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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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2
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Shaked O, Loza BL, Olthoff KM, Reddy KR, Keating BJ, Testa G, Asrani SK, Shaked A. Donor and recipient genetics: Implications for the development of posttransplant diabetes mellitus. Am J Transplant 2024; 24:1794-1802. [PMID: 38782187 DOI: 10.1016/j.ajt.2024.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 04/16/2024] [Accepted: 05/16/2024] [Indexed: 05/25/2024]
Abstract
Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated. Among recipients in the highest T2D-PRS quintile, donor T2D-PRS did not contribute significantly to PTDM. However, in recipients with the lowest T2D genetic risk, donor livers with the highest T2D-PRS contributed to the development of PTDM (OR [95% CI] = 3.79 [1.10-13.1], P = .035). Recipient risk was linked to factors associated with insulin secretion (OR [95% CI] = 0.85 [0.74-0.98], P = .02), while donor livers contributed to PTDM via gene pathways involved in insulin sensitivity (OR [95% CI] = 0.86 [0.75-0.99], P = .03). Recipient and donor PRS independently and collectively serve as predictors of PTDM onset. The genetically influenced biological pathways in recipients primarily pertain to insulin secretion, whereas the genetic makeup of donors exerts an influence on insulin sensitivity.
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Affiliation(s)
- Oren Shaked
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Bao-Li Loza
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kim M Olthoff
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kuchikula Rajender Reddy
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Brendan J Keating
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Giuliano Testa
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA
| | - Sumeet K Asrani
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA
| | - Abraham Shaked
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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3
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Zubkov MR, Moore HB, Lopez R, Brosi D, Choudhury RA, Arrigain S, Saben J, Conzen KD, Pomposelli JJ, Pomfret EA, Schold JD. Prognostic value of body mass index is highly modified by sex among recipients of liver transplant. Liver Transpl 2024; 30:962-966. [PMID: 38687166 DOI: 10.1097/lvt.0000000000000389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 03/22/2024] [Indexed: 05/02/2024]
Affiliation(s)
- Micaella R Zubkov
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Hunter B Moore
- AdventHealth Transplant Institute, Porter, Denver, Colorado
| | - Rocio Lopez
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Deena Brosi
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Rashikh A Choudhury
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Susana Arrigain
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jessica Saben
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kendra D Conzen
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - James J Pomposelli
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Elizabeth A Pomfret
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jesse D Schold
- Department of Surgery, University of Colorado, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Epidemiology, University of Colorado, Aurora, Colorado, USA
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4
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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5
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Gabrielli F, Golfieri L, Nascimbeni F, Andreone P, Gitto S. Metabolic Disorders in Liver Transplant Recipients: The State of the Art. J Clin Med 2024; 13:1014. [PMID: 38398327 PMCID: PMC10889804 DOI: 10.3390/jcm13041014] [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: 01/25/2024] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
Liver transplantation represents a chief therapeutic approach for acute liver failure, end-stage liver disease and hepatocellular carcinoma. Despite witnessing advancements in short- and medium-term survival over recent decades, attributed to refinements in surgical techniques and immunosuppressive protocols, long-term mortality remains impervious to modification. Notably, cardiovascular disease emerges as a predominant cause of mortality among liver transplant recipients. This trend is accentuated by the increasing prominence of non-alcoholic steatohepatitis-related cirrhosis as an indication for liver transplantation. Moreover, the administration of immunosuppressive agents is intricately linked to the degradation of the metabolic profile in liver transplant recipients, thereby contributing to the initiation or exacerbation of cardiovascular risk factors, such as hypertension, diabetes, and dyslipidaemia. In addition, the post-liver transplantation period is marked by a decline in lifestyle quality and a failure to acknowledge the psychological distress experienced by patients throughout the transplant process. These factors can precipitate a deterioration in the patient's metabolic profile, exacerbated by suboptimal therapeutic compliance. This narrative review aims to comprehensively address the principal metabolic disorders intricately associated with liver transplantation.
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Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Department of Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Lucia Golfieri
- Clinical Psychology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, 40138 Bologna, Italy
| | - Fabio Nascimbeni
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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6
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Stepanova M, Kumar A, Brandt P, Gundurao N, Cusi K, Al Qahtani S, Younossi ZM. Impact of Type 2 Diabetes on the Outcomes of Solid Organ Transplantations in the U.S.: Data From a National Registry. Diabetes Care 2023; 46:2162-2170. [PMID: 37748128 DOI: 10.2337/dc23-1085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 08/30/2023] [Indexed: 09/27/2023]
Abstract
OBJECTIVE Type 2 diabetes (T2D) is a major driver of chronic diseases around the globe. The aim was to assess the impact of T2D on the outcomes of solid organ transplantations. RESEARCH DESIGN AND METHODS We used the Scientific Registry of Transplant Recipients from 2006 to 2021 to collect data for all patients age ≥18 years who received a lung, heart, liver, or kidney transplant in the U.S. RESULTS We included 462,692 solid organ transplant recipients: 31,503 lung, 38,004 heart, 106,639 liver, and 286,440 kidney transplantations. The prevalence of pretransplantation T2D was 15% in lung, 26% in heart, 25% in liver, and 30% in kidney transplant recipients, increasing over time. Posttransplantation mortality was significantly higher among transplant recipients with T2D versus those without T2D (lung 32.1% vs. 29.3% [3 years], 46.4% vs. 42.6% [5 years]; P < 0.01; heart 11.2% vs. 9.1% [1 year], 24.4% vs. 20.6% [5 years]; P < 0.0001; liver 10.6% vs. 8.9% [1 year], 26.2% vs. 22.0% [5 years]; P < 0.0001; kidney 5.3% vs. 2.5% [1 year], 20.8% vs. 10.1% [5 years]; P < 0.0001). Independent association of pretransplantation T2D with higher posttransplantation mortality was significant after adjustment for clinicodemographic confounders (adjusted hazard ratio in lung transplant recipients 1.08 [95% CI 1.03-1.13]; heart 1.26 [1.20-1.32]; liver 1.25 [1.21-1.28]; kidney 1.65 [1.62-1.68]; P < 0.01). CONCLUSIONS The prevalence of T2D in solid organ transplantation candidates is increasing. In all solid organ transplantations, pretransplantation T2D was independently associated with higher posttransplantation mortality, most profoundly in kidney transplantations.
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Affiliation(s)
- Maria Stepanova
- Global NASH Council, Washington, DC
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA
| | - Ameeta Kumar
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA
| | - Pamela Brandt
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA
- Obesity Medicine Program, Inova Medicine, Inova Health System, Falls Church, VA
| | - Nagashree Gundurao
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA
- Division of Endocrinology, Inova Medicine, Inova Health System, Falls Church, VA
| | - Kenneth Cusi
- Global NASH Council, Washington, DC
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Saleh Al Qahtani
- Global NASH Council, Washington, DC
- King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - Zobair M Younossi
- Global NASH Council, Washington, DC
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA
- Center for Outcomes Research in Liver Diseases, Washington, DC
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Mehtani R, Saigal S. Long Term Complications of Immunosuppression Post Liver Transplant. J Clin Exp Hepatol 2023; 13:1103-1115. [PMID: 37975039 PMCID: PMC10643541 DOI: 10.1016/j.jceh.2023.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 06/18/2023] [Indexed: 11/19/2023] Open
Abstract
Improvement in immunosuppression has led to a remarkable improvement in short-term and long-term outcomes post-liver transplant (LT). However, with improvements in long-term survival, complications related to immunosuppressive drugs, either directly or indirectly, have also increased. The adverse events could be drug-specific, class-specific, or generic. Calcineurin inhibitors (cyclosporine and tacrolimus) are the backbone of the immunosuppression after LT and the main culprit associated with most of the complications, including renal failure, post-transplant diabetes mellitus (PTDM), and metabolic syndrome. Steroids are also implicated in the development of diabetes, osteoporosis, and metabolic syndrome post-LT. The development of infections and de novo malignancies (DNMs) is a generic effect linked to the overall cumulative immunosuppression. The development of these complications significantly hampers the quality of life and leads to increased morbidity and mortality post-LT. Thus, it is important to minimize the cumulative immunosuppression dose while simultaneously preventing allograft rejection. This review provides up-to-date, comprehensive knowledge of the complications of long-term immunosuppression post-LT along with associated risk factors and strategies to minimize the risk of complications.
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Affiliation(s)
- Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, Haryana – 121001, India
| | - Sanjiv Saigal
- Transplant Hepatology, Centre for Liver and Biliary Sciences, Max Superspecialty Hospital, Saket, New Delhi, India
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8
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Salman AA, Salman MA, Said M, Elkassar H, El Sherbiny M, Youssef A, Elbaz M, Elmeligui AM, Hassan MB, Omar MG, Samir H, Abdelkader Morad M, Shaaban HED, Youssef M, Moustafa A, Tourky MS, Elewa A, Khalid S, Monazea K, Shawkat M. Albuminuria as a predictor of mortality in type II diabetic patients after living-donor liver transplantation. Ann Med 2022; 54:2598-2605. [PMID: 36164711 PMCID: PMC9521493 DOI: 10.1080/07853890.2022.2124446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 09/02/2022] [Accepted: 09/08/2022] [Indexed: 11/01/2022] Open
Abstract
PURPOSE Diabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection. Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality. This study evaluated albuminuria as a predictor of the outcome of living donor liver transplantation (LDLT) in patients with pre-existing DM. METHODS This retrospective study involved 103 type II diabetic patients with end-stage liver disease who received LDLT. Preoperative spot urine albumin: creatinine ratio was used to determine the degree of albuminuria. The primary outcome measure was the impact of urinary albumin excretion on the 3-year mortality rate after LDLT in this diabetic cohort. RESULTS Hepatitis C virus infection was the main cause of cirrhosis. Albuminuria was detected in 41 patients (39.8%); 15 had macroalbuminuria, while 26 had microalbuminuria. Patients with microalbuminuria were significantly older than those with macroalbuminuria and normal albumin in urine. After 3 years, twenty-four patients (23.3%) died within 3 years after LT. Myocardial infarction was the leading cause of death (25%). Albuminuria was an independent factor affecting 3-year mortality with an odds ratio of 5.17 (95% CI: 1.86-14.35). CONCLUSION Preoperative albuminuria is an independent factor affecting mortality within 3 years after LDLT in type II diabetic patients. Myocardial infarction was the leading cause of death in 25% of cases, followed by hepatocellular carcinoma recurrence, sepsis, and graft failure.KEY MESSAGESDiabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection.Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality.Preoperative albuminuria is a significant predictor of mortality within 3 years after LDLT in diabetic patients.
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Affiliation(s)
| | | | - Mostafa Said
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elkassar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohammad El Sherbiny
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Youssef
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohammed Elbaz
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed M. Elmeligui
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Badr Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mahmoud Gouda Omar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hussien Samir
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Hossam El-Din Shaaban
- Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Youssef
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Moustafa
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Sabry Tourky
- Department of Surgery, Great Western Hospitals NHS Foundation Trust, Swindon, UK
| | - Ahmed Elewa
- General Surgery Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Sadaf Khalid
- General Surgery Department, Royal Free Hospital, London, UK
| | - Khaled Monazea
- General Surgery Department, Assiut Faculty of Medicine for Boys, Al-Azhar University, Cairo, Egypt
| | - Mohamed Shawkat
- Internal Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt
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9
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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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10
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Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO). Eat Weight Disord 2022; 27:1603-1619. [PMID: 34914079 PMCID: PMC9123074 DOI: 10.1007/s40519-021-01287-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the past years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato, the Società Italiana di Diabetologia and the Società Italiana dell'Obesità reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure and Istituto Superiore di Sanità. Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources.Level of evidence Level of evidence of recommendations for each PICO question were reported according to available evidence.
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11
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Hyperglycemia-triggered ATF6-CHOP pathway aggravates acute inflammatory liver injury by β-catenin signaling. Cell Death Dis 2022; 8:115. [PMID: 35289326 PMCID: PMC8921205 DOI: 10.1038/s41420-022-00910-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 01/08/2022] [Accepted: 02/18/2022] [Indexed: 12/12/2022]
Abstract
Although hyperglycemia has been documented as an unfavorable element that can further induce liver ischemia–reperfusion injury (IRI), the related molecular mechanisms remain to be clearly elaborated. This study investigated the effective manner of endoplasmic reticulum (ER) stress signaling in hyperglycemia-exacerbated liver IRI. Here we demonstrated that in the liver tissues and Kupffer cells (KCs) of DM patients and STZ-induced hyperglycemic mice, the ER stress-ATF6-CHOP signaling pathway is activated. TLR4-mediated pro-inflammatory activation was greatly attenuated by the addition of 4-phenylbutyrate (PBA), one common ER stress inhibitor. The liver IRI in hyperglycemic mice was also significantly reduced after PBA treatment. In addition, deficiency of CHOP (CHOP−/−) obviously alleviates the hepatic IRI, and pro-inflammatory effects deteriorated by hyperglycemia. In hyperglycemic mice, β-catenin expression was suppressed while the ATF6-CHOP signal was activated. In the liver tissues of PBA-treated or CHOP−/− hyperglycemic mice, the expression of β-catenin was restored. Furthermore, CHOP deficiency can induce protection against hyperglycemia-related liver IRI, which was disrupted by the knockdown of β-catenin will cause this protection to disappear. High glucose (HG) treatment stimulated ATF6-CHOP signaling, reduced cellular β-catenin accumulation, and promoted the TLR4-related inflammation of BMDMs. But the above effects were partially rescued in BMDMs with CHOP deficiency or by PBA treatment. In BMDMs cultured in HG conditions, the anti-inflammatory functions of CHOP−/− were destroyed by the knockdown of β-catenin. Finally, chimeric mice carrying WT or CHOP−/− BMDMs by bone marrow transplantation were adopted to verify the above conclusion. The current study suggested that hyperglycemia could trigger ER stress-ATF6-CHOP axis, inhibit β-catenin activation, accelerate inflammation, and deteriorate liver IRI, thus providing the treatment potential for management of sterile liver inflammation in DM patients.
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12
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Brodosi L, Petta S, Petroni ML, Marchesini G, Morelli MC. Management of Diabetes in Candidates for Liver Transplantation and in Transplant Recipients. Transplantation 2022; 106:462-478. [PMID: 34172646 PMCID: PMC9904447 DOI: 10.1097/tp.0000000000003867] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/31/2021] [Accepted: 06/02/2021] [Indexed: 11/25/2022]
Abstract
Diabetes is common in patients waitlisted for liver transplantation because of end-stage liver disease or hepatocellular cancer as well as in posttransplant phase (posttransplantation diabetes mellitus). In both conditions, the presence of diabetes severely affects disease burden and long-term clinical outcomes; careful monitoring and appropriate treatment are pivotal to reduce cardiovascular events and graft and recipients' death. We thoroughly reviewed the epidemiology of diabetes in the transplant setting and the different therapeutic options, from lifestyle intervention to antidiabetic drug use-including the most recent drug classes available-and to the inclusion of bariatric surgery in the treatment cascade. In waitlisted patients, the old paradigm that insulin should be the treatment of choice in the presence of severe liver dysfunction is no longer valid; novel antidiabetic agents may provide adequate glucose control without the risk of hypoglycemia, also offering cardiovascular protection. The same evidence applies to the posttransplant phase, where oral or injectable noninsulin agents should be considered to treat patients to target, limiting the impact of disease on daily living, without interaction with immunosuppressive regimens. The increasing prevalence of liver disease of metabolic origin (nonalcoholic fatty liver) among liver transplant candidates, also having a higher risk of noncirrhotic hepatocellular cancer, is likely to accelerate the acceptance of new drugs and invasive procedures, as suggested by international guidelines. Intensive lifestyle intervention programs remain however mandatory, both before and after transplantation. Achievement of adequate control is mandatory to increase candidacy, to prevent delisting, and to improve long-term outcomes.
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Affiliation(s)
- Lucia Brodosi
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Maria L. Petroni
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Giulio Marchesini
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Maria C. Morelli
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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13
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Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO). Dig Liver Dis 2022; 54:170-182. [PMID: 34924319 DOI: 10.1016/j.dld.2021.04.029] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 03/22/2021] [Accepted: 04/21/2021] [Indexed: 12/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
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14
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Iacob S, Beckebaum S, Iacob R, Gheorghe C, Cicinnati V, Popescu I, Gheorghe L. Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation. Front Nutr 2022; 8:787430. [PMID: 35096933 PMCID: PMC8795078 DOI: 10.3389/fnut.2021.787430] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/22/2021] [Indexed: 12/11/2022] Open
Abstract
Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.
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Affiliation(s)
- Speranta Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
- *Correspondence: Speranta Iacob
| | | | - Razvan Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Cristian Gheorghe
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | | | - Irinel Popescu
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Liana Gheorghe
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
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15
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Marchesini G, Bugianesi E, Burra P, Marra F, Miele L, Alisi A, Vajro P, Masarone M, Petta S, Persico M, Svegliati-Baroni G, Valenti L, Federici M, Purrello F, Sasso FC, Targher G, Busetto L, Petroni ML, Santini F, Cammà C, Colli A. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO). Nutr Metab Cardiovasc Dis 2022; 32:1-16. [PMID: 34924246 DOI: 10.1016/j.numecd.2021.04.028] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
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16
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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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17
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Sharpton SR, Terrault NA, Tavakol MM, Posselt AM. Sleeve gastrectomy prior to liver transplantation is superior to medical weight loss in reducing posttransplant metabolic complications. Am J Transplant 2021; 21:3324-3332. [PMID: 33780129 DOI: 10.1111/ajt.16583] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/23/2021] [Accepted: 03/15/2021] [Indexed: 01/25/2023]
Abstract
Strategies to optimize the management of obesity-related metabolic complications after liver transplantation (LT) are needed. We examined the effect of pre-LT sleeve gastrectomy (SG), as compared to medical weight loss (MWL), on post-LT outcomes. This is a cohort study of adults (≥18 years) with medically complicated obesity who were eligible for pre-LT SG and underwent LT from January 1, 2006 to June 1, 2016. Logistic regression models evaluated the association of SG on post-LT diabetes and hypertension, defined as new-onset or progressive disease post-LT. Cox regression models evaluated the association of SG on recurrent and de novo nonalcoholic fatty liver disease (NAFLD). Among 70 LT recipients who were eligible for pre-LT SG, 14 (20%) underwent SG and 56 (80%) underwent MWL only. Mean follow-up was 5.2 years post-LT. The SG cohort sustained higher % total body weight loss at 3 years post-LT (28.9% vs. 5.4%, p < .001). In multivariable analyses, SG was associated with significantly lower risk of post-LT diabetes (OR 0.04, 95% CI 0.00-0.41, p = .01), hypertension (OR 0.15, 95% CI 0.04-0.67, p = .01), and recurrent and de novo NAFLD (HR 0.19, 95% CI 0.04-0.91, p = .04). When compared to MWL, SG resulted in sustained weight loss and significantly lower risk of diabetes, hypertension, and recurrent and de novo NAFLD post-LT.
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Affiliation(s)
- Suzanne R Sharpton
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine at the University of Southern California, Los Angeles, California, USA
| | - Mehdi M Tavakol
- Department of Surgery, University of California San Francisco, San Francisco, California, USA
| | - Andrew M Posselt
- Department of Surgery, University of California San Francisco, San Francisco, California, USA
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18
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Khan MQ, Watt KD. Scientific Relief: When Science and Technology Agree and Lead. Liver Transpl 2021; 27:484-485. [PMID: 37160032 DOI: 10.1002/lt.25998] [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: 12/02/2020] [Accepted: 12/17/2020] [Indexed: 01/13/2023]
Affiliation(s)
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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19
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Choudhary NS, Saraf N, Saigal S, Soin AS. Long-term Management of the Adult Liver Transplantation Recipients. J Clin Exp Hepatol 2021; 11:239-253. [PMID: 33746450 PMCID: PMC7953009 DOI: 10.1016/j.jceh.2020.06.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 06/14/2020] [Indexed: 12/12/2022] Open
Abstract
The survival of liver transplantation (LT) recipients has been improved remarkably in short-term. The major causes of mortality in long-term include nonimmunological causes such as cardiovascular, de novo malignancy, chronic kidney disease, and recurrence of primary disease. Rejection-related mortality is rare in the long-term after LT. We discuss nonrejection causes of long-term morbidity/mortality, risk factors, and management strategies in LT recipients. In addition, we discuss osteoporosis, contraception, and pregnancy in LT recipients.
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Key Words
- AIH, autoimmune hepatitis
- BMI, body mass index
- CKD, chronic kidney disease
- CNI, calcineurin inhibitors
- CVD, cardiovascular disease
- DDLT, deceased donor liver transplantation
- DM, diabetes mellitus
- DNM, de novo malignancy
- HCV, hepatitis C virus
- HR, hazard ratio
- IUCD, Intrauterine contraceptive devices
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MDRD, Modification of Diet in Renal Disease
- MMF, mycophenolate
- MS, metabolic syndrome
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- OR, odds ratio
- PBC, primary biliary cholangitis
- PSC, primary sclerosing cholangitis
- PTDM, posttransplantation diabetes mellitus
- PTMS, posttransplantation metabolic syndrome
- SVR, sustained virological response
- cardiovascular disease
- de novo malignancy
- eGFR, estimated glomerular filtration rate
- mTORi, Mammalian target of rapamycin inhibitors
- osteoporosis
- pregnancy
- recurrence
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Sanjiv Saigal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
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20
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Abstract
Obesity is increasing in prevalence in liver transplant candidates and recipients. The rise in liver transplantation for nonalcoholic steatohepatitis reflects this increase. Management of obesity in liver transplant candidates can be challenging due to the presence of decompensated cirrhosis and sarcopenia. Obesity may increase peritransplant morbidity but does not have an impact on long-term post-transplant survival. Bariatric surgery may be a feasible option in select patients before, during, or after liver transplantation. Use of weight loss drugs and/or endoscopic therapies for obesity management ultimately may play a role in liver transplant patients, but more research is needed to determine safety.
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21
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Gill MG, Majumdar A. Metabolic associated fatty liver disease: Addressing a new era in liver transplantation. World J Hepatol 2020; 12:1168-1181. [PMID: 33442446 PMCID: PMC7772736 DOI: 10.4254/wjh.v12.i12.1168] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/08/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD), previously termed non-alcoholic fatty liver disease, is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation. The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management, including in the setting of liver transplantation. Patients with MAFLD present significant challenges in the pre-, peri- and post-transplant settings, largely due to the presence of medical comorbidities that include obesity, metabolic syndrome and cardiovascular risk factors. As the community prevalence of MAFLD increases concurrently with the obesity epidemic, donor liver steatosis is also a current and future concern. This review outlines current epidemiology, nomenclature, management issues and outcomes of liver transplantation in patients with MAFLD.
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Affiliation(s)
- Madeleine G Gill
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia
| | - Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia
- Central Clinical School, The University of Sydney, Sydney 2050, New South Wales, Australia
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22
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Li C, Zhang W, Zhao Q, Ye M, Ju W, Wu L, Ma Y, Hu A, Wang G, Zhu X, Guo Z, Wang D, He X. Outcomes of Combined Liver and Pancreas Transplantation: A Review of the SRTR National Database and a Report of the Largest Single Center Series. Front Med (Lausanne) 2020; 7:542905. [PMID: 33195293 PMCID: PMC7605456 DOI: 10.3389/fmed.2020.542905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 08/31/2020] [Indexed: 11/15/2022] Open
Abstract
Purposes: This study was intended to summarize the characteristics and clinical outcome of Liver and Pancreas (LPTx) recipients in the Scientific Registry of Transplant Recipients (SRTR) database vs. the largest series from the First Affiliated Hospital (FAH), Sun Yat-sen University. Methods: The clinical data of 23 patients who underwent LPTx from 2000 to 2016 in the United States and 31 patients who underwent modified LPTx procedure (known as simplified multivisceral transplantation [SMT]) from 2008 to 2017 in our center were reviewed. The indications, surgical techniques, patient and graft survival, and complications were compared between the two groups. Results: All recipients in the FAH group were diagnosed with type 2 diabetes mellitus, while 10 of 23 recipients were diagnosed with type 1 diabetes mellitus in the SRTR group. The 1-, 3-, and 5-year cumulative patient survival rates were 81, 74, and 74% in the FAH group, respectively, and 51, 47, and 37% in the SRTR group, respectively (P = 0.023). No diabetes was observed during follow-up in the FAH group, while the diabetes recurrence rate was 22.2% in the SRTR group (P = 0.03). Conclusion: With multiple techniques modified and indications changed, the SMT procedure yielded a preferable outcome compared to that of the traditional LPTx procedure in records of SRTR. SMT has become a treatment option for patients with end-stage liver disease and concurrent diabetes.
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Affiliation(s)
- Cheukfai Li
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Science, Guangzhou, China
| | - Wei Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Medical Ultrasonics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiang Zhao
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Maodong Ye
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Weiqiang Ju
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Linwei Wu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Anbin Hu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guodong Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaofeng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dongping Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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23
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Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP Rep 2020; 2:100192. [PMID: 33163950 PMCID: PMC7607500 DOI: 10.1016/j.jhepr.2020.100192] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 08/06/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), specifically its progressive form non-alcoholic steatohepatitis (NASH), represents the fastest growing indication for liver transplantation in Western countries. Diabetes mellitus, morbid obesity and cardiovascular disease are frequently present in patients with NAFLD who are candidates for liver transplantation. These factors require specific evaluation, including a detailed pre-surgical risk stratification, in order to improve outcomes after liver transplantation. Moreover, in the post-transplantation setting, the incidence of cardiovascular events and metabolic complications can be amplified by immunosuppressive therapy, which is a well-known driver of metabolic alterations. Indeed, patients with NASH are more prone to developing early post-transplant complications and, in the long-term, de novo malignancy and cardiovascular events, corresponding to higher mortality rates. Therefore, a tailored multidisciplinary approach is required for these patients, both before and after liver transplantation. Appropriate candidate selection, lifestyle modifications and specific assessment in the pre-transplant setting, as well as pharmacological strategies, adjustment of immunosuppression and a healthy lifestyle in the post-transplant setting, play a key role in correct management.
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Key Words
- CKD, chronic kidney disease
- CNI, calcineurin inhibitors
- DM, diabetes mellitus
- DPP-4, dipeptidyl peptidase-4
- ELTR, European Liver Transplant Registry
- ESLD, end-stage liver disease
- GLP1 RAs, glucagon-like peptide-1 receptor agonists
- Graft survival
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- Hypertension
- IRR, incidence rate ratio
- Immunosuppressant
- LT, liver transplant
- MAFLD, metabolic dysfunction-associated fatty liver disease
- Metabolic complication
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- New-onset diabetes after transplantation
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis
- OR, odds ratio
- Obesity
- Patient survival
- SGLT2, sodium-glucose co-transporter-2
- Solid organ transplantation
- UNOS, United Network for Organ Sharing
- mTORi, mammalian target of rapamycin inhibitors
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
- Corresponding author. Address: Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital. Tel.: +39 0498212892; fax: + 390498217848.
| | - Chiara Becchetti
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
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Abstract
INTRODUCTION Liver transplantation is a life-changing event for patients and survival following transplantation has improved significantly since the first transplantation in 1967. Following liver transplantation, patients face a unique set of healthcare management decisions including transplantation-specific complications, recurrence of primary liver disease, as well as metabolic and malignancy concerns related to immunosuppression. As more patients with liver disease receive transplantation and live longer, understanding and managing these patients will require not only transplant specialist but also local subspecialist and primary care physicians. AREAS COVERED This review covers common issues related to the management of patients following liver transplantation including immunosuppression, liver allograft dysfunction, metabolic complications, as well as routine health maintenance such as immunizations and cancer screening. EXPERT OPINION Optimizing medical care for patients following liver transplant will benefit from ensuring all providers, not just transplant specialist, have a basic understanding of the common issues encountered in the post-transplant patient. This review provides an overview of common healthcare concerns and management options for patients following liver transplantation.
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Affiliation(s)
- Nicholas Hoppmann
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
| | - Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
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25
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Majumdar A, Tsochatzis EA. Changing trends of liver transplantation and mortality from non-alcoholic fatty liver disease. Metabolism 2020; 111S:154291. [PMID: 32531295 DOI: 10.1016/j.metabol.2020.154291] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 05/18/2020] [Accepted: 06/08/2020] [Indexed: 02/06/2023]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major international health concern. NAFLD is the leading global cause of liver disease with an estimated prevalence of 25% and is the fastest growing indication for liver transplantation (LT). The presence and severity of liver fibrosis is the only histologic predictor of clinical outcomes in this group. NAFLD poses several challenges in the peri-transplant setting including the management of multiple metabolic co-morbidities, post-transplant obesity and cardiovascular risk. However, post-LT outcomes in well-selected NAFLD patients appear similar to non-NAFLD indications, including in the setting of hepatocellular carcinoma (HCC). The rising prevalence of NAFLD may impact potential liver graft donors, which may in-turn adversely affect post-LT outcomes. This review outlines the current epidemiology, natural history and outcomes of NAFLD with a focus on pre- and post-liver transplant settings.
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Affiliation(s)
- Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia; Central Clinical School, The University of Sydney, Australia
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK; Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.
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26
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Chung W, Promrat K, Wands J. Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases. World J Hepatol 2020; 12:533-557. [PMID: 33033564 PMCID: PMC7522556 DOI: 10.4254/wjh.v12.i9.533] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
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Affiliation(s)
- Waihong Chung
- Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States.
| | - Kittichai Promrat
- Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
| | - Jack Wands
- Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
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27
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Kim NG, Sharma A, Saab S. Cardiovascular and metabolic disease in the liver transplant recipient. Best Pract Res Clin Gastroenterol 2020; 46-47:101683. [PMID: 33158470 DOI: 10.1016/j.bpg.2020.101683] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 08/31/2020] [Indexed: 01/31/2023]
Abstract
Liver transplantation has led to great improvements in long-term survival in patients with decompensated liver disease and hepatocellular carcinoma. Cardiovascular disease is the leading cause of non-graft-related deaths and has increased prevalence in liver allograft recipients. This is partly secondary to higher post-transplant rates of metabolic risk factors-notably obesity, hypertension, dyslipidemia, and diabetes mellitus, which comprise metabolic syndrome. Post-transplantation metabolic syndrome is expected to be a growing factor in morbidity and mortality as transplant candidates trend older, the rates of metabolic risk factors in the general population increase, non-alcoholic steatohepatitis grows disproportionally as an indication for transplantation, and post-transplantation survival lengthens. This review discusses the incidence and contributory factors for post-transplant increases in metabolic disease, as well as the burden of cardiovascular disease in the liver allograft recipient. Patients with pre-transplant diabetes or obesity are at particularly high risk for post-transplant metabolic syndrome, and would likely benefit from closer surveillance and more aggressive medical management of risk factors. In metabolic disease resistant to initial medical therapies, tailoring of immunosuppressive regimens may further assist in minimizing long-term cardiovascular disease, although this must be done with caution to avoid worsening the risk of graft failure.
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Affiliation(s)
- Nathan G Kim
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Avneesh Sharma
- Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA.
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28
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Steggerda JA, Mahendraraj K, Todo T, Noureddin M. Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis pre- and post-transplant: A multi-system challenge. World J Gastroenterol 2020; 26:4018-4035. [PMID: 32821068 PMCID: PMC7403794 DOI: 10.3748/wjg.v26.i28.4018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/07/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease worldwide, and the fastest growing indication for liver transplantation in the United States. NASH is now the leading etiology for liver transplantation in women, the second leading indication for men, and the most common cause amongst recipients aged 65 years and older. Patients with end-stage liver disease related to NASH represent a unique and challenging patient population due the high incidence of associated comorbid diseases, including obesity, type 2 diabetes (T2D), and hypertension. These challenges manifest in the pre-liver transplantation period with increased waitlist times and waitlist mortality. Furthermore, these patients carry considerable risk of morbidity and mortality both before after liver transplantation, with high rates of T2D, cardiovascular disease, chronic kidney disease, poor nutrition, and disease recurrence. Successful transplantation for these patients requires identification and management of their comorbidities in the face of liver failure. Multidisciplinary evaluations include a thorough pre-transplant workup with a complete cardiac evaluation, control of diabetes, nutritional support, and even, potentially, consultation with a bariatric surgeon. This article provides a comprehensive review of the conditions and challenges facing patients with NASH cirrhosis undergoing liver transplantation and provides recommendations for evaluation and management to optimize them before liver transplantation to produce successful outcomes.
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Affiliation(s)
- Justin A Steggerda
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Krishnaraj Mahendraraj
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Tsuyoshi Todo
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Mazen Noureddin
- Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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29
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Maliakkal BJ. Pathogenesis of non-alcoholic fatty liver disease and implications on cardiovascular outcomes in liver transplantation. Transl Gastroenterol Hepatol 2020; 5:36. [PMID: 32632387 DOI: 10.21037/tgh.2019.12.02] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 11/05/2019] [Indexed: 12/15/2022] Open
Abstract
Along with the obesity epidemic there has been a major increase in non-alcoholic fatty liver disease (NAFLD) prevalence, paralleling a steady increase in cirrhosis of the liver and hepatocellular cancer (HCC) related to NAFLD. Currently, NAFLD (related HCC and cirrhosis) is the second most common cause for liver transplantation (LT) and it is projected to take the top spot in the next 3-5 years. Patients with NAFLD cirrhosis and HCC have a unique set of comorbidities which potentially increases their risk for cardiovascular disease (CVD) and mortality. However, a review of the published data in NAFLD patients who undergo LT, does not paint a clear picture. While CVD is the most common cause of non-graft related mortality over the long-term, the short and intermediate-term survival post LT in NAFLD cirrhosis appears to be on par with other etiologies when age and comorbidities are factored. The cardiovascular complications are increased in the immediate post-transplant period but there is a shift from ischemic complications to arrhythmias and heart failure (HF). NAFLD recurs in 80-100% patients and occurs de novo in about 50% after LT, potentially impacting their long-term morbidity and mortality. This review summarizes the available data on CVD in NAFLD patients before and after LT, explains what is currently known about the epidemiology and pathogenesis of CVD in NAFLD and posits strategies to improve wait-list and post-transplant survival.
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30
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Gadiparthi C, Spatz M, Greenberg S, Iqbal U, Kanna S, Satapathy SK, Broder A, Ahmed A. NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States. J Clin Transl Hepatol 2020; 8:215-221. [PMID: 32832402 PMCID: PMC7438346 DOI: 10.14218/jcth.2020.00014] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 04/15/2020] [Accepted: 05/05/2020] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggressive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.
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Affiliation(s)
- Chiranjeevi Gadiparthi
- Division of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter’s University Hospital, New Brunswick, NJ, USA
| | - Moshe Spatz
- Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA
| | - Simi Greenberg
- Nova Southeastern University College of Osteopathic Medicine, Davie, FL, USA
| | - Umair Iqbal
- Geisinger Commonwealth School of Medicine, Danville, PA, USA
| | - Sowjanya Kanna
- Division of Gastroenterology, Allegheny Health Network, Tarentum, PA, USA
| | - Sanjaya K Satapathy
- Northwell Health, Division of Hepatology & Sandra Atlas Bass Center for Liver Diseases, Manhasset, NY, USA
| | - Arkady Broder
- Division of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter’s University Hospital, New Brunswick, NJ, USA
| | - Aijaz Ahmed
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Stanford, CA, USA
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31
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Management of metabolic syndrome and cardiovascular risk after liver transplantation. Lancet Gastroenterol Hepatol 2020; 4:731-741. [PMID: 31387736 DOI: 10.1016/s2468-1253(19)30181-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 04/22/2019] [Accepted: 04/23/2019] [Indexed: 12/11/2022]
Abstract
Cardiovascular events are the second most prevalent cause of non-hepatic mortality in liver transplant recipients. The incidence of these events is projected to rise because of the growing prevalence of non-alcoholic steatohepatitis as a transplant indication and the ageing population of liver transplant recipients. Recipients with metabolic syndrome are up to four times more likely to have a cardiovascular event than recipients without, therefore prevention and optimal treatment of the components of metabolic syndrome are key in reducing the risk of these events. Although data on the treatment of metabolic comorbidities specifically in liver transplant recipients are scarce, there is detailed guidance from learned societies that mostly mirrors the guidance for patients at increased cardiovascular risk in the general population. In this Review, we discuss the management of the components of metabolic syndrome following liver transplantation and provide practical stepwise guidance. We also emphasise the need for adequately powered studies for the treatment of metabolic comorbidities in liver transplant recipients.
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32
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Cotter TG, Charlton M. Nonalcoholic Steatohepatitis After Liver Transplantation. Liver Transpl 2020; 26:141-159. [PMID: 31610081 DOI: 10.1002/lt.25657] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/07/2019] [Indexed: 02/07/2023]
Abstract
Currently, nonalcoholic steatohepatitis (NASH) is the second leading indication for liver transplantation (LT), behind alcohol-related liver disease. After transplant, both recurrent and de novo nonalcoholic fatty liver disease are common; however, recurrence rates of NASH and advanced fibrosis are low. Identification of high-risk groups and optimizing treatment of metabolic comorbidities both before and after LT is paramount to maintaining a healthy allograft, especially with the additional consequences of longterm immunosuppression. In addition, NASH LT recipients are at an increased risk of cardiovascular events and malignancy, and their condition warrants a tailored approach to management. The optimal approach to NASH LT recipients including metabolic comorbidities management, tailored immunosuppression, the role of bariatric surgery, and nutritional and pharmacotherapy of NASH are discussed in this review. Overall, aggressive management of metabolic syndrome after LT via medical and surgical modalities and a minimalist approach to immunosuppression is advised.
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Affiliation(s)
- Thomas G Cotter
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
| | - Michael Charlton
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
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33
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Infante M, Padilla N, Madiraju S, Alvarez A, Baidal D, Ricordi C, Alejandro R. Combined liver and islet transplantation in hepatogenous diabetes, cluster exenteration, and cirrhosis with type 1 diabetes. TRANSPLANTATION, BIOENGINEERING, AND REGENERATION OF THE ENDOCRINE PANCREAS 2020:439-453. [DOI: 10.1016/b978-0-12-814833-4.00037-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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34
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The Impact of Preexisting and Post-transplant Diabetes Mellitus on Outcomes Following Liver Transplantation. Transplantation 2019; 103:2523-2530. [DOI: 10.1097/tp.0000000000002757] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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35
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International Liver Transplantation Consensus Statement on End-stage Liver Disease Due to Nonalcoholic Steatohepatitis and Liver Transplantation. Transplantation 2019; 103:45-56. [PMID: 30153225 DOI: 10.1097/tp.0000000000002433] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonalcoholic steatohepatitis (NASH)-related cirrhosis has become one of the most common indications for liver transplantation (LT), particularly in candidates older than 65 years. Typically, NASH candidates have concurrent obesity, metabolic, and cardiovascular risks, which directly impact patient evaluation and selection, waitlist morbidity and mortality, and eventually posttransplant outcomes. The purpose of these guidelines is to highlight specific features commonly observed in NASH candidates and strategies to optimize pretransplant evaluation and waitlist survival. More specifically, the working group addressed the following clinically relevant questions providing recommendations based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system supported by rigorous systematic reviews and consensus: (1) Is the outcome after LT similar to that of other etiologies of liver disease? (2) Is the natural history of NASH-related cirrhosis different from other etiologies of end-stage liver disease? (3) How should cardiovascular risk be assessed in the candidate for LT? Should the assessment differ from that done in other etiologies? (4) How should comorbidities (hypertension, diabetes, dyslipidemia, obesity, renal dysfunction, etc.) be treated in the candidate for LT? Should treatment and monitoring of these comorbidities differ from that applied in other etiologies? (5) What are the therapeutic strategies recommended to improve the cardiovascular and nutritional status of a NASH patient in the waiting list for LT? (6) Is there any circumstance where obesity should contraindicate LT? (7) What is the optimal time for bariatric surgery: before, during, or after LT? (8) How relevant is donor steatosis for LT in NASH patients?
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36
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Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation. Transplantation 2019; 103:22-27. [PMID: 30335697 DOI: 10.1097/tp.0000000000002484] [Citation(s) in RCA: 264] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population with a range of 13.5% in Africa and 31.8% in the Middle East. Nonalcoholic fatty liver disease is closely associated with a constellation of metabolic comorbidities which include: obesity, type 2 diabetes mellitus, hypertension, and hypercholesteremia. In fact, the increasing number of metabolic comorbidities not only increases the prevalence of NAFLD but also places patients at higher risk for progressive liver disease. As such, NAFLD is presently among the top etiologies for hepatocellular carcinoma and an indication for liver transplantation (LT) in the United States. Therefore, the following recommendations are made based on our current knowledge of NAFLD and its consequences: (1) the evaluation of the risk of liver disease progression can be affected by patient's ethnic origin and sex; (2) fibrosis in NAFLD is the most important predictor of mortality; (3) we recommend that individuals who present with features of metabolic syndrome in the presence of elevated liver enzymes should be screened for NAFLD and, more importantly, nonalcoholic steatohepatitis (NASH); (4) we recommend that NAFLD patients, especially those with multiple risk factors, should be screened for cardiovascular diseases and managed accordingly; (5) comorbidities in NAFLD/NASH patients who are considered for LT need to be assessed in the pretransplant and posttransplant settings because these factors can affect waitlist mortality, resource utilization, as well as posttransplant complications, morbidity, and perhaps, mortality; (6) any attempt to decrease the incidence of NAFLD should ideally address the development of obesity in childhood and early adulthood, favoring the adoption of healthy lifestyles through comprehensive health policy programs.
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37
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Grancini V, Resi V, Palmieri E, Pugliese G, Orsi E. Management of diabetes mellitus in patients undergoing liver transplantation. Pharmacol Res 2019; 141:556-573. [PMID: 30690071 DOI: 10.1016/j.phrs.2019.01.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 01/24/2019] [Accepted: 01/24/2019] [Indexed: 02/07/2023]
Abstract
Diabetes is a common feature in cirrhotic individuals both before and after liver transplantation and negatively affects prognosis. Certain aetiological agents of chronic liver disease and loss of liver function per se favour the occurrence of pre-transplant diabetes in susceptible individuals, whereas immunosuppressant treatment, changes in lifestyle habits, and donor- and procedure-related factors contribute to diabetes development/persistence after transplantation. Challenges in the management of pre-transplant diabetes include the profound nutritional alterations characterizing cirrhotic individuals and the limitations to the use of drugs with liver metabolism. Special issues in the management of post-transplant diabetes include the diabetogenic potential of immunosuppressant drugs and the increased cardiovascular risk characterizing solid organ transplant survivors. Overall, the pharmacological management of cirrhotic patients undergoing liver transplantation is complicated by the lack of specific guidelines reflecting the paucity of data on the impact of glycaemic control and the safety and efficacy of anti-hyperglycaemic agents in these individuals.
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Affiliation(s)
- Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Veronica Resi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Eva Palmieri
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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38
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Diwan TS, Rice TC, Heimbach JK, Schauer DP. Liver Transplantation and Bariatric Surgery: Timing and Outcomes. Liver Transpl 2018; 24:1280-1287. [PMID: 30080949 DOI: 10.1002/lt.25303] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Accepted: 06/18/2018] [Indexed: 12/12/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) is projected to become the leading indication for liver transplantation (LT) in the next decade in the United States. Strategies to treat the underlying etiology of NASH, which is almost always obesity, are being pursued. One such strategy is the utilization of bariatric surgery (BS) in the peritransplant period. The use of BS prior to LT could prevent the progression of NASH and abrogate the need for LT. BS at the time of LT or postoperatively has the potential to not only improve obesity-associated conditions such as diabetes, but also the potential to influence the incidence of NASH in the post-LT setting. However, there continues to be no consensus on the use and timing of BS in this patient population. This review aims to discuss the current literature and possible future action.
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Affiliation(s)
- Tayyab S Diwan
- Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati Collaborative on Obesity Research, Cincinnati, OH
| | - Teresa C Rice
- Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati Collaborative on Obesity Research, Cincinnati, OH
| | - Julie K Heimbach
- Division of Transplantation Surgery, Mayo Clinic College of Medicine, Rochester, MN
| | - Daniel P Schauer
- Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati Collaborative on Obesity Research, Cincinnati, OH
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39
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Peláez-Jaramillo MJ, Cárdenas-Mojica AA, Gaete PV, Mendivil CO. Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment. Diabetes Ther 2018; 9:521-543. [PMID: 29411291 PMCID: PMC6104273 DOI: 10.1007/s13300-018-0374-8] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Indexed: 02/08/2023] Open
Abstract
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.
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Affiliation(s)
| | | | - Paula V Gaete
- Universidad de los Andes School of Medicine, Bogotá, Colombia
| | - Carlos O Mendivil
- Universidad de los Andes School of Medicine, Bogotá, Colombia.
- Endocrinology Section, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
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40
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Carter D, Dieterich DT, Chang C. Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis in Liver Transplantation. Clin Liver Dis 2018; 22:213-227. [PMID: 29128058 DOI: 10.1016/j.cld.2017.08.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The number of transplants caused by nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) has been progressively increasing and this is expected to become the most common indication for liver transplant in the United States. Patients with NASH show many features of the metabolic syndrome and, as a result, are at higher risk for postoperative cardiovascular morbidity and mortality. Despite this, patients with NASH have long-term graft and patient survival rates comparable with other causes of chronic liver disease. Posttransplant metabolic syndrome is a common occurrence that increases the risk of steatosis in the graft liver.
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Affiliation(s)
- Danielle Carter
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 17 East 102nd Street, 2nd Floor, New York, NY 10029, USA.
| | - Douglas T Dieterich
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 17 East 102nd Street, 2nd Floor, New York, NY 10029, USA
| | - Charissa Chang
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 17 East 102nd Street, 2nd Floor, New York, NY 10029, USA
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41
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Kim Y, Jung AD, Dhar VK, Tadros JS, Schauer DP, Smith EP, Hanseman DJ, Cuffy MC, Alloway RR, Shields AR, Shah SA, Woodle ES, Diwan TS. Laparoscopic sleeve gastrectomy improves renal transplant candidacy and posttransplant outcomes in morbidly obese patients. Am J Transplant 2018; 18:410-416. [PMID: 28805345 DOI: 10.1111/ajt.14463] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 08/04/2017] [Accepted: 08/04/2017] [Indexed: 01/25/2023]
Abstract
Morbid obesity is a barrier to kidney transplantation due to inferior outcomes, including higher rates of new-onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in kidney transplant candidates, but the effect of surgical weight loss on posttransplantation outcomes is unknown. Reviewing single-center medical records, we identified all patients who underwent LSG before kidney transplantation from 2011-2016 (n = 20). Post-LSG kidney recipients were compared with similar-BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed-rank test were used to compare groups. Among post-LSG patients, mean BMI ± standard deviation (SD) was 41.5 ± 4.4 kg/m2 at initial encounter, which decreased to 32.3 ± 2.9 kg/m2 prior to transplantation (P < .01). No complications, readmissions, or mortality occurred following LSG. After transplantation, one patient (5%) experienced DGF, and no patients experienced NODAT. Allograft and patient survival at 1-year posttransplantation was 100%. Compared with non-LSG patients, post-LSG recipients had lower rates of DGF (5% vs 20%) and renal dysfunction-related readmissions (10% vs 27.5%) (P < .05 each). Perioperative complications, allograft survival, and patient survival were similar between groups. These data suggest that morbidly obese patients with end-stage renal disease who undergo LSG to improve transplant candidacy, achieve excellent posttransplantation outcomes.
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Affiliation(s)
- Y Kim
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - A D Jung
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - V K Dhar
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - J S Tadros
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - D P Schauer
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - E P Smith
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - D J Hanseman
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - M C Cuffy
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - R R Alloway
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - A R Shields
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - S A Shah
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - E S Woodle
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - T S Diwan
- Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
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42
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Chitturi S, Wong VWS, Chan WK, Wong GLH, Wong SKH, Sollano J, Ni YH, Liu CJ, Lin YC, Lesmana LA, Kim SU, Hashimoto E, Hamaguchi M, Goh KL, Fan J, Duseja A, Dan YY, Chawla Y, Farrell G, Chan HLY. The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 2: Management and special groups. J Gastroenterol Hepatol 2018; 33:86-98. [PMID: 28692197 DOI: 10.1111/jgh.13856] [Citation(s) in RCA: 108] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 05/31/2017] [Accepted: 06/25/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Shiv Chitturi
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Wah-Kheong Chan
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Simon Kin-Hung Wong
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | | | - Yen-Hsuan Ni
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, Hepatitis Research Center, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yu-Cheng Lin
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | | | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Etsuko Hashimoto
- Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | | | - Khean-Lee Goh
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Jiangao Fan
- Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yock Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yogesh Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Geoff Farrell
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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43
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Cheung A, Levitsky J. Follow-up of the Post-Liver Transplantation Patient: A Primer for the Practicing Gastroenterologist. Clin Liver Dis 2017; 21:793-813. [PMID: 28987263 DOI: 10.1016/j.cld.2017.06.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The focus in liver transplantation in the next 10 years will likely change from preventing viral disease recurrence to minimizing the toll of rejection and fatty liver disease, minimizing the complications from immunosuppression with withdrawal strategies, and more optimal management of long-term risks, such as malignancy, cardiovascular disease, and renal failure. In addition, now that short-term results (<1 year) have improved significantly, there will be a shift toward improving long-term patient and graft survival, as well as a focus on primary care preventive strategies.
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Affiliation(s)
- Amanda Cheung
- Division of Gastroenterology and Hepatology, Northwestern University, 676 North Saint Clair, Suite 1400, Chicago, IL 60611, USA
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University, 676 North Saint Clair, Suite 1400, Chicago, IL 60611, USA.
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44
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He XS, Fu SJ, Zhao Q, Zhu XF, Wang DP, Han M, Ju WQ, Ma Y, Jiao XY, Yuan XP, Hu AB, Guo ZY. A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus. Liver Transpl 2017; 23:1161-1170. [PMID: 28422396 DOI: 10.1002/lt.24774] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2016] [Revised: 03/25/2017] [Accepted: 04/06/2017] [Indexed: 01/13/2023]
Abstract
In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.
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Affiliation(s)
- Xiao-Shun He
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Shun-Jun Fu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Qiang Zhao
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xiao-Feng Zhu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Dong-Ping Wang
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Ming Han
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Wei-Qiang Ju
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Yi Ma
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xing-Yuan Jiao
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xiao-Peng Yuan
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - An-Bin Hu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Zhi-Yong Guo
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
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45
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Wong RJ, Saab S, Ahmed A. Extrahepatic Manifestations of Hepatitis C Virus After Liver Transplantation. Clin Liver Dis 2017; 21:595-606. [PMID: 28689596 DOI: 10.1016/j.cld.2017.03.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Chronic hepatitis C virus (HCV) infection remains a leading cause of chronic liver disease in the United States. Although the hepatic impact of chronic HCV leading to cirrhosis and the need for liver transplantation is paramount, the extrahepatic manifestations of chronic HCV infection are equally important. In particular, a better understanding of the prevalence and impact of extrahepatic manifestations of chronic HCV infection in the post-liver transplant setting relies on understanding the interplay between the effects of chronic HCV infection in a posttransplant environment characterized by strong immunosuppression and the associated risks of this milieu.
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Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, 1411 East 31st Street, Highland Hospital - Highland Care Pavilion 5th Floor, Oakland, CA 94602, USA.
| | - Sammy Saab
- Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, 200 UCLA Medical Plaza, Suite 214, Los Angeles, CA 90095, USA; Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 200 UCLA Medical Plaza, Suite 214, Los Angeles, CA 90095, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite # 210, Palo Alto, CA 94304, USA
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46
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Orsi E, Grancini V, Menini S, Aghemo A, Pugliese G. Hepatogenous diabetes: Is it time to separate it from type 2 diabetes? Liver Int 2017; 37:950-962. [PMID: 27943508 DOI: 10.1111/liv.13337] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 11/29/2016] [Indexed: 12/12/2022]
Abstract
By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent "toxic" effect on pancreatic islets resulting in β-cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.
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Affiliation(s)
- Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Stefano Menini
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
| | - Alessio Aghemo
- Division of Gastroenterology and Hepatology, A.M. and A. Migliavacca Center for Liver Disease, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
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47
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Abstract
Obesity has become increasingly prevalent, and the number of obese patients in need of liver transplant is expected to continue to increase. In addition, liver disease due to nonalcoholic fatty liver disease is expected to become the leading cause of liver transplantation in the near future. However, obesity remains a relative contraindication in liver transplant. New strategies in managing this patient population are clearly needed. To this end, the authors review the current literature on the efficacy of bariatric surgery in the setting of liver transplantation in obese patients.
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Affiliation(s)
- Duminda Suraweera
- Department of Medicine, Olive-View Medical Center, 14445 Olive View Drive, 2B-182, Sylmar, CA 91342, USA
| | - Erik Dutson
- Department of Surgery, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA
| | - Sammy Saab
- Department of Surgery, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA; Department of Medicine, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA.
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48
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Kim Y, Shi J, Freeman CM, Jung AD, Dhar VK, Shah SA, Woodle ES, Diwan TS. Addressing the challenges of sleeve gastrectomy in end-stage renal disease: Analysis of 100 consecutive renal failure patients. Surgery 2017; 162:358-365. [PMID: 28411866 DOI: 10.1016/j.surg.2017.02.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 02/01/2017] [Accepted: 02/24/2017] [Indexed: 01/07/2023]
Abstract
BACKGROUND While previous studies have demonstrated short-term efficacy of laparoscopic sleeve gastrectomy in candidates awaiting renal transplantation, the combination of morbid obesity and end-stage renal disease presents unique challenges to perioperative care. We demonstrate how increasing experience and the development of postoperative care guidelines can improve outcomes in this high-risk population. METHODS Single-center medical records were reviewed for renal transplantation candidates undergoing laparoscopic sleeve gastrectomy between 2011 and 2015 by a single surgeon. Postoperative care protocols were established and continually refined throughout the study period, including a multidisciplinary approach to inpatient management and hospital discharge planning. The first 100 laparoscopic sleeve gastrectomy patients were included and divided into 4 equal cohorts based on case sequence. RESULTS Compared with the first 25 patients undergoing laparoscopic sleeve gastrectomy, the last 25 patients had shorter operative times (97.8 ± 27.9 min vs 124.2 ± 33.6 min), lower estimated blood loss (6.6 ± 20.8 mL vs 34.0 ± 38.1 mL), and shorter hospital duration of stay (1.7 ± 2.1 days vs 2.9 ± 0.7 days) (P < .01 each). Readmission rates, complications, and 1-year mortality did not differ significantly. CONCLUSION Increasing experience and the development of clinical care guidelines in this high-risk population is associated with reduced health care resource utilization and improved perioperative outcomes.
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Affiliation(s)
- Young Kim
- Department of Surgery, Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Junzi Shi
- University of Cincinnati College of Medicine, Cincinnati, OH
| | - Christopher M Freeman
- Department of Surgery, Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Andrew D Jung
- Department of Surgery, Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Vikrom K Dhar
- Department of Surgery, Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Shimul A Shah
- Department of Surgery, Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH
| | - E Steve Woodle
- Department of Surgery, Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Tayyab S Diwan
- Department of Surgery, Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH; University of Cincinnati College of Medicine, Cincinnati, OH.
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49
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Stepanova M, Clement S, Wong R, Saab S, Ahmed A, Younossi ZM. Patients With Diabetes and Chronic Liver Disease Are at Increased Risk for Overall Mortality: A Population Study From the United States. Clin Diabetes 2017; 35:79-83. [PMID: 28442821 PMCID: PMC5391819 DOI: 10.2337/cd16-0018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
IN BRIEF Chronic liver disease (CLD) and type 2 diabetes have both been linked to increased morbidity and mortality. In this study, the impact of CLD and diabetes on all-cause mortality was quantified at the population level using U.S. population data. Both type 2 diabetes and CLD were found to be independently associated with increased mortality (age-adjusted hazard ratio [aHR] 1.98 and 1.37 for diabetes and CLD, respectively), and having both diabetes and CLD substantially increased the risk of mortality (aHR 2.41).
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Affiliation(s)
- Maria Stepanova
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
| | - Stephen Clement
- Section of Endocrinology, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA
| | - Robert Wong
- Division of Gastroenterology and Hepatology, Alameda Health System—Highland Hospital Campus, Oakland, CA
| | - Sammy Saab
- Departments of Medicine and Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA
| | - Aijaz Ahmed
- Department of Surgery, Stanford University School of Medicine, Stanford, CA
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
| | - Zobair M. Younossi
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
- Department of Medicine, Inova Fairfax Hospital, Falls Church, VA
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50
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Beckmann S, Nikolic N, Denhaerynck K, Binet I, Koller M, Boely E, De Geest S. Evolution of body weight parameters up to 3 years after solid organ transplantation: The prospective Swiss Transplant Cohort Study. Clin Transplant 2017; 31. [PMID: 28008650 DOI: 10.1111/ctr.12896] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2016] [Indexed: 01/04/2023]
Abstract
Obesity and weight gain are serious concerns after solid organ transplantation (Tx); however, no unbiased comparison regarding body weight parameter evolution across organ groups has yet been performed. Using data from the prospective nationwide Swiss Transplant Cohort Study, we compared the evolution of weight parameters up to 3 years post-Tx in 1359 adult kidney (58.3%), liver (21.7%), lung (11.6%), and heart (8.4%) recipients transplanted between May 2008 and May 2012. Changes in mean weight and body mass index (BMI) category were compared to reference values from 6 months post-Tx. At 3 years post-Tx, compared to other organ groups, liver Tx recipients showed the greatest weight gain (mean 4.8±10.4 kg), 57.4% gained >5% body weight, and they had the highest incidence of obesity (38.1%). After 3 years, based on their BMI categories at 6 months, normal weight and obese liver Tx patients, as well as underweight kidney, lung and heart Tx patients had the highest weight gains. Judged against international Tx patient data, the majority of our Swiss Tx recipients' experienced lower post-Tx weight gain. However, our findings show weight gain pattern differences, both within and across organ Tx groups that call for preventive measures.
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Affiliation(s)
- Sonja Beckmann
- Institute of Nursing Science, University of Basel, Basel, Switzerland.,Department of Abdomen-Metabolism, University Hospital Zurich, Zurich, Switzerland
| | - Nataša Nikolic
- Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
| | - Kris Denhaerynck
- Institute of Nursing Science, University of Basel, Basel, Switzerland
| | - Isabelle Binet
- Nephrology and Transplantation Medicine, Cantonal Hospital St Gallen, St Gallen, Switzerland
| | - Michael Koller
- Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Elsa Boely
- University Hospital of Geneva, Geneva, Switzerland
| | - Sabina De Geest
- Institute of Nursing Science, University of Basel, Basel, Switzerland.,Department of Public Health and Primary Care, Academic Center for Nursing and Midwifery, KU Leuven, Leuven, Belgium
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