Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I

Caldéraro, Julien; Labrune, Philippe; Morcrette, Guillaume; Rebouissou, Sandra; Franco, Dominique; Prévôt, Sophie; Quaglia, Alberto; Bédossa, Pierre; Libbrecht, Louis; Terracciano, Luigi; Smit, Gerrit; Bioulac‐Sage, Paulette; Zucman‐Rossi, Jessica

doi:10.1016/j.jhep.2012.09.030

Cited by 146 publications

(134 citation statements)

References 36 publications

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“…The risk of malignancy was clearly overestimated in the group with GSD because the literature considers this underlying disease as a risk factor for the MT of adenomas. (8) These data are supported by a high frequency of b-CAT-mutated adenomas (5,7) in this pathology. NOTE: Data are given as n (%).…”

Section: Chiche Et Al Liver Transplantation April 2016mentioning

confidence: 53%

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Liver transplantation for adenomatosis: European experience

et al. 2016

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The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case‐by‐case basis. In this report, we propose a simplified approach to this decision‐making process.

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Section: Chiche Et Al Liver Transplantation April 2016mentioning

confidence: 53%

“…(4)(5)(6)(7)(8)(9)(10) However, this surgical approach can be difficult or impossible in cases of LA due to the large number of adenomas. Therefore, liver transplantations (LTs) have been reported in the literature.…”

Section: Liver Transplantation 22 516-526 2016 Aasldmentioning

confidence: 99%

Liver transplantation for adenomatosis: European experience

et al. 2016

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“…Quantitative RT-PCR was performed as previously described, 16 using primers and probe sets from Applied Biosystems: R18S (Ribosomal 18S; 4352930), FABP1 (Hs00203685_m1), UGT2B7 (Hs00426592_m1), GLUL (Hs00374213_m1), LGR5 (Hs00173664_m1), CRP (Hs00265044_m1), and SAA2 (Hs01667582_m1). Gene expression was normalized to ribosomal 18S mRNA, and expression level of the tumor sample was compared with the mean level of the corresponding gene expression in normal liver tissues (n = 4), and expressed as an n-fold ratio.…”

Section: Rna Extraction and Quantitative Real-time Pcrmentioning

confidence: 99%

Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis

et al. 2016

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Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed welldifferentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n = 8; STAT3, n = 1; and GNAS, n = 1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis.

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“…Thus a large proportion of patients older than 20 years show hepatic tumors and/or progressive chronic renal disease, which are the leading causes of morbidity in GSD1 patients with aging. The first hepatic tumors generally appear during adolescence and are mainly classified as hepatocellular adenomas (HCA), which can transform into hepatocellular carcinomas (HCC) (Rake et al 2002b;Franco et al 2005;Wang et al 2011;Calderaro et al 2013). Tumor resection or liver transplantation are recommended if the tumors are associated with serious compression or hemorrhage, or show signs of malignant transformation into HCC (Rake et al 2002a;Reddy et al 2009).…”

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confidence: 99%

Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease

Rajas

Clar

Gautier‐Stein

et al. 2014

J of Inher Metab Disea

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Patients with glycogen storage diseases type 1 (GSD1) suffer from life-threatening hypoglycaemia, when left untreated. Despite an intensive dietary treatment, patients develop severe complications, such as liver tumors and renal failure, with aging. Until now, the animal models available for studying the GSD1 did not survive after weaning. To gain further insights into the molecular mechanisms of the disease and to evaluate potential treatment strategies, we have recently developed novel mouse models in which the catalytic subunit of glucose-6 phosphatase (G6pc) is deleted in each glucose-producing organ specifically. For that, B6.G6pc(ex3lox/ex3lox) mice were crossed with transgenic mice expressing a recombinase under the control of the serum albumin, the kidney androgen protein or the villin promoter, in order to obtain liver, kidney or intestine G6pc(-/-) mice, respectively. As opposed to total G6pc knockout mice, tissue-specific G6pc deficiency allows mice to maintain their blood glucose by inducing glucose production in the other gluconeogenic organs. Even though it is considered that glucose is produced mainly by the liver, liver G6pc(-/-) mice are perfectly viable and exhibit the same hepatic pathological features as GSD1 patients, including the late development of hepatocellular adenomas and carcinomas. Interestingly, renal G6pc(-/-) mice developed renal symptoms similar to the early human GSD1 nephropathy. This includes glycogen overload that leads to nephromegaly and morphological and functional alterations in the kidneys. Thus, our data suggest that renal G6Pase deficiency per se is sufficient to induce the renal pathology of GSD1. Therefore, these new mouse models should allow us to improve the strategies of treatment on both nutritional and pharmacological points of view.

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Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I

Cited by 146 publications

References 36 publications

Liver transplantation for adenomatosis: European experience

Liver transplantation for adenomatosis: European experience

Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis

Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease

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