Gastrointestinal Issues in Liver Disease

Olson, Jody C.; Saeian, Kia

doi:10.1016/j.ccc.2016.03.007

Cited by 12 publications

(8 citation statements)

References 68 publications

(64 reference statements)

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“…Gastrointestinal hemorrhages are common complications in patients with advanced liver disease and are directly linked to liver function as many factors in the coagulation pathways are synthesized in liver [ 25 , 26 ]. To understand the absence of accelerated thrombosis in I278T mice and elucidate intestinal hemorrhage in deceased I278T mice on the HMD diet, we performed RNA-seq analysis of liver tissue and found that expression of FXI was significantly decreased.…”

Section: Discussionmentioning

confidence: 99%

Hypermethioninemia Leads to Fatal Bleeding and Increased Mortality in a Transgenic I278T Mouse Model of Homocystinuria

et al. 2020

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Severely elevated plasma homocysteine and methionine lead to thromboembolic events and strokes in homocystinuric (HCU) patients. Mouse models of HCU failed to exhibit prothrombotic phenotype, presumably due to lack of hypermethioninemia. We evaluated the impact of hypermethioninemia together with hyperhomocysteinemia on murine HCU phenotype and compared the efficacy of the current and novel therapies for HCU. High methionine intake decreased survival of I278T mice, which died from intestinal bleeding with hepatic and pancreatic failure. I278T mice on normal or increased methionine intake developed endothelial dysfunction, but paradoxically demonstrated delayed occlusion in an induced arterial thrombosis model. RNA-seq analysis suggested that expression of coagulation factor XI (FXI) is downregulated in livers of I278T mice. Indeed, plasma concentrations of FXI were decreased in I278T mice on normal diet and further reduced by increased methionine intake. Dietary methionine restriction normalized the observed phenotype. Similarly, treatment with OT-58, a novel enzyme therapy for HCU, corrected the phenotype in I278T mice regardless of their dietary methionine intake. Hypermethioninemia does not contribute to prothrombotic phenotype in murine HCU. Downregulation of FXI may contribute to the lack of prothrombotic tendency in I278T mice. Methionine restriction or treatment with OT-58 corrects vascular disease in the I278T mouse model of HCU.

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Section: Discussionmentioning

confidence: 99%

Hypermethioninemia Leads to Fatal Bleeding and Increased Mortality in a Transgenic I278T Mouse Model of Homocystinuria

et al. 2020

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“…The severe and life-threatening complications of liver fibrosis have made it a global challenge (3). However, limited agents are available to treat liver fibrosis, and liver transplantation remains the only effective therapy, particularly for end-stage liver disease (4).…”

Section: Introductionmentioning

confidence: 99%

Expression of cyclooxygenase-2 is correlated with lncRNA-COX-2 in cirrhotic mice induced by carbon tetrachloride

Tang

Gao

Wen

et al. 2017

Molecular Medicine Reports

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Multiple long non-coding RNAs (lncRNAs) have been demonstrated to be involved in liver disease. Increased cyclooxygenase-2 (COX-2) levels have also been reported to be involved in the progression of liver cirrhosis. In the present study, the correlations between lncRNA-COX-2 RNA expression levels, COX-2 mRNA expression levels and liver fibrosis were examined. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) in mice for 2 months (CCl4-2M) or 3 months (CCl4-3M). Liver histopathological evaluation was conducted using hematoxylin and eosin and Masson trichrome staining. Hepatic expression of COX-2 and lncRNA-COX-2 was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. Compared with the control group, fibrotic areas were increased four and nine times in the CCl4-2M group and the CCl4-3M group, respectively. LncRNA-COX-2 and COX-2 upregulation were observed in the cirrhotic liver. COX-2 mRNA expression levels and lncRNA-COX-2 RNA expression levels were significantly positively correlated with the fibrotic area. In addition, COX-2 mRNA expression was significantly positively correlated with lncRNA-COX-2 expression. These results suggest that expression of COX-2 and lncRNA-COX-2 increased with the progression of liver fibrosis. LncRNA-COX-2 may potentially be considered as a novel therapeutic target for liver fibrosis.

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“…Because of low numbers, statistical analysis was not performed to evaluate for site dependent differences in occurrence of erosions or ulcers in each disease category. The median (range) total endoscopic score was 7 [6][7][8][9][10][11] in the inflammation group, 10 (9-30) in the cirrhosis group, 7 [6][7][8][9][10][11][12][13][14][15][16] in the congenital group, and 6 (6-30) in the other group, with no significant difference detected among the groups (P = .21; Figure 2; Table S1).…”

Section: Discussionmentioning

confidence: 99%

Gastroduodenal ulceration in dogs with liver disease

O'Kell

Gallagher

Cooke

2022

Veterinary Internal Medicne

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Background: Liver disease is frequently cited as a cause of gastroduodenal ulceration (GDU) in dogs but studies regarding GDU and liver disease are limited.Objectives: To document the presence of GDU in dogs with liver disease.Animals: Forty dogs that underwent liver biopsy, computed tomographic (CT) angiography or both at the University of Florida Small Animal Hospital to diagnose congenital or acquired liver disease.Methods: Cross-sectional study. Dogs had gastroduodenoscopy performed with photographic and video documentation in a standardized fashion. Lesions (hemorrhage, erosions, ulcers) in the esophagus, stomach, and duodenum were scored based on a grading scale. Presence of esophageal varices was recorded. Dogs were categorized into 4 groups according to cause of liver disease (inflammatory disease, cirrhosis, congenital, other). Presence or absence of ulcers, erosions or both as well as total endoscopic scores were compared among groups.Results: Forty dogs were enrolled with the following distribution: 13 congenital, 13 inflammatory, 3 cirrhosis, and 11 other. Four dogs had GDU (10%; 95% confidence interval [CI], 3%-24%) and 6 dogs had erosions (15%; 95% CI, 6%-30%). No difference was found in total endoscopic score (P = .21) or in the proportion of dogs with ulcers, erosions or both versus those without (P = .25) among the groups.Conclusions and Clinical Importance: Gastroduodenal ulceration was found in 10% of dogs with liver disease in this population. Additional studies are warranted to confirm these findings in larger numbers of dogs with specific disease etiologies.

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Gastrointestinal Issues in Liver Disease

Cited by 12 publications

References 68 publications

Hypermethioninemia Leads to Fatal Bleeding and Increased Mortality in a Transgenic I278T Mouse Model of Homocystinuria

Hypermethioninemia Leads to Fatal Bleeding and Increased Mortality in a Transgenic I278T Mouse Model of Homocystinuria

Expression of cyclooxygenase-2 is correlated with lncRNA-COX-2 in cirrhotic mice induced by carbon tetrachloride

Gastroduodenal ulceration in dogs with liver disease

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