PT  - JOURNAL ARTICLE
AU  - Yu-Hsin Hsieh
AU  - Hui-Chun Huang
AU  - Ching-Chih Chang
AU  - Chiao-lin Chuang
AU  - Fa-Yauh Lee
AU  - Shao-Jung Hsu
AU  - Yi-Hsiang Huang
AU  - Ming-Chih Hou
AU  - Shou-Dong Lee
TI  - Nucleos(t)ide analogs do not independently influence hepatic fibrosis and portal hypertension beyond viral suppression in CBDL-induced cirrhotic rat
AID  - 10.1124/jpet.118.250431
DP  - 2018 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.118.250431
4099  - http://jpet.aspetjournals.org/content/early/2018/09/07/jpet.118.250431.short
4100  - http://jpet.aspetjournals.org/content/early/2018/09/07/jpet.118.250431.full
AB  - Chronic hepatitis is the major cause of liver cirrhosis and portal hypertension. Several factors affect portal pressure, including liver fibrosis, splanchnic vasodilatation and pathological 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 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 non-viral 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 per oral with lamivudine (30 mg/kg/day), entecavir (0.09 mg/kg/day), tenofovir (50 mg/kg/day) or distilled water (vehicle control) since the 15th day after CBDL. On the 29th day, liver cirrhosis and 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 non-viral cirrhosis. Though the mesenteric VEGF receptor 2 phosphorylation was down-regulated 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 non-viral cirrhosis.