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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Golabi P, Bush H, Stepanova M, Locklear CT, Jacobson IM, Mishra A, Trimble G, Erario M, Venkatesan C, Younossi I, Goodman Z, Younossi ZM. Liver Transplantation (LT) for Cryptogenic Cirrhosis (CC) and Nonalcoholic Steatohepatitis (NASH) Cirrhosis: Data from the Scientific Registry of Transplant Recipients (SRTR): 1994 to 2016. Medicine (Baltimore) 2018; 97:e11518. [PMID: 30075518 PMCID: PMC6081090 DOI: 10.1097/md.0000000000011518] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH)-related cirrhosis and cryptogenic cirrhosis (CC) have become leading indications for liver transplantation (LT) in the US. Our aim was to compare the trends, clinical presentation, and outcomes for transplant candidates with NASH and CC.The Scientific Registry of Transplant Recipients (1994-2016) was used to select adult LT candidates and recipients with primary diagnoses of NASH and CC without hepatocellular carcinoma.Two lakh twenty-three thousand three hundred ninety-one LT candidates were listed between 1994 and 2016. Of these, 16,214 (7.3%) were listed for CC and 11,598 (5.2%) for NASH. Before 2004, NASH was seldom coded for an indication for LT, but became more common after 2009. Averaged across the study period, CC candidates compared with NASH candidates were younger and had fewer conditions of metabolic syndrome (MS). CC patients were more likely to have MS components in comparison to candidates with other chronic liver diseases (CLDs) (all P < .0001). For most of the study period, patients with CC or NASH were similarly more likely to be taken off the list due to deterioration or death, with to patients with other CLDs. Post-LT data were available for 14,052 transplant recipients with NASH or CC. With the exception of post-transplant diabetes, the outcomes of patients transplanted for CC and NASH were similar to those of other CLD patients.Number of LT due to CC and NASH cirrhosis is increasing. In the past decade, there is a shift from LT listing diagnosis from CC to NASH potentially related to increased awareness about NASH in transplant centers in the US.
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Affiliation(s)
- Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
| | - Haley Bush
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
| | - Maria Stepanova
- Center for Outcomes Research in Liver Diseases, Washington, DC
| | - Cameron T. Locklear
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
| | - Ira M. Jacobson
- Department of Medicine, Mount Sinai Beth Israel Hospital, New York, NY
| | - Alita Mishra
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
| | - Gregory Trimble
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
| | - Madeline Erario
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
| | - Chapy Venkatesan
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
| | - Issah Younossi
- Center for Outcomes Research in Liver Diseases, Washington, DC
| | - Zachary Goodman
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
| | - Zobair M. Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
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Younossi ZM. Long-Term Outcomes of Nonalcoholic Fatty Liver Disease: From Nonalcoholic Steatohepatitis to Nonalcoholic Steatofibrosis. Clin Gastroenterol Hepatol 2017; 15:1144-1147. [PMID: 28549675 DOI: 10.1016/j.cgh.2017.05.029] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Zobair M Younossi
- Department of Medicine, Inova Fairfax Medical Campus, Beatty Liver and Obesity Program, Inova Health System, Falls Church, Virginia.
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Love S, Mudasir MA, Bhardwaj SC, Singh G, Tasduq SA. Long-term administration of tacrolimus and everolimus prevents high cholesterol-high fructose-induced steatosis in C57BL/6J mice by inhibiting de-novo lipogenesis. Oncotarget 2017; 8:113403-113417. [PMID: 29371918 PMCID: PMC5768335 DOI: 10.18632/oncotarget.15194] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Accepted: 11/02/2016] [Indexed: 12/15/2022] Open
Abstract
Aim To investigate the effects of tacrolimus (TC) and everolimus (EV) on non-alcoholic steatohepatitis (NASH) induced by high fat, high cholesterol and fructose (fast food) diet in C57BL/6J mice. Materials and Methods C57BL/6J mice were divided into four groups (n=8). 1) Standard Chow (SC); 2) Fast food (FF) diet; 3) FF + Tacrolimus (TC, 1mg/kg) and; 4) FF + Everolimus (EV, 1mg/kg) and treated for 16 weeks. Serum and tissue samples were analyzed for evidence of inflammation, fibrosis, lipogenesis, and apoptosis. Results TC and EV treatments significantly reduced the hepatic lipid accumulation, improved liver-body weight ratio, blood biochemistry, and insulin resistance in mice fed with FF diet. However, inflammation, enlarged portal tracts, and fibrosis were pronounced in EV treated group. The lipogenic parameters, Peroxisome proliferator-activated receptor gamma (PPAR-γ), Sterol regulatory element-binding protein 1(SREBP-1), mammalian target of rapamycin (m-TOR), Stearoyl-CoA desaturase-1 (SCD-1) and fatty acid translocase (CD36) were significantly down-regulated in livers of TC and EV treated groups as compared to FF group. TC improved Bcl2/Bax ratio, decreased apoptosis, CYP2E1 protein expression and liver fibrosis levels, however, EV offered no such protection. Further, in an In-vitro model of lipotoxicity using the mouse hepatocyte (AML-12) cell line, treatment with TC and EV significantly reduced lipid accumulation and lipogenic and apoptotic markers induced with palmitic acid. Conclusion In FF diet induced model of NASH, both TC and EV inhibited hepatic lipid accumulation and improved metabolic parameters such as insulin resistance and dyslipidemia. However, mice administered with EV exhibited inflammatory and fibrotic responses despite reduced hepatic steatosis.
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Affiliation(s)
- Sharma Love
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.,Academy of Scientific and Innovative Research (AcSIR), Chennai, India
| | - Malik A Mudasir
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India
| | - Subhash C Bhardwaj
- Department of Pathology, Government Medical College, Jammu, Jammu and Kashmir, India
| | - Gurdarshan Singh
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.,Academy of Scientific and Innovative Research (AcSIR), Chennai, India
| | - Sheikh A Tasduq
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.,Academy of Scientific and Innovative Research (AcSIR), Chennai, India
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Karam V, Sebagh M, Rifai K, Yilmaz F, Bhangui P, Danet C, Saliba F, Samuel D, Castaing D, Adam R, Feray C. Quality of life 10 years after liver transplantation: The impact of graft histology. World J Transplant 2016; 6:703-711. [PMID: 28058221 PMCID: PMC5175229 DOI: 10.5500/wjt.v6.i4.703] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 09/06/2016] [Accepted: 09/22/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the relationship between the state of transplanted liver graft and the recipient quality of life (QOL) of histologically proven lesions in a 10-year post liver transplantation (LT) cohort of patients.
METHODS Seventy-two recipients with a functional first graft at 10 years post-LT underwent liver biopsy and completed a QOL questionnaire. Logistic regression analysis was used to explore associations between histological, clinical and QOL criteria.
RESULTS Ten years after LT, fibrosis was detected in 53% of patients, and affected the general health perception, while ductopenia, present in 36%, affected the well-being (P = 0.05). Hepatic steatosis (HS) was present in 33% of patients and was associated with the worst QOL score on multiple domains. When compared to patients without HS, patients with HS had significantly higher incidence of fibrosis (P = 0.03), hepatitis C virus (HCV) infection (P = 0.007), and more patients had retired from their job (P = 0.03). Recurrent or de novo HCV-associated fibrosis and patient retirement as objective variables, and abdominal pain or discomfort and joint aches or pains as subjective variables, emerged as independent determinants of HS.
CONCLUSION Long-term liver graft lesions, mainly HS presumably as a surrogate marker of HCV infection, may have a substantial impact on QOL 10 years after LT.
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Liu J. Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver. World J Gastroenterol 2014; 20:14672-14685. [PMID: 25356030 PMCID: PMC4209533 DOI: 10.3748/wjg.v20.i40.14672] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 03/18/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease.
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Recurrent diseases following liver transplantation: current concepts. Curr Opin Organ Transplant 2013; 17:293-302. [PMID: 22498649 DOI: 10.1097/mot.0b013e32835365f6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE OF REVIEW Liver transplantation is the treatment of choice for patients with chronic end-stage liver disease. The posttransplant setting is complex, and an improved long-term graft and patient survival adds to the complexity. There are often multiple causes of graft dysfunction and the associated morbidity and disorder are varied. This review focuses on the current concepts of several recurrent diseases, emphasizing the interpretation of the posttransplant liver biopsies in long-term survivors as challenging and clinically more relevant then ever. It confirms the importance and the necessity of clinico-pathologic correlation in the posttransplant setting. RECENT FINDINGS The long-term graft and patient survival following liver transplantation has improved significantly over the past decade. The spectrum of histopathologic patterns seen in liver biopsies and our understanding of them have evolved and expanded considerably, so much so, that both pathologists and clinicians alike now recognize new and emerging disease patterns not previously encountered in the nontransplant setting. SUMMARY Typical histopathologic features are usually easily identified and interpreted in liver biopsies. There are, however, a number of atypical histopathologic patterns, especially in the setting of recurrent diseases, often modified by immunosuppression, or altered by other immune-mediated processes, autoimmunity, or hepatotoxicity. Several conditions and entities, especially in the late posttransplant setting, including atypical allograft rejection, idiopathic posttransplant hepatitis, the spectrum of changes seen in recurrent hepatitis C, nodular regenerative hyperplasia, and de-novo disease occurrence, to name a few, have all been recognized in the past several years.
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Brunt EM, Neuschwander-Tetri BA, Burt AD. Fatty liver disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2012:293-359. [DOI: 10.1016/b978-0-7020-3398-8.00006-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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MR spectroscopy as a tool for in vivo determination of steatosis in liver transplant recipients. MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE 2011; 24:297-304. [DOI: 10.1007/s10334-011-0264-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Revised: 06/03/2011] [Accepted: 06/08/2011] [Indexed: 01/01/2023]
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Zahmatkeshan M, Geramizadeh B, Eshraghian A, Nikeghbalian S, Bahador A, Salahi H, Malek-Hosseini SA. De novo fatty liver due to vascular complications after liver transplantation. Transplant Proc 2011; 43:615-617. [PMID: 21440778 DOI: 10.1016/j.transproceed.2011.01.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The incidence, risk factors, and natural history of de novo nonalcoholic fatty liver disease (NAFLD) after liver transplantation have not been well described. In this report we examined the risk factors and demographic characteristics of 3 patients. MATERIALS AND METHODS During a 16-year period, we performed 900 liver transplantations. We reviewed donor and recipient liver biopsies to identify patients who developed de novo fatty liver following liver transplantation, recording the pretransplantation and posttransplantation blood sugar values and lipid profiles as well as body mass indices (BMI) of affected patients. RESULTS Three patients developed de novo fatty liver after transplantation. The primary liver diseases among these patients were as follows: Crigler-Najjar syndrome, biliary atresia, and tyrosinemia. All of the patients who developed NAFLD were children. None of them had obesity; all had normal blood sugar values and lipid profiles (triglyceride cholesterol) at the time of and after the operation. Two patients received liver allografts from living related donors and 1 from a deceased donor. The BMI, lipid profile, and blood sugars of all donors were normal. Preoperative donor liver biopsy specimens showed normal histological findings with no evidence of a fatty liver, but the postoperative liver biopsy in recipients specimens revealed steatosis and fatty liver (20%-40% fat). Portal vein thrombosis and hepatic artery thrombosis were observed in the patients using color Doppler sonography. CONCLUSION De novo NAFLD after liver transplantation occurred less frequently than noted in previous reports. All 3 patients experienced complicated courses. Portal vein thrombosis and hepatic artery thrombosis seemed to be important factors for development of de novo fatty liver after transplantation.
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Affiliation(s)
- M Zahmatkeshan
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Namazi Hospital, Shiraz, Iran
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