Only some patients show a substantial hepatic venous pressure gradient (HVPG) reduction after propranolol, which makes it desirable to investigate drugs with greater portal hypotensive effect. The aim of this study was to investigate whether carvedilol, a nonselective beta-blocker with anti-alpha 1-adrenergic activity, may cause a greater HVPG reduction than propranolol. Thirty-five cirrhotic patients had hemodynamic measurements before and after the random administration of carvedilol (n 14), proprano-lol (n 14), or placebo (n 7). Carvedilol markedly reduced HVPG, from 19.5 1.3 to 15.4 1 mm Hg (P F .0001). This HVPG reduction was greater than after pro-pranolol (20.4 2 vs. 12.7 2%, P F .05). Moreover, carvedilol decreased HVPG greater than 20% of baseline values or to I12 mm Hg in a greater proportion of patients (64% vs. 14%, P F .05). Both drugs caused similar reductions in hepatic and azygos blood flows, suggesting that the greater HVPG decrease by carvedilol was because of reduced hepatic and portocollateral resistance. Proprano-lol caused greater reductions in heart rate and cardiac output than carvedilol, whereas carvedilol caused a greater decrease in mean arterial pressure (23.1 vs. 11%, P F .05). Thus, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis, suggesting a greater therapeutic potential. However, it causes arterial hypotension, which calls for careful evaluation before its long-term use. (HEPATOLOGY 1999;30:79-83.) Propranolol, a nonselective beta-blocker, is widely used in the pharmacological treatment of portal hypertension. Its efficacy has been clearly proven for the prevention of first variceal bleeding 1,2 and rebleeding. 3,4 Several studies have shown that to achieve effective protection from the risk of variceal bleeding, the portal pressure gradient (usually measured as the hepatic venous pressure gradient [HVPG]) has to decrease to 12 mm Hg 5,6 or at least by 20% of baseline values. 6 However, the HVPG response to propranolol administration is heterogeneous, with less than one third of patients achieving such a decrease in portal pressure. 5-8 Combination therapy, associating beta-blockers with nitro-vasodilators, has been introduced to overcome this limitation. 9 Vasodilators such as isosorbide-5-mononitrate enhance the portal pressure reducing effect of beta-blockers by decreasing the portohepatic vascular resistance. 10-13

Prevention of variceal rebleeding is mandatory in cirrhotic patients. We compared the efficacy, safety, and cost of transjugular intrahepatic portosystemic shunt (TIPS) versus pharmacologic therapy in preventing variceal rebleeding in patients with advanced cirrhosis. A total of 91 Child-Pugh class B/C cirrhotic patients surviving their first episode of variceal bleeding were randomized to receive TIPS (n ‫؍‬ 47) or drug therapy (propranolol ؉ isosorbide-5-mononitrate) (n ‫؍‬ 44) to prevent variceal rebleeding. Mean follow-up was 15 months. Rebleeding occurred in 6 (13%) TIPS-treated patients versus 17 (39%) drugtreated patients (P ‫؍‬ .007). The 2-year rebleeding probability was 13% versus 49% (P ‫؍‬ .01). A similar number of reinterventions were required in the 2 groups; these were mainly angioplasty ؎ restenting in the TIPS group (90 of 98) and endoscopic therapy for rebleeding in the medical group (45 of 62) (not significant). Encephalopathy was more frequent in TIPS than in drug-treated patients (38% vs. 14%, P ‫؍‬ .007). Child-Pugh class improved more frequently in drug-treated than in TIPS-treated patients (72% vs. 45%; P ‫؍‬ .04). The 2-year survival probability was identical (72%). The identified cost of therapy was double for TIPS-treated patients. In summary, medical therapy was less effective than TIPS in preventing rebleeding. However, it caused less encephalopathy, identical survival, and more frequent improvement in Child-Pugh class with lower costs than TIPS in high-risk cirrhotic patients. This suggests that TIPS should not be used as a first-line treatment, but as a rescue for failures of medical/endoscopic treatments (first-option therapies). (HEPATOLOGY 2002;35:385-392.) S ince its introduction in 1989, 1 transjugular intrahepatic portosystemic shunt (TIPS) has become very popular in the treatment of portal hypertension, as reflected by an increasing number of publications. 2 TIPS is relatively easy to perform, quite safe, and causes a portal decompression similar to that achieved by surgical shunts. 3,4 Randomized controlled trials (RCTs) 5-15 and meta-analyses [16][17][18][19] have shown that TIPS is more effective than endoscopic therapy in preventing variceal rebleeding. However, some studies reported an increased incidence of encephalopathy following TIPS. [16][17][18][19][20][21][22] The frequent development of TIPS dysfunction calls for repeated angioplasty and/or restenting during the follow-up. 4,[16][17][18][19][23][24][25] Finally, TIPS does not improve survival as compared with endoscopic therapy. [16][17][18][19] Pharmacologic therapy with nonselective beta-blockers, alone or combined with isosorbide-5-mononitrate (ISMN), is widely used to prevent first variceal bleeding and rebleeding. [26][27][28] Pharmacologic therapy has the advantages of safety, availability, easy administration, and low cost. Recent RCTs using beta-blockers plus ISMN have shown this therapy to be significantly more effective than endoscopic injection sclerotherapy, 29 and equal to or better than endoscop...

Entecavir and tenofovir achieved high biochemical and virological response. Renal function remained stable with both drugs. A Page-B cut-off ≥10 selected all patients at risk of HCC development.

A significant proportion of patients with Crohn's disease suffer from vitamin B12 and/or folate deficiency, suggesting that regular screening should be performed, with closer monitoring in patients with ileal resection or active disease.

Urgent TIPS is an effective alternative for the treatment of acute variceal bleeding refractory to endoscopic and pharmacological therapy, but sometimes is associated with major complications. Because of the high operative mortality rate in patients with severe liver failure, careful selection of patients is required before TIPS.