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Ourfali MB, Hirsch D, Scranton M, Jabbour TE. Post-transplant liver biopsies: a concise and practical approach for beginners. J Pathol Transl Med 2025; 59:1-10. [PMID: 39815741 PMCID: PMC11736277 DOI: 10.4132/jptm.2024.11.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 11/14/2024] [Accepted: 11/15/2024] [Indexed: 01/18/2025] Open
Abstract
Exposure to post-transplant liver biopsies varies among pathology residencies and largely depends on the institution's training program, particularly if the hospital has a liver transplant program. The interpretation of biopsies from transplanted livers presents its own set of challenges, even for those with a solid understanding of non-transplant medical liver biopsies. In this review, we aim to provide a succinct, step-by-step approach to help you interpret liver transplant biopsies. This article may be beneficial for residents interested in liver pathology, gastrointestinal and liver pathology fellows in the early stages of training, clinical gastroenterology and hepatology fellows, hepatologists and general pathologists who are curious about this niche.
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Affiliation(s)
| | - David Hirsch
- Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT, USA
| | - Marianna Scranton
- Connecticut GI, Hartford, CT, USA
- The Comprehensive Liver Center, Hartford Hospital, Hartford, CT, USA
| | - Tony El Jabbour
- Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT, USA
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Han DW, Xu K, Jin ZL, Xu YN, Li YH, Wang L, Cao Q, Kim KP, Ryu D, Hong K, Kim NH. Customized liver organoids as an advanced in vitro modeling and drug discovery platform for non-alcoholic fatty liver diseases. Int J Biol Sci 2023; 19:3595-3613. [PMID: 37497008 PMCID: PMC10367556 DOI: 10.7150/ijbs.85145] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 06/12/2023] [Indexed: 07/28/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) have presented a major and common health concern worldwide due to their increasing prevalence and progressive development of severe pathological conditions such as cirrhosis and liver cancer. Although a large number of drug candidates for the treatment of NASH have entered clinical trial testing, all have not been released to market due to their limited efficacy, and there remains no approved treatment for NASH available to this day. Recently, organoid technology that produces 3D multicellular aggregates with a liver tissue-like cytoarchitecture and improved functionality has been suggested as a novel platform for modeling the human-specific complex pathophysiology of NAFLD and NASH. In this review, we describe the cellular crosstalk between each cellular compartment in the liver during the pathogenesis of NAFLD and NASH. We also summarize the current state of liver organoid technology, describing the cellular diversity that could be recapitulated in liver organoids and proposing a future direction for liver organoid technology as an in vitro platform for disease modeling and drug discovery for NAFLD and NASH.
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Affiliation(s)
- Dong Wook Han
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China
- International Healthcare Innovation Institute (Jiangmen), Jianghai, Jiangmen, Guangdong Province, China
- Research and Development, Qingdao Haier Biotech Co. Ltd, Qingdao, China
- Guangdong ORGANOID Biotechnology Co. Ltd, Jiangmen, China
| | - KangHe Xu
- Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Zhe-Long Jin
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China
- International Healthcare Innovation Institute (Jiangmen), Jianghai, Jiangmen, Guangdong Province, China
- Guangdong ORGANOID Biotechnology Co. Ltd, Jiangmen, China
| | - Yong-Nan Xu
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China
- International Healthcare Innovation Institute (Jiangmen), Jianghai, Jiangmen, Guangdong Province, China
| | - Ying-Hua Li
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China
- International Healthcare Innovation Institute (Jiangmen), Jianghai, Jiangmen, Guangdong Province, China
| | - Lin Wang
- Research and Development, Qingdao Haier Biotech Co. Ltd, Qingdao, China
| | - Qilong Cao
- Research and Development, Qingdao Haier Biotech Co. Ltd, Qingdao, China
| | - Kee-Pyo Kim
- Department of Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - DongHee Ryu
- Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Kwonho Hong
- Department of Stem Cell and Regenerative Biotechnology, The institute of advanced regenerative science, Konkuk University, Seoul, Republic of Korea
| | - Nam-Hyung Kim
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China
- International Healthcare Innovation Institute (Jiangmen), Jianghai, Jiangmen, Guangdong Province, China
- Research and Development, Qingdao Haier Biotech Co. Ltd, Qingdao, China
- Guangdong ORGANOID Biotechnology Co. Ltd, Jiangmen, China
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3
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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Martinez-Castillo M, Altamirano-Mendoza I, Zielinski R, Priebe W, Piña-Barba C, Gutierrez-Reyes G. Collagen matrix scaffolds: Future perspectives for the management of chronic liver diseases. World J Clin Cases 2023; 11:1224-1235. [PMID: 36926129 PMCID: PMC10013111 DOI: 10.12998/wjcc.v11.i6.1224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/21/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023] Open
Abstract
Approximately 1.5 billion chronic liver disease (CLD) cases have been estimated worldwide, encompassing a wide range of liver damage severities. Moreover, liver disease causes approximately 1.75 million deaths per year. CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process, cell death, over deposition of extracellular matrix proteins, and dysregulated regeneration. Overall, these processes impair the correct function of this vital organ. Cirrhosis and liver cancer are the main complications of CLD, which accounts for 3.5% of all deaths worldwide. Liver transplantation is the optimal therapeutic option for advanced liver damage. The liver is one of the most common organs transplanted; however, only 10% of liver transplants are successful. In this context, regenerative medicine has made significant progress in the design of biomaterials, such as collagen matrix scaffolds, to address the limitations of organ transplantation (e.g., low donation rates and biocompatibility). Thus, it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.
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Affiliation(s)
- Moises Martinez-Castillo
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Itzel Altamirano-Mendoza
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
| | - Rafal Zielinski
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Waldemar Priebe
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Cristina Piña-Barba
- Materials Research Institute, Universidad Nacional Autónoma de México, Mexico City 06726, Mexico City, Mexico
| | - Gabriela Gutierrez-Reyes
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
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Liu Z, Lyu J, Li X, Yu L, Que S, Xu J, Geng L, Zheng S. Graft-to-recipient weight ratio exerts nonlinear effects on prognosis by interacting with donor liver macrosteatosis. Front Surg 2023; 9:1075845. [PMID: 36733681 PMCID: PMC9887135 DOI: 10.3389/fsurg.2022.1075845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/16/2022] [Indexed: 01/18/2023] Open
Abstract
Aim To investigate the interactions between the graft-to-recipient weight ratio (GWRWR) and other risk factors responsible for inferior allograft outcomes. Methods A total of 362 patients who received liver transplantation (LT) were enrolled. Indicators such as graft/recipient weight and other prognostic factors were collected. Comparisons of indicators and survival analysis were performed in groups categorized by the GWRWR. Interactions of large-for-size grafts (LFSGs) with graft macrosteatosis (MaS) were evaluated in terms of relative excess risk caused by interaction (RERI) and attributable proportion (AP). Cytoscape visualized the role of LFSGs in the risk profile for poor prognosis. Results Based on the GWRWR, LT cases can be categorized into three subgroups, standard (1%-2.5%), optimal (2.5%-3.0%), and inferior prognosis (>3.0%). Survival analysis confirmed clear separations in cases categorized by the above-defined limits on the GWRWR (P < 0.05). LFSGs caused inferior prognosis by initiating positive interactions with MaS severity. Conclusion The GWRWR exerted nonlinear effects on prognosis in deceased donor LT cases. LFSGs (GWRWR > 3.0%) caused inferior outcomes, while grafts sized within (2.5%-3.0%) had optimal post-transplant prognosis. MaS increased the risk of poor prognosis by exerting positive synergistic effects on LFSGs.
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Affiliation(s)
- Zhengtao Liu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China,NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Shulan (Hangzhou) Hospital, Hangzhou, China,Correspondence: Zhengtao Liu ; Shusen Zheng
| | - Jingting Lyu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Xiang Li
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Lu Yu
- Shulan (Hangzhou) Hospital, Hangzhou, China,School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | | | - Jun Xu
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Lei Geng
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shusen Zheng
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China,NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Shulan (Hangzhou) Hospital, Hangzhou, China,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,Correspondence: Zhengtao Liu ; Shusen Zheng
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Kalogirou MS, Giouleme O. Growing challenge of post-liver transplantation non-alcoholic fatty liver disease. World J Transplant 2022; 12:281-287. [PMID: 36187880 PMCID: PMC9516490 DOI: 10.5500/wjt.v12.i9.281] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/19/2022] [Accepted: 08/16/2022] [Indexed: 02/05/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide, with an estimated prevalence of 25%. Post-liver transplantation (LT) recurrent or de novo hepatic steatosis is a common complication in recipients, irrespective of transplantation indication. Risk factors for graft steatosis mainly include obesity, immunosuppression, donor steatosis, and genetic factors. Liver transplant recipients are at high risk of developing insulin resistance, new-onset diabetes, and post-transplantation metabolic syndrome that is highly associated with immunosuppressive treatment. Post-LT NAFLD is often underdiagnosed due to the poor sensitivity of most routine imaging methods. The gold standard for the diagnosis of hepatic steatosis is liver biopsy, which is, however, limited to more complex cases due to its invasive nature. There is no approved pharmacotherapy in NAFLD. Lifestyle modification remains the cornerstone in NAFLD treatment. Other treatment strategies in post-LT NAFLD include lifestyle modifications, pharmacotherapy, bariatric surgery, and tailored immunosuppression. However, these approaches originate from recommendations in the general population, as there is scarce data regarding the safety and efficacy of current management strategies for NAFLD in liver transplant patients. Future prospective studies are required to achieve tailored treatment for these patients.
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Affiliation(s)
- Maria Styliani Kalogirou
- Gastroenterology and Hepatology Division of the Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Olga Giouleme
- Gastroenterology and Hepatology Division of the Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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