34555422 DOI: 10.1016/j.jhep.2021.09.007] [Citation(s) in RCA: 157] [Impact Index Per Article: 52.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/17/2021] [Accepted: 09/09/2021] [Indexed: 12/11/2022]
Abstract
In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent an increasingly important underlying aetiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation are characterised by several unique features: in contrast to virally driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis and annual HCC incidence is comparatively low, complicating current surveillance strategies. On average, patients are older and are more frequently diagnosed at an advanced stage. While locoregional treatments are probably equally effective regardless of HCC aetiology, the picture is less clear for systemic therapy. Tyrosine kinase inhibitors are probably equally effective, while there have been initial signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC than in viral HCC. Current international clinical practice guidelines for HCC do not consider aetiology, as there are insufficient data to draw specific conclusions or to recommend aetiology-specific modifications to the current management of patients with HCC. However, in light of the growing relevance of NAFLD-HCC, future clinical trials should assess whether HCC aetiology - and NAFLD/NASH in particular - influence the safety and efficacy of a given treatment.
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Affiliation(s)
- Friedrich Foerster
- Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany
| | - Simon Johannes Gairing
- Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany
| | - Lukas Müller
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes-Gutenberg University Mainz, Germany
| | - Peter Robert Galle
- Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany.
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41
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Tripodi A, Lombardi R, Primignani M, La Mura V, Peyvandi F, Fracanzani AL. Hypercoagulability in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD): Causes and Consequences. Biomedicines 2022; 10:249. [PMID: 35203457 PMCID: PMC8869363 DOI: 10.3390/biomedicines10020249] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is anticipated that it could become even more prevalent in parallel with an increase in the incidence of metabolic diseases closely related to NAFLD, such as obesity, type II diabetes, dyslipidemia, and arterial hypertension. In addition to liver impairment, NAFLD is associated with cardiovascular diseases. Fibrosis, atherosclerosis, and venous thrombosis are basically the pathogenic mechanisms behind these clinical manifestations, and all are plausibly associated with hypercoagulability that may, in turn, develop because of an imbalance of pro- vs. anticoagulants and the presence of such procoagulant molecular species as microvesicles, neutrophil extracellular traps (NETs), and inflammation. The assessment of hypercoagulability by means of thrombin generation is a global procedure that mimics the coagulation process occurring in vivo much better than any other coagulation test, and is considered to be the best candidate laboratory tool for assessing, with a single procedure, the balance of coagulation in NAFLD. In addition to defining the state of hypercoagulability, the assessment of thrombin generation could also be used to investigate, in clinical trials, the best approach (therapeutic and/or lifestyle changes) for minimizing hypercoagulability and, hence, the risk of cardiovascular diseases, progression to atherosclerosis, and liver fibrosis in patients with NAFLD.
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Affiliation(s)
- Armando Tripodi
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, 20122 Milan, Italy; (V.L.M.); (F.P.)
| | - Rosa Lombardi
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Unit of Internal Medicine and Metabolic Disease, 20122 Milan, Italy; (R.L.); (A.L.F.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
| | - Massimo Primignani
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, First Division of Gastroenterology, 20122 Milan, Italy;
| | - Vincenzo La Mura
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, 20122 Milan, Italy; (V.L.M.); (F.P.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
| | - Flora Peyvandi
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, 20122 Milan, Italy; (V.L.M.); (F.P.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
| | - Anna L. Fracanzani
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Unit of Internal Medicine and Metabolic Disease, 20122 Milan, Italy; (R.L.); (A.L.F.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
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Plaz MC, Tsochatzis EA. Metabolic Complications Before and After Liver Transplantation. TEXTBOOK OF LIVER TRANSPLANTATION 2022:357-371. [DOI: 10.1007/978-3-030-82930-8_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Kaur H, Premkumar M. Diagnosis and Management of Cirrhotic Cardiomyopathy. J Clin Exp Hepatol 2022; 12:186-199. [PMID: 35068798 PMCID: PMC8766707 DOI: 10.1016/j.jceh.2021.08.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/13/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Cirrhotic cardiomyopathy refers to the structural and functional changes in the heart leading to either impaired systolic, diastolic, electrocardiographic, and neurohormonal changes associated with cirrhosis and portal hypertension. Cirrhotic cardiomyopathy is present in 50% of patients with cirrhosis and is clinically seen as impaired contractility, diastolic dysfunction, hyperdynamic circulation, and electromechanical desynchrony such as QT prolongation. In this review, we will discuss the cardiac physiology principles underlying cirrhotic cardiomyopathy, imaging techniques such as cardiac magnetic resonance imaging and scintigraphy, cardiac biomarkers, and newer echocardiographic techniques such as tissue Doppler imaging and speckle tracking, and emerging treatments to improve outcomes. METHODS We reviewed available literature from MEDLINE for randomized controlled trials, cohort studies, cross-sectional studies, and real-world outcomes using the search terms "cirrhotic cardiomyopathy," "left ventricular diastolic dysfunction," "heart failure in cirrhosis," "liver transplantation," and "coronary artery disease". RESULTS Cirrhotic cardiomyopathy is associated with increased risk of complications such as hepatorenal syndrome, refractory ascites, impaired response to stressors including sepsis, bleeding or transplantation, poor health-related quality of life and increased morbidity and mortality. The evaluation of cirrhotic cardiomyopathy should also guide the feasibility of procedures such as transjugular intrahepatic portosystemic shunt, dose titration protocol of betablockers, and liver transplantation. The use of targeted heart rate reduction is of interest to improve cardiac filling and improve the cardiac output using repurposed heart failure drugs such as ivabradine. Liver transplantation may also reverse the cirrhotic cardiomyopathy; however, careful cardiac evaluation is necessary to rule out coronary artery disease and improve cardiac outcomes in the perioperative period. CONCLUSION More data are needed on the new diagnostic criteria, molecular and biochemical changes, and repurposed drugs in cirrhotic cardiomyopathy. The use of advanced imaging techniques should be incorporated in clinical practice.
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Key Words
- 2-AG, 2-arachidonylglycerol
- 2D, two-dimensional
- AEA, Anandamide
- ANP, Atrial Natriuretic Peptide
- ASE, the American Society of Echocardiography
- AUC, area under the curve
- BA, bile acid
- BNP, Brain natriuretic peptide
- CAD, coronary artery disease
- CB-1, cannabinoid −1
- CCM, Cirrhotic Cardiomyopathy
- CMR, cardiovascular magnetic resonance imaging
- CO, cardiac output
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- CVP, central venous pressure
- DT, deceleration Time
- ECG, electrocardiogram
- ECV, extracellular volume
- EF, Ejection fraction
- EMD, electromechanical desynchrony
- ESLD, end-stage liver disease
- FXR, Farnesoid X receptor
- GI, gastrointestinal
- GLS, Global Longitudinal strain
- HCN, Hyperpolarization-activated cyclic nucleotide–gated
- HE, hepatic encephalopathy
- HF, heart failure
- HO, Heme oxygenase
- HPS, hepatopulmonary syndrome
- HR, heart rate
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- HfmrEF, heart failure with mid-range ejection fraction
- HfrEF, heart failure with reduced ejection fraction
- IVC, Inferior Vena Cava
- IVCD, IVC Diameter
- IVS, intravascular volume status
- L-NAME, NG-nitro-L-arginine methyl ester
- LA, left atrium
- LAVI, LA volume index
- LGE, late gadolinium enhancement
- LT, liver transplant
- LV, left ventricle
- LVDD, left ventricular diastolic dysfunction
- LVEDP, left ventricular end-diastolic pressure
- LVEDV, LV end diastolic volume
- LVEF, left ventricular ejection fraction
- LVESV, LV end systolic volume
- LVOT, left ventricular outflow tract
- MAP, mean arterial pressure
- MELD, Model for End-Stage Liver Disease
- MR, mitral regurgitation
- MRI, Magnetic resonance imaging
- MV, mitral valve
- NAFLD, Nonalcoholic fatty liver disease
- NO, nitric oxide
- NOS, Nitric oxide synthases
- NTProBNP, N-terminal proBNP
- PAP, pulmonary artery pressure
- PCWP, pulmonary capillary wedged pressure
- PHT, portal hypertension
- PWD, Pulsed-wave Doppler
- RV, right ventricle
- RVOT, right ventricular outflow tract
- SA, sinoatrial
- SD, standard deviation
- SV, stroke volume
- SVR, Systemic vascular resistance
- TDI, tissue Doppler imaging
- TIPS, transjugular intrahepatic portosystemic shunt
- TR, Tricuspid valve
- TRPV1, transient receptor potential cation channel subfamily V member 1
- TTE, transthoracic echocardiography
- USG, ultrasonography
- VTI, velocity time integral
- beta blocker
- cirrhotic cardiomyopathy
- hemodynamics in cirrhosis
- left ventricular diastolic dysfunction
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Affiliation(s)
| | - Madhumita Premkumar
- Address for correspondence: Dr. Madhumita Premkumar, M.D., D.M., Department of Hepatology, Postgraduate Institute of Medical Education and Research, 60012, Chandigarh, India. Tel.: ++91-9540951061 (mobile)
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Villeret F, Dumortier J, Erard-Poinsot D. How will NAFLD change the liver transplant landscape in the 2020s? Clin Res Hepatol Gastroenterol 2022; 46:101759. [PMID: 34311133 DOI: 10.1016/j.clinre.2021.101759] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/21/2021] [Indexed: 02/04/2023]
Abstract
Liver steatosis is the hepatic manifestation of the metabolic syndrome, and is now the leading cause of chronic liver disease worldwide. The treatment of metabolic cirrhosis with liver failure and/or hepatocellular carcinoma is liver transplantation (LT). During the past decade, metabolic cirrhosis represented an increasing cause for LT, especially in the United States. At listing, patients with metabolic cirrhosis are older, with numerous cardiovascular (CV) and renal comorbidities, and this requires multidisciplinary pre-transplant assessment. After LT, 5-year survival is similar to other indications. The leading causes of death are infectious, cancers and CV. The recurrence of the initial disease is very frequent, and a significant part of the patients progress towards graft cirrhosis. No specific immunosuppressive regimen is recommended, but the toxicity profiles must probably be taken into account. In these patients, the only etiological treatment is that of obesity, in the absence of specific therapy for non-alcoholic steatohepatitis. The place of bariatric surgery has to be defined, probably sleeve gastrectomy, in a stable patient, 6-12 months after LT.
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Affiliation(s)
- François Villeret
- Hepatology Department, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France
| | - Jérôme Dumortier
- Hepatogastroenterology Department, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
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Han MAT, Olivo R, Choi CJ, Pyrsopoulos N. De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation. World J Hepatol 2021; 13:1991-2004. [PMID: 35070003 PMCID: PMC8727208 DOI: 10.4254/wjh.v13.i12.1991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/27/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new acronym adopted from the consensus of international experts. Given the increasing prevalence of MAFLD in pre-transplant settings, de novo and recurrent graft steatosis/MAFLD are common in post-transplant settings. The impact of graft steatosis on long-term outcomes is unclear. The current knowledge of incidence rate, risk factors, diagnosis, long-term outcomes, and management of graft steatosis (both de novo and recurrent) is discussed in this review.
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Affiliation(s)
- Ma Ai Thanda Han
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Raquel Olivo
- Department of Gastroenterology and Hepatology, Rutgers University, New Jersey Medical School, Newark, NJ 07103, United States
| | - Catherine J Choi
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United
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Vernooij LM, van Klei WA, Moons KG, Takada T, van Waes J, Damen JA. The comparative and added prognostic value of biomarkers to the Revised Cardiac Risk Index for preoperative prediction of major adverse cardiac events and all-cause mortality in patients who undergo noncardiac surgery. Cochrane Database Syst Rev 2021; 12:CD013139. [PMID: 34931303 PMCID: PMC8689147 DOI: 10.1002/14651858.cd013139.pub2] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The Revised Cardiac Risk Index (RCRI) is a widely acknowledged prognostic model to estimate preoperatively the probability of developing in-hospital major adverse cardiac events (MACE) in patients undergoing noncardiac surgery. However, the RCRI does not always make accurate predictions, so various studies have investigated whether biomarkers added to or compared with the RCRI could improve this. OBJECTIVES Primary: To investigate the added predictive value of biomarkers to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Secondary: To investigate the prognostic value of biomarkers compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Tertiary: To investigate the prognostic value of other prediction models compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. SEARCH METHODS We searched MEDLINE and Embase from 1 January 1999 (the year that the RCRI was published) until 25 June 2020. We also searched ISI Web of Science and SCOPUS for articles referring to the original RCRI development study in that period. SELECTION CRITERIA We included studies among adults who underwent noncardiac surgery, reporting on (external) validation of the RCRI and: - the addition of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of the RCRI to other models. Besides MACE, all other adverse outcomes were considered for inclusion. DATA COLLECTION AND ANALYSIS We developed a data extraction form based on the CHARMS checklist. Independent pairs of authors screened references, extracted data and assessed risk of bias and concerns regarding applicability according to PROBAST. For biomarkers and prediction models that were added or compared to the RCRI in ≥ 3 different articles, we described study characteristics and findings in further detail. We did not apply GRADE as no guidance is available for prognostic model reviews. MAIN RESULTS We screened 3960 records and included 107 articles. Over all objectives we rated risk of bias as high in ≥ 1 domain in 90% of included studies, particularly in the analysis domain. Statistical pooling or meta-analysis of reported results was impossible due to heterogeneity in various aspects: outcomes used, scale by which the biomarker was added/compared to the RCRI, prediction horizons and studied populations. Added predictive value of biomarkers to the RCRI Fifty-one studies reported on the added value of biomarkers to the RCRI. Sixty-nine different predictors were identified derived from blood (29%), imaging (33%) or other sources (38%). Addition of NT-proBNP, troponin or their combination improved the RCRI for predicting MACE (median delta c-statistics: 0.08, 0.14 and 0.12 for NT-proBNP, troponin and their combination, respectively). The median total net reclassification index (NRI) was 0.16 and 0.74 after addition of troponin and NT-proBNP to the RCRI, respectively. Calibration was not reported. To predict myocardial infarction, the median delta c-statistic when NT-proBNP was added to the RCRI was 0.09, and 0.06 for prediction of all-cause mortality and MACE combined. For BNP and copeptin, data were not sufficient to provide results on their added predictive performance, for any of the outcomes. Comparison of the predictive value of biomarkers to the RCRI Fifty-one studies assessed the predictive performance of biomarkers alone compared to the RCRI. We identified 60 unique predictors derived from blood (38%), imaging (30%) or other sources, such as the American Society of Anesthesiologists (ASA) classification (32%). Predictions were similar between the ASA classification and the RCRI for all studied outcomes. In studies different from those identified in objective 1, the median delta c-statistic was 0.15 and 0.12 in favour of BNP and NT-proBNP alone, respectively, when compared to the RCRI, for the prediction of MACE. For C-reactive protein, the predictive performance was similar to the RCRI. For other biomarkers and outcomes, data were insufficient to provide summary results. One study reported on calibration and none on reclassification. Comparison of the predictive value of other prognostic models to the RCRI Fifty-two articles compared the predictive ability of the RCRI to other prognostic models. Of these, 42% developed a new prediction model, 22% updated the RCRI, or another prediction model, and 37% validated an existing prediction model. None of the other prediction models showed better performance in predicting MACE than the RCRI. To predict myocardial infarction and cardiac arrest, ACS-NSQIP-MICA had a higher median delta c-statistic of 0.11 compared to the RCRI. To predict all-cause mortality, the median delta c-statistic was 0.15 higher in favour of ACS-NSQIP-SRS compared to the RCRI. Predictive performance was not better for CHADS2, CHA2DS2-VASc, R2CHADS2, Goldman index, Detsky index or VSG-CRI compared to the RCRI for any of the outcomes. Calibration and reclassification were reported in only one and three studies, respectively. AUTHORS' CONCLUSIONS Studies included in this review suggest that the predictive performance of the RCRI in predicting MACE is improved when NT-proBNP, troponin or their combination are added. Other studies indicate that BNP and NT-proBNP, when used in isolation, may even have a higher discriminative performance than the RCRI. There was insufficient evidence of a difference between the predictive accuracy of the RCRI and other prediction models in predicting MACE. However, ACS-NSQIP-MICA and ACS-NSQIP-SRS outperformed the RCRI in predicting myocardial infarction and cardiac arrest combined, and all-cause mortality, respectively. Nevertheless, the results cannot be interpreted as conclusive due to high risks of bias in a majority of papers, and pooling was impossible due to heterogeneity in outcomes, prediction horizons, biomarkers and studied populations. Future research on the added prognostic value of biomarkers to existing prediction models should focus on biomarkers with good predictive accuracy in other settings (e.g. diagnosis of myocardial infarction) and identification of biomarkers from omics data. They should be compared to novel biomarkers with so far insufficient evidence compared to established ones, including NT-proBNP or troponins. Adherence to recent guidance for prediction model studies (e.g. TRIPOD; PROBAST) and use of standardised outcome definitions in primary studies is highly recommended to facilitate systematic review and meta-analyses in the future.
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Affiliation(s)
- Lisette M Vernooij
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Department of Anesthesiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Wilton A van Klei
- Department of Anesthesiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Anesthesiologist and R. Fraser Elliott Chair in Cardiac Anesthesia, Department of Anesthesia and Pain Management Toronto General Hospital, University Health Network and Professor, Department of Anesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Karel Gm Moons
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Toshihiko Takada
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Judith van Waes
- Department of Anesthesiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Johanna Aag Damen
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Sharma S, Stine JG, Verbeek T, Bezinover D. Management of Patients With Non-alcoholic Steatohepatitis Undergoing Liver Transplantation: Considerations for the Anesthesiologist. J Cardiothorac Vasc Anesth 2021; 36:2616-2627. [PMID: 34391652 DOI: 10.1053/j.jvca.2021.07.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/24/2021] [Accepted: 07/09/2021] [Indexed: 11/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) currently affects more than 25% of the world population and is rising. NAFLD can progress to non-alcoholic steatohepatitis that is associated with hepatic inflammation and fibrosis and can result in cirrhosis with subsequent liver failure. Non-alcoholic steatohepatitis (NASH) has now emerged as one of the leading etiologies for a liver transplant among adults in the United States. Given the rising incidence of liver transplants in patients with NASH-related cirrhosis, it is essential for anesthesiologists to be familiar with this condition as well as with NASH-related comorbidities and perioperative complications. Not only is NASH linked to metabolic syndrome, but it also is independently associated with cardiovascular disease, renal and thyroid dysfunction, obstructive sleep apnea (OSA), and a hypercoagulable state. The association with these conditions can affect the perioperative outcome of these patients, particularly because of increased mortality from major adverse cardiovascular events and sepsis. In order to decrease the perioperative morbidity and mortality of patients with NASH undergoing a liver transplant, a multidisciplinary approach to their perioperative management is essential, along with careful preoperative evaluation and aggressive intraoperative and postoperative monitoring. The focus of this review article is to provide a comprehensive overview of challenges associated with liver transplants in patients with NASH and to provide suggestions for appropriate patient selection and perioperative management.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA.
| | - Jonathan G Stine
- Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA; Department of Medicine and Public Health Sciences, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Cancer Institute, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA
| | - Thomas Verbeek
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA; Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA
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Prognostic Value of Computed Tomographic Coronary Angiography for Long-Term Major Adverse Cardiac Events after Liver Transplantation. J Clin Med 2021; 10:jcm10143132. [PMID: 34300296 PMCID: PMC8303180 DOI: 10.3390/jcm10143132] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 12/26/2022] Open
Abstract
Computed tomographic coronary angiography (CTCA) has prognostic value for early major adverse cardiac events (MACEs) after liver transplantation. However, the association between CTCA and long-term MACEs in liver transplant (LT) recipients remains unknown. We evaluated the association between CTCA and long-term MACEs within 5 years after living donor liver transplantation (LDLT). A total of 628 LDLT recipients who underwent CTCA were analyzed between 2010 and 2012. MACEs were investigated within 5 years after LDLT. The factors associated with long-term MACEs in transplant recipients were evaluated. Only 48 (7.6%) patients developed MACEs. In the Fine and Gray competing risk regression, a coronary artery calcium score (CACS) of >400 combined with obstructive coronary artery disease (CAD) (subdistribution hazard ratio: 5.01, 95% confidence interval: 2.37–10.58, p < 0.001), age (1.05, 1.01–1.10, p = 0.018), diabetes mellitus (2.43, 1.37–4.29, p = 0.002), dyslipidemia (2.45, 1.23–4.70, p = 0.023), and creatinine (1.19, 1.08–1.30, p < 0.001) were independently associated with long-term MACEs. CACS (>400) combined with obstructive CAD may be associated with MACEs within 5 years after LDLT, suggesting the importance of preoperative noninvasive CTCA in LT recipients. The evaluation of coronary artery stenosis on CTCA combined with CACS may have a prognostic value for long-term MACEs in LT recipients.
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Barman PM, VanWagner LB. Cardiac Risk Assessment in Liver Transplant Candidates: Current Controversies and Future Directions. Hepatology 2021; 73:2564-2576. [PMID: 33219576 PMCID: PMC8220582 DOI: 10.1002/hep.31647] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 09/25/2020] [Accepted: 10/13/2020] [Indexed: 12/12/2022]
Abstract
In the changing landscape of liver transplantation (LT), we are now evaluating older and sicker patients with more cardiovascular comorbidities, and the spectrum of cardiovascular disease is uniquely physiologically impacted by end-stage liver disease. Cardiac complications are now the leading cause of morbidity and mortality in LT recipients, and the pretransplant risk is exacerbated immediately during the transplant operation and continues long term under the umbrella of immunosuppression. Accurate risk estimation of cardiac complications before LT is paramount to guide allocation of limited health care resources and to improve both short-term and long-term clinical outcomes for patients. Current screening and diagnostic testing are limited in their capacity to accurately identify early coronary disease and myocardial dysfunction in persons with end-stage liver disease physiology. Furthermore, a number of testing modalities have not been evaluated in patients with end-stage liver disease. As a result, there is wide variation in cardiac risk assessment practices across transplant centers. In this review, we propose a definition for defining cardiac events in LT, evaluate the current evidence for surgery-related, short-term and long-term cardiac risk assessment in LT candidates, propose an evidence-based testing algorithm, and highlight specific gaps in knowledge and current controversies, identifying areas for future research.
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Affiliation(s)
- Pranab M. Barman
- Department of Medicine-Division of Gastroenterology & Hepatology, University of California San Diego, San Diego, CA
| | - Lisa B. VanWagner
- Department of Medicine-Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL,Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL,Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
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Liver-Related and Cardiovascular Outcome of Patients Transplanted for Nonalcoholic Fatty Liver Disease: A European Single-Center Study. Transplant Proc 2021; 53:1674-1681. [PMID: 34016462 DOI: 10.1016/j.transproceed.2021.02.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 01/18/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The increasing rate of liver transplantation (LT) for nonalcoholic fatty liver disease (NAFLD) raises concerns on cardiovascular morbidity and mortality after LT in these patients. METHODS We collected variables regarding the presence of metabolic risk factors, NAFLD recurrence, cardiovascular morbidity, and overall survival at time of listing and after LT of 112 patients with NAFLD and a control group of 120 patients with hepatitis C (HCV). RESULTS Metabolic syndrome and cardiovascular morbidity component rates (24.1% vs 12.5%) at the time of LT listing were higher in patients with NAFLD compared with patients with HCV (for all, P < .0390). Median follow-up after LT was 5.6 years in patients with NAFLD vs 13.5 years in patients with HCV (P = .0009). There was no difference in 6-weeks postoperative mortality (1.7% vs 2.5%) (P =1.0000). Metabolic syndrome components after LT were more frequent in patients with NAFLD than in patients with HCV (for all, P < .0008). The incidence of NAFLD 5 years after LT was higher in patients transplanted for NAFLD compared with HCV (43.5% vs 4.2%) (P < .0001). Patients with recurrent NAFLD more often had myocardial infarction compared with those without recurrence (8.3% vs 0%) (P = .0313). Five years after LT, cardiovascular morbidity was more frequent in the NAFLD group than in the HCV group (12.8% vs 9.3%) (P = .0256), whereas no difference in overall survival was observed. CONCLUSION LT for NAFLD is associated with satisfactory 5-year outcomes; however, our data underscore the need for close monitoring and aggressive management of cardiovascular risk factors in these patients.
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