RESUMEN
The presence of cirrhosis increases the mortality of patients with peptic ulcer bleeding (PUB). Both acute variceal bleeding (AVB) and PUB are associated with substantial mortality in cirrhosis. This multicenter cohort study was performed to assess whether the mortality of patients with cirrhosis with PUB is different from that of those with AVB. Patients with cirrhosis and acute gastrointestinal bleeding were consecutively included and treated with somatostatin and proton pump inhibitor infusion from admission and with antibiotic prophylaxis. Emergency endoscopy with endoscopic therapy was performed within the first 6 hours. 646 patients with AVB and 144 with PUB were included. There were baseline differences between groups, such as use of gastroerosive drugs or ß-blockers. Child-Pugh and Model for End-Stage Liver Disease MELD scores were similar. Further bleeding was more frequent in the AVB group than those in the PUB group (18% vs. 10%; odds ratio [OR] = 0.50; 95% confidence interval [CI] = 0.29-0.88). However, mortality risk at 45 days was similar in both groups (19% in the AVB group vs. 17% in the PUB group; OR = 0.85; 95% CI = 0.55-1.33; P = 0.48). Different parameters, such as Child-Pugh score, acute kidney injury, acute on chronic liver failure, or presence of shock or bacterial infection, but not the cause of bleeding, were related to the risk of death. Only 2% of the PUB group versus 3% of the AVB group died with uncontrolled bleeding (P = 0.39), whereas the majority of patients in either group died from liver failure or attributed to other comorbidities. CONCLUSION: Using current first-line therapy, patients with cirrhosis and acute peptic ulcer bleeding have a similar survival than those with variceal bleeding. The risk of further bleeding is higher in patients with variceal hemorrhage. However, few patients in both groups died from uncontrolled bleeding, rather the cause of death was usually related to liver failure or comorbidities. (Hepatology 2018;67:1458-1471).
Asunto(s)
Várices Esofágicas y Gástricas/mortalidad , Hemorragia Gastrointestinal/mortalidad , Cirrosis Hepática/mortalidad , Úlcera Péptica/mortalidad , Anciano , Profilaxis Antibiótica/métodos , Causas de Muerte , Estudios de Cohortes , Endoscopía Gastrointestinal/métodos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Femenino , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Úlcera Péptica/complicaciones , Úlcera Péptica/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Somatostatina/uso terapéutico , Tasa de SupervivenciaRESUMEN
Monitoring the hemodynamic response of portal pressure (PP) to drug therapy accurately stratifies the risk of variceal rebleeding (VRB). We assessed whether guiding therapy with hepatic venous pressure gradient (HVPG) monitoring may improve survival by preventing VRB. Patients with cirrhosis with controlled variceal bleeding were randomized to an HVPG-guided therapy group (N = 84) or to a control group (N = 86). In both groups, HVPG and acute ß-blocker response were evaluated at baseline and HVPG measurements were repeated at 2-4 weeks to determine chronic response. In the HVPG-guided group, acute responders were treated with nadolol and acute nonresponders with nadolol+nitrates. Chronic nonresponders received nadolol+prazosin and had a third HVPG study. Ligation sessions were repeated until response was achieved. The control group was treated with nadolol+nitrates+ligation. Between-group baseline characteristics were similar. During long-term follow-up (median of 24 months), mortality was lower in the HVPG-guided therapy group than in the control group (29% vs. 43%; hazard ratio [HR] = 0.59; 95% confidence interval [CI] = 0.35-0.99). Rebleeding occurred in 19% versus 31% of patients, respectively (HR = 0.53; 95% CI = 0.29-0.98), and further decompensation of cirrhosis occurred in 52% versus 72% (HR = 0.68; 95% CI = 0.46-0.99). The survival probability was higher with HVPG-guided therapy than in controls, both in acute (HR = 0.59; 95% CI = 0.32-1.08) and chronic nonresponders (HR = 0.48; 95% CI = 0.23-0.99). HVPG-guided patients had a greater reduction of HVPG and a lower final value than controls (P < 0.05). CONCLUSION: HVPG monitoring, by stratifying risk and targeting therapy, improves the survival achieved with currently recommended treatment to prevent VRB using ß-blockers and ligation. HVPG-guided therapy achieved a greater reduction in PP, which may have contributed to reduce the risk of rebleeding and of further decompensation of cirrhosis, thus contributing to a better survival. (Hepatology 2017;65:1693-1707).
Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Hemorragia Gastrointestinal/prevención & control , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Presión Portal , Anciano , Quimioterapia Combinada , Endoscopía Gastrointestinal , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Humanos , Hipertensión Portal/complicaciones , Dinitrato de Isosorbide/administración & dosificación , Dinitrato de Isosorbide/análogos & derivados , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , España/epidemiologíaRESUMEN
OBJECTIVES: In compensated cirrhosis, a threshold value of hepatic venous pressure gradient (HVPG) ≥10 mm Hg is required for the development of decompensation. However, whether the treatment of portal hypertension (PHT) can prevent the transition into development of ascites once this level has been reached is unclear. Our aim was to assess the relationship between changes in HVPG induced by ß-blockers and development of ascites in compensated cirrhosis with severe PHT. METHODS: Eighty-three patients without any previous decompensation of cirrhosis, with large esophageal varices and HVPG ≥12 mm Hg were included. After baseline hemodynamic measurements nadolol was administered and a second hemodynamic study was repeated 1-3 months later. RESULTS: During 53±30 months of follow-up, decompensation occurred in 52 patients (62%) and in 81% of them ascites was the first manifestation. Using receiver operating characteristic curve analysis a decrease in HVPG ≥10% was the best cutoff to predict ascites. As compared with nonresponders, patients with an HVPG decrease ≥10% had a lower probability of developing ascites (19% vs. 57% at 3 years, P<0.001), refractory ascites (P=0.007), and hepatorenal syndrome (P=0.027). By Cox regression analysis hemodynamic nonresponse was the best predictor of ascites. By stepwise logistic regression, development of ascites was independently associated with nonresponse, whereas refractory ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis were not. CONCLUSIONS: In patients with compensated cirrhosis and large varices treated with ß-blockers, an HVPG decrease ≥10% significantly reduces the risk of developing ascitic decompensation and other related complications such as refractory ascites or hepatorenal syndrome.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Ascitis/tratamiento farmacológico , Ascitis/etiología , Hipertensión Portal/complicaciones , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Ascitis/fisiopatología , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Hipertensión Portal/fisiopatología , Cirrosis Hepática/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Curva ROC , Resultado del TratamientoRESUMEN
INTRODUCTION: Given that beta-blockers reduce the incidence of bacterial translocation in cirrhotic rats, the aim of this study was to compare the long-term incidence of spontaneous bacterial peritonitis in cirrhotic patients submitted to pharmacologic versus endoscopic treatment to prevent variceal rebleeding. PATIENTS AND METHODS: Two hundred and thirty patients with variceal hemorrhage were included in two previous randomized trials performed to compare the efficacy of medication (nadolol plus isosorbide mononitrate, n=115) versus endoscopic treatment (n=115) with sclerotherapy or ligation for the prevention of rebleeding. RESULTS: The mean follow-up was 23+/-1.4 months. The characteristics of the patients and the number of patients on long-term prophylaxis with norfloxacin were similar in both groups. The incidence of spontaneous bacterial peritonitis was lower in the medication group (9 versus 14.7%, P=NS). The probability of spontaneous bacterial peritonitis was also lower in the medication group (6 versus 12% at 1 year, 22 versus 36% at 5 years; P=0.08), due to a significantly lower probability of community-acquired spontaneous bacterial peritonitis in this group (1 versus 10% at 1 year, 18 versus 32% at 5 years; P=0.02). Patients with no hemodynamic response to therapy had a significantly higher probability to develop community-acquired spontaneous bacterial peritonitis during follow-up than hemodynamic responders (P<0.03). Long-term probability of developing community-acquired spontaneous bacterial peritonitis is lower in patients submitted to pharmacologic treatment for preventing variceal rebleeding than in those submitted to endoscopic treatment. CONCLUSION: Long-term pharmacologic prophylaxis of variceal rebleeding contributes to the prevention of community-acquired spontaneous bacterial peritonitis.
Asunto(s)
Infecciones Bacterianas/prevención & control , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/prevención & control , Hipertensión Portal/tratamiento farmacológico , Peritonitis/prevención & control , Antagonistas Adrenérgicos beta/uso terapéutico , Infecciones Bacterianas/etiología , Infecciones Comunitarias Adquiridas/etiología , Infecciones Comunitarias Adquiridas/prevención & control , Quimioterapia Combinada , Métodos Epidemiológicos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/terapia , Esofagoscopía , Femenino , Hemorragia Gastrointestinal/etiología , Hemodinámica , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/terapia , Dinitrato de Isosorbide/análogos & derivados , Dinitrato de Isosorbide/uso terapéutico , Ligadura/métodos , Masculino , Persona de Mediana Edad , Nadolol/uso terapéutico , Peritonitis/etiología , Escleroterapia , Prevención Secundaria , Vasodilatadores/uso terapéuticoRESUMEN
OBJECTIVES: High dose of somatostatin infusion achieves a greater reduction of hepatic venous pressure gradient (HVPG) than the usual dose, and terlipressin decreases HVPG through mechanisms other than somatostatin. Our aim was to assess the hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose. METHODS: Hemodynamic studies were performed in 80 patients with cirrhosis and variceal bleeding during the first 3 days of admission. After baseline measurements, somatostatin was administered (250 microg/h with an initial bolus of 250 microg). Patients were considered responders when the HVPG decreased by >10% from baseline (n = 31). Nonresponders were randomized under double-blind conditions to a control group (n = 7), or to receive terlipressin (2 mg IV bolus, n = 22), or high dose of somatostatin (500 microg/h, n = 20). Final measurements were obtained 30 min later. RESULTS: Terlipressin caused a decrease in HVPG (from 22.2 +/- 5 to 19.1 +/- 5.2, p < 0.01) and heart rate (p < 0.01), while mean arterial pressure increased (p < 0.01). High somatostatin dose also reduced HVPG (from 21.8 +/- 3.4 to 19.6 +/- 3.1, p < 0.01), although this decrease was more pronounced with terlipressin (15%+/- 9%vs 10%+/- 6% from baseline, p= 0.05). Both terlipressin and high somatostatin dose achieved a significantly higher rate of response than that in the control group. A decrease in HVPG >20% was observed in 36% of cases with terlipressin versus 5% with high somatostatin dose (p= 0.02). CONCLUSIONS: In nonresponders to usual somatostatin dose, both terlipressin and high-dose of somatostatin infusion significantly decreased HVPG and increased the rate of hemodynamic responders. Such effects were greater with terlipressin. Both treatments may be an alternative when standard somatostatin fails.
Asunto(s)
Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Lipresina/análogos & derivados , Lipresina/farmacología , Somatostatina/administración & dosificación , Vasoconstrictores/farmacología , Anciano , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Circulación Hepática/efectos de los fármacos , Lipresina/administración & dosificación , Masculino , Persona de Mediana Edad , Terlipresina , Vasoconstrictores/administración & dosificación , Presión Venosa/efectos de los fármacosRESUMEN
BACKGROUND/AIMS: Following treatment with beta blockers in patients with cirrhosis and portal hypertension, reduction of hepatic venous pressure gradient (HVPG) to <12 mmHg or by >20% of baseline induces an extremely low risk of variceal bleeding. However, several factors such as compliance to therapy or alcohol abstinence may change the initial response after a long follow-up, and the effect of response on other complications of cirrhosis is less clear. The aim of this study was to assess the long-term maintenance of hemodynamic response and its influence on complications of cirrhosis. METHODS: One hundred and thirty two cirrhotic patients received nadolol and isosorbide mononitrate to prevent variceal rebleeding. HVPG was measured at baseline, after 1 to 3 months under treatment and again 12 to 18 months later. RESULTS: Sixty four patients were responders. After a longer follow-up, earlier response did not change in 81% of cases. Changes of response were mainly related to modifications in medication dose or in alcohol intake. As compared with poor-responders, responders had a lower probability of developing ascites (P<0.001) and related conditions, a greater improvement of Child-Pugh score (P=0.03), and a lower likelihood of developing encephalopathy (P=0.001) and of requiring liver transplantation (P=0.002). Eleven responders and 22 poor-responders died (P=0.029). CONCLUSIONS: Hemodynamic response to treatment of portal hypertension is usually sustained after a long-term follow-up. Response decreases the probability of developing complications of cirrhosis and the need for liver transplantation, and significantly improves survival.
Asunto(s)
Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/fisiopatología , Dinitrato de Isosorbide/análogos & derivados , Cirrosis Hepática/complicaciones , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Ascitis/etiología , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/prevención & control , Femenino , Hemodinámica/efectos de los fármacos , Encefalopatía Hepática/etiología , Humanos , Hipertensión Portal/etiología , Dinitrato de Isosorbide/uso terapéutico , Circulación Hepática/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Nadolol/uso terapéutico , PronósticoRESUMEN
Paracentesis-induced circulatory dysfunction (PICD) is a recently described complication that can be prevented with the administration of plasma expanders. The aim of this study was to compare the efficacy of saline versus albumin in the prevention of PICD. Patients were randomized to receive albumin or saline after total paracentesis. Patients readmitted as a consequence of a second episode of tense ascites were treated with total paracentesis and the alternative plasma expander. After randomization, 35 patients received saline and 37 received albumin. Twenty-one patients were readmitted for tense ascites and treated with the alternative expander. Significant increases in plasma renin activity (PRA) were found 24 hours and 6 days after paracentesis when saline was used (baseline, 5.6 +/- 5.7; 24 hours, 7.6 +/- 6.9; 6 days, 8.5 +/- 8.0 ng x mL(-1). hr(-1); P <.05 and P <.01 vs. baseline, respectively), whereas no significant changes were observed with albumin. The incidence of PICD was significantly higher in the saline group versus the albumin group (33.3% vs. 11.4%, respectively; P =.03). However, no significant differences were found when less than 6 L of ascitic fluid was evacuated (6.7% vs. 5.6% in the saline and albumin groups, respectively; P =.9). Similar results were observed when analyzing patients who received 2 consecutive paracentesis (i.e., a significant increase in PRA after saline [P <.01] without significant variations after albumin). In conclusion, albumin is more effective than saline in the prevention of PICD. Saline is a valid alternative to albumin when less than 6 L of ascitic fluid is evacuated.
Asunto(s)
Albúminas/administración & dosificación , Ascitis/terapia , Enfermedades Cardiovasculares/prevención & control , Enfermedades Renales/prevención & control , Cirrosis Hepática/terapia , Paracentesis/efectos adversos , Cloruro de Sodio/administración & dosificación , Anciano , Ascitis/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Incidencia , Enfermedades Renales/epidemiología , Enfermedades Renales/etiología , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Sustitutos del Plasma/administración & dosificación , Valor Predictivo de las Pruebas , Recurrencia , Resultado del TratamientoRESUMEN
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