Characteristics of Liver Transplantation in Argentina: A Multicenter Study.

INTRODUCTION: There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES: This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS: We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS: A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We believe the information contained in this article might be of value for reviewing current practices and developing local policies.

Extremely marginal liver grafts from deceased donors have outcome similar to ideal grafts.

BACKGROUND: Although there is a worldwide need to expand the donor pool, many cadaveric marginal livers are usually discarded for transplantation. Herein, we report the outcome of a series of patients receiving marginal grafts. METHODS: We analyzed all patients who underwent liver transplantation in our unit from August 2006 to March 2011 (n = 125) with the use of a prospectively collected database. Patients with ≥3 of donor (prolonged hypotensive episodes, donor age >55 years, high vasopressor drug requirement, hypernatremia, prolonged intensive care unit stay, elevated transaminases) and graft-related (cold ischemia >12 hours, warm ischemia time >40 minutes and steatosis >30%) extended criteria were defined as extremely marginal liver grafts (EMLG). The outcomes of patients receiving EMLG were compared with the recipients of grafts without any marginal criteria (ideal grafts). RESULTS: The EMLG group (n = 36) showed higher operative transfusion requirement (66.6% vs 55.6%) as well as 30-day (11.1% vs 55%) and 1-year (22.2% vs 5.5%) mortality rates, compared with the ideal grafts group (n = 18) but without a significant difference. Other variables, such as major complications, postoperative hemodialysis, ICU and hospital stay, and 1-year survival also were not significantly different. CONCLUSIONS: The liver pool can be safely expanded using EMLG from deceased donors for liver transplantation. These usually discarded liver grafts showed similar early and long-term outcomes compared with ideal organs.

Liver transplantation using Chagas-infected donors in uninfected recipients: a single-center experience without prophylactic therapy.

Organ shortage is the first cause of death on liver transplant waiting lists. As a consequence, we recently decided to expand liver acceptance to those organs that could potentially transmit infectious diseases to their recipients. On January 2010, we initiated a prospective protocol using livers from Chagas-infected donors for transplanting uninfected recipients without using prophylactic therapy. During a 13-month period, 9 of 37 (24%) liver transplants were performed within this protocol. After transplant, each recipient was sequentially and strictly monitored for infection transmission using the Strout method and promptly treated with benznidazole if this occurs. During follow-up, two patients died without Chagas infection and only two (donor-derived T. cruzi transmission rate: 2/9; 22%) patients developed donor-derived Chagas transmission without clinical symptoms. The median follow-up time of the seven live patients was 15 months (range: 13-20). At present, all are symptoms-free with excellent allograft function and without evidence of Chagas disease. In conclusion, we consider that Chagas-infected donors are a promising source of liver grafts that could reduce the growing mortality on liver waiting lists in America. Relevant data from larger prospective studies are required to confirm these preliminary excellent results.

Chronic administration of propylthiouracil ameliorates hyperdynamic circulation in portal hypertensive rats.

OBJECTIVE: To evaluate the effect of a hypothyroid state, induced by chronic propylthiouracil administration, on splanchnic and systemic hemodynamic parameters in rats with portal hypertension due to portal vein ligation. METHODS: Portal hypertension was induced by surgical stenosis of the portal vein. Cardiac index and portal blood flow were measured using radioactive microspheres. Measurements were performed after treatment with propylthiouracil (1 mg/ml in drinking water) for 5 days. RESULTS: Propylthiouracil-treated portal hypertensive rats had a lower portal pressure (12.4 +/- 1.9 versus 16.3 +/- 0.7 mmHg; p < 0.05) and portal blood flow (11.6 +/- 0.7 versus 13.2 +/- 1.3 ml/min/100 g; p < 0.05) than non-treated animals. Splanchnic vasoconstriction in treated animals was associated with a higher peripheral vascular resistance (2.3 +/- 0.4 versus 1.8 +/- 0.3 mmHg/ml/min/100 g; p < 0.05) than controls. CONCLUSION: These results suggest that portal pressure can be lowered by inducing a hypothyroid state by chronic administration of propylthiouracil.

[Dexamethasone, an inhibitor of the expression of inducible nitric oxide synthase, does not modify the hyperdynamic state in cirrhotic rats]. / La dexametasona, un inhibidor de la expresion de la óxido nítrico sintasa inducible, no modifica el estado hiperdinámico en ratas cirróticas.

Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of portal hypertension. It has been proposed that it could be related to stimulation of the inducible nitric oxide synthase by endotoxin. Therefore, the aim of the present study was to evaluate whether dexamethasone treatment, an inhibitor of the expression of the inducible enzyme, ameliorates the hyperdynamic circulation observed in cirrhotic rats due to chronic bile duct ligation. Systemic and splanchnic hemodynamic parameters were measured after administration of dexamethasone (3 mg/kg/day during 3 days, i.p.) or its vehicle. In cirrhotic rats dexamethasone treatment caused a mild but not significantly higher mean arterial pressure in comparison with vehicle while similar values of cardiac output, peripheral vascular resistance, portal blood flow and portal pressure were observed in both group of animals. A significant body weight loss over the three days of treatment was observed in rats receiving dexamethasone. In sham-operated rats, dexamethasone administration caused similar changes as observed in cirrhotic animals. Endotoxemia was observed in five of six cirrhotic rats while it was not detected in the control group. Our results show that dexamethasone administration does not modify systemic and splanchnic hemodynamic parameters in endotoxemic cirrhotic rats. This finding suggests that stimulation of the inducible nitric oxide synthase may not play a role in the increased nitric oxide production in portal hypertension.

La dexametasona, un inhibidor de la expresion de la óxido nítrico sintasa inducible, no modifica el estado hiperdinámico en ratas cirróticas. / [Dexamethasone, an inhibitor of the expression of inducible nitric oxide synthase, does not modify the hyperdynamic state in cirrhotic rats]

Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of portal hypertension. It has been proposed that it could be related to stimulation of the inducible nitric oxide synthase by endotoxin. Therefore, the aim of the present study was to evaluate whether dexamethasone treatment, an inhibitor of the expression of the inducible enzyme, ameliorates the hyperdynamic circulation observed in cirrhotic rats due to chronic bile duct ligation. Systemic and splanchnic hemodynamic parameters were measured after administration of dexamethasone (3 mg/kg/day during 3 days, i.p.) or its vehicle. In cirrhotic rats dexamethasone treatment caused a mild but not significantly higher mean arterial pressure in comparison with vehicle while similar values of cardiac output, peripheral vascular resistance, portal blood flow and portal pressure were observed in both group of animals. A significant body weight loss over the three days of treatment was observed in rats receiving dexamethasone. In sham-operated rats, dexamethasone administration caused similar changes as observed in cirrhotic animals. Endotoxemia was observed in five of six cirrhotic rats while it was not detected in the control group. Our results show that dexamethasone administration does not modify systemic and splanchnic hemodynamic parameters in endotoxemic cirrhotic rats. This finding suggests that stimulation of the inducible nitric oxide synthase may not play a role in the increased nitric oxide production in portal hypertension.

Von Willebrand factor could be an index of endothelial dysfunction in patients with cirrhosis: relationship to degree of liver failure and nitric oxide levels.

BACKGROUND/AIMS: The aim of this study was to evaluate the relationship between plasma levels of von Willebrand factor (vWF), a marker of endothelial cell activation, and nitric oxide, a powerful vasodilator synthesized by endothelial cells, in 27 patients with cirrhosis at different stages of the disease. These results were compared with those of age-matched normal, healthy subjects (n=10). METHODS: vWF:antigen was measured by electro-immunodiffusion test and serum nitrite and nitrate levels, the stable end products of nitric oxide metabolism, were determined by an enzymatic procedure. RESULTS: vWF:antigen and nitrite/nitrate levels were significantly higher in cirrhotic patients (367+/-185% and 29.3+/-10.8 micromol/l) than in healthy subjects (92+/-20% and 19.2+/-8.3 micromol/l, p<0.05, respectively). Higher levels of vWF:antigen and nitrites/nitrates were observed in patients with more advanced degrees of liver failure, as reflected by quantitative Child-Pugh's score (516+/-154% and 38.3+/-7.8 micromol/l in Child-Pugh > or = 9 vs 227+/-61% and 21.0+/-6.1 micromol/l in Child-Pugh <9, p<0.001, respectively). Moreover, both endothelial-related factors were higher in patients with ascites than those without ascites (543+/-158% and 37.8+/-8.9 micromol/l vs 262+/-103% and 24.4+/-8.8 micromol/l, p<0.001, respectively). In the overall series, a highly significant linear correlation between nitrites/nitrates and vWF:antigen levels was observed in patients with cirrhosis (r=0.79, p<0.001). CONCLUSIONS: These results support a cirrhosis-related endothelial dysfunction and suggest that plasma vWF measurement could be useful as a marker of endothelial disturbance in patients with cirrhosis.

Prolonged bleeding time in experimental cirrhosis: role of nitric oxide.

BACKGROUND/AIMS: Nitric oxide is a powerful in vitro inhibitor of platelet adhesion and aggregation. Our aim was to investigate whether the in vivo inhibition of nitric oxide release shortens bleeding time, in rats with cirrhosis induced by chronic bile duct ligation. METHODS: Mean arterial pressure and bleeding time were measured under basal conditions and 5, 15 and 30 min after administration of vehicle (0.9% saline) or an inhibitor of nitric oxide synthesis, Nw-nitro-L-arginine (5 mg/kg, iv). Mean arterial pressure was measured with an intra-arterial catheter and bleeding time with a standardized Simplate device. RESULTS: Cirrhotic rats showed a lower mean arterial pressure (116+/-4 mmHg) and a prolonged bleeding time (177+/-40 s) compared to control animals (133+/-6 mmHg and 95+/-12 s, respectively, p<0.01). In cirrhotic rats, Nw-nitro-L-arginine significantly increased mean arterial pressure (from 116+/-5 to 141+/-11 mmHg, p<0.05) and completely normalized bleeding time (from 170+/-39 to 103+/-21 s, p<0.05) 15 min after administration. Pretreatment with L-arginine (300 mg/kg, iv) prevented the hemodynamic and hemostatic changes induced by Nw-nitro-L-arginine. A trend to normalize platelet adhesion was observed in cirrhotic rats after the inhibition of nitric oxide production. In control animals, Nw-nitro-L-arginine increased mean arterial pressure, while no effect on bleeding time was observed. CONCLUSIONS: These findings support the concept that nitric oxide may be a mediator in the bleeding time abnormalities associated with experimental cirrhosis.

Splanchnic hyperemia after liver transplantation in patients with end-stage liver disease.

Systemic and splanchnic hemodynamic parameters were evaluated in 12 patients with cirrhosis before and 3 and 6 months after liver transplantation. Results were compared with those obtained in 8 healthy subjects. Three months after liver transplantation recipients had an increase in mean arterial pressure (98 +/- 7 v 78 +/- 9 mmHg; P < .05), an insignificant decrease in cardiac index (3. 4 +/- 0.6 v 4.0 +/- 1.0 L . min-1 . m-2), and a marked increase in peripheral vascular resistance (1,563 +/- 308 v 800 +/- 205 dyne . s . cm-5; P < .05) compared with pretransplantation values. Portal blood flow was also significantly increased (1,494 +/- 200 v 829 +/- 130 mL/min; P < .05). These hemodynamic changes were more pronounced 6 months after transplantation (mean arterial pressure, 100 +/- 8 mmHg; cardiac index, 3.0 +/- 1.0 L . min-1 . m-2; P < .01; peripheral vascular resistance, 1,680 +/- 405 dyne . s . cm-5; portal blood flow, 1,520 +/- 180 mL/min). Systemic hemodynamics 6 months after liver transplantation were similar to those observed in the healthy control group (mean arterial pressure, 95 +/- 6 mmHg; cardiac index, 2.9 +/- 0.9 L . min-1 . m-2; peripheral vascular resistance, 1,480 +/- 380 dyne . s . cm-5). However, portal blood flow was still significantly higher than in healthy controls at 6 months (1,520 +/- 180 v 910 +/- 140 mL/min; P < .05). This study shows that systemic hemodynamics are normalized after liver transplantation. However, an increase in portal blood flow occurs and persists for at least 6 months after liver transplantation. Further studies are needed to clarify the cause of the abnormally high portal flows.

Pentoxifylline reduces nephrotoxicity associated with cyclosporine in the rat by its rheological properties.

BACKGROUND: The goals of this study were to evaluate whether administration of pentoxifylline (POF) reduces the nephrotoxicity associated with cyclosporine (CsA) in the rat, and whether the effect of POF is related to its rheological properties. METHODS: Mean arterial pressure was measured by an intraarterial catheter. Glomerular filtration rate and renal plasma flow were determined by measuring inulin and para-aminohippurate clearances, after double-blind coadministration for 10 days of CsA (25 mg/kg/day) with either vehicle or POF (45 mg/kg every 12 hr). These results were compared with those obtained in control rats. Blood viscosity and erythrocyte deformability were also evaluated after treatment using a cone plate viscometer and a filtration method, respectively. RESULTS: No changes were observed in mean arterial pressure in both groups compared with controls. Glomerular filtration rate was significantly lower in CsA-treated rats (0.3+/-0.1 ml/min/100 g) than in control animals (0.6+/-0.1 ml/min/100 g, P<0.02). The coadministration of CsA with POF normalized the glomerular filtration rate (0.6+/-0.1 ml/min/100 g). A parallel decrease in renal plasma flow was observed in CsA-treated rats compared with controls (CsA+vehicle: 1.5+/-0.2 vs. control: 2.2+/-0.1 ml/min/100 g, P<0.02), this effect completely reversed by cotreatment with POF (3.1+/-0.2 ml/min/100 g). Blood viscosity was significantly higher in CsA-treated rats than in the control group (CsA+vehicle: 5.6+/-0.7 vs. control: 5.0+/-0.4 m x Pa x s, P<0.05). This effect was associated with a lower erythrocyte deformability (CsA+vehicle: 1.2+/-0.2 vs. control: 1.5+/-0.3 ml/min, P<0.05). These rheological abnormalities were normalized by coadministration with POF (blood viscosity: 4.9+/-0.7 m x Pa x s and erythrocyte deformability: 1.9+/-0.4 ml/min, P<0.05). CONCLUSIONS: Our results show that administration of POF prevents the nephrotoxicity associated with CsA. This beneficial effect could be related to its rheological properties.

Insuficiencia renal en pacientes con trasplante hepatico: incidencia y factores predisponentes / Renal failure in patients with liver transplat: incidence and predisposing factors

En los pacientes que son sometidos a un trasplante hepático se desarrolla con frecuencia insuficiencia renal. Sin embargo, su incidencia y los factores predisponentes al desarrollo de esta complicación no han sido bien establecidos. Por tanto, nuestro estudio ha sido dirigido a clarificar ambos aspectos en pacientes que han sido sometidos a un trasplante hepático en el Hospital Italiano de Buenos Aires. Para ello, se evaluaron em forma retrospectiva 38 pacientes adulltos receptores de un trasplante hepático durante su estadía en el hospital (40 + 10 días) (media + DS). En el an lisis final se excluyeron 3 pacientes (1 hepatitis fulminante y 2 con sobrevida menor a 72 hs). El tratamiento inmunosupresor se basó en el triple esquema: ciclosporina, corticoides y azatioprina. La presencia de insuficiencia renal se definió como la existencia de una creatinina sérica > 1.5 mg/dl y/o urea > 80 mg/dl. La insuficiencia renal se clasificó cronológicamente como precoz (días 0-6) y tardia (luego del día 6). Los siguientes par metros fueron evaluados en relación a la insuficiencia hepática: preoperatoria (función hepatocelular mediante la clasificación de Chil-Pugh y renal), intraoperatorios (cantidad de hemoderivados transfundidos, episodios de hipotensión, "by-pass" venovenoso, duración de la cirugía y de la fase anhepática) y postoperatorios (sepsis, rechazo, niveles plasm ticos de ciclosporina y uso de drogas nefrotóxicas). En veintiuno de los 35 pacientes (60 por ciento) con trasplante hepático se desarrolló insuficiencia renal. En 6 pacientes fue precoz y en 15 tardía. En la serie global, los pacientes con insuficiencia renal presentaron un mayor deterioro de la función hepática en el preoperatorio (8.6 + 0.3 vs 7.8 + 0.4, p<0.05), en el intraoperatorio un mayor requerimiento de hemoderivados (13.1 + 4.3 vs 10.1 + 3.8 unidades, p<0.05) y en el postoperatorio in nivel más elevado de ciclosporina (624 + 60 vs 430 + 30 ng/ml, p<0.05) que aquellos pacientes en quienes no se desarrolló complicación. Asimismo, en los pacientes que presentaron la insuficiencia renal en forma precoz se observó un mayor deterioro de la función hepatocelular y un mayor requerimiento de hemoderivados durante la cirugía. De otra parte, en los pacientes que la desarrollaron en forma tardía, la etiopatogenia de esta complicación fue multifactorial (falla del injerto, uso de drogas nefrotóxicas y ciclosporina). En 1 paciente hubo necesidad de realizar hemodiálisis y en otro hemofiltración...(AU)

Insuficiencia renal en pacientes con trasplante hepatico: incidencia y factores predisponentes / Renal failure in patients with liver transplat: incidence and predisposing factors

En los pacientes que son sometidos a un trasplante hepático se desarrolla con frecuencia insuficiencia renal. Sin embargo, su incidencia y los factores predisponentes al desarrollo de esta complicación no han sido bien establecidos. Por tanto, nuestro estudio ha sido dirigido a clarificar ambos aspectos en pacientes que han sido sometidos a un trasplante hepático en el Hospital Italiano de Buenos Aires. Para ello, se evaluaron em forma retrospectiva 38 pacientes adulltos receptores de un trasplante hepático durante su estadía en el hospital (40 + 10 días) (media + DS). En el an lisis final se excluyeron 3 pacientes (1 hepatitis fulminante y 2 con sobrevida menor a 72 hs). El tratamiento inmunosupresor se basó en el triple esquema: ciclosporina, corticoides y azatioprina. La presencia de insuficiencia renal se definió como la existencia de una creatinina sérica > 1.5 mg/dl y/o urea > 80 mg/dl. La insuficiencia renal se clasificó cronológicamente como precoz (días 0-6) y tardia (luego del día 6). Los siguientes par metros fueron evaluados en relación a la insuficiencia hepática: preoperatoria (función hepatocelular mediante la clasificación de Chil-Pugh y renal), intraoperatorios (cantidad de hemoderivados transfundidos, episodios de hipotensión, "by-pass" venovenoso, duración de la cirugía y de la fase anhepática) y postoperatorios (sepsis, rechazo, niveles plasm ticos de ciclosporina y uso de drogas nefrotóxicas). En veintiuno de los 35 pacientes (60 por ciento) con trasplante hepático se desarrolló insuficiencia renal. En 6 pacientes fue precoz y en 15 tardía. En la serie global, los pacientes con insuficiencia renal presentaron un mayor deterioro de la función hepática en el preoperatorio (8.6 + 0.3 vs 7.8 + 0.4, p<0.05), en el intraoperatorio un mayor requerimiento de hemoderivados (13.1 + 4.3 vs 10.1 + 3.8 unidades, p<0.05) y en el postoperatorio in nivel más elevado de ciclosporina (624 + 60 vs 430 + 30 ng/ml, p<0.05) que aquellos pacientes en quienes no se desarrolló complicación. Asimismo, en los pacientes que presentaron la insuficiencia renal en forma precoz se observó un mayor deterioro de la función hepatocelular y un mayor requerimiento de hemoderivados durante la cirugía. De otra parte, en los pacientes que la desarrollaron en forma tardía, la etiopatogenia de esta complicación fue multifactorial (falla del injerto, uso de drogas nefrotóxicas y ciclosporina). En 1 paciente hubo necesidad de realizar hemodiálisis y en otro hemofiltración...

Hemostatic and hemodynamic effects of vasopressin analogue DDAVP in patients with cirrhosis

Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleending time in patients with cirrhosis. The duration of this effect and the hemodynamic changes associated with DDAVP have been studied so far. To evaluate these issues, 14 cirrhotics with portal hypertension were studied in basal conditions and after DDAVP (0.3 uk/kg). In 8 patients, hemostatic tests were done at basal conditions and 1,3,6 and 24 hs after drug administration. In the remaining 6 patients, mean arterial pressure, cardiac output, portal and femoral blood flows were evaluated. Hemodynamic parameters were measured by Doppler ultrasound. DDAVP caused a marked decrease in bleeding time at 1,3,6 and 24 hs (14+9 vs 8+3, 7+4, 6+4 and 8+4 min, respectively); the decrease was maximal and statiscally significant at 6 hs (55+15 percent, p<0.02) after DDAVP infusion. Bleeding time reduction was observed in every patient studied. In the hemodynamic study, DDAVP caused a mild but significant decrease in mean arterial pressure (12+8 percent, p<0.05); no significant changes were observed in the rest of hemodynamic parameters studied. These findings show that DDAVP can be used to shorten the bleeding time for a period of at least 24 hs in patients with cirrhosis, without deleterious hemodynamic effects. This beneficial effect may be of potential relevance in the medical management of patients with chronic liver diseases. (AU)

Hemostatic and hemodynamic effects of vasopressin analogue DDAVP in patients with cirrhosis

Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleending time in patients with cirrhosis. The duration of this effect and the hemodynamic changes associated with DDAVP have been studied so far. To evaluate these issues, 14 cirrhotics with portal hypertension were studied in basal conditions and after DDAVP (0.3 uk/kg). In 8 patients, hemostatic tests were done at basal conditions and 1,3,6 and 24 hs after drug administration. In the remaining 6 patients, mean arterial pressure, cardiac output, portal and femoral blood flows were evaluated. Hemodynamic parameters were measured by Doppler ultrasound. DDAVP caused a marked decrease in bleeding time at 1,3,6 and 24 hs (14+9 vs 8+3, 7+4, 6+4 and 8+4 min, respectively); the decrease was maximal and statiscally significant at 6 hs (55+15 percent, p<0.02) after DDAVP infusion. Bleeding time reduction was observed in every patient studied. In the hemodynamic study, DDAVP caused a mild but significant decrease in mean arterial pressure (12+8 percent, p<0.05); no significant changes were observed in the rest of hemodynamic parameters studied. These findings show that DDAVP can be used to shorten the bleeding time for a period of at least 24 hs in patients with cirrhosis, without deleterious hemodynamic effects. This beneficial effect may be of potential relevance in the medical management of patients with chronic liver diseases.

Daily variation in portal blood flow and the effect of propranolol administration in a randomized study of patients with cirrhosis.

A nocturnal increase in portal pressure and blood flow was demonstrated in patients with cirrhosis, suggesting that these hemodynamic changes may contribute to the triggering of the hemorrhagic episodes observed during the night in these patients. It is known that propranolol reduces portal flow, thus reducing the risk of variceal bleeding. In a double-blind, placebo-controlled study, we evaluated the effect of long-term propranolol administration on the daily fluctuation of systemic and splanchnic hemodynamic parameters in 14 patients with cirrhosis. Cardiac output and portal blood flow were measured by the Doppler technique. A daily fluctuation of both cardiac output and portal blood flow was observed, peaking at midnight. beta-Adrenergic blockade was manifested by a significant reduction in heart rate (-21% +/- 4%, P < .01) and cardiac output (-12% +/- 2%, P < .05). A significant decrease in portal blood flow (-20% +/- 4%, P < .01) was also observed in these patients. Propranolol administration blunted the time-related changes in cardiac output and portal blood flow. In contrast, patients receiving placebo had a nocturnal peak of both parameters similar to that observed under basal conditions. Our study shows that chronic propranolol administration abolishes the nocturnal peak of portal blood flow in patients with cirrhosis and indicates a preventive effect of propranolol in these patients.