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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

Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.

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