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1
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Farsi N, Sanchez-Avila M, Duarte M, Requena DO, Alkathery T, Ronquillo NR, Garcia-Buitrago M, Stoll LM, Montgomery EA, Byrnes K. Hepatic segmental atrophy: a diagnostic challenge with variable clinicopathologic features and an association with cardiovascular disease. Virchows Arch 2025:10.1007/s00428-025-04094-6. [PMID: 40232381 DOI: 10.1007/s00428-025-04094-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 03/04/2025] [Accepted: 03/27/2025] [Indexed: 04/16/2025]
Abstract
Hepatic segmental atrophy is an underrecognized pseudotumor that can cause diagnostic challenges. These lesions can be mass-forming and demonstrate a range of pathologic features that can lead to diagnostic errors on both imaging studies, on frozen section, and in biopsy material. The aim of this study was to better understand the clinicopathologic features of this condition as well as its association with cardiovascular disease. A retrospective computerized search of the files of two institutions was conducted spanning 2012 to 2024. All surgical slides were reviewed, and clinical and demographic information was collected. There were 45 patients, including 23 men and 22 women with median age of 63 years. Most (35/45, 78%) patients had a history of hypertension or cardiovascular disease. Thirty patients had a history of malignant neoplasm, and seven had cirrhosis. Histologically, the cases showed variable histologic features, ranging from nodular elastosis to more subtle lesions featuring degenerative hepatocytes with relative preservation of bile ducts between them. Association of these lesions with remote vascular injury might be explained by cardiovascular disease, most commonly hypertension. The current case series emphasizes the importance of recognizing this lesion and its association with cardiovascular diseases. While lobular or segmental atrophy of the liver has been recognized as a complication of many benign and malignant conditions, pathologists should be aware that this can present as a mass lesion.
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Affiliation(s)
- Negin Farsi
- Department of pathology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
| | - Monica Sanchez-Avila
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Melissa Duarte
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Domenika Ortiz Requena
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Turky Alkathery
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Nemencio R Ronquillo
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Monica Garcia-Buitrago
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Lisa M Stoll
- Department of Pathology and Laboratory Medicine, Luke University Health Network, Bethlehem, StPA, 18015, USA
| | - Elizabeth A Montgomery
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Kathleen Byrnes
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63310, USA
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2
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Poddar U, Reddy DVU. Non-Cirrhotic Portal Hypertension in Children: Current Management Strategies. CURRENT HEPATOLOGY REPORTS 2023; 22:158-169. [DOI: 10.1007/s11901-023-00608-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/08/2023] [Indexed: 01/05/2025]
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3
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Yang AH, Sullivan B, Zerbe CS, De Ravin SS, Blakely AM, Quezado MM, Marciano BE, Marko J, Ling A, Kleiner DE, Gallin JI, Malech HL, Holland SM, Heller T. Gastrointestinal and Hepatic Manifestations of Chronic Granulomatous Disease. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2023; 11:1401-1416. [PMID: 36646382 DOI: 10.1016/j.jaip.2022.12.039] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 12/02/2022] [Accepted: 12/20/2022] [Indexed: 01/15/2023]
Abstract
Chronic granulomatous disease (CGD) is a rare inborn error of immunity, resulting from a defect in nicotinamide adenine dinucleotide phosphate oxidation and decreased production of phagocyte reactive oxygen species. The main clinical manifestations are recurrent infections and chronic inflammatory disorders. Current approaches to management include antimicrobial prophylaxis and control of inflammatory complications. Hematopoietic stem cell transplantation or gene therapy can provide definitive treatment. Gastrointestinal and hepatic manifestations are common in CGD and include structural changes, dysmotility, CGD-associated inflammatory bowel disease, liver abscesses, and noncirrhotic portal hypertension. The findings can be heterogeneous, and the management is complex in light of the underlying immune dysfunction. This review describes the various clinical findings and the latest studies in management of gastrointestinal and hepatic manifestations in CGD, as well as the management experience at the National Institutes of Health.
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Affiliation(s)
- Alexander H Yang
- Digestive Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md
| | - Brigit Sullivan
- Office of the Director, National Institutes of Health, Bethesda, Md
| | - Christa S Zerbe
- Immunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Suk See De Ravin
- Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Andrew M Blakely
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Md
| | - Martha M Quezado
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md
| | - Beatriz E Marciano
- Immunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Jamie Marko
- Department of Radiology, Clinical Center, National Institutes of Health, Bethesda, Md
| | - Alexander Ling
- Department of Radiology, Clinical Center, National Institutes of Health, Bethesda, Md
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md
| | - John I Gallin
- Clinical Pathophysiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Harry L Malech
- Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Steven M Holland
- Immunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Theo Heller
- Translational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.
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4
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Lima FMS, Toledo-Barros M, Alves VAF, Duarte MIS, Takakura C, Bernardes-Silva CF, Marinho AKBB, Grecco O, Kalil J, Kokron CM. Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms. Front Immunol 2022; 13:933463. [PMID: 36341360 PMCID: PMC9632424 DOI: 10.3389/fimmu.2022.933463] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/29/2022] [Indexed: 11/16/2022] Open
Abstract
Common variable immunodeficiency (CVID) is one of the inborn errors of immunity that have the greatest clinical impact. Rates of morbidity and mortality are higher in patients with CVID who develop liver disease than in those who do not. The main liver disorder in CVID is nodular regenerative hyperplasia (NRH), the cause of which remains unclear and for which there is as yet no treatment. The etiology of liver disease in CVID is determined by analyzing the liver injury and the associated conditions. The objective of this study was to compare CVID patients with and without liver–spleen axis abnormalities in terms of clinical characteristics, as well as to analyze liver and duodenal biopsies from those with portal hypertension (PH), to elucidate the pathophysiology of liver injury. Patients were divided into three groups: Those with liver disease/PH, those with isolated splenomegaly, and those without liver–spleen axis abnormalities. Clinical and biochemical data were collected. Among 141 CVID patients, 46 (32.6%) had liver disease/PH; 27 (19.1%) had isolated splenomegaly; and 68 (48.2%) had no liver–spleen axis abnormalities. Among the liver disease/PH group, patients, even those with mild or no biochemical changes, had clinical manifestations of PH, mainly splenomegaly, thrombocytopenia, and esophageal varices. Duodenal celiac pattern was found to correlate with PH (p < 0.001). We identified NRH in the livers of all patients with PH (n = 11). Lymphocytic infiltration into the duodenal mucosa also correlated with PH. Electron microscopy of liver biopsy specimens showed varying degrees of lymphocytic infiltration and hepatocyte degeneration, which is a probable mechanism of lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes. In comparison with the CVID patients without PH, those with PH were more likely to have lymphadenopathy (p < 0.001), elevated β2-microglobulin (p < 0.001), low B-lymphocyte counts (p < 0.05), and low natural killer-lymphocyte counts (p < 0.05). In CVID patients, liver disease/PH is common and regular imaging follow-up is necessary. These patients have a distinct immunological phenotype that may predispose to liver and duodenal injury from lymphocyte-mediated cytotoxicity. Further studies could elucidate the cause of this immune-mediated mechanism and its treatment options.
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Affiliation(s)
- Fabiana Mascarenhas Souza Lima
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- *Correspondence: Fabiana Mascarenhas Souza Lima,
| | - Myrthes Toledo-Barros
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Maria Irma Seixas Duarte
- Laboratory of the Discipline of Pathology of Transmissible Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Cleusa Takakura
- Laboratory of the Discipline of Pathology of Transmissible Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Carlos Felipe Bernardes-Silva
- Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Octavio Grecco
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Jorge Kalil
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- iii-Institute for Investigation in Immunology, Instituto Nacional de Ciência e Tecnologia (INCT), Sao Paulo, Brazil
| | - Cristina Maria Kokron
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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Jain P, Patel S, Simpson HN, Silver RM, Lewin DN, Campbell RC, Guimaraes M, Silver KC. Nodular Regenerative Hyperplasia of the Liver in Rheumatic Disease: Cases and Review of the Literature. J Investig Med High Impact Case Rep 2021; 9:23247096211044617. [PMID: 34514900 PMCID: PMC8436301 DOI: 10.1177/23247096211044617] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/25/2021] [Accepted: 08/19/2021] [Indexed: 12/05/2022] Open
Abstract
Nodular regenerative hyperplasia (NRH) is a rare disease that is characterized by benign transformation of the hepatic parenchyma into small nodules with little to no fibrosis. Nodular regenerative hyperplasia is a cause of noncirrhotic portal hypertension. Symptoms can range from asymptomatic disease to more serious complications of portal hypertension such as esophageal varices and ascites. Nodular regenerative hyperplasia has been described in association with a variety of different rheumatologic, hematologic, and oncologic diseases, as well as in immune deficiency states and with exposures to certain toxins. Diagnosis is made by histology, and the treatment involves addressing the underlying disease. The first description of this rare disease was actually described in a patient with rheumatoid arthritis, neutropenia, and splenomegaly (Felty's Syndrome). We describe 2 cases of NRH associated with underlying rheumatic disorders, in one of which NRH was actually the presenting feature of the patient's underlying autoimmune condition. Subsequently, we provide a brief review of the literature of NRH in autoimmune disease with respect to epidemiology, cause, clinical manifestations, diagnosis, and treatment.
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Affiliation(s)
| | - Sagar Patel
- Medical University of South Carolina, Charleston, USA
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6
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Fontan-associated liver disease: pathophysiology, investigations, predictors of severity and management. Eur J Gastroenterol Hepatol 2020; 32:907-915. [PMID: 31851099 DOI: 10.1097/meg.0000000000001641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cardiac hepatopathy is the liver injury resulting from congestion and ischaemia associated with acute or chronic heart failure. The improved longevity of adults with operated congenital heart disease who develop heart failure as an increasingly late event makes this form of liver injury increasingly clinically relevant. Patients with congenital heart disease with a single ventricle anomaly, who require creation of a Fontan circulation, are particularly vulnerable as they have elevated venous filling pressures with chronic liver congestion. Progression to liver fibrosis and eventually cirrhosis may occur, with its associated risks of liver failure and hepatocellular carcinoma. This risk likely increases over the patient's lifetime, related to the duration post-surgical repair and reflects the chronicity of congestion. Liver biopsy is rarely performed due to a higher risk of complications in the setting of elevated venous pressures, and the frequent use of anticoagulation. Non-invasive methods of liver assessment are poorly validated and different factors require consideration compared to other chronic liver diseases. This review discusses the current understanding of cardiac hepatopathy in congenital heart disease patients with a Fontan circulation. This entity has recently been called Fontan Associated Liver Disease in the literature, with the term useful in recognising that the pathophysiology is incompletely understood, and that long-standing venous pressure elevation and hypoxaemia are presumed to play an additional significant role in the pathogenesis of the liver injury.
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7
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Risk of Liver Cirrhosis and Hepatocellular Carcinoma after Fontan Operation: A Need for Surveillance. Cancers (Basel) 2020; 12:cancers12071805. [PMID: 32640555 PMCID: PMC7408507 DOI: 10.3390/cancers12071805] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/02/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023] Open
Abstract
Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.
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8
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Costa AF, Clarke SE, Stueck AE, McInnes MDF, Thipphavong S. Benign Neoplasms, Mass-Like Infections, and Pseudotumors That Mimic Hepatic Malignancy at MRI. J Magn Reson Imaging 2020; 53:979-994. [PMID: 32621572 DOI: 10.1002/jmri.27251] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 05/20/2020] [Accepted: 05/20/2020] [Indexed: 12/14/2022] Open
Abstract
A variety of conditions may mimic hepatic malignancy at MRI. These include benign hepatic tumors and tumor-like entities such as focal nodular hyperplasia-like lesions, hepatocellular adenoma, hepatic infections, inflammatory pseudotumor, vascular entities, and in the cirrhotic liver, confluent fibrosis, and hypertrophic pseudomass. These conditions demonstrate MRI features that overlap with hepatic malignancy, and can be challenging for radiologists to diagnose accurately. In this review we discuss the MRI manifestations of various conditions that mimic hepatic malignancy, and highlight features that may allow distinction from malignancy. Level of Evidence 5 Technical Efficacy Stage 3.
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Affiliation(s)
- Andreu F Costa
- Department of Diagnostic Radiology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
| | - Sharon E Clarke
- Department of Diagnostic Radiology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
| | - Ashley E Stueck
- Department of Anatomical Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
| | - Matthew D F McInnes
- Department of Radiology, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - Seng Thipphavong
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Women's College Hospital, and University of Toronto, Toronto, Ontario, Canada
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9
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Gusev EY, Zotova NV. Cellular Stress and General Pathological Processes. Curr Pharm Des 2020; 25:251-297. [PMID: 31198111 DOI: 10.2174/1381612825666190319114641] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 03/13/2019] [Indexed: 02/06/2023]
Abstract
From the viewpoint of the general pathology, most of the human diseases are associated with a limited number of pathogenic processes such as inflammation, tumor growth, thrombosis, necrosis, fibrosis, atrophy, pathological hypertrophy, dysplasia and metaplasia. The phenomenon of chronic low-grade inflammation could be attributed to non-classical forms of inflammation, which include many neurodegenerative processes, pathological variants of insulin resistance, atherosclerosis, and other manifestations of the endothelial dysfunction. Individual and universal manifestations of cellular stress could be considered as a basic element of all these pathologies, which has both physiological and pathophysiological significance. The review examines the causes, main phenomena, developmental directions and outcomes of cellular stress using a phylogenetically conservative set of genes and their activation pathways, as well as tissue stress and its role in inflammatory and para-inflammatory processes. The main ways towards the realization of cellular stress and its functional blocks were outlined. The main stages of tissue stress and the classification of its typical manifestations, as well as its participation in the development of the classical and non-classical variants of the inflammatory process, were also described. The mechanisms of cellular and tissue stress are structured into the complex systems, which include networks that enable the exchange of information with multidirectional signaling pathways which together make these systems internally contradictory, and the result of their effects is often unpredictable. However, the possible solutions require new theoretical and methodological approaches, one of which includes the transition to integral criteria, which plausibly reflect the holistic image of these processes.
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Affiliation(s)
- Eugeny Yu Gusev
- Laboratory of the Immunology of Inflammation, Institute of Immunology and Physiology, Yekaterinburg, Russian Federation
| | - Natalia V Zotova
- Laboratory of the Immunology of Inflammation, Institute of Immunology and Physiology, Yekaterinburg, Russian Federation.,Department of Medical Biochemistry and Biophysics, Ural Federal University named after B.N.Yeltsin, Yekaterinburg, Russian Federation
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10
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Merlen G, Raymond VA, Cassim S, Lapierre P, Bilodeau M. Oxaloacetate Protects Rat Liver From Experimental Warm Ischemia/Reperfusion Injury by Improving Cellular Energy Metabolism. Liver Transpl 2019; 25:627-639. [PMID: 30663275 DOI: 10.1002/lt.25415] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 01/13/2019] [Indexed: 12/13/2022]
Abstract
Liver ischemia/reperfusion injury (IRI) is an important cause of liver damage especially early after liver transplantation, following liver resection, and in other clinical situations. Using rat experimental models, we identified oxaloacetate (OAA) as a key metabolite able to protect hepatocytes from hypoxia and IRI. In vitro screening of metabolic intermediates beneficial for hepatocyte survival under hypoxia was performed by measures of cell death and injury. In vivo, the effect of OAA was evaluated using the left portal vein ligation (LPVL) model of liver ischemia and a model of warm IRI. Liver injury was evaluated in vivo by serum transaminase levels, liver histology, and liver weight (edema). Levels and activity of caspase 3 were also measured. In vitro, the addition of OAA to hepatocytes kept in a hypoxic environment significantly improved cell viability (P < 0.01), decreased cell injury (P < 0.01), and improved energy metabolism (P < 0.01). Administration of OAA significantly reduced the extent of liver injury in the LPVL model with lower levels of alanine aminotransferase (ALT; P < 0.01), aspartate aminotransferase (AST; P < 0.01), and reduced liver necrosis (P < 0.05). When tested in a warm IRI model, OAA significantly decreased ALT (P < 0.001) and AST levels (P < 0.001), prevented liver edema (P < 0.001), significantly decreased caspase 3 expression (P < 0.01), as well as histological signs of cellular vesiculation and vacuolation (P < 0.05). This was associated with higher adenosine triphosphate (P < 0.05) and energy charge levels (P < 0.01). In conclusion, OAA can significantly improve survival of ischemic hepatocytes. The hepatoprotective effect of OAA was associated with increased levels of liver bioenergetics both in vitro and in vivo. These results suggest that it is possible to support mitochondrial activity despite the presence of ischemia and that OAA can effectively reduce ischemia-induced injury in the liver.
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Affiliation(s)
- Grégory Merlen
- Laboratoire d'Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada
| | - Valérie-Ann Raymond
- Laboratoire d'Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada
| | - Shamir Cassim
- Laboratoire d'Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada
| | - Pascal Lapierre
- Laboratoire d'Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada.,Département de Médecine, Université de Montréal, Montreal, Quebec, Canada
| | - Marc Bilodeau
- Laboratoire d'Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada.,Département de Médecine, Université de Montréal, Montreal, Quebec, Canada
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11
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Lepelley M, Allouchery M, Long J, Boucherle D, Ranchoup Y, Le Marc'Hadour F, Villier C, Sturm N. Nodular Regenerative Hyperplasia Induced by Trastuzumab Emtansine: Role of Emtansine? Ann Hepatol 2018; 17:1067-1071. [PMID: 30600283 DOI: 10.5604/01.3001.0012.7207] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Trastuzumab is a monoclonal antibody targeted against the Human Epidermal Growth Factor Receptor 2 (HER2) overexpressed in some breast cancer. This targeted therapy significantly improves the prognosis of these cancers. Recently an anti-HER2 antibodydrug conjugate was shaped in order to facilitate the targeted delivery of potent cytotoxic drug to cancer cells and to reduce resistance. This formulation, called trastuzumab emtansine (T-DM1), consists of the monoclonal antibody trastuzumab linked to a cytotoxic drug (a derivative of maytansine) via a chemical linker. Little is known about adverse reactions due to this new formulation. Herein we described the case of a woman suffering from a HER2-positive breast cancer, treated with trastuzumab for 30 months followed by T-DM1 monotherapy. After 12 months of T-DM1 treatment, a nodular regenerative hyperplasia confirmed by liver biopsy occurred. T-DM1 was stopped and medical imagery showed a resolution of the nodular regenerative hyperplasia. Unfortunately, hepatic metastasis progressed. Few cases of nodular regenerative hyperplasia induced by T-DM1 have been described so far. Further studies are needed to explore pathogenesis of nodular regenerative hyperplasia with this new antibody-drug conjugate treatment.
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Affiliation(s)
- Marion Lepelley
- Centre régional de pharmacovigilance, CHU de Grenoble-Alpes, Grenoble, France. † Pharmacy, Groupe Hospitalier Mutualiste, Grenoble, France
| | | | - Jérôme Long
- Oncology, Groupe Hospitalier Mutualiste, Grenoble, France
| | | | | | | | - Céline Villier
- Centre régional de pharmacovigilance, CHU de Grenoble-Alpes, Grenoble, France
| | - Nathalie Sturm
- Department of pathology, CHU de Grenoble-Alpes, Grenoble, France
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12
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Torrisi C, Picone D, Cabibbo G, Matranga D, Midiri M, Brancatelli G. Gadoxetic acid-enhanced MRI of transient hepatic enhancement differences: Another cause of hypointense observation on hepatobiliary phase. Eur J Radiol 2018; 107:39-45. [PMID: 30292271 DOI: 10.1016/j.ejrad.2018.08.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Revised: 08/10/2018] [Accepted: 08/13/2018] [Indexed: 01/19/2023]
Abstract
PURPOSE To retrospectively determine the frequency, natural history and factors associated with the presence of transient hepatic enhancement difference showing hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced MRI. MATERIALS AND METHODS Gadoxetic acid-enhanced MRI of 125 patients (91 men; 34 women) with transient hepatic enhancement difference were retrospectively reviewed. Three readers qualitatively and quantitatively evaluated MR imaging features and evolution at follow up. The Chi-square test, Fisher's exact test and Kruskall-Wallis rank test were used for statistical analysis. RESULTS Transient hepatic enhancement difference were hypointense on hepatobiliary phase images in 20 of 125 cases (16%). At univariate analysis there was association with wedge-shape morphology (p < 0.001), size ≥21 mm (p < 0.001), hyperintensity on T2-weighted imaging (p < 0.001), restricted diffusion (p < 0.001) and previous treatment (p < 0.005). At multivariate analysis, the following factors were associated: previous treatment (p < 0.05), hyperintensity on T2-weighted imaging (p < 0.001) and size ≥21 mm (p < 0.001). Of 12 patients with hypointense transient hepatic enhancement difference on hepatobiliary phase images who had follow-up MRI, nine showed reduction in size. CONCLUSION Transient hepatic enhancement difference observations showing hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced MRI are not infrequent and may shrink at follow-up. They are more likely associated with size ≥21 mm, hyperintensity on T2-weighted images and previous treatment of adjacent tumor.
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Affiliation(s)
- Chiara Torrisi
- Section of Radiological Sciences, Department of Biopathology and Medical Biotechnologies, University of Palermo, Via del Vespro, 129 - 90127, Palermo, Italy.
| | - Dario Picone
- Section of Radiological Sciences, Department of Biopathology and Medical Biotechnologies, University of Palermo, Via del Vespro, 129 - 90127, Palermo, Italy.
| | - Giuseppe Cabibbo
- Section of Gastroenterology, Biomedical Department of Internal Medicine and Specialties, DiBiMIS, University of Palermo, Via del Vespro, 129 - 90127, Palermo, Italy.
| | - Domenica Matranga
- Department of Sciences for Health Promotion and Mother-Child Care "G. D'Alessandro", University of Palermo, Via del Vespro, 129 - 90127, Palermo, Italy.
| | - Massimo Midiri
- Section of Radiological Sciences, Department of Biopathology and Medical Biotechnologies, University of Palermo, Via del Vespro, 129 - 90127, Palermo, Italy. massimo.midiri.@unipa.it
| | - Giuseppe Brancatelli
- Section of Radiological Sciences, Department of Biopathology and Medical Biotechnologies, University of Palermo, Via del Vespro, 129 - 90127, Palermo, Italy.
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13
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Elnaggar AS, Griesemer AD, Bentley-Hibbert S, Brown RS, Martinez M, Lobritto SJ, Kato T, Emond JC. Liver atrophy and regeneration in noncirrhotic portal vein thrombosis: Effect of surgical shunts. Liver Transpl 2018; 24:881-887. [PMID: 29377486 DOI: 10.1002/lt.25024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 12/10/2017] [Accepted: 01/17/2018] [Indexed: 02/07/2023]
Abstract
The goal of the study is to characterize the relationship between portal vein thrombosis (PVT) and hepatic atrophy in patients without cirrhosis and the effect of various types of surgical shunts on liver regeneration and splenomegaly. Patients without cirrhosis with PVT suffer from presinusoidal portal hypertension, and often hepatic atrophy is a topic that has received little attention. We hypothesized that patients with PVT have decreased liver volumes, and shunts that preserve intrahepatic portal flow enhance liver regeneration. Sixty-four adult and pediatric patients with PVT who underwent surgical shunt placement between 1998 and 2011 were included in a retrospective study. Baseline liver volumes from adult patients were compared with standard liver volume (SLV) as well as a group of healthy controls undergoing evaluation for liver donation. Clinical assessment, liver function tests, and liver and spleen volumes from cross-sectional imaging were compared before and after surgery. A total of 40 patients received portal flow-preserving shunts (32 mesoportal and 8 selective splenorenal), whereas 24 received portal flow-diverting shunts (16 nonselective splenorenal and 8 mesocaval). Baseline adult liver volumes were 26% smaller than SLV (1248 versus 1624 cm3 ; P = 0.02) and 20% smaller than the control volumes (1248 versus 1552 cm3 ; P = 0.02). Baseline adult spleen volumes were larger compared with controls (1258 versus 229 cm3 ; P < 0.001). Preserving shunts were associated with significant increase in liver volumes (886 versus 1131 cm3 ; P = 0.01), whereas diverting shunts were not. Diverting shunts significantly improved splenomegaly. In conclusion, we have demonstrated that patients without cirrhosis with PVT have significant liver atrophy and splenomegaly. Significant liver regeneration was achieved after portal flow-preserving shunts. Liver Transplantation 24 881-887 2018 AASLD.
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Affiliation(s)
- Abdulrhman S Elnaggar
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
| | - Adam D Griesemer
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
| | - Stuart Bentley-Hibbert
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
| | - Robert S Brown
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
| | - Mercedes Martinez
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
| | - Steven J Lobritto
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
| | - Tomoaki Kato
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
| | - Jean C Emond
- Center for Liver Disease and Transplantation, Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY
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14
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Dakhoul L, Ghabril M, Chalasani N. Drug-induced chronic liver injury. J Hepatol 2018; 69:248-250. [PMID: 29598958 DOI: 10.1016/j.jhep.2018.01.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 12/01/2017] [Accepted: 01/02/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Lara Dakhoul
- Indiana University School of Medicine, Division of Gastroenterology & Hepatology, Indianapolis, IN, United States
| | - Marwan Ghabril
- Indiana University School of Medicine, Division of Gastroenterology & Hepatology, Indianapolis, IN, United States
| | - Naga Chalasani
- Indiana University School of Medicine, Division of Gastroenterology & Hepatology, Indianapolis, IN, United States.
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Abstract
Fontan-associated liver disease is a hepatic disorder arising from hemodynamic changes and systemic venous congestion following Fontan surgery. The histological changes produced in the liver are similar but not equivalent to those seen in other forms of cardiac liver disease. While the natural history of this form of liver disease is not well established, over time many Fontan patients develop portal hypertension-related complications such as ascites, variceal hemorrhage or encephalopathy. Fontan survivors also show an increased risk of hepatocellular carcinoma. Early diagnosis of advanced liver disease is mandatory for the prevention and treatment of complications such as hepatocellular carcinoma, esophageal varices and malnutrition. This review updates current knowledge of the pathophysiology and management of Fontan-associated liver disease including new diagnostic methods and treatments.
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Affiliation(s)
- Luis Téllez
- Hospital Universitario Ramón y Cajal. Universidad de Alcalá. Servicio de Gastroenterología y Hepatología
| | - Enrique Rodríguez-Santiago
- Hospital Universitario Ramón y Cajal. Universidad de Alcalá. Servicio de Gastroenterología y Hepatología
| | - Agustín Albillos
- Hospital Universitario Ramón y Cajal. Universidad de Alcalá. Servicio de Gastroenterología y Hepatología
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Téllez L, Rodríguez de Santiago E, Albillos A. Fontan-associated Liver Disease. ACTA ACUST UNITED AC 2018; 71:192-202. [PMID: 29433942 DOI: 10.1016/j.rec.2017.10.052] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 10/11/2017] [Indexed: 02/07/2023]
Abstract
Fontan-associated liver disease refers to the disturbance in the liver secondary to hemodynamic changes and systemic venous congestion following Fontan surgery. Although the natural history of this disease has not yet been established, patients with more advanced liver injury develop the complications of portal hypertension, such as ascites, variceal haemorrhage, or encephalopathy. Moreover, patients with Fontan surgery may have an increased risk of hepatocellular carcinoma. Periodic liver monitoring is essential to prevent this disease and provide early treatment of liver complications.
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Affiliation(s)
- Luis Téllez
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
| | | | - Agustín Albillos
- Centro de Investigación Biomédica en Red Área de Enfermedades Digestivas (CIBERehd).
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18
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Intagliata NM, Caldwell SH. Changes in hemostasis in liver disease. J Hepatol 2017; 67:1332-1333. [PMID: 29156209 DOI: 10.1016/j.jhep.2017.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 06/25/2017] [Accepted: 07/06/2017] [Indexed: 12/29/2022]
Affiliation(s)
- Nicolas M Intagliata
- University of Virginia Medical Center, Department of Medicine, Division of Gastroenterology and Hepatology, Charlottesville, VA 22908, United States
| | - Stephen H Caldwell
- University of Virginia Medical Center, Department of Medicine, Division of Gastroenterology and Hepatology, Charlottesville, VA 22908, United States.
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Abstract
PURPOSE To report a case of central retinal vein occlusion without macular edema associated with ulcerative colitis and its novel treatment with intravitreal dexamethasone. CASE REPORT A 40-year-old man with ulcerative colitis presented with sudden visual disturbances. An initial fundus examination showed subtle yellow-to-white patches within the inner retina of the right eye superotemporal to the fovea. There were intraretinal hemorrhages and cotton-wool spots within the superior vascular arcade and nasal to the optic disc. Despite initiation of systemic corticosteroids, 2 weeks later there was an increase in retinal hemorrhages, formation of cotton wool spots, and development of optic disc swelling in the right eye. The patient was eventually diagnosed with nonischemic central retinal vein occlusion associated with ulcerative colitis. He received sustained-release intravitreal dexamethasone, which led to the resolution of retinal hemorrhage, optic disc swelling, and cotton-wool spots. Three months after the injection, retinal hemorrhages were not detectable. However, ocular coherence imaging showed marked thinning of the inner retina at the locations that were previously hyper-reflective. CONCLUSIONS Central retinal vein occlusion is an uncommon ophthalmologic manifestation associated with ulcerative colitis. Injection of intravitreal dexamethasone could be a viable treatment option in these patients even without the presence of macular edema.
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20
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Gao X, Li C, Tang YL, Zhang H, Chan SW. Effect of Hedyotis diffusa water extract on protecting human hepatocyte cells (LO2) from H2O2-induced cytotoxicity. PHARMACEUTICAL BIOLOGY 2016; 54:1148-1155. [PMID: 26095111 DOI: 10.3109/13880209.2015.1056310] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
CONTEXT Natural products are good sources of natural dietary antioxidants that are believed to protect the body against hepatotoxic effect induced by oxidative stress. Hedyotis diffusa Willd (Rubiaceae) (HDW) is a traditional Chinese medicinal herb that has been shown to possess a variety of antioxidant properties. OBJECTIVE The present study examines and explains the cell protective property of HDW water extract (WEHDW). MATERIALS AND METHODS 2,2-Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay was used to measure the free radical scavenging property of WEHDW (0.001-10 mg/mL). The protective effect of WEHDW (0.3-10 mg/mL 2 h pretreatment) against hydrogen peroxide (H2O2, 200 μM for 6 h) induced cytotoxicity in human hepatic cells, LO2, was evaluated using cell viability assay and nuclear staining. The molecular pathway of WEHDW's effect was investigated by using Western blot assay. RESULTS WEHDW had a 50% scavenging concentration (SC50) at 0.153 mg/mL in the DPPH assay. Exposure of LO2 cells to H2O2 resulted in apoptosis which could be markedly attenuated by pre-treating WEHDW in a concentration-dependent manner (0.5, 1, 3, 5, or 10 mg/mL) (all with p < 0.001, versus control). Moreover, Hoechst (nuclear) staining showed that 1 mg/mL WEHDW could protect LO2 cells by attenuating apoptotic cell death mediated by H2O2. It was found that WEHDW reversed H2O2-induced activation of MEK/ERK pathway and H2O2-induced inhibition of P13-K/AKT/GSK3β pathway in LO2 cells. DISCUSSION AND CONCLUSION WEHDW may help to improve the antioxidant defense system, resulting in prevention of oxidative stress-related fatty liver diseases.
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Affiliation(s)
- Xin Gao
- a Food Safety and Technology Research Centre, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hong Kong , China
- b School of Biological Sciences, The University of Hong Kong , Hong Kong , China
| | - Chang Li
- a Food Safety and Technology Research Centre, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hong Kong , China
- b School of Biological Sciences, The University of Hong Kong , Hong Kong , China
| | - Yee-Ling Tang
- a Food Safety and Technology Research Centre, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hong Kong , China
| | - Huan Zhang
- a Food Safety and Technology Research Centre, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hong Kong , China
- c State Key Laboratory of Chinese Medicine and Molecular Pharmacology , Shenzhen , China , and
| | - Shun-Wan Chan
- a Food Safety and Technology Research Centre, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hong Kong , China
- c State Key Laboratory of Chinese Medicine and Molecular Pharmacology , Shenzhen , China , and
- d Faculty of Science and Technology , Technological and Higher Education Institute of Hong Kong , Hong Kong , China
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Mohite AR, Gambhire PA, Pawar SV, Jain SS, Contractor QQ, Rathi PM. Changing clinical profile and factors associated with liver enzyme abnormalities among HIV-infected persons. Trop Doct 2016; 47:205-211. [PMID: 27342920 DOI: 10.1177/0049475516655068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The spectrum of liver disease among HIV-infected patients is changing. In the era of antiretroviral therapy, opportunistic infections are diminishing and deranged liver function appears to be due usually to drug-induced liver injury, alcohol, non-alcoholic steatohepatitis (NASH) or chronic hepatitis B. To test this hypothesis, 98 HIV-positive patients with deranged liver function were compared with matched HIV-positive patients with normal liver function and likewise matched HIV-negative patients with normal liver function tests.
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Affiliation(s)
- Ashok R Mohite
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Pravir A Gambhire
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Sunil V Pawar
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Samit S Jain
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Qais Q Contractor
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Pravin M Rathi
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
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22
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Yue ZS, Zeng LR, Quan RF, Tang YH, Zheng WJ, Qu G, Xu CD, Zhu FB, Huang ZM. 4‑Phenylbutyrate protects rat skin flaps against ischemia‑reperfusion injury and apoptosis by inhibiting endoplasmic reticulum stress. Mol Med Rep 2015; 13:1227-33. [PMID: 26648447 PMCID: PMC4732847 DOI: 10.3892/mmr.2015.4636] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 11/18/2015] [Indexed: 01/07/2023] Open
Abstract
4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid, which has been demonstrated to regulate endoplasmic reticulum (ER) stress. ER stress-induced cell apoptosis has an important role in skin flap ischemia; however, a pharmacological approach for treating ischemia-induced ER dysfunction has yet to be reported. In the present study, the effects of 4-PBA-induced ER stress inhibition on ischemia-reperfusion injury were investigated in the skin flap of rats, and transcriptional regulation was examined. 4-PBA attenuated ischemia-reperfusion injury and inhibited cell apoptosis in the skin flap. Furthermore, 4-PBA reversed the increased expression levels of two ER stress markers: CCAAT/enhancer-binding protein-homologous protein and glucose-regulated protein 78. These results suggested that 4-PBA was able to protect rat skin flaps against ischemia-reperfusion injury and apoptosis by inhibiting ER stress marker expression and ER stress-mediated apoptosis. The beneficial effects of 4-PBA may prove useful in the treatment of skin flap ischemia-reperfusion injury.
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Affiliation(s)
- Zhen-Shuang Yue
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Lin-Ru Zeng
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Ren-Fu Quan
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Yang-Hua Tang
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Wen-Jie Zheng
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Gang Qu
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Can-Da Xu
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Fang-Bing Zhu
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
| | - Zhong-Ming Huang
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China
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23
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Marzano C, Cazals-Hatem D, Rautou PE, Valla DC. The significance of nonobstructive sinusoidal dilatation of the liver: Impaired portal perfusion or inflammatory reaction syndrome. Hepatology 2015; 62:956-63. [PMID: 25684451 DOI: 10.1002/hep.27747] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 02/08/2015] [Indexed: 12/21/2022]
Abstract
UNLABELLED Sinusoidal dilatation found in the absence of an impaired sinusoidal blood outflow has been so far of unclear significance. Sinusoidal dilatation may actually be a nonspecific feature of impaired portal venous blood inflow, whatever the cause, or a feature of severe systemic inflammatory reaction syndrome, whatever the cause. Sinusoidal dilatation is mainly located in the centrilobular area even in the absence of an outflow block. A predominantly periportal location is specifically found in oral contraceptive users, associated with an inflammatory condition. There is strong evidence for the association of sinusoidal dilatation and oxaliplatin-based chemotherapy but not for estroprogestative steroids or thiopurine derivatives. Exposure to anabolic androgen steroids appears to cause sinusoidal changes different from a mere sinusoidal dilatation. CONCLUSION There is evidence of activation of the interleukin-6 and vascular endothelial growth factor pathways in sinusoidal dilatation, but the mechanisms linking the activation of these pathways with the microvascular changes must be identified.
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Affiliation(s)
- Chiara Marzano
- Dipartimento di Medicina Clinica, UOC di Gastroenterologia, Umberto I Policlinico di Roma, Sapienza Università di Roma, Rome, Italy
| | - Dominique Cazals-Hatem
- DHU UNITY, Laboratoire Central d'Anatomie et de Cytologie Pathologiques, Hôpital Beaujon, HUPNVS, APHP, Clichy-la-Garenne, France
- DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France
- CRI Paris-Montmartre, UMR 1149, Université Paris Diderot, PRES SPC, Hôpital Bichat, Paris, France
| | - Pierre-Emmanuel Rautou
- DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France
- Inserm, U970, Paris Cardiovascular Research Center-PARCC, Université Paris Descartes, Sorbonne Paris Cité, UMR-S970, Paris, France
| | - Dominique-Charles Valla
- DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France
- CRI Paris-Montmartre, UMR 1149, Université Paris Diderot, PRES SPC, Hôpital Bichat, Paris, France
- Inserm U1149, Hôpital Bichat, Paris, France
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The influence of dietary restriction on hepatic mononuclear cell numbers and functions in mice. J Surg Res 2015; 198:120-6. [PMID: 26123114 DOI: 10.1016/j.jss.2015.05.061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Revised: 05/18/2015] [Accepted: 05/29/2015] [Indexed: 11/24/2022]
Abstract
BACKGROUND Surgical patients with gastrointestinal malignancies are at increased risk for malnutrition. However, the mechanism by which dietary restriction (DR), one form of malnutrition, impairs hepatic immunity remains to be clarified. The present study was designed to examine the influence of DR on hepatic mononuclear cell (MNC) numbers, subpopulations, and cytokine productions (tumor necrosis factor α [TNF-α], interferon gamma [IFN-γ], and interleukin 10 [IL-10]) in response to lipopolysaccharide (LPS) in mice. Immunoglobulin (Ig) A levels in the gallbladder and histopathologic changes in the liver were also assessed. MATERIAL AND METHODS Male Institute of Cancer Research mice were randomly assigned to three dietary groups: ad libitum (AD), mild restriction (MR), and severe restriction (SR). The AD, MR, and SR groups received daily mouse chow in amounts of 190, 133, and 76 g/kg, respectively, for 7 d. After the mice had been fed for 7 d, hepatic MNCs were isolated. Total hepatic MNCs were counted and subpopulations were determined by flow cytometry. Cytokine productions (TNF-α, IFN-γ, and IL-10) by hepatic MNCs in response to LPS were measured. Blood samples were analyzed for hepatobiliary biochemical parameters. IgA levels in gallbladder bile were measured with enzyme-linked immunosorbent assay. In addition, liver histologies were examined. RESULTS Hepatic MNC numbers were significantly lower in the MR and SR groups than in the AD group, with no significant difference between the MR and SR groups. The percentage of B cells was significantly lower in the SR group than in the MR and AD groups, whereas the T-cell percentage was higher in the SR group than in the MR and AD groups. The percentage of Kupffer cells was significantly lower in the SR group than in the AD group, whereas that in the MR group was midway between those in the SR and AD groups. TNF-α and IL-10 levels in hepatic MNC culture supernatants were increased LPS-dose dependently in the AD group. However, the increase was slight in the MR group and absent in the SR group. The IgA levels in gallbladder bile were significantly lower in the SR and MR groups than in the AD group. On the basis of hematoxylin and eosin staining of hepatic sections, livers from the SR group showed atrophic hepatocytes and sinusoidal dilatation, whereas these changes were absent in the AD group. CONCLUSIONS DR decreases hepatic MNC number with subpopulation changes, reduces IgA levels in gallbladder bile, blunts cytokine production by hepatic MNCs, and induces pathologic damage in the liver, which may be an important mechanism underlying the impaired host defense associated with malnutrition.
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25
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Current updates on the molecular genetics and magnetic resonance imaging of focal nodular hyperplasia and hepatocellular adenoma. Insights Imaging 2015; 6:347-62. [PMID: 25790815 PMCID: PMC4444792 DOI: 10.1007/s13244-015-0399-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 01/29/2015] [Accepted: 02/04/2015] [Indexed: 12/19/2022] Open
Abstract
UNLABELLED Focal nodular hyperplasia (FNH) and hepatocellular adenomas (HCAs) constitute benign hepatic neoplasms in adults. HCAs are monoclonal neoplasms characterised by an increased predilection to haemorrhage and also malignant transformation. On the other hand, FNH is a polyclonal tumour-like lesion that occurs in response to increased perfusion and has an uneventful clinical course. Recent advances in molecular genetics and genotype-phenotype correlation in these hepatocellular neoplasms have enabled a new classification system. FNHs are classified into the typical and atypical types based on histomorphological and imaging features. HCAs have been categorised into four subtypes: (1) HCAs with HNF-1α mutations are diffusely steatotic, do not undergo malignant transformation, and are associated with familial diabetes or adenomatosis. (2) Inflammatory HCAs are hypervascular with marked peliosis and a tendency to bleed. They are associated with obesity, alcohol and hepatic steatosis. (3) HCAs with β-catenin mutations are associated with male hormone administration and glycogen storage disease, frequently undergo malignant transformation and may simulate hepatocellular carcinoma on imaging. (4) The final type is unclassified HCAs. Each of these except the unclassified subtype has a few distinct imaging features, often enabling reasonably accurate diagnosis. Biopsy with immunohistochemical analysis is helpful in difficult cases and has strong implications for patient management. TEACHING POINTS • FNHs are benign polyclonal neoplasms with no risk of haemorrhage or malignancy. • HCAs are benign monoclonal neoplasms classified into four subtypes based on immunohistochemistry. • Inflammatory HCAs show an atoll sign with a risk of bleeding and malignant transformation. • HNF-1α HCAs are steatotic HCAs with minimal complications and the best prognosis. • β-Catenin HCA shows variable MRI features and a high risk of malignancy.
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26
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Intagliata NM, Saad WE, Caldwell SH. Effects of restoring portal flow with anticoagulation and partial splenorenal shunt embolization. Hepatology 2015; 61:1088-90. [PMID: 24867875 DOI: 10.1002/hep.27241] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2014] [Accepted: 05/17/2014] [Indexed: 12/28/2022]
Affiliation(s)
- Nicolas M Intagliata
- University of Virginia Health System, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA
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Sood A, Castrejón M, Saab S. Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review. World J Hepatol 2014; 6:55-63. [PMID: 24653794 PMCID: PMC3953810 DOI: 10.4254/wjh.v6.i1.55] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Accepted: 12/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia (NRH) in patients with human immunodeficiency virus (HIV).
METHODS: We performed a systematic review of the medical literature regarding NRH in patients with HIV. Inclusion criteria include reports with biopsy proven NRH. We studied the clinical features of NRH, in particular, related to its presenting manifestation and laboratory values. Combinations of the following keywords were implemented: “nodular regenerative hyperplasia”, “human immunodeficiency virus”, “noncirrhotic portal hypertension”, “idiopathic portal hypertension”, “cryptogenic liver disease”, “highly active antiretroviral therapy” and “didanosine”. The bibliographies of these studies were subsequently searched for any additional relevant publications.
RESULTS: The clinical presentation of patients with NRH varies from patients being completely asymptomatic to the development of portal hypertension – namely esophageal variceal bleeding and ascites. Liver associated enzymes are generally normal and synthetic function well preserved. There is a strong association between the occurrence of NRH and the use of antiviral therapies such as didanosine. The management of NRH revolves around treating the manifestations of portal hypertension. The prognosis of NRH is generally good since liver function is preserved. A high index of suspicion is required to make a identify NRH.
CONCLUSION: The appropriate management of HIV-infected persons with suspected NRH is yet to be outlined. However, NRH is a clinically subtle condition that is difficult to diagnose, and it is important to be able to manage it according to the best available evidence.
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Nodular regenerative hyperplasia (NRH) complicating oxaliplatin chemotherapy in patients undergoing resection of colorectal liver metastases. Eur J Surg Oncol 2013; 40:1016-20. [PMID: 24370284 DOI: 10.1016/j.ejso.2013.09.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Accepted: 09/10/2013] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION Sinusoidal obstructive syndrome (SOS) is well associated with the use oxaliplatin-based chemotherapy, and represents a spectrum of hepatotoxicity, with nodular regenerative hyperplasia (NRH) representing the most significant degree of injury. The aim of this study was to determine the prevalence of NRH in patients undergoing resection of colorectal liver metastases (CRLM) and to determine its impact on outcome. METHODS From January 2000 to December 2010, some 978 first primary liver resections were performed for CRLM. A prospectively maintained database was analysed to identify all patients with evidence of NRH in the non-tumour portion of their histopathology specimens. Clinical data of these patients was reviewed and outcomes assessed. RESULTS Five patients exhibited NRH (four males, one female) with a median age of 69 years (range: 35-74). Three patients presented with synchronous hepatic metastases, and two with metachronous lesions. All received at least 6 cycles of oxaliplatin as either adjuvant or neo-adjuvant chemotherapy. Only one patient developed a post-operative complication namely transient hepatic failure that required a 4-day stay in the intensive care unit. The median hospital stay was 6 days (range: 6-14 days). There were no 90-day mortalities. One patient is alive and disease free at 55 months, the remaining 4 died of recurrent disease between 37 and 70 months following diagnosis of their primary tumours. CONCLUSIONS NRH is not an uncommon finding amongst patients with SOS with all patients having received oxaliplatin-based chemotherapy. Data on outcome would suggest no increased morbidity and mortality associated with the presence of NRH.
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Abstract
Portal vein thrombosis (PVT) can contribute to significant morbidity and mortality; in patients with cirrhosis, this can make transplant more technically challenging. Additionally, the clot may extend further into the mesenteric and splenic veins, and disturbance of the hepatic blood flow may lead to faster progression of the cirrhosis. Development of PVT is associated with local risk factors, and many patients have associated systemic prothrombotic factors. Anticoagulation in noncirrhotic patients should be initiated at diagnosis, using low-molecular-weight heparin overlapping with vitamin K antagonists. Cirrhotic patients with PVT should be screened for varices and then anticoagulated with low-molecular-weight heparin for at least a 6-month period. All patients should be assessed for triggering factors and tumors, as well as systemic prothrombotic factors. Newer evidence suggests that prophylactic anticoagulation in patients with cirrhosis may have a role in clinical management with decreased incidence of PVT and improved survival; further study is needed.
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Affiliation(s)
- Stephen E Congly
- Department of Medicine, University of Calgary Liver Unit, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1
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Fuss IJ, Friend J, Yang Z, He JP, Hooda L, Boyer J, Xi L, Raffeld M, Kleiner DE, Heller T, Strober W. Nodular regenerative hyperplasia in common variable immunodeficiency. J Clin Immunol 2013; 33:748-58. [PMID: 23420139 DOI: 10.1007/s10875-013-9873-6] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Accepted: 01/23/2013] [Indexed: 01/21/2023]
Abstract
PURPOSE Patients with Common Variable Immunodeficiency (CVID) are subject to the development of a liver disease syndrome known as nodular regenerative hyperplasia (NRH). The purpose of this study was to define the characteristics and course of this complication of CVID. METHODS CVID patients were evaluated by retrospective and prospective clinical course review. Liver biopsy specimens were evaluated for evidence of NRH and studied via RT-PCR for cytokine analysis. RESULTS NRH in our CVID patient population occurred in approximately 5 % of the 261 patients in our total CVID study group, initially presenting in most cases with an elevated alkaline phosphatase level. While in some patients the disease remained static, in a larger proportion a more severe disease developed characterized by portal hypertension, the latter leading to hypersplenism with neutropenia and thrombocytopenia and, in some cases, to ascites. In addition, a substantial proportion of patients either developed or presented initially with an autoimmune hepatitis-like (AIH-like) liver disease that resulted in severe liver dysfunction and, in most cases to death due to infections. The liver histologic findings in these AIH-like patients were characterized by underlying NRH pattern with superimposed interface hepatitis, lymphocytic infiltration and fibrosis. Immunologic studies of biopsies of NRH patients demonstrated the presence of infiltrating T cells producing IFN-γ, suggesting that the NRH is due to an autoimmune process. CONCLUSION Overall, these studies provide evidence that NRH may not be benign but, can be a severe and potentially fatal disease complication of CVID that merits close monitoring and intervention.
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Affiliation(s)
- Ivan J Fuss
- Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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Chatopadhyay P, Pandey A, Chaurasia AK, Upadhyay A, Karmakar S, Singh L. Hepatic hyperplasia and damages induces by zearalenone Fusarium mycotoxins in BALB/c mice. ARQUIVOS DE GASTROENTEROLOGIA 2012; 49:77-81. [DOI: 10.1590/s0004-28032012000100013] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Accepted: 09/20/2011] [Indexed: 02/07/2023]
Abstract
CONTEXT: Zearalenone is a mycoestrogen and considered a mycotoxin. OBJECTIVE: To establish whether zearalenone produced hepatotoxicity via oral administration. METHODS: Zearalenone was orally administered at a dose of 50 mg, 100 mg and 200 mg ZEN/body weight/daily, respectively, for 14 days to three groups of BALB/c mice. Diagnostic modalities used to evaluate hepatic damage and impaired hepatic function pre- and post zearalenone administration included hepatic marker enzyme activity, pentobarbital sleeping time, cytochrome P-450 activities and histopathologic evaluation of liver. RESULTS: Significant histopathologic changes viz. sinusoidal congestion, cytoplasmic vacuolization, hepatocellular necrosis and neutrophil infiltration were observed after evaluating of liver section from each group after accumulated zearalenone exposure. Further, zearalenone exposure increased activities of alanine transaminase, aspartate transaminase and lipid peroxides whereas activities of tissue glutathione and cytochrome P450 were decreased as compared to control mice. Zearalenone also increased the sleeping time and decreased sleeping latency after pentobarbital through intraperitoneal route as compared to control mice which indicates that the impairment of hepatic metabolizing enzymes by zearalenone. CONCLUSION: Zearalenone is a potential hepatotoxin by oral route.
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Manzia TM, Gravante G, Di Paolo D, Orlando G, Toti L, Bellini MI, Ciano P, Angelico M, Tisone G. Liver transplantation for the treatment of nodular regenerative hyperplasia. Dig Liver Dis 2011; 43:929-934. [PMID: 21601542 DOI: 10.1016/j.dld.2011.04.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2010] [Revised: 03/28/2011] [Accepted: 04/04/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Nodular regenerative hyperplasia (NRH) is the leading cause of non-cirrhotic portal hypertension in Western countries. Although some patients are successfully managed medically or with shunting procedures, others require liver transplantation. The aim of this review was to assess the overall results obtained with liver transplantation and to better define its role in this setting. METHODS Systematic review of all published studies on liver transplantation for NRH without language restrictions, in Medline, Embase and Cochrane Library databases through March 2010. RESULTS 17 studies including a total of 73 patients were identified; 47 (64.3%) were excluded due to lacking inclusion criteria or clinical data and 26 (35.7%) were analysed. Before liver transplantation, the most frequent clinical presentation was gastroesophageal bleeding (65.3%) followed by ascites (61.5%), hepatic encephalopathy (30.7%) and liver failure (11.5%). The mean follow-up reported after liver transplantation was 30.6±27.6 months and patient and graft survival rate was 78.3%. Only one case reported a NRH recurrence 7 years after liver transplantation (LT). CONCLUSIONS Although there are no hard data supporting the role of liver transplantation in symptomatic NRH, onset of severe portal hypertension in this setting may represent a valid indication.
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Song X, Chen HQ, Chen YX, Cheng Y, Qu CQ, Liu EY, Guo S, Xu KS, Niu J, Shou NH. Individualized Management of Hepatic Diseases in Hereditary Hemorrhagic Telangiectasia. Am Surg 2011. [DOI: 10.1177/000313481107700314] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Liver involvement in patients with hereditary hemorrhagic telangiectasia (HHT) has not been fully characterized in China. The clinical manifestations, imaging studies, results of treatment in six patients and symptomatic liver involvement were analyzed. Patients included three women and three men with age from 35 to 62 years old. Two patients presented with shortness of breath, one patient with anemia and splenomegaly, and one with chronic gastrointestinal bleeding; the remaining two were asymptomatic. CT and CT angiography (CTA) showed arterioportal and arteriovenous shunting in liver. CTA showed at least one enlarged hepatic artery in all patients. One patient received ligation of the enlarged arteries with subsequent disappearance of symptoms at 56-month follow-up. The patient with gastrointestinal bleeding received interventional embolotherapy and resolved; interventional therapy to embolize the enlarged hepatic arteries was unsuccessful in another patient and the patient died of heart failure and liver dysfunction 38 months later. The patient with splenomegaly received a splenectomy and bandage of an enlarged hepatic artery. One of the two patients with no symptoms died of liver dysfunction 41 months after diagnosis. The other showed abnormal liver function and ascites, and traditional Chinese medicinal herb was used with no effect 21 months later. The symptoms disappeared after systemic medical treatment. Individualized and active therapy is advantageous and proper for patients with HHT.
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Affiliation(s)
- Xie Song
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Hong-Qiang Chen
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Yu-Xin Chen
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Yu Cheng
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Chuan-Qiang Qu
- Departments of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - En-Yu Liu
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Sen Guo
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Ke-Sen Xu
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Jun Niu
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
| | - Nan-Hai Shou
- Departments of Hepatobiliary Surgery and Shandong University, Jinan, China
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Cursio R, Gugenheim J, Ricci J, Crenesse D, Rostagno P, Maulon L, Saint-Paul MC, Ferrua B, Mouiel J, Auberger P. Caspase inhibition protects from liver injury following ischemia and reperfusion in rats. Transpl Int 2011. [DOI: 10.1111/j.1432-2277.2000.tb02108.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
Patients with critical illness are heterogeneous, with differing physiologic requirements over time. Goal-directed therapy in the emergency room demonstrates that protocolized care could result in improved outcomes. Subsequent studies have confirmed benefit with such a "bundle-based approach" in the emergency room and in preoperative and postoperative scenarios. However, this cannot be necessarily extrapolated to the medium-term and long-term care pathway of the critically ill patient. It is likely that the development of mitochondrial dysfunction could result in goal-directed types of approaches being detrimental. Equally, arterial pressure aims are likely to be considerably different as the patient's physiology moves toward "hibernation." The agents we utilize as sedative and pressor agents have considerable effects on immune function and the inflammatory profile, and should be considered as part of the total clinical picture. The role of gut failure in driving inflammation is considerable, and the drive to feed enterally, regardless of aspirate volume, may be detrimental in those with degrees of ileus, which is often a difficult diagnosis in the critically ill. The pathogenesis of liver dysfunction may be, at least in part, related to venous engorgement that will contribute toward portal hypertension and gut edema. This, in association with loss of the hepatosplanchnic buffer response, it is likely to contribute to venous pooling in the abdominal cavity, impaired venous return, and decreased central blood volumes. Therapies such as those used in "small-for-size syndrome" may have a role in the chronic stages of septic vascular failure.
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Abstract
Hepatic vascular disorders are a set of conditions that may be acute, or may be insidious and subclinical for many years. They can be organized into 3 categories: obstruction to hepatic vascular inflow, obstruction to blood flow through the liver, and obstruction to hepatic vascular outflow. In the first category are portal vein thrombosis, hepatic artery thrombosis, and presinusoidal causes of vascular obstruction. In the second category are sickle cell disease, disseminated intravascular coagulation, intrasinusoidal malignancy, and infection. In the third category are macroscopic hepatic venous thrombosis, thrombosis of the retrohepatic inferior vena cava, and venoocclusive disease. There are 2 nodular conditions of the liver that are not neoplastic but the result of occlusion of hepatic vasculature with compensatory hyperplasia of well-vascularized parenchyma. Hepatic vascular disorders constitute a heterogeneous group of conditions that must be considered in the differential diagnosis of any patient with hepatic compromise.
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Kim KH, Kum YS, Park YY, Park JH, Kim SJ, Lee WR, Lee KG, Han SM, Park KK. The protective effect of bee venom against ethanol-induced hepatic injury via regulation of the mitochondria-related apoptotic pathway. Basic Clin Pharmacol Toxicol 2010; 107:619-624. [PMID: 20210790 DOI: 10.1111/j.1742-7843.2010.00549.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Alcohol consumption increases apoptosis of hepatocytes. Death of hepatocytes is a characteristic feature of chronic liver disease for various causes. Bee venom (Apis mellifera) has been traditionally used for the treatment of various chronic diseases, such as chronic inflammatory arthritis and chronic liver disease. However, the precise mechanism for bee venom in chronic liver disease is not still cleared. To assess the effects of bee venom in chronic liver disease, we investigated the potential role of the bee venom in the ethanol-induced hepatocyte apoptosis. Bee venom treatment inhibited the apoptotic cell morphology and increased the cell viability in ethanol-induced hepatocyte apoptosis. With ethanol treatment, bee venom-treated hepatocytes increased activity of Bcl-2 and Bcl-xL, reduced activity of Bax, Caspase and PARP. In conclusion, bee venom treatment in ethanol-induced hepatocyte apoptosis occurred through the regulation of Bcl family with subsequent inactivation of the Caspase and PARP. These results suggest that bee venom could be an effective agent to reduce ethanol-induced hepatocyte apoptosis.
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Affiliation(s)
- Kyung-Hyun Kim
- Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, Republic of Korea
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Talaat RM. Soluble angiogenesis factors in sera of Egyptian patients with hepatitis C virus infection: correlation with disease severity. Viral Immunol 2010; 23:151-157. [PMID: 20373995 DOI: 10.1089/vim.2009.0089] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C virus (HCV) infection causes chronic hepatitis, which gradually progresses to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC). Angiogenesis plays a major role in chronic inflammation and may have prognostic value in disease progression. This study was designed to evaluate vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and tumor necrosis factor-alpha (TNF-alpha) as prognostic factors of disease progression in Egyptian patients with different stages of HCV-related cirrhosis and HCC. VEGF, PDGF, and TNF-alpha were measured using enzyme-linked immunosorbent assay (ELISA) in 82 HCV-infected patients (20 mild, 20 moderate, and 20 severe cirrhosis patients, and 22 HCC patients), and 20 healthy controls. Our results showed comparable increases in VEGF and PDGF levels in those with increasing clinical stages of disease, with maximal production seen in HCC patients. A gradual elevation of TNF-alpha levels was seen also in HCV-infected patients at different stages of disease and HCC. A statistically significantly positive correlation between serum levels of VEGF, PDGF, and TNF-alpha, and grade of disease was recorded. Thus assessment of these parameters in those with different stages of disease may be helpful in choosing the best treatment strategy, and indicate that anti-angiogenic therapy may be useful.
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Affiliation(s)
- Roba M Talaat
- Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Menofia University, Sadat City, Egypt.
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Jain R, L. Thiele D. Gastrointestinal and Hepatic Manifestations of Systemic Diseases. SLEISENGER AND FORDTRAN'S GASTROINTESTINAL AND LIVER DISEASE 2010:557-592.e11. [DOI: 10.1016/b978-1-4160-6189-2.00035-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
Nodular regenerative hyperplasia (NRH) of the liver is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma that may lead to noncirrhotic portal hypertension. The exact pathogenesis of NRH has not been established, but it has been suggested that a primary vascular abnormality causing local ischemia may initiate the nodular transformation. It is also known that this condition is associated with autoimmune disease, hematological disease, and some chemotherapy agents in which vasculopathy is a prominent feature. The patients with NRH are usually asymptomatic unless they develop complications related to portal hypertension. We report a case of a middle-aged female patient with florid carcinoid syndrome, speculating that vasoactive hormones including serotonin secreted by the tumor caused intrahepatic microcirculatory disturbances that eventually induced NRH. This association has not been reported earlier.
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Zois CD, Baltayiannis GH, Karayiannis P, Tsianos EV. Systematic review: hepatic fibrosis - regression with therapy. Aliment Pharmacol Ther 2008; 28:1175-87. [PMID: 18761707 DOI: 10.1111/j.1365-2036.2008.03840.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatic fibrosis occurs in response to chronic liver injury, regardless of the cause. An impressive amount of knowledge concerning the pathogenesis and treatment of liver fibrosis has emerged over the past few years. The hallmark of this event is the activation of the hepatic stellate cell. The latter event causes accumulation of extracellular matrix and formation of scar, leading to deterioration in hepatic function. AIM To assess chronic liver injury, many invasive and non-invasive methods have been suggested. METHODS Although transient elastography, image analysis of fractal geometry and fibrotest with actitest have been used in clinical practice, liver biopsy remains the recommended choice, especially when histological staging of fibrosis or response to treatment is needed. CONCLUSIONS The recent advances in anti-viral therapy have resulted in many reports on fibrosis and even on cirrhosis regression, especially early and in young people. A number of new agents have been suggested for the treatment of fibrosis, with promising results in animals; however, their efficacy in humans remains to be elucidated. The investigation of heterogeneity and plasticity of hepatic stellate cells is a topic of scientific interest and may result in improvements in patient management.
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Affiliation(s)
- C D Zois
- 1st Department of Internal Medicine and Hepato-Gastroenterology Unit, Medical School, University of Ioannina, Ioannina, Greece
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Feld JJ, Hussain N, Wright EC, Kleiner DE, Hoofnagle JH, Ahlawat S, Anderson V, Hilligoss D, Gallin JI, Liang TJ, Malech HL, Holland SM, Heller T. Hepatic involvement and portal hypertension predict mortality in chronic granulomatous disease. Gastroenterology 2008; 134:1917-26. [PMID: 18439425 PMCID: PMC2583937 DOI: 10.1053/j.gastro.2008.02.081] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2007] [Revised: 02/07/2008] [Accepted: 02/28/2008] [Indexed: 12/28/2022]
Abstract
BACKGROUND & AIMS Chronic granulomatous disease (CGD) is a rare genetic disorder, predisposing affected individuals to recurrent infectious complications and shortened survival. Liver involvement in CGD includes vascular abnormalities, which may lead to noncirrhotic portal hypertension. METHODS To evaluate the impact of noncirrhotic portal hypertension on survival in CGD, all records from 194 patients followed up at the National Institutes of Health with CGD were reviewed. Cox proportional hazards regression was used to determine factors associated with mortality. RESULTS Twenty-four patients died, all from infectious complications. By Cox regression, factors associated with mortality were as follows: (1) decreases in platelet count (>9000/microL/y; hazard ratio, 4.7; P = .007), (2) alkaline phosphatase level increases (>0.25/y; hazard ratio, 4.5; P = .01) and (3) history of liver abscess (hazard ratio, 3.1; P = .03). By regression analysis, decreasing platelet count was associated with increasing portal vein diameter, splenomegaly, increased serum immunoglobulin G level, and increasing number of alanine aminotransferase increases; greater number of alkaline phosphatase level increases and abscess were both associated with increasing age and number of infections. Prospective evaluation revealed increased hepatic-venous pressure gradients in 2 patients with progressive thrombocytopenia, suggestive of portal hypertension. CONCLUSIONS These data suggest mortality in patients with CGD is associated with the development of noncirrhotic portal hypertension, likely owing to injury to the microvasculature of the liver from repeated systemic and hepatic infections. The slope of decline in platelet count may be a useful measure of progression of portal hypertension over time. Furthermore, the data illustrate the potential independent effect of portal hypertension on clinical outcome outside the setting of cirrhosis.
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Affiliation(s)
- Jordan J. Feld
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | | | | | | | - Jay H. Hoofnagle
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | | | | | | | - John I. Gallin
- National Institute of Allergy and Infectious Diseases, NIH
| | - T. Jake Liang
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | | | | | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
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Dowman JK, Holt AP, Newsome PN, Adams DH. Emerging drugs for complications of end-stage liver disease. Expert Opin Emerg Drugs 2008; 13:159-74. [PMID: 18321155 DOI: 10.1517/14728214.13.1.159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND The prevalence of end-stage liver disease is rising rapidly and constitutes a major healthcare burden currently. Many cases are diagnosed at a later stage when liver transplantation is the only effective treatment option. There is thus an urgent need for novel treatments to reverse the earlier stages of cirrhosis as well as to treat the many associated life-threatening complications. OBJECTIVES To review the current drugs available for treating the complications of advanced liver disease. To address novel treatment strategies that are in development, with particular reference to the rapidly developing area of antifibrotic therapy. To assess how the obstacles that have so far impeded the development of effective new drugs for end-stage liver disease may be overcome in the future. METHODS The literature was reviewed to define current therapies and therapies in clinical trials. We used the current models of the molecular basis of liver fibrogenesis to determine potential new therapeutic targets for antifibrotic therapy. CONCLUSIONS Insights into the pathogenesis of liver injury and fibrosis have opened up new avenues for therapy and there are now candidates and targets with real potential for the development of a new generation of antifibrotic therapies.
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Affiliation(s)
- Joanna K Dowman
- The University of Birmingham Medical School, Liver Research Group, MRC Centre for Immune Regulation, Institute of Biomedical Research, 5th Floor, Wolfson Drive, Edgbaston, Birmingham B15 2TT, UK
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Nodular regenerative hyperplasia: the main liver disease in patients with primary hypogammaglobulinemia and hepatic abnormalities. J Hepatol 2008; 48:74-82. [PMID: 17998147 DOI: 10.1016/j.jhep.2007.08.011] [Citation(s) in RCA: 123] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2007] [Revised: 08/04/2007] [Accepted: 08/07/2007] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIMS Liver lesions associated with primary hypogammaglobulinemia have been poorly described. We aimed to assess the clinical, histological and immune features and outcome of hepatic injury in patients with primary hypogammaglobulinemia. METHODS The medical records of 51 patients (23 patients with liver biopsy) with primary hypogammaglobulinemia and liver abnormalities were retrospectively reviewed. Forty-three controls with primary hypogammaglobulinemia but with no hepatic manifestations were analyzed in parallel. RESULTS Cholestasis (65%), mainly anicteric, and portal hypertension (50%) were the main hepatic manifestations. Histological analysis revealed non-fibrosing architectural abnormalities consistent with nodular regenerative hyperplasia (NRH) in 84% of CVID patients and in all HIGM and XLA patients. Intrasinusoidal lymphocytic infiltration, abnormalities of portal vessels and epithelioid granulomas were observed in 90%, 43% and 44% of patients, respectively. NRH was associated with portal hypertension in 75% of the cases. These patients more often presented with autoimmune diseases and peripheral lymphocytic abnormalities than control patients (p < 0.05). CONCLUSIONS Liver involvement in primary hypogammaglobulinemia mainly consists of NRH leading to chronic cholestasis and portal hypertension. Association with intrasinusoidal T cell infiltration, portal vein endotheliitis, autoimmune diseases and peripheral lymphocytic abnormalities suggests an autoimmune mechanism.
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Zhang Y, Venugopal SK, He S, Liu P, Wu J, Zern MA. Ethanol induces apoptosis in hepatocytes by a pathway involving novel protein kinase C isoforms. Cell Signal 2007; 19:2339-50. [PMID: 17728104 DOI: 10.1016/j.cellsig.2007.07.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2007] [Revised: 07/11/2007] [Accepted: 07/18/2007] [Indexed: 11/29/2022]
Abstract
UNLABELLED Ethanol abuse is one of the major etiologies of cirrhosis. Ethanol has been shown to induce apoptosis via activation of oxidative stress, mitogen-activated protein kinases (MAPK), and tyrosine kinases. However, there is a paucity of data that examine the interplay among these molecules. In the present study we have systematically elucidated the role of novel protein kinase C isoforms (nPKC; PKCdelta and PKCepsilon) in ethanol-induced apoptosis in hepatocytes. Ethanol enhanced membrane translocation of PKCdelta and PKCepsilon, which was associated with the phosphorylation of p38MAPK, p42/44MAPK and JNK1/2, and the nuclear translocation of NF-kappaB and AP-1. This resulted in increased apoptosis in primary rat hepatocytes. Inhibition of both PKCdelta and PKCepsilon resulted in a decreased MAPK activation, decreased nuclear translocation of NF-kappaB and AP-1, and inhibition of apoptosis. In addition, ethanol activated the tyrosine phosphorylation of PKCdelta via tyrosine kinase in hepatocytes. The tyrosine phosphorylated PKCdelta was cleaved by caspase-3 and these fragments were translocated to the nucleus. Inhibition of ethanol-induced oxidative stress blocked the membrane translocation of PKCdelta and PKCepsilon, and the tyrosine phosphorylation of PKCdelta in hepatocytes. Inhibition of oxidative stress, tyrosine kinase or caspase-3 activity caused a decreased nuclear translocation of PKCdelta in response to ethanol, and was associated with less apoptosis. CONCLUSION These results provide a newly-described mechanism by which ethanol induces apoptosis via activation of nPKC isoforms in hepatocytes.
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Affiliation(s)
- Yanhong Zhang
- Department of Internal Medicine, Transplant Research Program, University of California, Davis Medical Center, Sacramento, CA 95817, USA
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Venturi A, Piscaglia F, Vidili G, Flori S, Righini R, Golfieri R, Bolondi L. Diagnosis and management of hepatic focal nodular hyperplasia. J Ultrasound 2007; 10:116-27. [PMID: 23396642 PMCID: PMC3478711 DOI: 10.1016/j.jus.2007.06.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Focal nodular hyperplasia (FNH) is the second most common benign tumor of the liver, after hemangioma. It is generally found incidentally and is most common in reproductive-aged women, but it also affects males and can be diagnosed at any age. Patients are rarely symptomatic, but FNH sometimes causes epigastric or right upper quadrant pain. The main clinical task is to differentiate it from other hypervascular hepatic lesions such as hepatic adenoma, hepatocellular carcinoma, or hypervascular metastases, but invasive diagnostic procedures can generally be avoided with the appropriate use of imaging techniques. Magnetic resonance (MR) imaging is more sensitive and specific than conventional ultrasonography (US) or computed tomography (CT), but Doppler US and contrast-enhanced US (CEUS) can greatly improve the accuracy in the diagnosis of FNH. Once a correct diagnosis has been made, in most cases there is no indication for surgery, and treatment includes conservative clinical follow-up in asymptomatic patients.
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Affiliation(s)
- A. Venturi
- Department of Internal Medicine and Gastroenterology, Policlinico St. Orsola-Malpighi, University of Bologna, Italy
| | - F. Piscaglia
- Department of Internal Medicine and Gastroenterology, Policlinico St. Orsola-Malpighi, University of Bologna, Italy
| | - G. Vidili
- Department of Internal Medicine and Gastroenterology, Policlinico St. Orsola-Malpighi, University of Bologna, Italy
| | - S. Flori
- Department of Internal Medicine and Gastroenterology, Policlinico St. Orsola-Malpighi, University of Bologna, Italy
| | - R. Righini
- Department of Internal Medicine and Gastroenterology, Policlinico St. Orsola-Malpighi, University of Bologna, Italy
| | - R. Golfieri
- Department of Radiology, Policlinico St. Orsola-Malpighi, University of Bologna, Italy
| | - L. Bolondi
- Department of Internal Medicine and Gastroenterology, Policlinico St. Orsola-Malpighi, University of Bologna, Italy
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47
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Morise Z, Urano M, Sugioka A, Mizoguchi Y, Kato R, Hoshimoto S, Kato T, Ikeda M, Kuroda M. A hypervascular pseudotumor in the liver with angiodysplasia in the center of the lesion: a new entity or a variant of focal nodular hyperplasia? Int J Surg Pathol 2007; 15:272-6. [PMID: 17652535 DOI: 10.1177/1066896907302230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
A unique case of hypervascular pseudotumor in the liver consisting of central angiodysplasia surrounded by atrophic liver tissue is described. A 45-year-old woman was referred for the incidentally found hepatic lesion. Computed tomography with contrast showed strong enhancement of the lesion in the arterial phase, and the effect persisted to the parenchymal phase. Doppler ultrasonography showed winding dilated blood flows into the lesion. Because the pathological examination of the biopsy specimen showed the possibility of a well-differentiated hepatocellular carcinoma, she underwent surgery. Final pathological findings showed that the lesion demonstrated atrophic change of the liver tissue with a cluster of abnormal vessels of various sizes in the center. Although there was no primary liver disease, multiple liver metastases from laryngeal carcinoma were found coincidentally. The present lesion could represent a new entity or a variant (or an unknown stage of development) of focal nodular hyperplasia.
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Affiliation(s)
- Zenichi Morise
- Department of Surgery, Fujita Health University School of Medicine, Kutsukakecho, Toyoake, Japan.
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48
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Assy N, Hussein O, Khalil A, Luder A, Szvalb S, Paizi M, Spira G. The beneficial effect of aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of cirrhosis. Dig Dis Sci 2007; 52:1187-93. [PMID: 17372820 DOI: 10.1007/s10620-006-9595-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to examine the effect of the antithrombotic drugs aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of liver cirrhosis and to determine if these two drugs are beneficial in animals with advanced fibrosis or with established cirrhosis undergoing partial hepatectomy. Thioacetamide-induced cirrhotic rats received saline (N=10), aspirin (N=7), or enoxaparin (N=11) for a 5-week treatment period. Hepatic fibrosis was assessed according to METAVIR score. Liver regeneration was monitored using PCNA immunostaining. Compared to untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the aspirin (43%; chi(2)=54, P<0.001) and enoxaparin (36%; chi(2)=43, P<0.001) treated groups. Postoperatively, total serum bilirubin levels were lower in the aspirin (1.4+/-0.18 mg/dl; P<0.01) and enoxaparin (1.8+/-0.35 mg/dl; P<0.05)-treated groups compared to untreated cirrhotic controls (3.2+/-0.6 mg/dl). Hepatic regenerative activity was significantly improved in the aspirin group (57.3%+/-6.8%, versus 34.2%+/-7.2% in untreated cirrhotic controls; P<0.01) but unchanged in the enoxaparin group. We conclude that aspirin and enoxaparin hold promise as a useful therapy for patients with extensive fibrosis.
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Affiliation(s)
- Nimer Assy
- Liver Clinic, Sieff Government Hospital, P.O.B. 1008, Safed 13100, Israel.
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49
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Hussain N, Feld JJ, Kleiner DE, Hoofnagle JH, Garcia-Eulate R, Ahlawat S, Koziel DE, Anderson V, Hilligoss D, Choyke P, Gallin JI, Liang TJ, Malech HL, Holland SM, Heller T. Hepatic abnormalities in patients with chronic granulomatous disease. Hepatology 2007; 45:675-83. [PMID: 17326162 DOI: 10.1002/hep.21524] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
UNLABELLED Chronic granulomatous disease (CGD) is a rare congenital disorder characterized by repeated bacterial and fungal infections. Aside from a high incidence of liver abscess, little is known about hepatic involvement in CGD. The aim of this study was to describe the spectrum of liver abnormalities seen in CGD. The charts of 194 patients with CGD followed at the NIH were reviewed, with a focus on liver abnormalities. Liver enzyme elevations occurred on at least one occasion in 73% of patients during a mean of 8.9 years of follow-up. ALT elevations were generally transient. Although transient alkaline phosphatase (ALP) elevations were also common, persistent ALP elevations lasting up to 17.6 years were seen in 25% of patients. Liver abscess occurred in 35% of patients. Drug-induced hepatotoxicity was documented in 15% of patients but likely occurred more frequently. Hepatomegaly was found in 34% and splenomegaly in 56% of patients. Liver histology showed granulomata in 75% and lobular hepatitis in 90% of specimens. Venopathy of the portal vein was common (80%) and associated with splenomegaly. Venopathy of the central vein was also common (63%) and was associated with the number of abscess episodes. Nodular regenerative hyperplasia (NRH) was seen in 9 patients, including 6 of 12 autopsy specimens. CONCLUSION Liver enzyme abnormalities occur frequently in patients with CGD. In addition to liver abscesses and granulomata, drug hepatotoxicity is likely underappreciated. Vascular lesions such as venopathy and--to a lesser extent--NRH are common. The cause and clinical consequences of venopathy await prospective evaluation.
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Affiliation(s)
- Nadeem Hussain
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD 20892-1800, USA
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50
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Mallet V, Blanchard P, Verkarre V, Vallet-Pichard A, Fontaine H, Lascoux-Combe C, Pol S. Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients. AIDS 2007; 21:187-92. [PMID: 17197809 DOI: 10.1097/qad.0b013e3280119e47] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To describe and explain the syndrome of HIV-associated cryptogenic liver disease in eight consecutive patients suffering from portal hypertension. METHODS The study was undertaken at a liver disease centre in Paris and involved eight of 97 consecutive HIV-infected patients presenting abnormal liver function tests and/or symptomatic portal hypertension of unknown origin. Serology, pathology, and liver function tests were performed. RESULTS A clear nodular architecture corresponding to nodular regenerative hyperplasia was observed in seven patients and suggested in one, based on the presence of sinusoidal dilatation in a clinical context of portal hypertension, without overt liver disease. CONCLUSIONS Nodular regenerative hyperplasia appears to be a new cause of portal hypertension in HIV-infected patients. This syndrome can be of critical importance as patients can be exposed to the significant complications of portal hypertension and to refractory ascites which may require liver transplantation.
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