Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting

AIM： TO study if T-cell activation related to portasystemic shunting causes osteoclast-mediated bone loss through RANKL-dependent pathways. We also investigated if T-cell inhibition using rapamycin would protect against bone loss in rats. METHODS： Portasystemic shunting was performed in male Sprague-Dawley rats and rapamycin 0.1 mg/kg was administered for 15 wk by gavage. Rats received powderized chow and supplemental feeds to prevent the effects of malnutrition on bone composition. Weight gain and growth was restored after surgery in shunted animals. At termination, biochemical parameters of bone turnover and quantitative bone histology were assessed. Markers of T-cell activation, inflammatory cytokine production, and RANKL-dependent pathways were measured. In addition, the roles of IGF-1 and hypogonadism were investigated. RESULTS： Portasystemic shunting caused low turnover osteoporosis that was RANKL independent. Bone resorbing cytokine levels, including IL-1, IL-6 and TNFα, were not increased in serum and TNFα and RANKL expression were not upregulated in PBMC. Portasystemic shunting increased the circulating CD8＋ T-cell population. Rapamycin decreased the circulating CD8＋ T-cell population, increased CD8＋ CD25＋ T-regulatory cell population and improved all parameters of bone turnover. CONCLUSION： Osteoporosis caused by portasystemic shunting may be partially ameliorated by rapamycin in the rat model of hepatic osteodystrophy.

Transjugular portosystemic stent shunt in treatment of liver diseases

INTRODUCTIONMore than 10 years ago ,an interventional technique for the creation of an intrahepatic decompressive shunt between a branch of the portal vein and a main hepatic vein using expandable metallic stents has been intriduced for the treatmint of portal hypertension[1,2],This transjugular portosystemic intrahepatic stent shunt (TIPS) functions as a side to side shunt ,similarly to surgical shunts .

Comparison of a new stent and Wallstent for transjugular intrahepatic portosystemic shunt in a porcine model

AIM: To evaluate a new balloon-expandable stainless steel stent (Cordis stent) in a transjugular intrahepatic portosystemic shunt (TIPS) porcine model and compared with Wallstent. METHODS: TIPS was performed in 26 normal domestic pigs weighing 20 kg-30 kg using a Cordis stent or Wallstent (13 pigs in each stent). All pigs were sacrificed at the 14th day after TIPS. The stent deployment delivery system, stent patency, and stent recoil after placement were evaluated.Proliferative response in representative histological sections from the center,hepatic and portal regions of the two stent designs were quantified. RESULTS: The shunt was widely patent in 4 pigs in the Cordis stent group (4/12, premature dead in 1 pig), and in 5 pigs in the Wallstent group (5/13). All remaining stents of both designs were occluded or stenotic. The mean quantified proliferation including thickness of the proliferation and the ratio of proliferation: total area in three assayed regions in Cordis stent and Wallstent was 2.18 mm:2.00 mm, and 59.18 mm2:51.66 mm2, respectively (P 】 0.05). The delivery system and mechanical properties of the Cordis stent functioned well. CONCLUSION: The new Cordis stent is appropriate for TIPS procedure.

Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: Influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC

AIM:To investigate the systemic availability of budesonide in a patient with Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma,who developed serious side effects. METHODS:Serum levels of budesonide,6β-OH-budesonide and 16α-OH-prednisolon were measured by HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear imaging.All values were compared with a matched control patient without side effects. RESULTS:Serum levels of budesonide were 13-fold increased in the index patient.The ratio between serum levels of the metabolites 6β-OH-budesonide and 16α-OH- prednisolone,respectively,and serum levels of budesonide was diminished (1.0 vs.4.0 for 6β-OH-budesonide,4.2 vs. 10.7 for 16α-OH-prednisolone).Both patients had portosystemic SI (5.7 % and 3.1%) within the range of healthy subjects.CONCLUSION:Serum levels of budesonide Vary uP to 13-fold in AIH Patients with Child A eirrhosis in the absenee ofrelevant Portosystemic shunting.Redueed hePatiemetabolism,as indicated by redueed metabolite-to-drugratio,rather than Portosystemie shunting may explainsystemic side effects of this drug in cirrhosis

Comparison of embolic agents for varices during transjugular intrahepatic portosystemic shunt for variceal bleeding: Tissue gel or coil?

Purpose:We aimed to compare treatment efficacy,safety and material cost between tissue gel and coil regarding variceal embolization during transjugular intrahepatic portosystemic shunt(TIPS).Materials&Methods:This retrospective study including cirrhotic patients with variceal bleeding treated with TIPS combined with variceal embolization between January 2016 and August 2017.Patients were divided into three groups according to embolic agents used in variceal embolization:tissue gel group(Group A),combination group(Group B),and coil group(Group C).The primary endpoint was 1-year rebleeding rate after TIPS creation.The secondary endpoints included shunt dysfunction,overt hepatic encephalopathy,liver function,and embolic agents-related expense.Results:A total of 60 patients(30,10,and 20 in Group A,B,and C)were included.Variceal rebleeding occurred in3(10%),0(0%),and 4(20%)patients within one year after TIPS creation in Group A,B,and C,respectively.Stent dysfunction occurred in 2(3.3%)patients and 9(15.0%)patients experienced overt hepatic encephalopathy.No significant differences were observed between three groups regarding primary and secondary endpoints except embolic agents-related expense,with a significantly lower cost in Group A when compared to the other two groups.Stent dysfunction occurred in two patients,with one patient in Group A developed acute occlusion caused by thrombus and another patient in Group C underwent stent stenosis during follow-up.Conclusions:Compares to coil alone or combines with coil,tissue gel has similar treatment efficacy and safety,but with significantly lower cost for variceal bleeding during TIPS.

Early Hepatic Encephalopathy after a Transjugular Intrahepatic Portosystemic Shunt Procedure: Case Report

Patients with decompensated hepatic cirrhosis may present systemic alterations and dysfunction of multiple organs. Ascites, portal hypertension, esophageal varices, and hepatic encephalopathy are common complications arising from cirrhosis. The aim of this paper is to report a case of a patient with liver cirrhosis and the complications of a transjugular intrahepatic portosystemic shunt. Male, elderly, and ex-alcoholic, diagnosed with liver cirrhosis, ascites, and esophageal varices. He underwent transjugular intrahepatic portosystemic shunt due to portal hypertension and returned to the hospital after 24 hours with agitation and mental confusion. He had a bowel movement stop, neurological worsening, loss of renal function, hepatic hydrothorax, hepatic encephalopathy, hypernatremia, hypocalcemia, and hypophosphatemia. He underwent a new procedure to occlude the transjugular intrahepatic portosystemic shunt, showing improvement of the mental status and ascites. However, continued with decompensation and hydro-electrolytic disorders. He evolved with worsening of the ventilatory pattern, and neurological and renal function, with a fatal outcome. Esophageal varices due to portal hypertension can be corrected with the transjugular intrahepatic portosystemic shunt. However, complications such as hypernatremia, hepatic hydrothorax, and hepatic encephalopathy may occur. Therefore, there is a need for reintervention to shunt or reduce its caliber. Thus, for patients with advanced age and decompensated cirrhosis, the potential risks and benefits of this procedure should be carefully evaluated due to the risk of complications and death.

Could there be light at the end of the tunnel? Mesocaval shunting for refractory esophageal varices in patients with contraindications to transjugular intrahepatic portosystemic shunt

Cirrhotic patients with recurrent variceal bleeds who have failed prior medical and endoscopic therapies and are not transjugular intrahepatic portosystemic shunt candidates face a grim prognosis with limited options. We propose that mesocaval shunting be offered to this group of patients as it has the potential to decrease portal pressures and thus decrease the risk of recurrent variceal bleeding. Mesocaval shunts are stent grafts placed by interventional radiologists between the mesenteric system, most often the superior mesenteric vein, and the inferior vena cava. This allows flow to bypass the congested hepatic system, reducing portal pressures. This technique avoids the general anesthesia and morbidity associated with surgical shunt placement and has been successful in several case reports. In this paper we review the technique, candidate selection, potential pitfalls and benefits of mesocaval shunt placement.

Heat shock protein 72 normothermic ischemia,and the impact of congested portal blood reperfusion on rat liver

INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .

Innuence of portal pressure change on intestinal permeability in patients with portal hypertension

Objective: To investigate intestinal permeability in patients with portal hypertension and its relationship with portal pressure. Methods: Twenty patients with portal hypertension were divided into two groups (A, B), 10 patients per group. In group A, patients were treated with com- bined transjugular intrahepatic portosystemic shunt (TIPS) and modified Sugiura. In group B, patients were treated with modified Sugiura only. Intestinal permeability was assessed before operation, two weeks after TIPS. and two weeks after modified Sug- iura; 20 healthy control subjects were also assessed. Results: Intestinal permeability was significantly higher in the patients than in the control group (P< 0. 01). In group A, portal pressure, intestinal per- meability decreased two weeks after TIPS (P< 0. 05), and no obvious change was noted two weeks after modified Sugiura; but they were significantly lower than those before TIPS (P<0. 05). In group B, intestinal permeability was not different before and after operation. Intestinal permeability in group A was not different from that in group B before treatment, but significantly lower after modified Su- giura (P<0. 05). Portal pressure was significantly correlated with intestinal permeability (r=0. 627, P <0. 01). Conclusions: This study shows that combined TIPS and modified Sugiura can lower portal pressure and intestinal permeability, and enhance the therapeutic efficacy on portal hypertension.