Xiao-Ling Wu

Clinical effects and complications of TIPS for portal hypertension due to cirrhosis: A single center

AIM To determine the clinical effects and complications of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension due to cirrhosis. METHODS Two hundred and eighty patients with portal hypertension due to cirrhosis who underwent TIPS were retrospectively evaluated. Portal trunk pressure was measured before and after surgery. The changes in hemodynamics and the condition of the stent were assessed by ultrasound and the esophageal and fundic veins observed endoscopically. RESULTS The success rate of TIPS was 99.3%. The portal trunk pressure was 26.8 ± 3.6 cmH2O after surgery and 46.5 ± 3.4 cmH2O before surgery (P < 0.01). The velocity of blood flow in the portal vein increased. The internal diameters of the portal and splenic veins were reduced. The short-term hemostasis rate was 100%. Esophageal varices disappeared completely in 68% of patients and were obviously reduced in 32%. Varices of the stomach fundus disappeared completely in 80% and were obviously reduced in 20% of patients. Ascites disappeared in 62%, were markedly reduced in 24%, but were still apparent in 14% of patients. The total effective rate of ascites reduction was 86%. Hydrothorax completely disappeared in 100% of patients. The incidence of post-operative stent stenosis was 24% at 12 mo and 34% at 24 mo. The incidence of post-operative hepatic encephalopathy was 12% at 3 mo, 17% at 6 mo and 19% at 12 mo. The incidence of post-operative recurrent hemorrhage was 9% at 12 mo, 19% at 24 mo and 35% at 36 mo. The cumulative survival rate was 86% at 12 mo, 81% at 24 mo, 75% at 36 mo, 57% at 48 mo and 45% at 60 mo. CONCLUSION TIPS can effectively lower portal hypertension due to cirrhosis. It is significantly effective for hemorrhage of the digestive tract due to rupture of esophageal and fundic veins and for ascites and hydrothorax caused by portal hypertension.

Meta-analysis of the Efficacy of Sorafenib for Hepatocellular Carcinoma

PURPOSE By carrying out a meta-analysis of randomized controlled trials that compared sorafenib or combined chemotherapy with placebo or combined chemotherapy, the effectiveness of sorafenib in hepatocellular carcinoma was evaluated in the present study, which also provided clinical practice guidelines of evidence-based-medicine. METHODS We reviewed PubMed citations concerning sorafenib treating hepatocellular carcinoma in randomized controlled trials from Jan 2000 to July 2012. All the literature was extracted by Cochrane systematic reviews and underwent meta-analysis with RewMan 5.0 software. RESULTS Finally, four papers documenting randomized controlled studies were included. Compared with controls, sorafenib was shown to significantly increase overall survival (OS), time to progression (TTP), and disease control rates (DCR), but not the time to symptom progression (TTSP) in hepatocellular carcinoma patients. The incidence of grade-III/IV adverse reactions, including hand- foot-skin reactions, diarrhea, hypertension and skin rash or desquamation, in sorafenib treatment group was higher than that in controls. However, there was no significant difference in the incidence of hypodynamia between the two groups. CONCLUSIONS Sorafenib exerts significant curative effects in hepatocellular carcinoma.

Lamivudine plus adefovir is a good option for chronic hepatitis B patients with viral relapse after cessation of lamivudine treatment

AimCurrently, there is no consensus on the retreatment recommendation of chronic hepatitis B (CHB) patients with viral rebound after cessation of treatment. In the search of reasonable treatment, we compared the efficacy and safety of adefovir (ADV) plus lamivudine (LAM) and LAM alone for the retreatment of patients with viral relapse but without genotypic resistance after cessation of LAM.MethodsThis is a prospective controlled study, and a total of 53 hepatitis B e antigen (HBeAg)-positive patients with viral rebound but without resistance were received either LAM plus ADV or LAM alone treatment.ResultsAfter 1-year treatment, more patients who received LAM plus ADV than those who received LAM alone had ALT normalization (84% versus 53.6%, P = 0.018) or HBV DNA levels below 1000 copies/mL (80% versus 42.9%, P < 0.006). Seven patients receiving LAM plus ADV had HBeAg seroconversion, as compared with 0 in patients receiving ALM alone (28% versus 0%, P = 0.003). During 1-year retreatment, five patients receiving LAM alone had virological breakthrough and all of them had LAM resistance strains (rtM204V/I), while no LAM- or ADV- associated resistance strains were detected in patients receiving LAM plus ADV. All patients receiving LAM plus ADV were well tolerated, and no serious side effects were noted.ConclusionsPatients treated with LAM plus ADV exhibited significantly greater virological, biochemical and serological responses compared with LAM alone. These data suggested that combination of LAM plus ADV would be a good option for the retreatment of CHB patients with viral relapse after cessation of LAM.

Repeated pancreatitis-induced splenic vein thrombosis leads to intractable gastric variceal bleeding: A case report and review.

Gastric varices (GV) are one of the most common complications for patients with portal hypertension. Currently, histoacryl injection is recommended as the initial treatment for bleeding of GV, and this injection has been confirmed to be highly effective for most patients in many studies. However, this treatment might be ineffective for some types of GV, such as splenic vein thrombosis-related localized portal hypertension (also called left-sided, sinistral, or regional portal hypertension). Herein, we report a case of repeated pancreatitis-induced complete splenic vein thrombosis that led to intractable gastric variceal bleeding, which was treated by splenectomy. We present detailed radiological and pathological data and blood rheology analysis (the splenic artery - after a short gastric vein or stomach vein - gastric coronary vein - portal vein). The pathophysiology can be explained by the abnormal direction of blood flow in this patient. To our knowledge, this is the first reported case for which detailed pathology and blood rheology data are available.

The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates pancreatic cancer

Aim To determine the regulation and function of the neural precursor cell expressed developmentally down regulated protein 4 (NEDD4) in PDAC and to determine its dependency on phosphatase and tensin homolog (PTEN) and PI3K/AKT signaling. Methods We investigated the expression of NEDD4 and the tumor suppressor PTEN in normal immortalized human pancreatic duct epithelial cell line and pancreatic adenocarcinoma (PDAC) cell lines. We further evaluated whether RNAi-mediated depletion of NEDD4 can attenuate PDAC cell proliferation and migration. We subsequently determined the crosstalk between NEDD4 expression and the PTEN/PI3K/AKT signaling pathway. Finally, we determined the mechanism behind differential NEDD4 protein expression in pancreatic cancer. Results The expression of NEDD4 was heterogeneous in PDAC cells, but was significantly higher compared to normal pancreatic ductal epithelial cells. Analogically, PTEN was decreased in the PDAC cells. A combination of MTT assay, wound healing migration assay, and transwell invasion assays confirmed that depletion of NEDD4 decreased the proliferation and migration ability of PDAC cells. Western blot and immunofluorescence results revealed that NEDD4 could affect PTEN/PI3K/AKT signaling pathway in PDAC cells. Polysomal profiling revealed that higher NEDD4 protein expression in PDAC cells was due to undefined mechanism involving translational activation. Conclusions Our results reveal a novel mechanism of upregulation of NEDD4 expression in PDAC. Our findings indicate that NEDD4 potentially plays a critical role in activating the PI3K/AKT signaling pathway by negatively regulating PTEN levels in PDAC cells, which promotes pancreatic cancer cell proliferation and metastasis. Therefore, NEDD4 may be a potential therapeutic target in PDAC.

Alpha-Fetoprotein as a Predictive Marker for Patients with Hepatitis B-Related Acute-on-Chronic Liver Failure

Background and Aims The value of alpha-fetoprotein (AFP) in hepatitis B-related acute-on-chronic liver failure (HBACLF) is not fully understood. The present study aimed to evaluate the prognostic effect of AFP on the prediction of HBACLF outcomes. Methods We investigated a cohort of patients with HBACLF admitted from January 2013 to May 2017. The endpoint of followup was 180 days, death, or liver transplantation. AFP concentrations were estimated on admission. To make statistical comparisons, we used chi-squared test, receiver operating characteristic (ROC) curve analysis, survivorship curve analysis, and Cox proportional-hazards model. Results A total of 92 patients (81.5% male, median age of 46 years) were included. Overall survival rate within 180 days was 43.48%, and the value of log10AFP⁡  ≥ 2.04 indicated a better prognosis with 76.9% specificity and 62.5% sensitivity for patients with HBACLF. Age (HR 1.041), total bilirubin (HR 1.004), log10AFP⁡  (HR 2.155), and INR (HR 1.446) were found to be risk factors of survival. Conclusion AFP could be a useful marker to predict outcomes of acute-on-chronic liver failure.

Gastric Variceal Bleeding Caused by an Arterioportal Fistula Formation After TIPS and Related Complications.

A 70-year-old man was referred to our institution due to 2 days of vomiting and melena, 20 months after the placement of a transjugular intrahepatic portosystemic shunt (TIPS). He underwent TIPS treatment in another hospital due to repeated upper gastrointestinal variceal bleeding (GI) secondary to alcoholic cirrhosis and portal hypertension. Up until this point, abdominal ultrasound follow-up indicated intrahepatic stent patency, and gastrointestinal bleeding did not occur again. Suddenly and without an obvious trigger, he vomited approximately 1000 ml of blood and produced 500 g of black stool without blood clots, cough, sputum, or discomfort. Despite transfusion of 8 u of packed RBCs and 400 ml plasma, hemostasis, rehydration and anti-infective measures, he continued to frequently vomit large volumes and produce bright red stools. Emergency endoscopy revealed severe esophageal and gastric variceal bleeding. His esophageal varices were ligated, and the fundus varices were treated by tissue glue injection. A CT revealed arterial phase enhancement of the right portal vein which was markedly widened, and that arterial phase had developed with intrahepatic stent patency (Fig. 1). Based on these data, we surmised that an arterioportal fistula had formed. Hepatic arteriography and arterioportal fistula occlusion were performed through the femoral artery. Briefly, after the catheter was inserted into the target liver artery end of fistula, a suitable size rim (3 mm, COOK, USA) was put into the fistula, and appropriate gelatin sponge tablets were injected into the fistula. Then, another hepatic arteriography showed no portal vein development, and the hepatic artery showed significantly enhanced development compared with before fistula occlusion (Fig. 2). After fistula occlusion, hematemesis ceased, and the melena disappeared over 6 months.