Resveratrol suppresses cholestasis-induced liver injury and fibrosis in rats associated with the inhibition of TGFß1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers.

Cholestasis caused by slowing or blockage of bile flow is a serious liver disease that can lead to liver fibrosis and cirrhosis. The link between transforming growth factor beta 1 (TGFß1), Smad family member 3 (Smad3), and microRNA 21 (miR21) in bile duct ligation (BDL)-induced liver fibrosis in the presence and absence of the anti-inflammatory and antioxidant compound, resveratrol (RSV), has not been previously studied. Therefore, we tested whether RSV can protect against BDL-induced liver fibrosis associated with the inhibition of the TGFß1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers. The model group of rats had their bile duct ligated (BDL) for 3 weeks before being killed, whereas, the BDL-treated rats were separated into three groups that received 10, 20, and 30 mg/kg RSV daily until the end of the experiment. Using light microscopy and ultrasound examinations, we documented in the BDL group, the development of hepatic injury and fibrosis as demonstrated by hepatocytes necrosis, bile duct hyperplasia, collagen deposition, enlarged liver with increased echogenicity, irregular nodular border and dilated common bile duct, which were more effectively inhibited by the highest used RSV dosage. In addition, RSV significantly (p ≤ 0.0027) inhibited BDL-induced hepatic TGFß1, Smad3, miR21, the profibrogenic biomarker tissue inhibitor of metalloproteinases-1 (TIMP-1), malondialdehyde (MDA), interleukin-17a (IL-17a), and blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. These findings show that RSV at 30 mg/kg substantially protects against BDL-induced liver injuries, which is associated with the inhibition of TGFß1-Smad3-miR21 axis, and biomarkers of profibrogenesis, oxidative stress, and inflammation.

Sarcopenia increases 1-year mortality after surgical resection of hepatocellular carcinoma.

BACKGROUND: Liver resection is a well-recognized modality for hepatocellular carcinoma. Cirrhotic patients are more prone to adverse consequences after liver resection. This work assesses the prognostic significance of sarcopenic hepatocellular carcinoma cases for whom surgical resection was performed. METHODS: The present prospective work included 52 cirrhotic cases. Computed tomography scans were used to determine the skeletal muscle index (SMI) at the plane of the third lumbar vertebra (L3). L3 SMI was used for the definition of sarcopenia. The primary outcome measure was the predictive value of sarcopenia for 1-year post-hepatectomy mortality. RESULTS: Sarcopenia was diagnosed in 27 patients (51.9%). All patients had a Child-Turcotte-Pugh score A. At a 1-year follow-up, 20 cases died; that is the 1-year mortality rate was 38.5%. Sarcopenia was more commonly associated with older age and non-viral causes of cirrhosis. The risk of 1-year mortality is 7.6 times higher in sarcopenic patients with a risk ratio of 3.7 (95% confidence interval 1.4-9.6). CONCLUSION: Sarcopenia diagnosed using L3 SMI is an independent prognostic factor for 1-year deaths in cases with hepatic malignancy with Child-Turcotte-Pugh score A undergoing surgical resection.