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Bellamy CO, Burt AD. Liver in Systemic Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:1039-1095. [DOI: 10.1016/b978-0-7020-8228-3.00015-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Soon GST, Torbenson M. The Liver and Glycogen: In Sickness and in Health. Int J Mol Sci 2023; 24:ijms24076133. [PMID: 37047105 PMCID: PMC10094386 DOI: 10.3390/ijms24076133] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/20/2023] [Accepted: 03/23/2023] [Indexed: 04/14/2023] Open
Abstract
The liver is a major store of glycogen and is essential in maintaining systemic glucose homeostasis. In healthy individuals, glycogen synthesis and breakdown in the liver are tightly regulated. Abnormal glycogen metabolism results in prominent pathological changes in the liver, often manifesting as hepatic glycogenosis or glycogen inclusions. This can occur in genetic glycogen storage disease or acquired conditions with insulin dysregulation such as diabetes mellitus and non-alcoholic fatty liver disease or medication effects. Some primary hepatic tumors such as clear cell hepatocellular carcinoma also demonstrate excessive glycogen accumulation. This review provides an overview of the pathological manifestations and molecular mechanisms of liver diseases associated with abnormal glycogen accumulation.
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Affiliation(s)
- Gwyneth S T Soon
- Department of Pathology, National University Hospital, Singapore 119074, Singapore
| | - Michael Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
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Cox BK, Guindi M, Hutchings D, Kim SA, Waters KM, Larson BK. Glycogenic hepatopathy is associated with type 1 diabetes mellitus in only a minority of cases in a contemporary adult population. Ann Diagn Pathol 2023; 64:152130. [PMID: 36965212 DOI: 10.1016/j.anndiagpath.2023.152130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/02/2023] [Indexed: 03/09/2023]
Abstract
OBJECTIVES This study examines the clinical-pathological profiles of patients with glycogenic hepatopathy in a contemporary cohort of patients at an adult acute care hospital. METHODS Liver biopsies with glycogenic hepatopathy were retrieved from the departmental surgical pathology database, the histological findings were studied, and the clinical findings were reviewed. RESULTS Five cases of glycogenic hepatopathy were found, including cases associated with type 1 diabetes mellitus (n = 1), type 2 diabetes mellitus (n = 1), corticosteroids (n = 2), and anorexia (n = 2, including the patient with type 1 diabetes). AST and ALT were normal to mildly elevated (13-115 U/L and 7-126 U/L, respectively). Trace ascites was present in two patients. Hepatomegaly was only present in the patient with type 1 diabetes at the time of diagnosis. CONCLUSIONS Four of five cases were associated with etiologies other than type 1 diabetes, which is widely reported as the most common etiology of glycogenic hepatopathy. This study suggests that etiologies currently only rarely recognized may actually be more common causes of glycogenic hepatopathy than type 1 diabetes in a contemporary adult population. It is important not only to recognize that these rarely reported causes of glycogenic hepatopathy may be underrecognized, but that the clinical presentation may also be mild.
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Affiliation(s)
- Brian K Cox
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, United States of America
| | - Maha Guindi
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, United States of America
| | - Danielle Hutchings
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, United States of America
| | - Stacey A Kim
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, United States of America
| | - Kevin M Waters
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, United States of America
| | - Brent K Larson
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, United States of America.
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Mertens J, De Block C, Spinhoven M, Driessen A, Francque SM, Kwanten WJ. Hepatopathy Associated With Type 1 Diabetes: Distinguishing Non-alcoholic Fatty Liver Disease From Glycogenic Hepatopathy. Front Pharmacol 2021; 12:768576. [PMID: 34759828 PMCID: PMC8573337 DOI: 10.3389/fphar.2021.768576] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 10/06/2021] [Indexed: 12/14/2022] Open
Abstract
Autoimmune destruction of pancreatic β-cells results in the permanent loss of insulin production in type 1 diabetes (T1D). The daily necessity to inject exogenous insulin to treat hyperglycemia leads to a relative portal vein insulin deficiency and potentiates hypoglycemia which can induce weight gain, while daily fluctuations of blood sugar levels affect the hepatic glycogen storage and overall metabolic control. These, among others, fundamental characteristics of T1D are associated with the development of two distinct, but in part clinically similar hepatopathies, namely non-alcoholic fatty liver disease (NAFLD) and glycogen hepatopathy (GlyH). Recent studies suggest that NAFLD may be increasingly common in T1D because more people with T1D present with overweight and/or obesity, linked to the metabolic syndrome. GlyH is a rare but underdiagnosed complication hallmarked by extremely brittle metabolic control in, often young, individuals with T1D. Both hepatopathies share clinical similarities, troubling both diagnosis and differentiation. Since NAFLD is increasingly associated with cardiovascular and chronic kidney disease, whereas GlyH is considered self-limiting, awareness and differentiation between both condition is important in clinical care. The exact pathogenesis of both hepatopathies remains obscure, hence licensed pharmaceutical therapy is lacking and general awareness amongst physicians is low. This article aims to review the factors potentially contributing to fatty liver disease or glycogen storage disruption in T1D. It ends with a proposal for clinicians to approach patients with T1D and potential hepatopathy.
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Affiliation(s)
- Jonathan Mertens
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.,Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
| | - Christophe De Block
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
| | - Maarten Spinhoven
- Department of Radiology, Antwerp University Hospital, Edegem, Belgium
| | - Ann Driessen
- Department of Pathology, Antwerp University Hospital, Antwerp, Belgium.,CORE, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
| | - Sven M Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
| | - Wilhelmus J Kwanten
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
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Khoury J, Zohar Y, Shehadeh N, Saadi T. Glycogenic hepatopathy. Hepatobiliary Pancreat Dis Int 2018; 17:113-118. [PMID: 29709217 DOI: 10.1016/j.hbpd.2018.02.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 11/24/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Glycogenic hepatopathy (GH) is a disorder associated with uncontrolled diabetes mellitus, most commonly type 1, expressed as right upper quadrant abdominal pain, hepatomegaly and increased liver enzymes. The diagnosis may be difficult, because laboratory and imaging tests are not pathognomonic. Although GH may be suggested based on clinical presentation and imaging studies, the gold standard for diagnosis is a liver biopsy, showing a significant accumulation of glycogen within the hepatocytes. GH may be diagnosed also after elevated liver enzymes in routine blood tests. GH usually regresses after tight glycemic control. Progression to end-stage liver disease has never been reported. This review aims to increase the awareness to this disease, to suggest a pathway for investigation that may reduce the use of unnecessary tests, especially invasive ones. DATA SOURCES A PubMed database search (up to July 1, 2017) was done with the words "glycogenic hepatopathy", "hepatic glycogenosis", "liver glycogenosis" and "diabetes mellitus-associated glycogen storage hepatopathy". Articles in which diabetes mellitus-associated liver glycogen accumulation was described were included in this review. RESULTS A total of 47 articles were found, describing 126 patients with GH. Hepatocellular disturbance was more profound than cholestatic disturbance. No synthetic failure was reported. CONCLUSIONS GH may be diagnosed conservatively, based on corroborating medical history, physical examination, laboratory tests, imaging studies and response to treatment, even without liver biopsy. In case of doubt about the diagnosis or lack of clinical response to treatment, a liver biopsy may be considered. There is no role for noninvasive tests like fibroscan or fibrotest for the diagnosis of GH or for differentiation of this situation from nonalcoholic fatty liver disease.
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Affiliation(s)
- Johad Khoury
- Internal Medicine B, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Liver Unit, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Yaniv Zohar
- Department of Pathology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Naim Shehadeh
- Meyer Children's Hospital of Haifa, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Institute of Diabetes, Endocrinology and Metabolism, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Tarek Saadi
- Liver Unit, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Department of Gastroenterology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
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Bannasch P, Ribback S, Su Q, Mayer D. Clear cell hepatocellular carcinoma: origin, metabolic traits and fate of glycogenotic clear and ground glass cells. Hepatobiliary Pancreat Dis Int 2017; 16:570-594. [PMID: 29291777 DOI: 10.1016/s1499-3872(17)60071-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 08/14/2017] [Indexed: 02/05/2023]
Abstract
Clear cell hepatocellular carcinoma (CCHCC) has hitherto been considered an uncommon, highly differentiated variant of hepatocellular carcinoma (HCC) with a relatively favorable prognosis. CCHCC is composed of mixtures of clear and/or acidophilic ground glass hepatocytes with excessive glycogen and/or fat and shares histology, clinical features and etiology with common HCCs. Studies in animal models of chemical, hormonal and viral hepatocarcinogenesis and observations in patients with chronic liver diseases prone to develop HCC have shown that the majority of HCCs are preceded by, or associated with, focal or diffuse excessive storage of glycogen (glycogenosis) which later may be replaced by fat (lipidosis/steatosis). In ground glass cells, the glycogenosis is accompanied by proliferation of the smooth endoplasmic reticulum, which is closely related to glycogen particles and frequently harbors the hepatitis B surface antigen (HBsAg). From the findings in animal models a sequence of changes has been established, commencing with preneoplastic glycogenotic liver lesions, often containing ground glass cells, and progressing to glycogen-poor neoplasms via various intermediate stages, including glycogenotic/lipidotic clear cell foci, clear cell hepatocellular adenomas (CCHCA) rich in glycogen and/or fat, and CCHCC. A similar process seems to take place in humans, with clear cells frequently persisting in CCHCC and steatohepatitic HCC, which presumably represent intermediate stages in the development rather than particular variants of HCC. During the progression of the preneoplastic lesions, the clear and ground glass cells transform into cells characteristic of common HCC. The sequential cellular changes are associated with metabolic aberrations, which start with an activation of the insulin signaling cascade resulting in pre-neoplastic hepatic glycogenosis. The molecular and metabolic changes underlying the glycogenosis/lipidosis are apparently responsible for the dramatic metabolic shift from gluconeogenesis to the pentose phosphate pathway and Warburg-type glycolysis, which provide precursors and energy for an ever increasing cell proliferation during progression.
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Affiliation(s)
| | - Silvia Ribback
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald, Germany
| | - Qin Su
- Cell Marque, Millipore-Sigma Rocklin, USA
| | - Doris Mayer
- German Cancer Research Center, Heidelberg, Germany
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Glycogenic Hepatopathy in Type 1 Diabetes Mellitus. Case Reports Hepatol 2015; 2015:236143. [PMID: 26347835 PMCID: PMC4546963 DOI: 10.1155/2015/236143] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 07/28/2015] [Indexed: 12/16/2022] Open
Abstract
Glycogenic hepatopathy is a rare cause of high transaminase levels in type 1 diabetes mellitus. This condition, characterized by elevated liver enzymes and hepatomegaly, is caused by irreversible and excessive accumulation of glycogen in hepatocytes. This is a case report on a 19-year-old male case, diagnosed with glycogenic hepatopathy. After the diagnosis was documented by liver biopsy, the case was put on glycemic control which led to significant decline in hepatomegaly and liver enzymes. It was emphasized that, in type 1 diabetes mellitus cases, hepatopathy should also be considered in the differential diagnoses of elevated liver enzyme and hepatomegaly.
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Julián MT, Alonso N, Ojanguren I, Pizarro E, Ballestar E, Puig-Domingo M. Hepatic glycogenosis: An underdiagnosed complication of diabetes mellitus? World J Diabetes 2015; 6:321-325. [PMID: 25789113 PMCID: PMC4360425 DOI: 10.4239/wjd.v6.i2.321] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Revised: 10/15/2014] [Accepted: 12/19/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatic glycogenosis (HG) is characterized by excessive glycogen accumulation in hepatocytes and represents a hepatic complication of diabetes that particularly occurs in patients with longstanding poorly controlled type 1 diabetes (T1D). HG has been reported to be a very rare disease, although it is believed to be extremely underdiagnosed because it is not possible to distinguish it from non-alcoholic fatty liver disease (NAFLD) unless a liver biopsy is performed. In contrast to HG, NAFLD is characterized by liver fat accumulation and is the more likely diagnosis for patients with type 2 diabetes and metabolic syndrome. The pathogenesis of HG involves the concomitant presence of insulin and excess glucose, which increases glycogen storage in the liver. HG is characterized by a transient elevation in liver transaminases and hepatomegaly. Differentiating between these two conditions is of the utmost importance because HG is a benign disease that is potentially reversible by improving glycemic control, whereas NAFLD can progress to cirrhosis. Therefore, HG should be suspected when liver dysfunction occurs in patients with poorly controlled T1D. The aim of this article is to review the epidemiology, clinical characteristics, pathogenesis and histology of HG.
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Bannasch P. Glycogenotic hepatocellular carcinoma with glycogen-ground-glass hepatocytes: A heuristically highly relevant phenotype. World J Gastroenterol 2012; 18:6701-6708. [PMID: 23239906 PMCID: PMC3520157 DOI: 10.3748/wjg.v18.i46.6701] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Revised: 09/21/2012] [Accepted: 11/15/2012] [Indexed: 02/06/2023] Open
Abstract
Glycogenotic hepatocellular carcinoma (HCC) with glycogen-ground-glass hepatocytes has recently been described as an allegedly “novel variant” of HCC, but neither the historical background nor the heuristic relevance of this observation were put in perspective. In the present contribution, the most important findings in animal models and human beings related to the emergence and further evolution of excessively glycogen storing (glycogenotic) hepatocytes with and without ground glass features during neoplastic development have been summarized. Glycogenotic HCCs with glycogen-ground-glass hepatocytes represent highly differentiated neoplasms which contain subpopulations of cells phenotypically resembling those of certain types of preneoplastic hepatic foci and benign hepatocellular neoplasms. It is questionable whether the occurrence of glycogen-ground-glass hepatocytes in a glycogenotic HCC justifies its classification as a specific entity. The typical appearance of ground-glass hepatocytes is due to a hypertrophy of the smooth endoplasmic reticulum, which is usually associated with an excessive storage of glycogen and frequently also with an expression of the hepatitis B surface antigen. Sequential studies in animal models and observations in humans indicate that glycogen-ground-glass hepatocytes are a facultative, integral part of a characteristic cellular sequence commencing with focal hepatic glycogenosis potentially progressing to benign and malignant neoplasms. During this process highly differentiated glycogenotic cells including ground-glass hepatocytes are gradually transformed via various intermediate stages into poorly differentiated glycogen-poor, basophilic (ribosome-rich) cancer cells. Histochemical, microbiochemical, and molecular biochemical studies on focal hepatic glycogenosis and advanced preneoplastic and neoplastic lesions in tissue sections and laser-dissected specimens in rat and mouse models have provided compelling evidence for an early insulinomimetic effect of oncogenic agents, which is followed by a fundamental metabolic switch from gluconeogenesis towards the pentose-phosphate pathway and the Warburg type of glycolysis during progression from preneoplastic hepatic glycogenosis to the highly proliferative malignant phenotype.
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Abstract
Islet autoimmunity in type 1 diabetes results in the loss of the pancreatic β-cells. The consequences of insulin deficiency in the portal vein for liver fat are poorly understood. Under normal conditions, the portal vein provides 75% of the liver blood supply. Recent studies suggest that non-alcoholic fatty liver disease (NAFLD) may be more common in type 1 diabetes than previously thought, and may serve as an independent risk marker for some chronic diabetic complications. The pathogenesis of NAFLD remains obscure, but it has been hypothesized that hepatic fat accumulation in type 1 diabetes may be due to lipoprotein abnormalities, hyperglycemia-induced activation of the transcription factors carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein 1c (SREBP-1c), upregulation of glucose transporter 2 (GLUT2) with subsequent intrahepatic fat synthesis, or a combination of these mechanisms. Novel approaches to non-invasive determinations of liver fat may clarify the consequences for liver metabolism when the pancreas has ceased producing insulin. This article aims to review the factors potentially contributing to hepatic steatosis in type 1 diabetes, and to assess the feasibility of using liver fat as a prognostic and/or diagnostic marker for the disease. It provides a background and a case for possible future studies in the field.
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Affiliation(s)
- Simon E Regnell
- Lund University, CRC, Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Skåne University Hospital, Malmö, Sweden.
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Aljabri KS, Bokhari SA, Fageeh SM, Alharbi AM, Abaza MA. Glycogen hepatopathy in a 13-year-old male with type 1 diabetes. Ann Saudi Med 2011; 31:424-7. [PMID: 21727748 PMCID: PMC3156523 DOI: 10.4103/0256-4947.81803] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Glycogenic hepatopathy (GH ) is a rare cause of serum transaminase elevations in type 1 diabetes mellitus. We describe a 13-year-old male with a history of poorly controlled type 1 diabetes mellitus who presented with hepatomegaly and severe transaminase flares. Liver histology confirmed GH. Treatment consists of improving glycemic control. Hepatomegaly due to excess glycogen storage in poorly controlled type 1 diabetics has been associated with younger patients with poor glycemic control, occurring about 2-4 weeks after starting insulin treatment, and resolving upon glucose stabilization. We conclude that glycogenic hepatopathy can cause hepatomegaly and significant transaminase elevations in individuals with type I diabetes mellitus, The recovery of severe transaminase elevations in this patient illustrates the more benign course of GH, which is a condition with a far better prognosis. Clinician awareness of GH should prevent diagnostic delay and will provide better insight into the prevalence of GH.
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Affiliation(s)
- Khalid S Aljabri
- Department of Medicine, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.
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Fridell JA, Saxena R, Chalasani NP, Goggins WC, Powelson JA, Cummings OW. Complete reversal of glycogen hepatopathy with pancreas transplantation: two cases. Transplantation 2007; 83:84-6. [PMID: 17220798 DOI: 10.1097/01.tp.0000239510.27872.07] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Glycogen hepatopathy is the pathological overloading of hepatocytes with glycogen that is associated with poorly controlled diabetes mellitus. Clinically, it presents with abdominal discomfort, tender hepatomegaly and elevated transaminases. In this report, we describe our experience with two cases of type I diabetes mellitus and glycogen hepatopathy. The patients underwent isolated pancreas transplantation, following which, we have been able to demonstrate complete histological resolution of glycogen hepatopathy associated with control of glucose metabolism.
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Affiliation(s)
- Jonathan A Fridell
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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Torbenson M, Chen YY, Brunt E, Cummings OW, Gottfried M, Jakate S, Liu YC, Yeh MM, Ferrell L. Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus. Am J Surg Pathol 2006; 30:508-13. [PMID: 16625098 DOI: 10.1097/00000478-200604000-00012] [Citation(s) in RCA: 146] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Reported are the clinical and pathologic features of glycogenic hepatopathy, a pathologic overloading of hepatocytes with glycogen that is associated with poorly controlled diabetes mellitus. Fourteen cases were studied by stains, including hematoxylin and eosin, trichrome, periodic acid-Schiff, and periodic acid-Schiff with diastase. Ultrastructural analysis was performed in 2 cases. Medical records were reviewed for clinical presentations, laboratory findings, and clinical outcomes. The individuals ranged from 8 to 25 years of age. All had type I diabetes mellitus with poor glycemic control. The clinical presentations included hepatomegaly, abdominal pain, and elevated transaminases (range, 50-1600 IU/L). The transaminases were dramatically elevated in 3 cases to greater than 10 times the upper limit of normal. All biopsies showed diffusely pale staining hepatocytes on hematoxylin and eosin stains, with excessive glycogen accumulation demonstrated by periodic acid-Schiff stains. Ultrastructural examination revealed marked glycogen accumulation in the cytoplasm and nuclei. Most cases showed no evidence for fatty liver disease: steatosis was absent in 12 of 14 cases, simple steatosis was seen in 1 of 14 cases, and mild steatohepatitis was present in 1 of 14 cases. Mallory hyaline was absent in all cases, acidophil bodies were only rarely seen, and inflammation was absent or minimally present. Fibrosis was typically absent, with only 2 cases demonstrating focal mild fibrosis. Three patients had adequate follow-up and demonstrated improvement of liver enzyme levels with control of blood glucose. We conclude that glycogenic hepatopathy can cause hepatomegaly and significant transaminase elevations in individuals with type I diabetes mellitus. The pathology is distinct from steatohepatitis.
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Affiliation(s)
- Michael Torbenson
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
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Tomihira M, Kawasaki E, Nakajima H, Imamura Y, Sato Y, Sata M, Kage M, Sugie H, Nunoi K. Intermittent and recurrent hepatomegaly due to glycogen storage in a patient with type 1 diabetes: genetic analysis of the liver glycogen phosphorylase gene (PYGL). Diabetes Res Clin Pract 2004; 65:175-82. [PMID: 15223230 DOI: 10.1016/j.diabres.2003.12.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Revised: 02/12/2003] [Accepted: 12/12/2003] [Indexed: 12/13/2022]
Abstract
We report a 19-year-old woman who had a history of type 1 diabetes with recurrent glycogen accumulation in the liver. During her infantile period she presented with no hepatomegaly nor growth retardation. On admission she was diagnosed with diabetic ketoacidosis (DKA). She also had hepatomegaly and elevated transaminase levels, but these abnormalities had resolved after administration of insulin. However, 4 weeks after DKA marked hepatomegaly and elevated transaminases were reappeared with simultaneous hypoglycemia which suggested an impaired glycogenolysis in the extraordinary conditions. We supposed the partial deficiency of liver glycogen phosphorylase activity in this patient and analyzed the liver glycogen phosphorylase gene (PYGL). Deduced amino acid sequence of the PYGL in this patient was completely identical to that reported by Burwinkel et al. (Y15233), however, the nucleotide sequence of PYGL cDNA was heterozygous for substitutions at positions Asp339 (GAT to GAC) on exon 9 and Ala703 (GCT to GCC on exon 17, respectively. These SNPs were also screened in 51 Japanese normal subjects by PCR-based direct sequencing or PCR-RFLP method. The same genotype observed in this patient was detected in 2 of 51(3.9%) normal subjects. These results suggest that the structure of PYGL coding sequence in this patient is unlikely to account for her excessive liver glycogen accumulation. Further studies including genetic analysis on the promoter region of the gene are necessary to clarify the etiology of susceptibility to excessive liver glycogen storage in patients with type 1 diabetes.
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Affiliation(s)
- Masako Tomihira
- Division of Endocrinology and Metabolism, St. Mary's Hospital, 422 Tsubukuhonmachi, Kurume, Fukuoka, Japan
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POSEN S. Glycogen storage disease with unusual renal lesions; report of a case with autopsy and enzyme studies. AUSTRALASIAN ANNALS OF MEDICINE 1957; 6:238-43. [PMID: 13471424 DOI: 10.1111/imj.1957.6.3.238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/22/2023]
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BEASER SB. Diabetes mellitus. N Engl J Med 1956; 255:223-31; concl. [PMID: 13348844 DOI: 10.1056/nejm195608022550506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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ENDEMIC goitre in South Africa. BRITISH MEDICAL JOURNAL 1955; 2:190-1. [PMID: 14389726 PMCID: PMC1980359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
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