Transjugular Intrahepatic Portosystemic Shunts With Covered Stents Increase Transplant-Free Survival of Patients With Cirrhosis and Recurrent Ascites.

BACKGROUND & AIMS: There is controversy over the ability of transjugular intrahepatic portosystemic shunts (TIPS) to increase survival times of patients with cirrhosis and refractory ascites. The high rate of shunt dysfunction with the use of uncovered stents counteracts the benefits of TIPS. We performed a randomized controlled trial to determine the effects of TIPS with stents covered with polytetrafluoroethylene in these patients. METHODS: We performed a prospective study of 62 patients with cirrhosis and at least 2 large-volume paracenteses within a period of at least 3 weeks; the study was performed at 4 tertiary care centers in France from August 2005 through December 2012. Patients were randomly assigned to groups that received covered TIPS (n = 29) or large-volume paracenteses and albumin as necessary (LVP+A, n = 33). All patients maintained a low-salt diet and were examined at 1 month after the procedure then every 3 months until 1 year. At each visit, liver disease-related complications, treatment modifications, and clinical and biochemical variables needed to calculate Child-Pugh and Model for End-Stage Liver Disease scores were recorded. Doppler ultrasonography was performed at the start of the study and then at 6 and 12 months after the procedure. The primary study end point was survival without a liver transplant for 1 year after the procedure. RESULTS: A higher proportion of patients in the TIPS group (93%) met the primary end point than in the LVP+A group (52%) (P = .003). The total number of paracenteses was 32 in the TIPS group vs 320 in the LVP+A group. Higher proportions of patients in the LVP+A group had portal hypertension-related bleeding (18% vs 0%; P = .01) or hernia-related complications (18% vs 0%; P = .01) than in the TIPS group. Patients in LVP+A group had twice as many days of hospitalization (35 days) as the TIPS group (17 days) (P = .04). The 1-year probability of remaining free of encephalopathy was 65% for each group. CONCLUSIONS: In a randomized trial, we found covered stents for TIPS to increase the proportion of patients with cirrhosis and recurrent ascites who survive transplantation-free for 1 year, compared with patients given repeated LVP+A. These findings support TIPS as the first-line intervention in such patients. ClinicalTrials.gov ID: NCT00222014.

Successful treatment of fibrosing cholestatic hepatitis with pegylated interferon, ribavirin and sofosbuvir after a combined kidney-liver transplantation.

Fibrosing cholestatic hepatitis (FCH) is a classical but rare and severe form of recurrent hepatitis C virus (HCV) after liver transplantation. Classical anti-HCV therapy, that is pegylated-interferon (peg-interferon) and ribavirin, has been shown to have limited efficacy in treating FCH. Herein, we report on the first case of successful use of peg-interferon, ribavirin, plus sofosbuvir to treat HCV-induced FCH in a combined liver-kidney transplant patient. Antiviral therapy was given for 24 weeks. HCV clearance occurred within 4 weeks after starting therapy and was maintained until 4 weeks after the end of therapy. Antiviral tolerance was good. We conclude that the use of sofosbuvir-based anti-HCV therapy can be successfully used to treat FCH after a liver or combined kidney-liver transplantation.

Early use of TIPS in patients with cirrhosis and variceal bleeding.

BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients. METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients). RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events. CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)

Electrografting of a biodegradable layer as a primer adhesion coating onto a metallic stent: in vitro and in vivo evaluations.

Drug-eluting stents have been developed to reduce the risk of restenosis after angioplasty. To facilitate the adhesion of a poly(lactic acid) (PLA) overlayer loaded with rapamycin (20 wt%), a biodegradable macromonomer based on poly(lactic acid) (HEMA-PLA) was grafted onto the metallic stent by electrografting in a one-step reaction involving the immobilization of aryl diazonium onto the metal followed by an in situ surface electro-polymerization. The HEMA-PLA coating was chemically characterized. Mechanical performance during stent expansion was tested. Morphology examinations showed a strong adhesion of PLA topcoat in the presence of the electrografted layer. Biocompatibility and degradation of the coating were studied in vitro and in vivo in rabbit iliac arteries. These 28 days implantations resulted in a minimal inflammatory process with a partial degradation of the coating. These results suggest that this kind of anchoring of a biodegradable layer shows great potential for drug-eluting stents.

Management of gastric varices: a French national survey.

BACKGROUND AND AIMS: Bleeding from gastric varices is more severe than that from esophageal varices, but its management remains debated. We aimed to determine how French hepatogastroenterologists manage cirrhotic patients with gastric varices. METHODS: Hepatogastroenterologists (n=1163) working in general or university hospitals received a self-administered questionnaire. RESULTS: Overall, 155 hepatogastroenterologists (13.3%) from 112 centers (33.3%; 39/40 university hospitals, 73/296 general hospitals) answered. Primary prophylaxis was used by 98.1% of hepatogastroenterologists as follows: ß-blockers 96.1% (93.8 vs. 97.0%; university vs. general hospitals respectively; P=0.57), glue obliteration 16.9% (17.2 vs. 16.3%; P=0.88), and transjugular intrahepatic portosystemic shunt (TIPS) 8.0% (12.7 vs. 4.6%; P=0.12). To manage bleeding, university hospitals had greater local access to glue obliteration (95.4 vs. 68.2%; P<0.001) and TIPS (78.5 vs. 3.5%; P<0.001). Early TIPS was proposed by 53.6% (72.1 vs. 39.2%; P<0.001). Glue obliteration was performed under general anesthesia (86.1%) using Glubran (43.1%) or Histoacryl (52.9%), and lipiodol (78.8%) with varying degrees of dilution (1 : 10 to 3 : 4). The injected volume per varix varied widely (1-20 ml). Glue obliteration, band ligation, or both were used by, respectively, 64.2, 18.2, and 17.5% of practitioners. Almost all hepatogastroenterologists (98%) performed secondary prophylaxis: ß-blockers 74.7% (75.0 vs. 74.4%, university vs. general hospitals; P=0.93), glue obliteration 66.0% (76.9 vs. 57.6%; P=0.013), and TIPS 30.0% (39.1 vs. 23.3%; P=0.037). CONCLUSION: The management of gastric varices in France is heterogeneous across centers. University hospitals have better access to techniques such as glue obliteration and TIPS. As bleeding from gastric varices has a poor outcome, guidelines should be established to standardize clinical practices and design further studies.

Patency of stents covered with polytetrafluoroethylene in patients treated by transjugular intrahepatic portosystemic shunts: long-term results of a randomized multicentre study.

An 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of complications of portal hypertension. The use of covered stents could improve shunt patency; however, long-term effect and safety remain unknown. Eighty patients randomized to be treated by TIPS either with a covered stent (Group 1) or an uncovered prosthesis (Group 2) were followed-up for 2 years. Doppler US was performed every 3 months. Angiography and portosystemic pressure gradient measurement were performed every 6 months or whenever dysfunction was suspected. Actuarial rates of primary patency in Groups 1 and 2 were 76% and 36% respectively (P=0.001). Clinical relapse occurred in four patients (10%) in Group 1 and 12 (29%) in Group 2 (P<0.05). Actuarial rates of being free of encephalopathy were 67% in Group 1 and 51% in Group 2 (P<0.05). Probability of survival was 58% and 45% at 2 years, respectively, in Groups 1 and 2 (NS). The mean Child-Pugh score improved only in Group 1 (from 8.1+/-1.6 to 7+/-2.2 at 2 years -P<0.05). We also compared the Doppler-US parameters between patent and dysfunctioning shunts. In patent shunts, the mean velocity within the portal vein was significantly higher but the performance of Doppler-US was not accurate enough to predict shunt dysfunction. In conclusion, the improvement in TIPS patency by using covered prostheses is maintained over time with a decreased risk of encephalopathy, while the risk of death was not increased.

Preliminary results of a new expanded-polytetrafluoroethylene-covered stent-graft for transjugular intrahepatic portosystemic shunt procedures.

OBJECTIVE: The purpose of our study was to evaluate the feasibility and the safety of transjugular intrahepatic portosystemic shunts (TIPS) with a new expanded-polytetrafluoroethylene-covered stent and the influence of the covering on occlusion rate. SUBJECTS AND METHODS: Twenty cirrhotic patients (57 +/- 11 years old) admitted with a history of esophageal variceal bleeding (n = 11), refractory ascites (n = 5), or both (n = 4) were included. Five of the patients were treated for TIPS revision, and 15 as de novo TIPS placements. The endoprostheses used were composed of a 2-cm noncovered nitinol stent and a 4- to 8-cm expanded-polytetrafluoroethylene graft covering, and were placed from the portal vein to the ostium of the hepatic vein. Patients underwent Doppler sonography at discharge and again at 1, 3, 6, 9, 12, and 15 months and underwent venography with portosystemic pressure gradient measurement at 6 months and whenever necessary. RESULTS: At the time of this writing, complications included three TIPS restenoses and one recurrent ascites successfully treated by balloon dilation, two cases of segmentary liver ischemia, and one patient with encephalopathy that required shunt reduction. After TIPS placement, the portosystemic pressure gradient dropped from 18 +/- 5 to 5 +/- 4 mm Hg. Primary and secondary patency rates were 80% and 100%, respectively, at 387 days. CONCLUSION: These results clearly show the feasibility of TIPS placement with the Gore TIPS endoprosthesis stent-graft and its improved patency compared with results in the literature for bare stents. These preliminary results must be certified further with randomized comparative trials between covered and noncovered TIPS stents.

Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study.

BACKGROUND & AIMS: A 50% dysfunction rate at 1 year is one of the main drawbacks of the transjugular intrahepatic portosystemic shunt procedure. Preliminary experimental and clinical studies suggest that the use of stents covered with polytetrafluoroethylene could tremendously decrease this risk. METHODS: Eighty patients with cirrhosis and uncontrolled bleeding (n = 23), recurrent bleeding (n = 25), or refractory ascites (n = 32) were randomized to be treated by transjugular intrahepatic portosystemic shunts with either a polytetrafluoroethylene-covered stent (group 1; 39 patients) or a usual uncovered prosthesis (group 2; 41 patients). Follow-up Doppler ultrasound was scheduled at day 7, at 1 month, and then every 3 months for 2 years. Angiography and portosystemic pressure gradient measurements were performed 6, 12, and 24 months after the transjugular intrahepatic portosystemic shunt procedure and whenever dysfunction was suspected. Dysfunction was defined as a >50% reduction of the lumen of the shunt at angiography or a portosystemic pressure gradient >12 mm Hg. RESULTS: After a median follow-up of 300 days, 5 patients (13%) in group 1 and 18 (44%) in group 2 experienced shunt dysfunction (P < 0.001). Clinical relapse occurred in 3 patients (8%) in group 1 and 12 (29%) in group 2 (P < 0.05). Actuarial rates of encephalopathy were 21% in group 1 and 41% in group 2 at 1 year (not significant). Estimated probabilities of survival were 71% and 60% at 1 year and 65% and 41% at 2 years in groups 1 and 2, respectively (not significant). CONCLUSIONS: The use of polytetrafluoroethylene-covered prostheses improves transjugular intrahepatic portosystemic shunt patency and decreases the number of clinical relapses and reinterventions without increasing the risk of encephalopathy.