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Brito CF, Fonseca RC, Rodrigues-Ribeiro L, Guimarães JSF, Vaz BF, Tofani GSS, Batista ACS, Diniz AB, Fernandes P, Nunes NAM, Pessoa RM, Oliveira ACC, Lula IS, Cardoso VN, Fernandes SOA, Poletini MO, Alvarez-Leite JI, Menezes GB, Ferreira AVM, Magalhães MTQ, Gorshkov V, Kjeldsen F, Verano-Braga T, Araujo AM, Oliveira AG. Vagus Nerve Mediated Liver-Brain-Axis Is a Major Regulator of the Metabolic Landscape in the Liver. Int J Mol Sci 2025; 26:2166. [PMID: 40076796 PMCID: PMC11901116 DOI: 10.3390/ijms26052166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/17/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
The liver serves as a major energetic reservoir for other tissues and its metabolic function is controlled by humoral and neural factors. The vagus nerve innervating the gastrointestinal tract plays an important role in regulating peripheral metabolism and energy expenditure. Although the liver receives vagus nerve fibers, the impact of this circuitry in the regulation of hepatic metabolism is still poorly understood. Herein, we used a combination of quantitative proteomics and in vivo imaging techniques to investigate the impact of the vagus nerve on liver metabolism in male mice. Liver-brain axis was impaired by vagotomy (VNX) or knocking down of the vesicular acetylcholine transporter (VAChT-KD). Mice were challenged with high carbohydrate or high-fat feeding. The vagus nerve shapes the metabolic framework of the liver, as vagotomy led to a significant alteration of the hepatic proteome landscape. Differential protein expression and pathway enrichment analyses showed that glycolytic and fatty acid biosynthesis were increased following VNX, whereas β-oxidation was decreased. These results were corroborated in VAChT-KD mice. This metabolic shift facilitated lipid accumulation in hepatocytes in mice fed with a standard commercial diet. Furthermore, VNX worsened liver steatosis following high-carbohydrate or high-fat dietary challenges. This study describes the liver-brain axis mediated by the vagus nerve as an important regulator of the hepatic metabolic landscape.
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Affiliation(s)
- Camila F. Brito
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Roberta C. Fonseca
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Lucas Rodrigues-Ribeiro
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - João S. F. Guimarães
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Bruna F. Vaz
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Gabriel S. S. Tofani
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Ana C. S. Batista
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Ariane B. Diniz
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Paola Fernandes
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Núbia A. M. Nunes
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Rafaela M. Pessoa
- Department of Clinical and Toxicological Analysis, College of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Amanda C. C. Oliveira
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Ivana S. Lula
- Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil;
| | - Valbert N. Cardoso
- Department of Clinical and Toxicological Analysis, College of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Simone O. A. Fernandes
- Department of Clinical and Toxicological Analysis, College of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Maristela O. Poletini
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Jacqueline I. Alvarez-Leite
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Gustavo B. Menezes
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Adaliene V. M. Ferreira
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Mariana T. Q. Magalhães
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Vladimir Gorshkov
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark
| | - Frank Kjeldsen
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark
| | - Thiago Verano-Braga
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
| | - Alan M. Araujo
- Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Monell Chemical Senses Center, Philadelphia, PA 19104, USA
| | - André G. Oliveira
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; (C.F.B.); (R.C.F.)
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Makino K, Ishii T, Ogiso S, Nakakura A, Nishio T, Fukumitsu K, Uebayashi EY, Munekage F, Horie H, Iwaki K, Ito T, Hatano E. Combination of risk alleles of PNPLA3, TM6SF2, and HSD17B13 of donors can predict recurrence of steatotic liver disease after liver transplantation. Hepatol Res 2024; 54:1148-1157. [PMID: 39031833 DOI: 10.1111/hepr.14086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/25/2024] [Accepted: 06/05/2024] [Indexed: 07/22/2024]
Abstract
AIMS This study aimed to identify the genetic risk factors from donors or recipients that contribute to postliver transplantation (LT) steatotic liver disease (SLD), focusing on the genetic risk score (GRS) based on single nucleotide polymorphisms (SNPs) in SLD patients. METHODS This retrospective study included 55 Japanese SLD recipients and their respective donors. Genotyping of PNPLA3, TM6SF2, and HSD17B13 was undertaken, and the combined GRS was calculated. The relationship between the GRS and the incidence of posttransplant SLD was also evaluated. RESULTS The SLD recipients had a high prevalence of post-LT graft steatosis/steatohepatitis (76.4% and 58.2%, respectively). Although the recipients had a high frequency of risk alleles, there was no relationship between the number of risk alleles for each SNP and the incidence of posttransplant SLD. In contrast, an increased number of risk alleles for any SNP in the donor was correlated with high incidence rates of both post-LT steatosis and steatohepatitis. A multivariable analysis showed that a high donor GRS was an independent risk factor for graft steatosis (odds ratio 8.77; 95% CI, 1.94-52.94; p = 0.009). Similarly, a high donor GRS was an independent risk factor (odds ratio 6.76; 95% CI, 1.84-30.78; p = 0.007) for post-LT graft steatohepatitis. CONCLUSIONS Donor risk alleles of PNPLA3, TM6SF2, and HSD17B13, rather than recipient risk alleles, have been implicated in the development of posttransplant SLD. The combination of these donor risk alleles into a GRS could predict the development of posttransplant SLD.
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Affiliation(s)
- Kenta Makino
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akiyoshi Nakakura
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiro Nishio
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ken Fukumitsu
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | - Fumiaki Munekage
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroshi Horie
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kentaro Iwaki
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takashi Ito
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Campos‐Murguia A, Guetzlaff L, Bosselmann E, Engel B, Hartleben B, Wedemeyer H, Jaeckel E, Taubert R, Hupa‐Breier KL. Overweight Impacts Histological Disease Activity of De Novo Metabolic Dysfunction-Associated Steatotic Liver Disease After Liver Transplantation. Clin Transplant 2024; 38:e70039. [PMID: 39575514 PMCID: PMC11582943 DOI: 10.1111/ctr.70039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 10/16/2024] [Accepted: 11/09/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading indication for liver transplantation (LT), but also occurs after LT. The prevalence of de novo MASLD (dnMASLD) after LT, based on both surveillance (svLbx) and indication biopsies (indLbx), is unknown. Furthermore, the impact of the distinct cardiometabolic risk factors on histological disease activity has not been assessed. We aimed to evaluate the prevalence of dnMASLD and the association between the cardiometabolic risk factors and histological disease activity. METHODS We performed a retrospective single-center study in a LT cohort with indLbx and svLbx. Patients with NAFLD before LT were excluded. RESULTS We analyzed 249 patients who underwent either svLbx or indLbx. Forty-eight (19.2%) had either dnMASLD (n = 26/249, 10.4%) or metabolic dysfunction associated steatohepatitis (dnMASH) (n = 22/249, 8.8%). Although dnMASLD/dnMASH was more frequent in indLbx (35.1%, p < 0.01), still 16.5% of patients with svLbx had dnMASLD/dnMASH. While overweight (p < 0.01) and diabetes (p = 0.01) were more frequent in patients with dnMASH, only overweight was associated with histological disease activity in the multivariate analysis. No impact of dnMASLD on the overall survival was observed. CONCLUSION While dnMASLD is more frequent in patients with indLBX, it also occurs in 16.5% of patients without signs of graft dysfunction. Overweight has the strongest impact on histological disease activity and should be monitored carefully after LT.
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Affiliation(s)
- Alejandro Campos‐Murguia
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Lea Guetzlaff
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Emily Bosselmann
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Bastian Engel
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Björn Hartleben
- Institut of Pathology, Hannover Medical SchoolHannoverGermany
| | - Heiner Wedemeyer
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Elmar Jaeckel
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
- Ajmera Transplant CentreToronto General Hospital, United Health Network, University of TorontoTorontoCanada
| | - Richard Taubert
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Katharina Luise Hupa‐Breier
- Department of GastroenterologyHepatologyInfectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
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Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024; 81:492-542. [PMID: 38851997 DOI: 10.1016/j.jhep.2024.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 06/10/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obes Facts 2024; 17:374-444. [PMID: 38852583 PMCID: PMC11299976 DOI: 10.1159/000539371] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/15/2024] [Indexed: 06/11/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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Mang Y, Gao Y, Yang Y, Dong M, Yang Q, Li H, Ran J, Li L, Ma J, Chen G, Yang B, Xie Y, Wu Y, Zhao Y, Zhang S. Experience on AMR Diagnosis and Treatment Following Liver Transplantation: Case Series. Transplant Direct 2024; 10:e1598. [PMID: 38464427 PMCID: PMC10923386 DOI: 10.1097/txd.0000000000001598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/23/2023] [Accepted: 12/11/2023] [Indexed: 03/12/2024] Open
Affiliation(s)
- Yuanyi Mang
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Yang Gao
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Yan Yang
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Mei Dong
- Hemodialysis Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Kunming, China
| | - Qian Yang
- Department of Pathology, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Kunming, China
| | - Hong Li
- Department of Ultrasonic Medicine, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Kunming, China
| | - Jianghua Ran
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Li Li
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Jun Ma
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Guoyu Chen
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Bin Yang
- Medical Imaging Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Kunming, China
| | - Ying Xie
- Medical Imaging Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Kunming, China
| | - Yunsong Wu
- Hemodialysis Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Kunming, China
| | - Yingpeng Zhao
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Shengning Zhang
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, The Calmette Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
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Choudhary NS, Dhampalwar S, Saraf N, Rastogi A, Bhangui P, Soin AS. Post-transplant Non-alcoholic Fatty Liver Disease and Metabolic Syndrome After Living Donor Liver Transplantation in Indians. J Clin Exp Hepatol 2024; 14:101281. [PMID: 38076440 PMCID: PMC10709496 DOI: 10.1016/j.jceh.2023.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/06/2023] [Indexed: 09/20/2024] Open
Abstract
Background Post-transplant non-alcoholic fatty liver disease (NAFLD) is common but is not well described in the living donor liver transplantation (LDLT) setting. Methods The study was conducted at a large volume LDLT center in north India. Adult (age >18 years at the time of transplant) liver transplantation (LT) recipients were included. Patients with any history of alcohol use were excluded. The study was conducted prospectively from July 2022 to April 2023, and all patients with a minimum of 1-year follow-up after transplant attending outpatient services were included. NAFLD was diagnosed by ultrasound showing steatosis in the absence of other etiologies. Results The study cohort included 103 males and 14 females, aged 48 ± 10 years at the time of LT and 53 ± 10 years at the time of inclusion in the study. The median follow-up from LT was 62 (32-97 months). A total of 39 (33%) patients suffered from post-LT NAFLD. NAFLD was recurrent in 9/23 (39%, in patients with NASH or cryptogenic cirrhosis as etiology of LT) and de novo in 30/94 (31%). Pre and post-LT higher body mass index, presence of diabetes and higher serum triglycerides values were associated with the development of post-LT NAFLD. Post-transplant metabolic syndrome was present in 58/95 (61%) LDLT recipients using HbA1c 5.7 to 6.4 as a marker of prediabetes. Conclusion Post-LT NAFLD was present in one-third of the patients and metabolic syndrome in the majority of the patients at a median follow-up of 62 months after LDLT.
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation & Regenerative Medicine, Medanta – The Medicity, Gurugram, India
| | - Swapnil Dhampalwar
- Institute of Liver Transplantation & Regenerative Medicine, Medanta – The Medicity, Gurugram, India
| | - Neeraj Saraf
- Institute of Liver Transplantation & Regenerative Medicine, Medanta – The Medicity, Gurugram, India
| | - Amit Rastogi
- Institute of Liver Transplantation & Regenerative Medicine, Medanta – The Medicity, Gurugram, India
| | - Prashant Bhangui
- Institute of Liver Transplantation & Regenerative Medicine, Medanta – The Medicity, Gurugram, India
| | - Arvinder S. Soin
- Institute of Liver Transplantation & Regenerative Medicine, Medanta – The Medicity, Gurugram, India
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Choudhary NS, Dhampalwar S, Saraf N, Soin AS. Metabolic dysfunction-associated steatotic liver disease: Where does non-alcoholic fatty liver disease in liver transplant recipients fit in this new definition? J Hepatol 2024; 80:e77-e79. [PMID: 37717602 DOI: 10.1016/j.jhep.2023.09.009] [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: 08/29/2023] [Accepted: 09/01/2023] [Indexed: 09/19/2023]
Affiliation(s)
- Narendra Singh Choudhary
- Institute of Liver Transplantation & Regenerative Medicine, Medanta- The Medicity, Gurugram, India.
| | - Swapnil Dhampalwar
- Institute of Liver Transplantation & Regenerative Medicine, Medanta- The Medicity, Gurugram, India
| | - Neeraj Saraf
- Institute of Liver Transplantation & Regenerative Medicine, Medanta- The Medicity, Gurugram, India
| | - Arvinder S Soin
- Institute of Liver Transplantation & Regenerative Medicine, Medanta- The Medicity, Gurugram, India
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Silva AC, Nogueira P, Machado MV. Hepatic steatosis after liver transplantation: a systematic review and meta-analysis. Liver Transpl 2023; 29:431-448. [PMID: 36735478 DOI: 10.1097/lvt.0000000000000060] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/16/2022] [Indexed: 02/04/2023]
Abstract
NAFLD can occur after liver transplantation (LT), as recurrence or de novo hepatic steatosis (HS). We aimed to evaluate the literature on prevalence, risk factors, and prognosis of post-LT HS. Systematic review with meta-analysis through a search on: PUBMED, Scopus, and Web-of-Science, from inception until the September 30, 2021. Forty studies were included, representing 6979 patients. The post-LT HS prevalence was 39.76% (95% CI, 34.06-45.46), with a rising kinetics (11.06% increase per decade, p =0.04), and a geographical distribution (15.10% more prevalent in American continent compared with Europe and Asia). Recurrent HS was up to 5-fold more likely than de novo HS [OR: 5.38 (2.69-10.76)]. Metabolic disturbances were stronger risk factors in the post-LT recipient [obesity: OR: 4.62 (3.07-6.96); metabolic syndrome: OR: 3.26 (2.03-5.25)] as compared with pre-LT recipients, with the exception of diabetes mellitus, which doubled the risk at any set [pre-LT diabetes mellitus: OR: 2.06 (1.58-2.68); post-LT diabetes mellitus: OR: 2.12 (1.73-2.59)]. Donor factors were not the relevant risk factors for post-LT HS and the only immunosuppressive drug associated with increased risk was sirolimus [OR: 1.68 (1.07-2.64)]. The prevalence of post-LT steatohepatitis was 28.82% (19.62-38.03) and the strongest risk factor was pre-LT NAFLD. Limited outcomes data suggest that post-LT HS did not increase the risk for liver cirrhosis or mortality in these studies. Two out of 5 patients submitted to LT will develop post-LT HS, being recurrent HS more common than de novo HS. Diabetes mellitus and post-LT metabolic syndrome are the strongest risk factors for HS and baseline NAFLD for steatohepatitis. All transplanted patients should be enrolled in lifestyle interventions to prevent post-LT metabolic syndrome, and sirolimus should be avoided in high-risk patients.
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Affiliation(s)
- Ana C Silva
- Gastroenterology Department, Medicine School, Lisbon University, Lisbon, Portugal
| | - Paulo Nogueira
- Biostatistic Department, Medicine School, Lisbon University, Lisbon, Portugal
| | - Mariana V Machado
- Gastroenterology Department, Medicine School, Lisbon University, Lisbon, Portugal
- Gastroenterology Department, Vila Franca de Xira Hospital, Lisbon, Portugal
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10
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Li J, Sato T, Hernández-Tejero M, Beier JI, Sayed K, Benos PV, Wilkey DW, Humar A, Merchant ML, Duarte-Rojo A, Arteel GE. The plasma degradome reflects later development of NASH fibrosis after liver transplant. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.30.526241. [PMID: 36778394 PMCID: PMC9915514 DOI: 10.1101/2023.01.30.526241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease, and decreased survival. Lack of risk stratification strategies hamper liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.e., 'degradome') of the ECM and other proteins increase in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. To investigate whether inflammatory liver injury caused by post-LT NASH would yield a unique degradome profile, predictive of severe post-LT NASH fibrosis, we performed a retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without). Total plasma peptides were isolated and analyzed by 1D-LC-MS/MS analysis using a Proxeon EASY-nLC 1000 UHPLC and nanoelectrospray ionization into an Orbitrap Elite mass spectrometer. Qualitative and quantitative peptide features data were developed from MSn datasets using PEAKS Studio X (v10). LC-MS/MS yielded ∼2700 identifiable peptide features based on the results from Peaks Studio analysis. Several peptides were significantly altered in patients that later developed fibrosis and heatmap analysis of the top 25 most significantly-changed peptides, most of which were ECM-derived, clustered the 2 patient groups well. Supervised modeling of the dataset indicated that a fraction of the total peptide signal (∼15%) could explain the differences between the groups, indicating a strong potential for representative biomarker selection. A similar degradome profile was observed when the plasma degradome patterns were compared being obesity sensitive (C57Bl6/J) and insensitive (AJ) mouse strains. Both The plasma degradome profile of post-LT patients yields stark difference based on later development of post-LT NASH fibrosis. This approach could yield new "fingerprints" that can serve as minimally-invasive biomarkers of negative outcomes post-LT.
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11
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Nishio T, Ito T, Hata K, Taura K, Hatano E. Current status of liver transplantation for non-B non-C liver cirrhosis and hepatocellular carcinoma. Ann Gastroenterol Surg 2023; 7:42-52. [PMID: 36643372 PMCID: PMC9831911 DOI: 10.1002/ags3.12612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 08/05/2022] [Indexed: 01/18/2023] Open
Abstract
Recently, non-B non-C chronic liver diseases, including alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), have markedly increased worldwide. Liver transplantation (LT) is an effective curative therapy for hepatocellular carcinoma (HCC) as well as decompensated liver cirrhosis. In Japan, where the source of liver grafts is strongly dependent on living donors, efforts have been made to unify the indications for eligibility of HCC patients for LT, leading to the development of 5-5-500 criteria. Along with the expansion of eligibility for LT, the current changing trends in underlying liver diseases of LT recipients, which are related to the rising tide of non-B non-C cirrhosis and HCC, are highlighting the importance of peri-transplant management of patients with various comorbidities. The post-LT prognosis of patients with ALD is significantly affected by de novo malignancies and metabolic syndrome-related complications as well as posttransplant alcohol relapse. NAFLD/NASH patients often suffer from obesity, type 2 diabetes mellitus, and other metabolic syndrome-related disorders, and nonneoplastic factors such as cardiovascular events and recurrence of NAFLD/NASH have a significant impact on post-LT outcomes. Patient management in the peri-transplant period as well as risk assessment for LT are key to improving post-LT outcomes in the era of a growing number of cases of LT for non-B non-C liver diseases.
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Affiliation(s)
- Takahiro Nishio
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takashi Ito
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Koichiro Hata
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kojiro Taura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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12
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Lonardo A, Mantovani A, Petta S, Carraro A, Byrne CD, Targher G. Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation. Nat Rev Endocrinol 2022; 18:638-650. [PMID: 35840803 DOI: 10.1038/s41574-022-00711-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2022] [Indexed: 11/08/2022]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major health concern worldwide. NAFLD - specifically its more advanced form, non-alcoholic steatohepatitis (NASH)-related cirrhosis - is now the fastest growing indication for liver transplantation in the USA and Europe. Although the short-term and mid-term overall survival rates of patients who receive a liver transplant for NASH-related cirrhosis are essentially similar to those of patients who receive a transplant for other liver indications, recipients with NASH-related cirrhosis have an increased risk of waiting-list mortality and of developing recurrent liver disease and cardiometabolic complications in the longer term after liver transplantation. This Review provides a brief overview of the epidemiology of NAFLD and NASH and the occurrence of NAFLD or NASH in patients after liver transplantation for NASH and other liver indications. It also discusses the putative metabolic mechanisms underlying the emergence of NAFLD or NASH after liver transplantation as well as optimal therapeutic approaches for recipients of liver transplants, including the management of cardiometabolic comorbidities, tailored immunosuppression, lifestyle changes and pharmacotherapy for NAFLD.
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Affiliation(s)
- Amedeo Lonardo
- Metabolic Syndrome Unit, University of Modena, Modena, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Amedeo Carraro
- Liver Transplant Unit, University of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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13
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Choudhary NS, Saraf N, Dhampalwar S, Mishra S, Gautam D, Lipi L, Rastogi A, Bhangui P, Chaudhary RJ, Gupta A, Yadav K, Soin AS. Nonalcoholic Fatty Liver Disease in Living Donor Liver Transplant Recipients: A Histology-Based Study. J Clin Exp Hepatol 2022; 12:1328-1332. [PMID: 36157151 PMCID: PMC9500106 DOI: 10.1016/j.jceh.2022.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/12/2022] [Indexed: 12/12/2022] Open
Abstract
Background Recurrent or de novo nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common after liver transplantation (LT) and may be associated with rapid progression to fibrosis; however, there is limited data in this regard after living donor liver transplantation (LDLT). Material and methods This is a retrospective study at a high volume LDLT center of all liver biopsies performed in patients with post-transplant NAFLD diagnosed on ultrasound of the abdomen. Liver biopsy was indicated for raised transaminases and/or high liver stiffness on TE. The association between these prebiopsy parameters and inflammation and fibrosis on histology was analyzed. Data are shown as mean ± standard deviation or median (25-75 interquartile range). Results The study cohort consisted of 31 males and 3 females, aged 43 ± 10 years. The LT to liver biopsy interval was 44 (28-68) months. The prebiopsy AST and ALT were 71 (38-119) and 66 (50-156), respectively. The histology suggested no nonalcoholic steatohepatitis (NASH) in 7 (20%), borderline NASH in 15 (44%), and NASH in 12 (35%) patients. A total of 15 patients (44%) had stage 1 or stage 2 fibrosis. The proportion of patients having fibrosis was significantly higher in patients with NASH (83%) compared to patients with borderline NASH (33%) or no NASH (none had fibrosis, P = 0.001). Among 18 patients who underwent TE (on FibroScan), liver stiffness was significantly higher in patients with fibrosis [18.1 (9.7-22.5)] than in those without fibrosis [9.7 (4.0-12.7); P = 0.043]. Conclusion Over a third of the LDLT recipients with post-transplant NAFLD developed NASH, and nearly half, borderline NASH 3-5 years after transplant. Most with established NASH also had fibrosis on histology. Prevention of risk factors and early diagnosis is warranted in these patients.
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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
| | - Swapnil Dhampalwar
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Saurabh Mishra
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Dheeraj Gautam
- Department of Pathology, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Lipika Lipi
- Department of Pathology, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Amit Rastogi
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Rohan J. Chaudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Ankur Gupta
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Kamal Yadav
- 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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14
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Ahmad MI, Khan MU, Kodali S, Shetty A, Bell SM, Victor D. Hepatocellular Carcinoma Due to Nonalcoholic Fatty Liver Disease: Current Concepts and Future Challenges. J Hepatocell Carcinoma 2022; 9:477-496. [PMID: 35673598 PMCID: PMC9167599 DOI: 10.2147/jhc.s344559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 05/14/2022] [Indexed: 12/24/2022] Open
Abstract
Obesity has been labeled as the global pandemic of the 21st century, resulting from a sedentary lifestyle and caloric excess. Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic steatosis, is strongly associated with obesity and metabolic syndrome and is estimated to be present in one-quarter of the world population, making it the most common cause of the chronic liver disease (CLD). NAFLD spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The burden of NAFLD has been predicted to increase in the coming decades resulting in increased rates of decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths. In the current review, we describe the pathophysiology of NAFLD and NASH, risk factors associated with disease progression, related complications, and mortality. Later, we have discussed the changing epidemiology of HCC, with NAFLD emerging as the most common cause of CLD and HCC. We have also addressed the risk factors of HCC development in the NAFLD population (including demographic, metabolic, genetic, dietary, and lifestyle factors), presentation of NAFLD-associated HCC, its prognosis, and the issue of HCC development in non-cirrhotic NAFLD. Lastly, the problems related to HCC screening in the NAFLD population, the remaining challenges, and future directions, especially the need to identify the high-risk individuals, will be discussed. We will conclude the review by summarizing the clinical evidence for treating fibrosis and preventing HCC in those at risk with NAFLD-associated HCC.
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Affiliation(s)
- Muhammad Imran Ahmad
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
| | - Muhammad Umair Khan
- Department of Gastroenterology and Hepatology, Hamad Medical Corporation, Doha, Qatar
- ECPE- Executive and Continuing Professional Education, Harvard T.H Chan School of Public Health, Boston, MA, 02115-5810, USA
| | - Sudha Kodali
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - Akshay Shetty
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - S Michelle Bell
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - David Victor
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
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15
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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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16
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Shaked O, Demetris J, Levitsky J, Feng S, Loza BL, Punch J, Reyes J, Klintmalm G, Jackson W, DesMarais M, Sayre P, Shaked A, Reddy KR. Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation. Transplantation 2022; 106:106-116. [PMID: 33982909 PMCID: PMC8349377 DOI: 10.1097/tp.0000000000003681] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients. METHODS Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist. RESULTS One hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis. CONCLUSIONS In a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential.
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Affiliation(s)
- Oren Shaked
- Department of Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Jack Demetris
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Josh Levitsky
- Division of Hepatology and Comprehensive Transplant Center, Northwestern Memorial Hospital, Chicago, IL, USA
| | - Sandy Feng
- Department of Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Bao-Li Loza
- Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Jeff Punch
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Jorge Reyes
- Department of Surgery, University of Washington, Seattle, WA, USA
| | - Goran Klintmalm
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA
| | - Whitney Jackson
- Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO, USA
| | | | - Peter Sayre
- Immune Tolerance Network, San Francisco, CA, USA
| | - Abraham Shaked
- Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
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17
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Han MAT, Olivo R, Choi CJ, Pyrsopoulos N. De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation. World J Hepatol 2021; 13:1991-2004. [PMID: 35070003 PMCID: PMC8727208 DOI: 10.4254/wjh.v13.i12.1991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/27/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new acronym adopted from the consensus of international experts. Given the increasing prevalence of MAFLD in pre-transplant settings, de novo and recurrent graft steatosis/MAFLD are common in post-transplant settings. The impact of graft steatosis on long-term outcomes is unclear. The current knowledge of incidence rate, risk factors, diagnosis, long-term outcomes, and management of graft steatosis (both de novo and recurrent) is discussed in this review.
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Affiliation(s)
- Ma Ai Thanda Han
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Raquel Olivo
- Department of Gastroenterology and Hepatology, Rutgers University, New Jersey Medical School, Newark, NJ 07103, United States
| | - Catherine J Choi
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United
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18
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Azhie A, Sheth P, Hammad A, Woo M, Bhat M. Metabolic Complications in Liver Transplantation Recipients: How We Can Optimize Long-Term Survival. Liver Transpl 2021; 27:1468-1478. [PMID: 34165872 DOI: 10.1002/lt.26219] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 06/14/2021] [Accepted: 06/17/2021] [Indexed: 12/27/2022]
Abstract
Liver transplantation (LT) recipients have experienced a significant improvement in short-term survival during the past 3 decades attributed to advancements in surgical techniques, perioperative management, and effective immunosuppressive regimens. However, long-term survival is affected by a high incidence of metabolic disorders and their consequences, including cardiovascular disease (CVD) and malignancies. Pretransplant metabolic impairments especially in those with nonalcoholic steatohepatitis cirrhosis are aggravated by the addition of posttransplant weight gain, physical inactivity, and reversal from catabolic to anabolic state. Moreover, although immunosuppressants are vital to avoid graft rejection, long-term exposure to these medications is implicated in metabolic impairments after LT. In this review, we summarize the molecular pathogenesis of different metabolic disorders after LT, including diabetes mellitus, dyslipidemia, and nonalcoholic fatty liver disease. Furthermore, CVD, malignancies, and graft rejections were provided as significant complications of post-LT metabolic conditions threatening both the patient and graft survival. Ultimately, emerging preventive and treatment strategies for posttransplant diabetes mellitus are summarized. This review highlights the significant need for more clinical trials of antihyperglycemic agents in LT recipients. Also, translational studies will help us to better understand the molecular and genetic factors underlying these metabolic complications and could lead to more personalized management in this high-risk population.
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Affiliation(s)
- Amirhossein Azhie
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Priya Sheth
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Ahmed Hammad
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of General Surgery, Mansoura University, Mansoura, Egypt
| | - Minna Woo
- Division of Endocrinology and Metabolism, Department of Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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The Danish comorbidity in liver transplant recipients study (DACOLT): a non-interventional prospective observational cohort study. BMC Gastroenterol 2021; 21:145. [PMID: 33794793 PMCID: PMC8017840 DOI: 10.1186/s12876-021-01733-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 03/23/2021] [Indexed: 11/10/2022] Open
Abstract
Background Liver transplantation is the only curative treatment for patients with end-stage liver disease. Short-term survival has improved due to improved surgical techniques and greater efficacy of immunosuppressive drugs. However, long-term survival has not improved to the same extent as the short-term survival, and the 10-year survival after liver transplantation is 60%. In addition to liver- and transplant-related causes, comorbidities such as cardiovascular, pulmonary, renal, and metabolic diseases have emerged as leading causes of morbidity and mortality in liver transplant recipients. The objective of this study is to assess the burden of comorbidities and identify both liver- and transplant-related risk factors as well as traditional risk factors that contribute to the pathogenesis of comorbidity in liver transplant recipients.
Methods/design The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study is an observational, longitudinal study. We aim to include all adult liver transplant recipients in Denmark (n = approx. 600). Participants will be matched by sex and age to controls from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). Physical and biological measures including blood pressure, ankle–brachial index, spirometry, exhaled nitric oxide, electrocardiogram, transthoracic echocardiography, computed tomography (CT) angiography of the heart, unenhanced CT of chest and abdomen and blood samples will be collected using uniform protocols in participants in DACOLT, CGPS, and CCHS. Blood samples will be collected and stored in a research biobank. Follow-up examinations at regular intervals up to 10 years of follow-up are planned. Discussion There is no international consensus standard for optimal clinical care or monitoring of liver transplant recipients. This study will determine prevalence, incidence and risk factors for comorbidity in liver transplant recipients and may be used to provide evidence for guidelines on management, treatment and screening and thereby contribute to improvement of the long-term survival. Trial registration ClinicalTrials.gov: NCT04777032; date of registration: March 02, 2021.
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Mikolasevic I, Stojsavljevic S, Blazic F, Mijic M, Radic-Kristo D, Juric T, Skenderevic N, Klapan M, Lukic A, Filipec Kanizaj T. Noninvasive markers of liver steatosis and fibrosis after liver transplantation - Where do we stand? World J Transplant 2021; 11:37-53. [PMID: 33816145 PMCID: PMC8009059 DOI: 10.5500/wjt.v11.i3.37] [Citation(s) in RCA: 4] [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: 07/21/2020] [Revised: 12/10/2020] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
In the last two decades, advances in immunosuppressive regimens have led to fewer complications of acute rejection crisis and consequently improved short-term graft and patient survival. In parallel with this great success, long-term post-transplantation complications have become a focus of interest of doctors engaged in transplant medicine. Metabolic syndrome (MetS) and its individual components, namely, obesity, dyslipidemia, diabetes, and hypertension, often develop in the post-transplant setting and are associated with immuno-suppressive therapy. Nonalcoholic fatty liver disease (NAFLD) is closely related to MetS and its individual components and is the liver manifestation of MetS. Therefore, it is not surprising that MetS and its individual components are associated with recurrent or "de novo" NAFLD after liver transplantation (LT). Fibrosis of the graft is one of the main determinants of overall morbidity and mortality in the post-LT period. In the assessment of post-LT steatosis and fibrosis, we have biochemical markers, imaging methods and liver biopsy. Because of the significant economic burden of post-LT steatosis and fibrosis and its potential consequences, there is an unmet need for noninvasive methods that are efficient and cost-effective. Biochemical scores can overestimate fibrosis and are not a good method for fibrosis evaluation in liver transplant recipients due to frequent post-LT thrombocytopenia. Transient elastography with controlled attenuation parameter is a promising noninvasive method for steatosis and fibrosis. In this review, we will specifically focus on the evaluation of steatosis and fibrosis in the post-LT setting in the context of de novo or recurrent NAFLD.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia; Department of Gastroenterology, Clinical hospital Merkur, Zagreb, Croatia; Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sanja Stojsavljevic
- Department of Gastroenterology, University Hospital Center “Sestre Milosrdnice”, Zagreb 10000, Croatia
| | - Filip Blazic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka 51000, Croatia
| | - Maja Mijic
- Department of Gastroenterology, University Hospital Merkur, Zagreb 10000, Croatia
| | - Delfa Radic-Kristo
- Department of Hematology, University Hospital Merkur, Zagreb, Croatia; Faculty of Medicine, University of Zagreb, Zagreb, Croatia
| | - Toni Juric
- School of Medicine, School of Medicine, Rijeka 51000, Croatia
| | - Nadija Skenderevic
- Department of Gastroenterology, University Hospital Merkur, Zagreb 10000, Croatia
| | - Mia Klapan
- School of Medicine, School of Medicine, Rijeka 51000, Croatia
| | - Andjela Lukic
- School of Medicine, School of Medicine, Rijeka 51000, Croatia
| | - Tajana Filipec Kanizaj
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia; Faculty of Medicine, University of Zagreb, Zagreb, Croatia
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21
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Bhat M, Usmani SE, Azhie A, Woo M. Metabolic Consequences of Solid Organ Transplantation. Endocr Rev 2021; 42:171-197. [PMID: 33247713 DOI: 10.1210/endrev/bnaa030] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Indexed: 12/12/2022]
Abstract
Metabolic complications affect over 50% of solid organ transplant recipients. These include posttransplant diabetes, nonalcoholic fatty liver disease, dyslipidemia, and obesity. Preexisting metabolic disease is further exacerbated with immunosuppression and posttransplant weight gain. Patients transition from a state of cachexia induced by end-organ disease to a pro-anabolic state after transplant due to weight gain, sedentary lifestyle, and suboptimal dietary habits in the setting of immunosuppression. Specific immunosuppressants have different metabolic effects, although all the foundation/maintenance immunosuppressants (calcineurin inhibitors, mTOR inhibitors) increase the risk of metabolic disease. In this comprehensive review, we summarize the emerging knowledge of the molecular pathogenesis of these different metabolic complications, and the potential genetic contribution (recipient +/- donor) to these conditions. These metabolic complications impact both graft and patient survival, particularly increasing the risk of cardiovascular and cancer-associated mortality. The current evidence for prevention and therapeutic management of posttransplant metabolic conditions is provided while highlighting gaps for future avenues in translational research.
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Affiliation(s)
- Mamatha Bhat
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Shirine E Usmani
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
| | - Amirhossein Azhie
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Minna Woo
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
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22
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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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23
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Tejedor-Tejada J, Valenzuela EF, Muñoz RN, Gómez LH, García-Pajares F, Álvarez CA, Sánchez-Martín F, Alonso-Martín C, Sánchez-Antolín G. De-novo nonalcoholic fatty liver disease at 5 years after liver transplantation: prevalence and predictive factors. Eur J Gastroenterol Hepatol 2021; 33:399-406. [PMID: 32317584 DOI: 10.1097/meg.0000000000001736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver transplantation and identify predictive risk factors. METHODS This was a retrospective analysis of de-novo-NAFLD at 5-year post-liver transplantation. NAFLD was defined as the radiological evidence of steatosis. Data from transplanted patients between November 2001 and May 2014 were collected. Noninvasive fibrosis scores were calculated. Predictors of de-novo NAFLD and survival were assessed by multivariate analyses and Kaplan-Meier method. RESULTS A total of 252 liver transplantations were evaluated after applying exclusion criteria, (78.6% men) with 54.9 years old (SD ± 9.5). Prevalence of de-novo NAFLD at 5-year post-liver transplantation was 36.1%. Cardiovascular events were presented in 19.88% and 23.08% of non-NAFLD and NAFLD patients, (P = 0.58). On multivariate analysis, male sex (OR, 5.40; P = 0.001), obesity (OR, 3.72; P = 0.017), metabolic syndrome (OR, 4.69; P < 0.001) and de-novo diabetes (OR, 2.79; P = 0.018), were predictive. Significant fibrosis (≥F2) was presented in 58-86%. The mean survival in NAFLD and control group was 166.3 and 173.6 months, respectively (P = 0 0.50). CONCLUSION De-novo NAFLD at fifth-year post-liver transplantation is frequently and associated with cardiovascular comorbidity. Male sex, obesity, de-novo diabetes and metabolic syndrome were factors associated with de-novo NAFLD. A significant proportion of patients had advanced fibrosis. This group trends toward worse patients' survival.
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Affiliation(s)
- Javier Tejedor-Tejada
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitario Rio Hortega, Valladolid, Spain
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24
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Mikolasevic I, Hauser G, Mijic M, Domislovic V, Radic-Kristo D, Krznaric Z, Razov-Radas M, Pavic T, Matasin M, Filipec Kanizaj T. Assessment of Steatosis and Fibrosis in Liver Transplant Recipients Using Controlled Attenuation Parameter and Liver Stiffness Measurements. Can J Gastroenterol Hepatol 2021; 2021:6657047. [PMID: 33628759 PMCID: PMC7889377 DOI: 10.1155/2021/6657047] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/15/2021] [Indexed: 12/15/2022] Open
Abstract
AIM The primary objective of this study was to evaluate the prevalence of increased controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as surrogate markers of liver steatosis and fibrosis in liver transplant recipient (LTR). Secondary objectives were to determine the predictors of increased CAP and LSM in population of LTR. METHODS In this prospective, cross-sectional study, we have evaluated 175 LTRs' mean age as 61 (53-65) with a functioning graft for more than one year who came for regular outpatient examinations to the Department of Gastroenterology, University Hospital (UH) Merkur, Zagreb, Croatia. RESULTS Of 175 analyzed LTRs, 34.28% had obesity, 64.00% had hypertension, 38.28% had diabetes, and 58.85% had hyperlipidemia. The prevalence of liver steatosis was 68.57%, while the prevalence of severe liver steatosis was 46.85%. On multivariate analysis, independent factors associated with liver steatosis were male gender, total cholesterol as positive predictor, and HDL as negative predictor, and independent factors positively associated with severe liver steatosis were higher body mass index (BMI) and higher triglyceride levels. The prevalence of moderate liver fibrosis was 54.85%, while the prevalence of advanced liver fibrosis was 24%. On multivariate analysis, independent factors positively associated with moderate fibrosis were gamma-glutamyl transferase (GGT) and CAP, while the independent factor positively associated with advanced fibrosis was GGT. CONCLUSION Our study showed high prevalence of increased CAP and LSM measurements as surrogate markers of liver steatosis and fibrosis. Metabolic syndrome components were highly present and were associated with CAP and LSM values as well as in the pretransplant setting. Due to high prevalence of metabolic comorbidities and nonalcoholic fatty liver disease in LTRs and the lack of the abnormal liver test in a significant number of these patients, TE with CAP may be a reasonable initial assessment for LTRs with one or more components of the metabolic syndrome.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
- Faculty of Medicine, Rijeka, Croatia
| | - Goran Hauser
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia
- Faculty of Medicine, Rijeka, Croatia
- Faculty of Health Studies, Rijeka, Croatia
| | - Maja Mijic
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
| | - Viktor Domislovic
- Department for Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
| | - Delfa Radic-Kristo
- Department of Hematology, University Hospital Merkur, Zagreb, Croatia
- Faculty of Medicine, Zagreb, Croatia
| | - Zeljko Krznaric
- Department for Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
- Faculty of Medicine, Zagreb, Croatia
| | - Melanija Razov-Radas
- Division of Gastroenterology, Department of Internal Medicine, Zadar General Hospital, Zadar, Croatia
| | - Tajana Pavic
- Faculty of Medicine, Zagreb, Croatia
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia
| | | | - Tajana Filipec Kanizaj
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
- Faculty of Medicine, Zagreb, Croatia
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25
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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: 125] [Impact Index Per Article: 25.0] [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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26
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Abstract
The purpose of this systematic review and meta-analysis was to investigate the relationship between liver transplantation and kidney cancer. Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines were followed. PubMed, the Web of Science, and the Cochrane databases were searched for peer-reviewed cohort studies in which standardized incidence of kidney cancer post-transplant was compared to the general population by means of standardized incidence ratio (SIR) with 95% confidence interval (CI). No limits were placed on language or year of publication. A fixed-effects model was used for pooling the data. Of the 937 citations identified from the electronic databases, we included nine cohort studies with 53913 liver transplant patients, a male percentage of 56.8% and a minimum follow-up of 12.4 months and more. The meta-analysis revealed that liver transplant recipients faced a significantly higher risk of developing kidney cancer than the general population with the pooled SIR of 2.02 (95% CI, 1.64-2.50; P < 0.001). No significant between-study heterogeneity was observed (I = 0, Phet = 0.553). On sensitivity analysis after removing the study by Engles et al. with the largest sample size (37 888 liver transplant recipients), the SIR remained stable (SIR 2.75; 95% CI, 1.85-4.10; P < 0.001). Overall, our synthesis of the literature indicates that an increased risk of kidney cancer exists after liver transplantation. Future studies should evaluate the potential risk factors associated with kidney cancer.
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27
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Donor PNPLA3 and TM6SF2 Variant Alleles Confer Additive Risks for Graft Steatosis After Liver Transplantation. Transplantation 2020; 104:526-534. [PMID: 31356578 DOI: 10.1097/tp.0000000000002876] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The rs58542926 polymorphism in transmembrane 6 superfamily member 2 (TM6SF2) is a genetic factor predisposing to nonalcoholic fatty liver disease. We aimed to explore the effect of recipient and donor TM6SF2 rs58542926 genotypes on liver graft fat content after liver transplantation. METHODS Steatosis was evaluated in liver biopsies from 268 adult recipients. The influence of recipient and donor TM6SF2 genotypes, patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 genotypes, and nongenetic factors on the steatosis grade assessed 6-30 months after transplantation was analyzed by ordinal logistic regression. RESULTS The presence of the TM6SF2 c.499A allele in the donor (P = 0.014), PNPLA3 c.444G allele in the donor (P < 0.001), posttransplant body mass index (P < 0.001), and serum triglycerides (P = 0.047) independently predicted increased liver fat content on multivariable analysis, whereas noncirrhotic liver disease, as an indication for liver transplantation, was associated with lower risk of steatosis (P = 0.003). The effects of the donor TM6SF2 A and PNPLA3 G alleles were additive, with an odds ratio of 4.90 (95% confidence interval, 2.01-13.00; P < 0.001), when both minor alleles were present compared with an odds ratio of 2.22 (95% confidence interval, 1.42-3.61; P = 0.002) when only one of these alleles was present. CONCLUSIONS The donor TM6SF2 c.499A allele is an independent risk factor of liver graft steatosis after liver transplantation that is additive to the effects of donor PNPLA3 c.444G allele.
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28
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Ip S, Bhanji RA, Ebadi M, Mason AL, Montano-Loza AJ. De novo and recurrent liver disease. Best Pract Res Clin Gastroenterol 2020; 46-47:101688. [PMID: 33158472 DOI: 10.1016/j.bpg.2020.101688] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/03/2020] [Accepted: 09/18/2020] [Indexed: 01/31/2023]
Abstract
Decompensated cirrhosis due to nonalcoholic steatohepatitis (NASH), and autoimmune liver diseases (AILD) are the most common indications for liver transplantation (LT). AILD include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). NASH and AILD share some peculiarities as they can recur in the new graft, compromising the quality of life, and graft and patient survival. De novo NASH or AIH connotes the development of these liver diseases in patients transplanted for other indications. The diagnosis of recurrent or de novo liver disease usually requires a liver biopsy aside from recurrent PSC, which can be diagnosed with compatible imaging studies and exclusion of other causes of biliary strictures. The treatment of recurrent NASH is lifestyle modifications aiming for weight loss. Recurrent and de novo AIH is usually treated with corticosteroids with or without azathioprine. Recurrent PBC should be treated with ursodeoxycholic acid. There are no proven treatment options for recurrent PSC. Patients with graft failure should be considered for repeat LT. Future investigations should use standardized diagnostic criteria for each disease, seek diagnostic biomarkers, and evaluate treatments that improve outcomes.
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Affiliation(s)
- Stephen Ip
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Rahima A Bhanji
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Maryam Ebadi
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Andrew L Mason
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Aldo J Montano-Loza
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
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29
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Yuan L, Kardashian A, Sarkar M. NAFLD in women: Unique pathways, biomarkers and therapeutic opportunities. ACTA ACUST UNITED AC 2020; 18:425-432. [PMID: 32523869 DOI: 10.1007/s11901-019-00495-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose of review In this review article we evaluate sex differences in the natural history of NAFLD and highlight distinct risk profiles of women with NAFLD, as well as unique treatment considerations and research gaps. Summary of findings Reproductive factors, such as menopausal status should be considered when evaluating NAFLD risk in women, as well as additional reproductive risk factors such as age at menarche, presence of polycystic ovary syndrome, and gestational diabetes. Women do appear to have lower risk for hepatocellular carcinoma from NASH, as well as lower mortality from NASH cirrhosis than men, although among women, NASH is now the leading indication for liver transplant. Data on sex differences in biomarker development and clinical trials are lacking, and researchers should be encouraged to evaluate biomarker performance by sex, and specifically report clinical trial endpoints in women.
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Affiliation(s)
- Liyun Yuan
- University of Southern California, Division of GI/Hepatology
| | - Ani Kardashian
- University of California, San Francisco, Division of GI/Hepatology
| | - Monika Sarkar
- University of California, San Francisco, Division of GI/Hepatology
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30
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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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31
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Chayanupatkul M, Dasani DB, Sogaard K, Schiano TD. The Utility of Assessing Liver Allograft Fibrosis and Steatosis Post-Liver Transplantation Using Transient Elastography With Controlled Attenuation Parameter. Transplant Proc 2020; 53:159-165. [PMID: 32434740 DOI: 10.1016/j.transproceed.2020.02.160] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 02/09/2020] [Indexed: 12/15/2022]
Abstract
AIM Allograft steatosis is an emerging concern after liver transplantation (LT). The use of transient elastography (TE) with controlled attenuation parameter (CAP) may facilitate early detection of and intervention for allograft steatosis. This study aimed to evaluate the prevalence and risk factors of allograft steatosis using TE and CAP. METHODS The presence of steatosis and severe steatosis were defined by CAP ≥222 and ≥290 dB/m, respectively. Demographics and clinical characteristics were compared between patients with and without severe steatosis. Regression analyses were performed to determine factors associated with severe steatosis. RESULTS Of 150 patients, 105 (70%) had steatosis while 40% of these had severe steatosis. Thirty-four (81.0%) patients with severe steatosis had normal alanine transaminase at the time of TE. In multivariable analyses, age at LT (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.08), post-LT obesity (OR 5.34, 95% CI 1.53-18.65), and alcoholic liver disease (OR 12.86, 95% CI 2.24-73.74) were significant predictors of severe steatosis. Five patients underwent liver biopsies as a result of advance fibrosis seen on TE and were later diagnosed with chronic allograft rejection. Two of these patients had normal liver chemistries, and the remaining 3 had mild elevation of alkaline phosphatase. CONCLUSION Steatosis was present in 70% of patients who underwent TE after LT. Advanced age at LT, post-LT obesity, and alcoholic liver disease were significant predictors for severe steatosis. The majority of patients with severe steatosis had normal liver enzymes. TE should be considered as a screening modality for allograft steatosis and fibrosis even when liver chemistries are normal.
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Affiliation(s)
- Maneerat Chayanupatkul
- Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Division of Liver Diseases, Department of Medicine, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Divya B Dasani
- Division of Liver Diseases, Department of Medicine, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kristian Sogaard
- Division of Liver Diseases, Department of Medicine, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Thomas D Schiano
- Division of Liver Diseases, Department of Medicine, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Performance of B-mode ratio and 2D shear wave elastography for the detection and quantification of hepatic steatosis and fibrosis after liver transplantation. Eur J Gastroenterol Hepatol 2020; 32:222-230. [PMID: 31464783 DOI: 10.1097/meg.0000000000001500] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To evaluate the diagnostic performance of B-mode ratio and shear wave elastography (SWE) for the assessment of steatosis and liver fibrosis after liver transplantation. MATERIALS AND METHODS Patients hospitalized for a systematic check-up after liver transplantation underwent the same day hepatic ultrasound with B-mode ratio and SWE, followed by liver biopsy and biological examinations. Steatosis was measured using hepatorenal sonographic index of B-mode ratio and liver stiffness using SWE. Liver biopsy, used as gold standard, graded steatosis S0(<5%), S1(5-<33%), S2(33-<66%), or S3(≥66%) and liver fibrosis according to the Metavir score. The results were tested against two external validation cohorts. RESULTS Fifty-eight patients were included. Mean B-ratio value was significantly higher in patients with steatosis (0.95 ± 0.13 versus 1.39 ± 0.41, P < 0.001). A B-mode ratio cutoff values at least 0.985 was found optimal for steatosis' detection [area under the receiver operating characteristic curve (AUROC) 0.902 ± 0.05, sensitivity 95%, specificity 79%]. A B-mode ratio value below 0.9 ruled out steatosis and above 1.12 ruled in steatosis. Mean SWE value for patients without significant fibrosis (≤F1) was 15.90 ± 9.2 versus 19.27 ± 7.7 kPa for patients with fibrosis (P = 0.185). A 2D-SWE value below 7.85 kPa ruled out significant fibrosis and above 26.35 kPa ruled it in. CONCLUSION The B-mode ratio is an efficient and accurate tool for the noninvasive diagnostic of steatosis in postliver transplantation patients. Yet, because liver stiffness is higher in postliver transplantation patients, 2D-SWE is not reliable in the diagnosis of significant fibrosis after liver transplantation.
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Samji NS, Verma R, Keri KC, Singal AK, Ahmed A, Rinella M, Bernstein D, Abdelmalek MF, Satapathy SK. Liver Transplantation for Nonalcoholic Steatohepatitis: Pathophysiology of Recurrence and Clinical Challenges. Dig Dis Sci 2019; 64:3413-3430. [PMID: 31312990 DOI: 10.1007/s10620-019-05716-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 07/02/2019] [Indexed: 02/08/2023]
Abstract
Nonalcoholic steatohepatitis is the fastest-growing indication for the liver transplant and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the USA. Post-transplant nonalcoholic hepatic steatosis and steatohepatitis are frequent complications of liver transplantation. Nonalcoholic steatohepatitis poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome, coronary artery disease, chronic kidney disease, and obstructive sleep apnea. While optimal therapy is not yet available in the post-liver transplant setting, lifestyle interventions continue to remain as the mainstay of therapy for post-transplant nonalcoholic steatohepatitis. Early recognition with protocol biopsies and noninvasive modalities, along with modification of known risk factors, are the most effective methods to curtail the progression of nonalcoholic steatohepatitis in the absence of FDA-approved pharmacologic therapy.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
| | - Rajanshu Verma
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | | | - Ashwani K Singal
- University of South Dakota Sanford School of Medicine, Avera Transplant Institute, S. Cliff Ave, Sioux Falls, SD, 57105, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Mary Rinella
- Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - David Bernstein
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology/Hepatology, Duke University, 40 Duke Medicine Cir, Durham, NC, USA
| | - Sanjaya K Satapathy
- Division of Hepatology at Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY, 11030, USA.
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Choudhary NS, Saigal S, Saraf N, Soin AS. Predictors of De Novo Nonalcoholic Fatty Liver Disease After Liver Transplantation and Associated Fibrosis. Liver Transpl 2019; 25:967-968. [PMID: 30884094 DOI: 10.1002/lt.25450] [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: 02/12/2019] [Accepted: 03/08/2019] [Indexed: 01/13/2023]
Affiliation(s)
- Narendra S Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Gurugram, India
| | - Sanjiv Saigal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Gurugram, India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Gurugram, India
| | - Arvinder S Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Gurugram, India
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Gitto S, Marra F, De Maria N, Bihl F, Villa E, Andreone P, Burra P. Nonalcoholic steatohepatitis before and after liver transplant: keeping up with the times. Expert Rev Gastroenterol Hepatol 2019; 13:173-178. [PMID: 30791778 DOI: 10.1080/17474124.2019.1551132] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In the last years, nonalcoholic steatohepatitis (NASH) has become a leading indication for liver transplant (LT). After transplant, both recurrent and de novo nonalcoholic fatty liver disease (NAFLD) can be commonly diagnosed. However, dedicated surveillance programs for patients with pre- or post-transplant NAFLD are not available. Areas covered: Patients waiting for LT for NASH show specific peculiarities and would deserve targeted stratification of mortality risk. Obesity, hyperlipidemia, and diabetes mellitus can be often found after transplant. These conditions, together with immunosuppressive regimen, make LT recipients a high-risk population for both recurrent and de novo NAFLD. Development of fatty liver disease after LT has a relevant impact on both morbidity and mortality. Expert commentary: A targeted stratification of neoplastic and cardiovascular risk for patients with NASH waiting for LT would be mandatory. In both pre- and post-transplant period, NAFLD should be considered not only a liver disease but also a cardiovascular risk factor. Patients within Transplant Program, especially those with known metabolic risk factors, should be followed with personalized diagnostic and life-style interventions before and after LT.
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Affiliation(s)
- Stefano Gitto
- a Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Fabio Marra
- a Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Nicola De Maria
- b Department of Gastroenterology , Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia , Modena , Italy
| | - Florian Bihl
- c Hepatology Service , EOC , Bellinzona , Switzerland
| | - Erica Villa
- b Department of Gastroenterology , Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia , Modena , Italy
| | - Pietro Andreone
- d Department of Medical and Surgical Sciences , University of Bologna and Azienda Ospedaliero-Universitaria di Bologna , Bologna , Italy
| | - Patrizia Burra
- e Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology , Padua University Hospital , Padua , Italy
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Choudhary NS, Saigal S. Preventive Strategies for Nonalcoholic Fatty Liver Disease After Liver Transplantation. J Clin Exp Hepatol 2019; 9:619-624. [PMID: 31695252 PMCID: PMC6823688 DOI: 10.1016/j.jceh.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
Post-transplant nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is common and can be recurrent or de novo. The available data suggest that progression of fibrosis is accelerated in these patients compared to NASH in general population. The long-term data suggest more risk of metabolic syndrome and associated metabolic comorbidities and cardiovascular disease in these patients. The current review focuses on prevalence and prevention/treatment of post-transplant NAFLD or NASH.
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Affiliation(s)
| | - Sanjiv Saigal
- Address for correspondence: Sanjiv Saigal, Director, Hepatology & Liver Transplant, Medanta Institute of Digestive & Hepatobiliary Sciences &Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, PIN 122001, India.
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