Martin Rössle

The Transjugular Intrahepatic Portosystemic Stent-Shunt Procedure for Variceal Bleeding

BACKGROUND Transjugular placement of an intrahepatic stent is a new technique to establish a portosystemic shunt for treatment of portal hypertension. A puncture needle is advanced in a catheter through the inferior vena cava into a hepatic vein; then an intrahepatic branch of the portal vein is punctured and an expandable stent of metallic mesh is implanted to establish the shunt. METHODS We attempted the stent-shunt procedure in 100 of 112 consecutive patients with variceal bleeding due to cirrhosis, who were then followed for a mean (+/- SD) of 12 +/- 6 months. Of the 100 patients, 22 had Child-Pugh class C cirrhosis, 10 were treated on an emergency basis, and 68 had alcoholic cirrhosis. The shunt was established with use of Palmaz stents expanded to 8 to 12 mm in diameter. RESULTS Technical success was achieved in 93 percent of the patients. The mean (+/- SD) time for the procedure was 1.2 +/- 0.3 hours. The shunt reduced the portal venous pressure gradient by 57 percent. Major complications were hemorrhage (intraabdominal bleeding in six patients, biliary bleeding in four, and bleeding in the liver capsule in three) and migration of the stent into the pulmonary artery (in two patients). At follow-up, stenosis of the shunt was evident in 21 patients and occlusion in 10 patients; 10 of these 31 patients had variceal rebleeding. Stenoses and occlusions of the shunt were all treated successfully by redilation, thrombolysis, or implantation of an additional stent. Hepatic encephalopathy (stages I to III) developed in 25 percent of the patients. The proportion of patients with shunts who remained free of variceal rebleeding was 92 percent at six months and 82 percent at one year. The 30-day mortality was 3 percent. The cumulative one-year survival was 85 percent. CONCLUSIONS These results suggest that the transjugular placement of an intrahepatic portosystemic stent is an effective and safe treatment for variceal hemorrhage in patients with portal hypertension due to cirrhosis.

A Comparison of Paracentesis and Transjugular Intrahepatic Portosystemic Shunting in Patients with Ascites

BACKGROUND In patients with cirrhosis and ascites, creation of a transjugular intrahepatic portosystemic shunt may reduce the ascites and improve renal function. However, the benefit of this procedure as compared with that of large-volume paracentesis is uncertain. METHODS We randomly assigned 60 patients with cirrhosis and refractory or recurrent ascites (Child-Pugh class B in 42 patients and class C in 18 patients) to treatment with a transjugular shunt (29 patients) or large-volume paracentesis (31 patients). The mean (+/-SD) duration of follow-up was 45+/-16 months among those assigned to shunting and 44+/-18 months among those assigned to paracentesis. The primary outcome was survival without liver transplantation. RESULTS Among the patients in the shunt group, 15 died and 1 underwent liver transplantation during the study period, as compared with 23 patients and 2 patients, respectively, in the paracentesis group. The probability of survival without liver transplantation was 69 percent at one year and 58 percent at two years in the shunt group, as compared with 52 percent and 32 percent in the paracentesis group (P=0.11 for the overall comparison, by the log-rank test). In a multivariate analysis, treatment with transjugular shunting was independently associated with survival without the need for transplantation (P=0.02). At three months, 61 percent of the patients in the shunt group and 18 percent of those in the paracentesis group had no ascites (P=0.006). The frequency of hepatic encephalopathy was similar in the two groups. Of the patients assigned to paracentesis in whom this procedure was unsuccessful, 10 received a transjugular shunt a mean of 5.5+/-4 months after randomization; 4 had a response to this rescue treatment. CONCLUSIONS In comparison with large-volume paracentesis, the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites.

The transjugular intrahepatic portosystemic stent - shunt procedure for refractory ascites

BACKGROUND Previous studies have suggested that the transjugular placement of an intrahepatic stent to establish a portosystemic shunt is an effective treatment of uncomplicated ascites accompanying variceal bleeding. We studied the stent shunt for use in patients with liver cirrhosis and ascites refractory to medical treatment. METHODS Fifty of 62 consecutive patients with cirrhosis and refractory ascites (18 with Child-Pugh class B liver disease and 32 with class C) were treated with the stent shunt--an expandable stent of metallic mesh placed between a major branch of the portal vein and one of the hepatic veins. Patients were followed for a mean (+/- SD) of 426 +/- 333 days. Those with advanced cancer, severe heart failure, or severe liver failure were excluded. RESULTS The stent shunt was successfully placed in all patients and reduced the pressure gradient between the portal vein and the inferior vena cava by an average of 63 percent. Thirty-seven patients (74 percent) had complete responses (total remission of ascites within three months), and nine patients (18 percent) had partial responses (ascites detected by ultrasound but with no need for paracentesis). Four patients did not respond, including two who died within two weeks of shunt placement. After the procedure, 25 patients had hepatic encephalopathy, as compared with 20 patients before the procedure; although encephalopathy improved in 3 patients, new encephalopathy developed in 8 patients. In the 28 of the 33 patients followed for more than six months who were evaluated, the mean serum creatinine concentration was 1.5 +/- 0.09 mg per deciliter (133 +/- 8 mumol per liter) before placement of the stent shunt, 1.5 +/- 1.6 mg per deciliter (133 +/- 141 mumol per liter) one week after the procedure, and 0.9 +/- 0.3 mg per deciliter (80 +/- 27 mumol per liter) after six months (P = 0.008 for the comparison of concentrations before and six months after the procedure). Renal function did not improve in the six patients with organic kidney disease. Procedure-related complications developed in 16 patients, including intraabdominal bleeding requiring blood transfusions in 2 patients. Thrombotic occlusion of the stent shunt occurred within two weeks in 5 patients, and later insufficiency of the shunt occurred in 16 patients, including 12 with recurrence of ascites after complete remission. During followup, an additional 29 patients died--10 of progressive liver disease and 19 of other causes. Survival for at least one year was associated with a patients being under 60 years of age, having a serum bilirubin level before placement of the stent shunt of less than 1.3 mg per deciliter (22 mumol per liter), and having a complete response. CONCLUSIONS Our findings in an uncontrolled prospective study suggest that the transjugular intrahepatic porto-systemic stent-shunt procedure was an effective treatment for many patients with liver cirrhosis and refractory ascites, but mortality from underlying diseases was substantial.

High‐dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double‐blind, randomized, placebo‐controlled trial

In uncontrolled clinical studies, ursodeoxycholic acid (UDCA) had a beneficial effect on nonalcoholic steatohepatitis (NASH). However, a large controlled trial using UDCA (13‐15 mg/kg/day) was unable to confirm these results. Accordingly, a randomized, placebo‐controlled study was initiated with a high dose of UDCA (23‐28 mg/kg/day). The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score (NAS). With the modified Brunt score, 185 patients with histologically proven NASH were randomized [intention to treat (ITT)], and 147 were treated per protocol (PP). With the NAS, 137 patients were confirmed to have NASH, 48 had borderline NASH, and 1 did not have NASH. The treatment time was 18 months. At entry, the treatment groups were comparable. A second biopsy sample was obtained from 139 of 185 patients (NAS: 107/137). The primary criterion for evaluation was a change in the liver histology; the secondary criteria were single histological variables and liver biochemistry. Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score (P = 0.881) or NAS (P = 0.355). Only lobular inflammation improved significantly (P for the modified Brunt score = 0.011, P for NAS = 0.005). In subgroup analyses, significant improvements in lobular inflammation were also observed in males, younger patients up to 50 years of age, slightly overweight patients, and patients with hypertension and an increased histology score. The fibrosis score did not change (P for ITT = 0.133, P for PP = 0.140). With the exception of γ‐glutamyl transferase, UDCA did not improve laboratory data. Conclusion: High‐dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo. Hepatology 2010

Treatment of refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt: long-term results in 40 patients.

Background/aims Hepatic hydrothorax is a complication of portal hypertension secondary to ascites. In this study, we investigated retrospectively the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on hepatic hydrothorax refractory to diuretic treatment. Methods Forty patients (Child–Pugh class B, 24 patients; Child–Pugh class C, 16 patients) with hydrothorax refractory to diuretic treatment, pleurocenteses or pleurodesis were included. The TIPS implantation was successful in all patients, who were then followed for 16 ± 14 months (range 1 day–54 months). Results TIPS reduced the portosystemic pressure gradient from 26 ± 6 to 10 ± 5 mmHg. In the 17 patients whom we followed for 12 months or longer, improvements were found for the Child–Pugh score (8.6 ± 1.8 v. 6.7 ± 1.5), serum albumin concentration (3.1 ± 0.5 v. 3.6 ± 0.5 g/l), and urinary sodium excretion (22 ± 29 v. 89 ± 43 mmol/24 h) (P < 0.05). Two patients developed severe hepatic encephalopathy requiring shunt occlusion. Hydrothorax improved in 82% of patients and resolved in 71% of patients. Fifty per cent of patients developed shunt insufficiency within 7 ± 9 months, contributing to a probability of relapse-free 1-year survival of 35%. In these patients, shunt revision resulted in a secondary response rate of 82.3%. The 1-year survival was 64%. Both hydrothorax response and survival showed a significant inverse correlation with age over 60 years (P < 0.01 and P < 0.003, respectively) but not with other biomedical variables. Conclusion TIPS is effective for hydrothorax refractory to diuretic treatment and other standard interventions to bridge the time to transplantation. Patients older than 60 years have a poor response and short survival.

TIPS: 25 years later

In the 25 years since the first TIPS intervention has been performed, technical standards, indications, and contraindications have been set up. The previous considerable problem of shunt failure by thrombosis or intimal proliferation in the stent or in the draining hepatic vein has been reduced considerably by the availability of polytetrafluoroethylene (PTFE)-covered stents resulting in reduced rebleeding and improved survival. Unfortunately, most clinical studies have been performed prior to the release of the covered stent and, therefore, do not represent the present state of the art. In spite of this, TIPS has gained increasing acceptance in the treatment of the various complications of portal hypertension and vascular diseases of the liver.

Transjugular intrahepatic portosystemic stent-shunt (TIPS) in the treatment of Budd-Chiari syndrome

Budd-Chiari syndrome is characterized by splanchnic congestion due to obstruction of the hepatic venous outflow. A variety of treatment modalities have limited applicability due to their invasive nature, complications or low effectivity. The transjugular intrahepatic portosystemic stent-shunt (TIPS) offers a new treatment by creating an intraparenchymal duct between a main branch of the portal vein and hepatic vein i.e. the intrahepatic part of the inferior vena cava. This paper describes the treatment of two patients with fulminant and subacute Budd-Chiari syndrome treated 2 days and 2 months after the onset of clinical symptoms. It demonstrates that TIPS is a feasible treatment of Budd-Chiari syndrome that restores splanchnic blood flow, reduces collateral circulation and ascites and provides sufficient time to allow for elective liver transplantation, if indicated. Further studies are required to evaluate the effect of TIPS on liver function and survival.

TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update

Refractory ascites is a frequent complication of advanced cirrhosis and is associated with hepatorenal syndrome and hepatic hydrothorax. Large volume paracentesis and pleurodesis are regarded as first-line treatments in patients who do not respond adequately to diuretics. These treatments, however, do not prevent recurrence and carry the risk of worsening of the circulatory dysfunction leading to hepatorenal syndrome. The transjugular intrahepatic portosystemic shunt (TIPS) has been proposed as an alternative to paracentesis. TIPS reduces the rate of ascites recurrence mainly due to the reduction in the filtration pressure. In addition, TIPS results in a positive effect on renal function, including hepatorenal syndrome, demonstrated by a rapid increase in urinary sodium excretion, urinary volume, and improvement in plasma creatinine concentration. Furthermore, plasma renin activity, aldosterone, and noradrenalin concentrations improve gradually after TIPS insertion suggesting a positive effect on systemic underfilling, the factor of hepatorenal syndrome. As demonstrated recently in two meta-analyses including five randomised studies, TIPS also improves survival when compared with paracentesis. However, the evidence is based on relatively few studies with only 305 patients included. The positive effects of the TIPS are opposed by an increased frequency and severity of episodes of hepatic encephalopathy which may be reduced by both patient selection and reduced shunt diameter. Based on the present knowledge the recommended hierarchy of treatments for refractory ascites may be reconsidered upgrading TIPS in suitable candidates.

Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical Therapy

BACKGROUND & AIMS Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis. METHODS We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures. RESULTS A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups. CONCLUSIONS Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.

How much reduction in portal pressure is necessary to prevent variceal rebleeding? A longitudinal study in 225 patients with transjugular intrahepatic portosystemic shunts.

OBJECTIVES:This longitudinal study determines the risk of rebleeding in relation to the reduction of the portosystemic pressure gradient in patients with a transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding.METHODS:The study included 225 patients in whom a TIPS revision was indicated by the endoscopic finding of varices with a high risk for rebleeding (n = 167) or a recent variceal rebleed (n = 58). The portosystemic pressure gradient was determined before and after TIPS placement and at revision performed after a mean of 10 ± 15 months.RESULTS:The portosystemic pressure gradient at revision approached the index pressure gradient before TIPS implantation (23.1 ± 5.5 mm Hg) by 8.4 ± 31%. Rebleeding was inversely correlated with the reduction in index pressure gradient found at revision. Thus, 80% of rebleedings occurred with pressure gradients close to the index pressure gradient (<25% reduction) or with gradients equal to or greater than the index pressure gradient. In contrast, only one patient (0.4%) and three patients (1.3%) rebled with a pressure gradient of <12 mm Hg or a reduction of the index pressure gradient by >50%, respectively. Kaplan-Meier analysis of rebleeding, which included the 225 patients at risk, showed a probability of rebleeding of 18%, 7%, and 1% for a reduction of the index pressure gradient by 0%, 25–50%, and >50%, respectively.CONCLUSIONS:Most rebleedings occurred with pressure gradients similar to the index-pressure gradient measured at first bleeding. Accordingly, a graded reduction by 25–50% sufficiently prevents rebleeding. It can be assumed that, in comparison with the widely used threshold value of 12 mm Hg, a reduction by 25–50% may have a favorable benefit-to-risk ratio with respect to shunt-induced hepatic encephalopathy and liver failure. It should therefore be a goal in the decompressive treatment of portal hypertension and maintained during follow-up of patients with variceal bleeding.