International Congress Highlights 2004 Clinical Update in GI disease Portal Hypertension P. Michielsen University of Antwerp

55th Annual Meeting AASLD

Discussed abstracts Bureau C. et al. A randomized study cmparing the use of polytrtrafluoroethylene (PFTE) covered stents and non- covered stents for TIPS: long term patency. Hepatology 2004;40 (suppl. 1): 186A. Bolondi L. et al. Potassium canrenoate decreases the incidence of portal hypertension-related complications in compensated cirrhosis. A double-blind randomized study. Hepatology 2004;40 (suppl. 1): 224A Thabut C. et al. Diagnostic value of fibrosis biochemical markers (Fibrotest-Fibrosure) for the prediction of severe portal hypertension in patients with and without cirrhosis. Hepatology 2004;40 (supppl. 1): 202A

Covered TIPS (Viatorr) vs uncovered stents C. Bureau et al. (Toulouse, Barcelona, Montréal) Background –50% dysfunction rate at 1 year major drawback TIPS procedure –Use of polytetrafluoroethylene (PTFE) covered stents decreases rate TIPS dysfunction at 1 year (Bureau et al. Gastroenterology 2004;126:469-75) Aim: report long-term patency at 2 years

Covered TIPS (Viatorr) vs uncovered stents C. Bureau et al. (Toulouse, Barcelona, Montréal) Methods –80 cirrhotic patients treated by TIPS 24 for active variceal bleeding 24 for prevention of rebleeding 32 for refractory ascites –Randomization Group A (n=39): PTFE covered stent Group B (n=41): uncovered stent –Follow-up Doppler US day 7, 1 month, then every 3 months Angiography and HVPG measurement every 6 months and when stent dysfunction suspected –Shunt dysfunction stenosis > 50% of lumen and/or HVPG > 12 mm Hg

Covered TIPS (Viatorr) vs uncovered stents C. Bureau et al. (Toulouse, Barcelona, Montréal) Results at 2 years –Shunt dysfunction Group A (covered): 15% Group B (uncovered): 44% (p<0.005) –Primary patency Group A (covered): 76% Group B (uncovered): 36% (p=0.001) –Recurrent complications portal hypertension Group A (covered): 19% Group B (uncovered): 38% (p=0.002) –Survival: similar –Encephalopathy Group A (covered): 33% Group B (uncovered): 49% (p<0.05)

Covered TIPS (Viatorr) vs uncovered stents C. Bureau et al. (Toulouse, Barcelona, Montréal) Conclusions : PTFE covered stents –improve long-term patency of TIPS –prevent clinical relapses –decrease rate of encephalopathy

Covered TIPS (Viatorr) vs uncovered stents Comment: M. Rössle (Freiburg) and K.D. Mullen (Cleveland, OH), Hepatology 2004;40:495-7 Risk HE lower in covered stents explained by decreased need to revise TIPS But: diameter bare stents 11.7  0.8 mm vs covered 10.5  0.9 mm –Greater bare stents to prevent early insufficiency –Smaller covered stents to reduce risk HE

Covered TIPS (Viatorr) vs uncovered stents Comment: M. Rössle (Freiburg) and K.D. Mullen (Cleveland, OH), Hepatology 2004;40:495-7 Proposal –Small diameter (8 mm) covered stents to be used in patients with variceal bleeding (where partial pressure reduction may be effective in preventing rebleeding) –Bare stents In patients with higher risk HE and liver failure In patients with refractory ascites (10-12 mm): large stent more effective + protection against HE at long-term follow-up

K canrenoate and portal hypertension related complications in compensated cirrhosis L. Bolondi et al., Italy Background –Aldosterone-dependent renal sodium retention in compensated cirrhosis contributes to portal hypertension and ascites formation –Chronic spironolactone administration has been shown to effectively reduce variceal pressure (Nevens et al., Hepatology 1996;23: )

K canrenoate and portal hypertension related complications in compensated cirrhosis L. Bolondi et al., Italy Aim: Evaluation oral K canrenoate in patients with preascitic cirrhosis for 1 year on –Appearance of esophageal varices –Worsening stage F1 esophageal varices –De novo appearance of ascites

K canrenoate and portal hypertension related complications in compensated cirrhosis L. Bolondi et al., Italy Methods –Multicenter prospective double-blind randomized controlled study with 2 arms. –Inclusion: Child A viral cirrhosis No present or past ascites F1 or no varices Presence of endoscopic or US signs portal hypertension –120 patients enrolled Group 1: K canrenoate 100 mg/d (n=66) Group 2: placebo (n = 54) –Evaluation: baseline, wk 2, 17, 34, 52

K canrenoate and portal hypertension related complications in compensated cirrhosis L. Bolondi et al., Italy Results –Complete follow-up K canreanoate: 50/66 Placebo: 43/54 –Worsening varices: 30.1% in placebo vs 18% in K canrenoate (ns) –Appearance ascites: 10.6% in placebo vs 2% in K canrenoate (ns) –Any primary endpoint (risk ascites, appearance or worsening esophageal varices): 38.3% in placebo vs 17.6% in K canrenoate (p<0.05) –Adverse events: no difference

K canrenoate and portal hypertension related complications in compensated cirrhosis L. Bolondi et al., Italy Conclusion Oral K canrenoate is well tolerated and significantly decreases development of portal hypertension related complications in compensated liver disease over 1 year.

Diagnostic value fibrosis biochemical markers (Fibrotest- Fibrosure) for prediction of severe portal hypertension Thabut et al., Paris, France Background –Best way to estimate degree PH is measurement HVPG –Fibrotest ® (Biopredictive) is a marker of liver fibrosis, combining 5 components 3 proteins: –α2 macroglobulin –apolipoprotein-A2 –haptoglobin bilirubin γ-GT adjusted to age and gender. It ranges from 0 to 1

Diagnostic value fibrosis biochemical markers (Fibrotest- Fibrosure) for prediction of severe portal hypertension Thabut et al., Paris, France Aim –Assess predictive value Fibrotest (FT) for diagnosis of severe PH in cirrhosis –Determine if FT can help in diagnosis severe PH in patients without cirrhosis Methods –Transjugular catheterisation (end point HVPG > 12 mm Hg) and biopsy –Measurement biochemical values

Diagnostic value fibrosis biochemical markers (Fibrotest- Fibrosure) for prediction of severe portal hypertension Thabut et al., Paris, France Results : 179 patients included HistologyFibrotestHVPG Normal architecture (26%) Fibrosis (21%) 0.76*10* Cirrhosis (53%) 0.93*18* *p<0.001 Significant correlation HVPG and FT

Diagnostic value fibrosis biochemical markers (Fibrotest- Fibrosure) for prediction of severe portal hypertension Thabut et al., Paris, France Results : Cirrhosis HVPGFT <12 mm Hg (n=8)0.76 >12 mm Hg 0.87 (p=0.04) Fibrosis (n = 38) HVPGFT <12 mm Hg0.67 >12 mm Hg (n=12)0.86 (p=0.003) Normal liver architecture (n = 46) HVPGFT <12 mm Hg 0.47 >12 mm Hg (n = 3)0.97 (p=0.02)

Diagnostic value fibrosis biochemical markers (Fibrotest- Fibrosure) for prediction of severe portal hypertension Thabut et al., Paris, France

Conclusions –In cirrhosis, FT can discriminate patients with severe PH –In non cirrhosis, FT can help to detect severe PH