The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope ؊0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope ؊0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT. (HEPATOLOGY 2002;35: 680-687.) C irrhosis caused by hepatitis C virus (HCV) infection is the main indication of liver transplantation (LT) in most transplant programs. Infection of the liver graft after transplantation is almost universal and persistent infection leading to chronic hepatitis, cirrhosis, and graft failure is common. 1,2 In our geographic area, 30% of patients undergoing LT for HCV-related liver disease are already cirrhotic 5 years after transplantation. 3 Regretfully, prophylaxis of HCV infection of the graft is not feasible because no specific anti-HCV immune globulin is available. In addition, antiviral treatment in patients on waiting lists for LT appears to be poorly effective and may cause severe adverse effects. 4,5 Currently, treatment of hepatitis C infection after LT seems the most feasible strategy to eradicate HCV. 6-8 Treatment of HCV infection after LT can be initiated before liver damage occurs or once liver disease is already established. Treatment in the early phase of LT seems a reasonable approach because eradication of HCV would prevent liver damage. 9-11 However, there are only a few studies analyzing the efficacy of antiviral therapy in the early posttransplantation period. Interferon monotherapy is not effective in achieving sustained virologic response in ...

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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

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Short-term carvedilol administration is more powerful than propranolol in decreasing hepatic venous pressure gradient (HVPG) in cirrhotic patients, but induces arterial hypotension that may prevent its long-term use in portal hypertensive patients. This study compared the HVPG reduction and safety of long-term carvedilol and propranolol. Fifty-one cirrhotic patients were randomly assigned to receive carvedilol (n = 26) and propranolol (n = 25). Hemodynamic measurements and renal function were assessed at baseline and after 11.1 +/- 4.1 weeks. Carvedilol caused a greater decrease in HVPG than popranolol (-19 +/- 2% vs. -12 +/- 2%; P <.001). The proportion of patients achieving an HVPG reduction >/=20% or