Nucleos(t)ide analogs do not independently influence hepatic fibrosis and portal hypertension beyond viral suppression in CBDL-induced cirrhotic rat

Yu Hsin Hsieh, Hui Chun Huang, Ching Chih Chang, Chiao Lin Chuang, Fa Yauh Lee, Shao Jung Hsu*, Yi Hsiang Huang, Ming Chih Hou, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chronic hepatitis is the major cause of liver cirrhosis and portal hypertension. Several factors affect portal pressure, including liver fibrosis, splanchnic vasodilatation, and pathologic angiogenesis. Nucleos(t)ide analogs (NUCs), the oral antiviral agents, effectively attenuate chronic hepatitis B-related liver cirrhosis and portal hypertension via viral suppression and alleviation of hepatitis. On the other hand, NUCs affect tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and nitric oxide, which participate in fibrogenesis, vasodilatation, and angiogenesis. However, whether NUCs independently influence liver fibrosis and portal hypertension beyond viral suppression is unknown. This study thus aimed to evaluate the influences of three frequently used NUCs in rats with nonviral cirrhosis. Male Sprague-Dawley rats received common bile duct ligation (CBDL) to induce cholestatic cirrhosis and portal hypertension. The rats were randomly allocated into four groups, treated by mouth with lamivudine (30 mg/kg per day), entecavir (0.09 mg/kg per day), tenofovir (50 mg/kg per day), or distilled water (vehicle control) from the 15th day after CBDL. On the 29th day, liver cirrhosisand portal hypertension-related parameters were evaluated. The results showed that chronic NUCs treatment did not affect hemodynamic parameters, plasma TNF-α concentration, and hepatic fibrogenesis protein expressions in rats with nonviral cirrhosis. Though the mesenteric VEGF receptor 2 phosphorylation was downregulated in NUCs-treated groups, the splanchnic angiogenesis was not influenced. In conclusion, lamivudine, entecavir, and tenofovir had no additional effects on liver cirrhosis and portal hypertension in rats with nonviral cirrhosis.

Original languageEnglish
Pages (from-to)260-266
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume367
Issue number2
DOIs
StatePublished - Nov 2018

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