Long term outcome after transjugular intrahepatic portosystemic stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: a phase II study

Abstract

Background: Recent small studies on hepatorenal syndrome (HRS) indicate some clinical benefit after transjugular intrahepatic portosystemic stent-shunt (TIPS) but sufficient long term data are lacking.

Aim: We studied prospectively feasibility, safety, and long term survival after TIPS in 41 non-transplantable cirrhotics with HRS (phase II study).

Patients and methods: HRS was diagnosed using current criteria (severe (type I) HRS, n=21; moderate (type II) HRS, n=20). Thirty one patients (14 type I, 17 type II) received TIPS (8-10 mm) while advanced liver failure excluded shunting in 10. During follow up (median 24 months) we analysed renal function and survival (Kaplan-Meier).

Results: TIPS markedly reduced the portal pressure gradient (21 (5) to 13 (4) mm Hg (mean (SD)); p<0.001) with one procedure related death (3.2%). Renal function deteriorated without TIPS but improved (p<0.001) within two weeks after TIPS (creatinine clearance 18 (15) to 48 (42) ml/min; sodium excretion 9 (16) to 77 (78) mmol/24 hours) and stabilised thereafter. Following TIPS, three, six, 12, and 18 month survival rates were 81%, 71%, 48%, and 35%, respectively. As only 10% of non-shunted patients survived three months, total survival rates were 63%, 56%, 39%, and 29%, respectively. Multivariate Cox regression analysis revealed bilirubin (p<0.001) and HRS type (p<0.05) as independent survival predictors after TIPS.

Conclusions: TIPS provides long term renal function and probably survival benefits in the majority of non-transplantable cirrhotics with HRS. These data warrant controlled trials evaluating TIPS in the management of HRS.

Figure 1

Mean (SD) serum creatinine levels (mg/dl; to convert values to µmol/l multiply by 88.4), creatinine clearance (ml/min), and sodium excretion (mmol/24 hours) up to one year after diagnosis of hepatorenal syndrome in 41 patients of whom 31 received a transjugular intrahepatic portosystemic stent-shunt (TIPS) and 10 were excluded from receiving TIPS. p values were calculated using the Mann-Whitney U test and represent comparisons with baseline for patients at risk or between treatment groups at given time intervals: *p<0.05, **p<0.01, ***p<0.001. Note that all values prior to and up to one week after TIPS were determined without diuretics. Thereafter, moderate diuretic medication with furosemide (40-80 mg/day) and spironolactone (100-200 mg/day) was reintroduced and adapted to the patients' needs.

Figure 2

Kaplan-Meier survival analysis. (A) Cohort of patients with hepatorenal syndrome (HRS) treated by transjugular intrahepatic portosystemic stent-shunt (TIPS) (n=31); (B) survival analysis after TIPS according to HRS subtypes at baseline; (C) survival analysis according to clinical response (improved sodium excretion and ascites control within one month) or no response after TIPS; (D) survival analysis of non-TIPS patients (n=10: type I HRS, n=7; type II HRS, n=3) receiving the best medical support. p values were derived from subgroup comparisons using the log rank test.