Xingshun Qi

Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with symptomatic portal hypertension in liver cirrhosis

BACKGROUND & AIMSnData on the management of portal vein thrombosis (PVT) in patients with decompensated cirrhosis are extremely limited, particularly in the cases of the transjugular intrahepatic portosystemic shunt (TIPS). We assessed the outcome of TIPS for PVT in patients with cirrhosis and symptomatic portal hypertension and determined the predictors of technical success and survival.nnnMETHODSnIn the retrospective study, 57 consecutive patients receiving TIPS were enrolled between December 2001 and September 2008. All were diagnosed with chronic PVT, and 30 had portal cavernoma. Indications for TIPS were variceal hemorrhage (n = 56) and refractory ascites (n = 1).nnnRESULTSnTIPS were successfully placed in 75% of patients (43/57). The independent predictors of technical success included portal cavernoma, and the degree of thrombosis within the main portal vein (MPV), the portal vein branches, and the superior mesenteric vein. Only one patient died of severe procedure-related complication. The cumulative 1-year shunt dysfunction and hepatic encephalopathy rates were 21% and 25%, respectively. The cumulative 1- and 5-year variceal re-bleeding rates differed significantly between the TIPS success and failure groups (10% and 28% versus 43% and 100%, respectively; p = 0.0004), while the cumulative 1- and 5-year survival rates were similar between the two groups (86% and 77% versus 78% and 62%, respectively; p = 0.34). The independent predictor of survival in PVT patients with decompensated cirrhosis was the degree of MPV occlusion (hazard ratio 0.189, 95% CI 0.042-0.848).nnnCONCLUSIONSnTIPS should be considered a safe and feasible alternative therapy for chronic PVT in selected patients with decompensated cirrhosis. Both technical success and survival were closely associated with the degree of MPV occlusion.

Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma.

Recurrence and metastasis remain the most common causes of lethal outcomes in hepatocellular carcinoma (HCC) after curative resection. Thus, it is critical to discover the mechanisms underlying HCC metastasis. Forkhead box C1 (FoxC1), a member of the Fox family of transcription factors, induces epithelial‐mesenchymal transition (EMT) and promotes epithelial cell migration. However, the role of FoxC1 in the progression of HCC remains unknown. Here, we report that FoxC1 plays a critical role in HCC metastasis. FoxC1 expression was markedly higher in HCC tissues than in adjacent noncancerous tissues. HCC patients with positive FoxC1 expression had shorter overall survival times and higher recurrence rates than those with negative FoxC1 expression. FoxC1 expression was an independent, significant risk factor for recurrence and survival after curative resection. FoxC1 overexpression induced changes characteristic of EMT and an increase in HCC cell invasion and lung metastasis. However, FoxC1 knockdown inhibited these processes. FoxC1 transactivated Snai1 expression by directly binding to the Snai1 promoter, thereby leading to the inhibition of E‐cadherin transcription. Knockdown of Snai1 expression significantly attenuated FoxC1‐enhanced invasion and lung metastasis. FoxC1 expression was positively correlated with Snai1 expression, but inversely correlated with E‐cadherin expression in human HCC tissues. Additionally, a complementary DNA microarray, serial deletion, site‐directed mutagenesis, and a chromatin immunoprecipitation assay confirmed that neural precursor cell expressed, developmentally down‐regulated 9 (NEDD9), which promotes the metastasis of HCC cells, is a direct transcriptional target of FoxC1 and is involved in FoxC1‐mediated HCC invasion and metastasis. Conclusions: FoxC1 may promote HCC metastasis through the induction of EMT and the up‐regulation of NEDD9 expression. Thus, FoxC1 may be a candidate prognostic biomarker and a target for new therapies. (HEPATOLOGY 2013;)

Patency and clinical outcomes of transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stents versus bare stents: A meta-analysis

Background and Aim:u2002 Transjugular intrahepatic portosystemic shunt (TIPS) with polytetrafluoroethylene‐(PTFE)‐covered stent has been increasingly used for patients with complications of portal hypertension. It is still debated whether the new endoprostheses will improve some clinical outcomes (except for shunt patency) compared to the bare stents. The aims of our meta‐analysis were to explore the patency and clinical outcomes of TIPS with PTFE‐covered stent‐grafts versus bare stents.

Predictors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in cirrhotic patients: A systematic review

Background and Aim:u2002 Hepatic encephalopathy (HE) is a very common complication in patients after transjugular intrahepatic portosystemic shunt (TIPS). The purpose of this study is to determine the most robust predictors of post‐TIPS HE by performing a systematic review of studies that identified the risk factors for patients with post‐TIPS HE.

Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression.

Forkhead box Q1 (FoxQ1) is a master regulator of tumor metastasis. However, the molecular mechanism of FoxQ1 in regulating hepatocellular carcinoma (HCC) metastasis remains unknown. Here we report a novel function for FoxQ1 in modifying the tumor microenvironment to promote HCC metastasis. FoxQ1 expression was an independent and significant risk factor for the recurrence and survival in two independent cohorts totaling 1,002 HCC patients. FoxQ1 induced epithelial‐mesenchymal transition (EMT) through the transactivation of ZEB2 expression by directly binding to the ZEB2 promoter. Knockdown of ZEB2 decreased FoxQ1‐enhanced HCC metastasis, whereas up‐regulation of ZEB2 rescued the decreased metastasis induced by FoxQ1 knocking down. Additionally, serial deletion, site‐directed mutagenesis, and a chromatin immunoprecipitation assays showed that VersicanV1, which promoted HCC metastasis and macrophage attraction, was a direct transcriptional target of FoxQ1. FoxQ1‐induced VersicanV1 expression promoted the secretion of chemokine (C‐C motif) ligand 2 (CCL2) from HCC cells. Chemotaxis assay showed that the culture media from FoxQ1‐overexpressing HCC cells increased the migratory activity of the macrophages. Inhibition of VersicanV1 and CCL2 expression significantly inhibited FoxQ1‐mediated macrophage migration. In animal studies, the up‐regulation of FoxQ1 in HCC cells promoted HCC metastasis and intratumoral tumor associated macrophage (TAM) infiltration, whereas knockdown of VersicanV1 reduced FoxQ1‐mediated HCC metastasis and intratumoral TAM infiltration. Depletion of macrophages using clodronate liposomes dramatically decreased FoxQ1‐enhanced HCC metastasis. In human HCC tissues, FoxQ1 expression was positively correlated with ZEB2 and VersicanV1 expression and intratumoral TAM infiltration. Patients with positive coexpression of FoxQ1 and ZEB2, FoxQ1, and VersicanV1, or FoxQ1 and intratumoral TAMs were associated with poorer prognosis. Conclusion: FoxQ1 promotes HCC metastasis by transactivating ZEB2 and VersicanV1 expression, resulting in the induction of EMT and the recruitment of macrophage infiltration. (Hepatology 2014;59:958–973)

Prevalence of the JAK2V617F mutation in Chinese patients with Budd‐Chiari syndrome and portal vein thrombosis: A prospective study

Background and Aim:u2002 Whether routine screening for the JAK2V617F mutation should be performed in Chinese patients with Budd‐Chiari syndrome (BCS) and portal vein thrombosis (PVT) is unclear. Therefore, we aimed to evaluate the prevalence of the JAK2V617F mutation in such patients and to explore the risk factors associated with the mutation.

Meta-analysis: the significance of screening for JAK2V617F mutation in Budd–Chiari syndrome and portal venous system thrombosis

Aliment Pharmacol Ther 2011; 33: 1087–1103

L-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis: a meta-analysis of randomized controlled trials

Several randomized, controlled trials that evaluated the effectiveness of l‐ornithine‐l‐aspartate (LOLA) in the treatment of hepatic encephalopathy (HE) have been published recently. The purpose of this study was to update the meta‐analysis to reevaluate the safety and efficacy of LOLA on HE in patients with cirrhosis.

Transjugular Intrahepatic Portosystemic Shunt for Portal Cavernoma with Symptomatic Portal Hypertension in Non-cirrhotic Patients

BackgroundPortal cavernoma is regarded as a contraindication to transjugular intrahepatic portosystemic shunt (TIPS).AimTo evaluate the feasibility, safety, and efficacy of TIPS for symptomatic portal hypertension in non-cirrhotic patients with portal cavernoma.MethodsBetween July 2002 and December 2009, 46 consecutive non-cirrhotic patients with portal cavernoma were admitted to our center. Twenty patients presented with variceal rebleeding (nxa0=xa020) and refractory ascites (nxa0=xa01), and were treated with TIPS. They were followed until either death or July 2010. Data were compared using the Fisher’s exact test or t test.ResultsTIPS were successfully placed in 35% (7/20) of patients via a transjugular approach alone (nxa0=xa01), a combined transjugular/transhepatic approach (nxa0=xa04), and a combined transjugular/transsplenic approach (nxa0=xa02). TIPS were inserted in a large collateral vein in two patients in whom recanalization of the occluded main portal vein was impossible. Procedure-related complication was hepatic capsule perforation in one patient who was cured by medical therapy alone. Shunt dysfunction occurred in two patients, but TIPS revision was failed in one of them. Portosystemic pressure gradient was significantly reduced in TIPS success group (26.3xa0±xa01.1 vs. 12.4xa0±xa01.1xa0mmHg, pxa0<xa00.001). The incidence of variceal bleeding in TIPS success group is lower than that in TIPS failure group (14 vs. 69%, pxa0=xa00.057). In TIPS success group, two patients died of systemic infection and accident, respectively. In TIPS failure group, two patients died of liver failure.ConclusionsTIPS procedures are feasible and safe in selected patients with portal cavernoma. Successful TIPS insertions may decrease the incidence of variceal rebleeding.

Studies on immunoregulatory and anti-tumor activities of a polysaccharide from Salvia miltiorrhiza Bunge.

In this study, we purified and characterized a polysaccharide (SMP-W1) from Salvia miltiorrhiza and investigated its anticancer and immunoregulatory potential in vitro and in vivo. The monosaccharide composition, protein content, uronic acid content, total carbohydrate content, viscosity and molecular weight of SMP-W1 were analyzed. In vitro, SMP-W1 had an antiproliferative effect on hepatocellular carcinoma H22 cells, especially at the high concentration of 400 μg/ml. Simultaneously the polysaccharide SMP-W1 significantly inhibited tumor growth and increased serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in rats, as well as the secretion of TNF-α. In addition, the body weight, spleen index and thymus index in tumor-bearing mice were significantly improved by SMP-W1 treatment. Taken together, these results indicated that SMP-W1 possessed strong in vivo and in vitro anti-tumor activity and improves the immune response in tumor-bearing mice. Therefore, it could be developed as an anti-tumor agent with immunomodulatory activity.