Guías para el diagnóstico y seguimiento de niños y adolescentes portadores de hipertensión portal / Guidelines for diagnosis and follow-up of children and adolescents with portal hypertension

La hipertensión portal es un síndrome complejo producido por un aumento de la resistencia al flujo venoso esplácnico a nivel de la vena porta o sus ramas, con una circulación sistémica hiperdinámica caracterizada por vasodilatación periférica y aumento del gasto cardíaco. El sitio de obstrucción al flujo portal puede ser prehepático (hígado normal), intrahepático (como en la cirrosis) o posthepático (síndrome de BuddChiari). En los pacientes pediátricos, las causas prehepáticas e intrahepáticas se reparten en proporciones casi iguales (aproximadamente el 50 % cada una). La expresión clínica y el impacto individual son muy variados, pero en todos los casos expresan un deterioro en la salud de los pacientes y la necesidad de corregir el problema, tanto en sus consecuencias como, idealmente, en sus causas.

Portal hypertension is a complex syndrome caused by increased resistance to the splachnic venous flow at the portal vein level, with a hyperdynamic systemic circulation characterized by peripheral vasodilation and high cardiac output. Portal flow can be obstructed at prehepatic (¨normal liver¨), intrahepatic (as in cirrhosis), or post-hepatic level (as in Budd-Chiari syndrome). In pediatric patients, prehepatic and intrahepatic causes are almost equally distributed (nearly 50% each). Clinical presentation and individual impact are heterogeneous, but in each case, it is the expression of a worsening condition and the need to solve the problem, either by treating its consequences or (ideally) its causes.

Hemodynamic effect of spironolactone in liver cirrhosis and propranolol-resistant portal hypertension.

OBJECTIVE: In a proportion of patients with liver cirrhosis, portal pressure does not decrease adequately with propranolol. These patients may benefit from another drug that may reduce portal pressure. We evaluated the role of spironolactone, alone or with propranolol, in such patients. METHODS: Patients with cirrhosis, with or without ascites, with esophageal varices and with hepatic venous pressure gradient exceeding 12 mmHg, which did not show a 20% reduction after an 80-mg oral dose of propranolol, were studied. They were allocated to receive spironolactone 100 mg orally once daily either alone (group 1, n=10) or with propranolol 40 mg orally twice daily (group 2, n=10), for 7 days, after which the hemodynamic study was repeated. RESULTS: Hepatic venous pressure gradient decreased in those receiving spironolactone and propranolol (p=0.007); 5 patients in group 1 and 7 in group 2 showed a reduction in hepatic venous pressure gradient by more than 20%. However, the reduction produced by spironolactone alone (20.5 [31.3]%) was not significantly different from that produced by combination therapy (30.3 [25.9]%; p=0.46). CONCLUSION: Spironolactone in combination with propranolol achieves adequate reduction (> or = 20%) in hepatic venous pressure gradient in propranolol-resistant portal hypertension in patients with liver cirrhosis. Spironolactone alone was also effective in some patients.

Comparison of Doppler Ultrasonography and Hepatic Venous Pressure Gradient in Assessing Portal Hypertension in Liver Cirrhosis / 대한간학회지

BACKGROUND/AIMS: This prospective study aimed to determine if Doppler ultrasonography can be representative of hepatic venous pressure gradient (HVPG) in assessing the severity of portal hypertension and response to drug reducing portal pressure. METHODS: The HVPG and the parameters of Doppler ultrasonography including portal venous velocity (PVV) and splenic venous velocity, the pulsatility and resistive index of hepatic, splenic and renal arteries were measured in 105 patients with liver cirrhosis. In 31 patients the changes of hepatic venous pressure gradient and portal venous velocity after administration of terlipressin were evaluated. The patients who showed a reduction in HVPG of more than 20% of the baseline were defined as responders to terlipressin. RESULTS: Any Doppler ultrasonographc parameters did not correlate with HVPG. Both HVPG and PVV showed a highly significant reduction after the administration of terlipressin(-28.3 +/- 3.9%, -31.2 +/- 2.2% respectively). However, PVV decreased significantly not only in responders(31.7 +/- 2.4%) but also in nonresponders(29.5 +/- 6.1%). CONCLUSION: Doppler ultrasonography can not be representative of HVPG in assessing the severity of portal hypertension and response to drug reducing portal pressure in liver cirrhosis.

Un análisis retrospectivo de cavernomatosis de la vena porta en Chile: II: hemorragia, tratamiento y pronóstico / A retrospective analysis of portal vein cavernomatosis in Chile: II: hemorrhage, treatment and prognosis

Objetivo: El tratamiento de la hipertensión portal de origen prehepático en niños es motivo de controversia. El objetivo de este estudio retrospectivo fue analizar la evolución, tratamiento y morbimortalidad de 34 niños con cabermomatosis de la vena porta. Pacientes y método: Se analizó la evolución antropométrica y hematológica, las características del sangramiento digestivo, el tratamiento médico, endoscópico y quirúrgico,y la morbimortalidad. Resultados: El 74 por ciento de los niños presentó uno o más episodios de sangramiento. El 56 por ciento de los niños recibió prepanolol como profilaxis y el 38 por ciento fue sometido a escleroterapia de várices esofágicas. Sólo seis niños requirieron de cirugia derivativa. La mortalidad fue el 5,6 por ciento y el seguimiento fue de 3,6 años por niño.Conclusión: Aun cuando la hemorragia digestiva alta por ruptura de las várices esofágicas fue la complicación más frecuente de la cavernomatosis de la porta en esta serie, el éxito del tratamiento médico y endoscópico en evitar un nuevo episodio de sangramiento sugieren que a futuro un número menor de pacientes requerirá de cirugía derivativa portosistémica

Drug treatment of portal hypertension.

Despite advances in endoscopic management, variceal bleeding is still associated with a significant mortality. In recent years, several therapeutic agents have been shown to lower the portal pressure and reduce variceal bleeding. In patients presenting with acute variceal bleeding, the drug of choice is somatostatin; it is as effective as endoscopic treatment and is virtually free of side-effects. The second-line drug therapy in acute variceal bleeding is a combination of vasopressin and nitroglycerine. Every patient with a history of variceal bleeding is at an increased risk of rebleeding and should receive some form of preventive therapy. In these patients, non-selective beta-blockers and endoscopic treatment are equally effective and either modality can be used. Since each episode of variceal bleeding carries a 30%-50% risk of death, cirrhotics who have never experienced variceal bleeding but are at high risk to develop this complication (high portal pressure, variceal grade III and IV, and presence of red wale markings over the varices) should be identified and treated. Beta-blockers are the treatment of choice and should be continued for the rest of the patient's life. Isosorbide-5-mononitrate is also useful in lowering the portal pressure and may be combined with beta-blockers in those who do not respond to the use of beta-blockers alone. However, isosorbide-5-mononitrate should not be given alone for a long duration because of its adverse haemodynamic effects. Additional measures which are useful in decreasing the risk of variceal bleeding are good control of ascites, especially with spironolactone and a low salt diet, and early recognition and treatment of bacterial infections.

Assessment of effects of propranolol on portal hemodynamics in cirrhosis by duplex ultrasonography.

OBJECTIVE: To study the effect of propranolol on portal hemodynamics in cirrhotics using duplex ultrasonography. METHODS: Portal venous flow was measured by duplex ultrasonography in 12 healthy volunteers and ten men with cirrhosis. The cirrhotics were evaluated prior to and after ingestion of propranolol (60 mg twice daily for seven days) or placebo in a randomized cross-over fashion. Variations in heart rate, blood pressure, portal vein diameter, and portal venous flow and velocity were evaluated. RESULTS: The mean (SD) portal venous flow in the volunteers was 746 (280) mL/min, portal flow velocity was 18.5 (3.6) cm/s and portal vein diameter was 9.2 (1.4) mm. In cirrhotics, propranolol decreased portal blood flow from 586 (220) to 413 (120) mL/min (p < 0.03), the overall reduction being 29.5%. This effect was due to decrease in portal flow velocity, from 12.5 (3.3) to 9.7 (2.3) cm/s (p < 0.03) without significant change in portal vein diameter. No changes were observed with placebo. CONCLUSIONS: Propranolol decreases portal flow velocity and thus portal venous flow in cirrhotics.

A hipertenão portal e o papel da determinação do gradiente de pressão portal em cirróticos com varizes esofágicas / The role of hepatic venous pressure determination on patients with chronic liver disease and hypertension

Os autores avaliaram a profilaxia medicamentosa do sangramento proveniente da ruptura de varizes de esôfago, em pacientes cirróticos, salientando o papel da determinação do gradiente de pressão portal. Consideram ser esse um método seguro para determinar com precisão e eficácia da terapia farmacológica, bem como seu papel prognóstico nos pacientes cirróticos, quando da indicação de cirurgia de ressecção de tumor primário nessa população de doentes. Concluem pela necessidade de que esse método seja amplamente utilizado, permitindo um melhor manejo dos pacientes com hepatopatias crônicas e hipertensão portal

Systemic and portal hemodynamic response to propranolol in patients with portal hypertension due to hepatitis c virus

Propranolol, a -adrenergic blocker, has been reported to reduce portal pressure in patients with alcoholic cirrhosis and thereby might be useful in the prophylaxis of variceal bleeding. Since it is not known if the response of patients with portal hypertension due to hepatitis C virus is similar, systemic and portal hemodynamic response to propranolol was evaluated in 10 patients with portal hypertension and hepatitis C virus infection. Patients were studied before the intravenous infusion of 0.15 mg/kg propranolol, and 30 min after the infusion. Propranolol induced highly significant systemic hemodynamic effects, reducing heart rate from 65 +/- 6 to 57 +/- 5 [p < 0.0001] and cardiac output from 6.7 +/- 1.6 to 5.0 +/- 1.1 [liters/min, p < 0.0005]. The effect on the pulmonary circulation was a mild increase in diastolic pulmonary artery pressure. Propranolol induced a mild and insignificant decrease in wedged hepatic vein pressure [WHVP], from 32 +/- 6 to 29 +/- 5 mm Hg, and hepatic venous pressure gradient from 18 +/- 3 to 16 +/- 5 mm Hg [p > 0.05]. Decrease of WHVP of more than 5 mm Hg occurred only in 3 out of 10 patients. It is suggested that propranolol may be useful only in some patients with portal hypertension associated with hepatitis C virus infection

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.

Effect of atrial natriuretic factor [ANF] on portal venous pressure in dogs

Dogs were allocated into three different groups of equal size. Group I was injected with atrial extract, group II was injected with phenylephrine [alpha 1 agonist] followed by atrial extract, while group III was injected with prazosin [alpha 1 antagonist] followed by atrial extract. The intravenous injection of atrial extract was coupled by a significant reduction in portal venous pressure in dogs whose portal venous pressure has not been altered as well as those which have been subjected to a pressure increase by the intravenous injection of phenylephrine or a decrease by the intravenous injection of prazocin. Moreover, atrial extract injection reduced significantly the serum sodium level in all groups without any effects on serum potassium level. It was concluded that, atrial extract has a hypotensive effect on portal venous pressure raising the possibility of using ANF as a new natural agent to reduce portal hypertension

Propranolol in bleeding oesophageal varices

Forty seven cases of portal hypertension with bleeding oesophageal varices were given oral propranolol in doses that reduced the resting heart rate by 25%. Patients were fallowed up for 2 years and on each visit pulse, number of bleeds and any side effects were recorded. Eighty three% patients did not bleed till 2 years while they were on propranolol. Titree patients died of gaslro-intestinnal bleeding during the follow up, while one developed bronchospasm, which was controlled on discontinuation of the drug therapy

Tratamento da hipertensäo portal de etiologia esquistossomótica / Treatment of portal hypertension in schistosomiasis

Historicamente tem sido utilizados, no tratamento de doentes esquistossomóticos com varizes esofagogástricas hemorrágicas, os mesmos métodos aplicados em todo o mundo para o tratamento da hipertensäo portal e outras etiologias, particulamente a cirrose alcoólica. Parece claro que, até o momento, todos estes métodos, conservadores ou cirurgicos, carecem de fundamentaçäo mais segura, baseada em resultados dos estudos comparativos realizados em esquistossomóticos, näo devendo, portanto, ser utilizados indiscriminadamente. Em relaçäo aos métodos operatórios, os autores enfatizam a necessidade de estudos prospectivos que tragam informaçäo mais objetiva em relaçäo ao trataemnto cirúrgico da esquistossomose. A avaliaçäo pós-operatória tardia (superior a cinco anos) de um grupo de doentes - portadores de esquistossomose na forma hepatosplênica "pura" e submetidos à anastomose esplenorrenal distal com perviedade comprovada por ocasiäo dessa avaliaçäo - permitiu concluir que esse tipo de técnica operatória apresenta vantagens em relaçäo aos outros métodos de tratamento da hipertensäo portal de etiologia esquistossomótica

Tratamento das varizes hemorrágicas de fundo gástrico com adesivo tecidual n-butil-2-cianoacrilato / Treatment of gastric fundus bleeding varices with n-butyl-2-cyanoacrylate

De janeiro de 1991 a fevereiro de 1995, foram estudados 19 pacientes (sete do sexo feminino, 12 do sexo masculino; idades de 34 a 74 anos, média de 43 anos) portadores de hipertensao portal nao segmentar (HPNS) e varizes de fundo gástrico (VFG). Cirrose por vírus B acometeu oito pacientes (42 por cento), por vírus C quatro (21 por cento), alcoólica três (16 por cento), criptogenética um (5 por cento), além de três (16 por cento) enfermos portadores de esquistossomose hepatesplênica. A maior parte dos hepatopatas foram Child-Pugh A e B (17 pacientes - 90 por cento). Quatorze pacientes (74 por cento) apresentaram sangramento digestivo maciço por rotura das VFG e receberam injeçao endoscópica intravasal de soluçao de n-butil-2-cianoacrilato e lipiodol, para interrupçao da hemorragia e erradicaçao do colateral gástrico, evitando novos episódios de sangramento. Em cinco pacientes (26 por cento), o tratamento com o adesivo tecidual foi profilático, motivado pelo aumento progressivo do volume dos colaterais (gástricos e adelgaçamento da mucosa que os recobria. Em período médio de seguimento de 17 meses, obteve-se o controle da rotura das VFG em 13 dos 14 (93 por cento) pacientes com sangramento prévio. A erradicaçao dos cordoes gástricos foi atingida em 17 dos 19 (90 por cento) enfermos. A mortalidade neste estudo foi de 1O por cento (dois pacientes), motivada por hemorragia incontrolável em um e encefalopatia e sepse em outro enfermo (apesar do controle do sangramento). A injeçao paravasal do adesivo provocou úlcera gástrica nao hemorrágica, que levou três meses para a cicatrizaçao: única complicaçao relacionada ao método (5 por cento). A alta eficácia desta técnica no controle das VFG motivou os autores a sugerirem estudos comparativos entre o uso do cianoacrilato e cirurgias de descompressao portal e até mesmo TIPS neste subgrupo de hepatopatas.

effect of praziquantel and histamine and serotonin blockers on portal pressure and hepatic granuloma in experimental schistosomiasis mansoni

The present study was conducted to determine the effect of Schistosomiasis mansoni infestation on the morbidity of the disease expressed in terms of portal pressure, liver granuloma diameter and blood levels of histamine and serotonin. These parameters were evaluated in infected untreated and treated mice either Praziquantel [PZQ] alone or combined with histamine and serotonin blockers. A total of 922 Swiss albino CFW1 mice were included in the study. The results of the present work showed that treatment with PZQ caused a significant increase in portal pressure, histamine and serotonin blood levels with a significant decrease in hepatic granuloma diameter. Combination of PZQ with histamine [H1] blocker or serotonin antagonist [5-HT2 blocker] produced significant reduction in portal pressure and granuloma diameter without affecting the blood level of histamine or serotonin respectively when compared with PZO treated group. On the other hand, combination of PZQ with H2 blocker had no significant effect on any of the parameters studied. These findings point to role of H1 or 5-HT2 blockers in the control of schistosome disease morbidity particularly in cases subjected to specific chemotherapy such as Praziquantel