문맥압항진증에서 Propranolol 및 Isorsorbide-5-Mononitrate의 효과

박찬국(Chan Guk Park),정규성(Kyu Sung Chung),김만우(Man Woo Kim) 대한소화기학회 1996 대한소화기학회지 Vol.28 No.2

N/A Background/Aims: Esophageal variceal bleeding is one of the major causes of death in patients with portal hypertension, mostly due to liver cirrhosis. Surgical portal-systemic shunvs, sclero- therapy and/or pharmacological treatment are used in the primary and secondary prevention of hernorrhages in high-risk patients, but the effect of tbis therapy has not improved. A major innovation in the treatment of portal hypertension was the use of phannacologic agent.; to prevent bleeding and death from ruptured esophageal varices. Porta] pressure can be reduced by decreasing blood flow and/or vascular resistance within the portal venous system. Up to now, the medical treatment of portal hypertension has been based on the use of drugs that reduce the splanchnic blood tlow, such as vasopressin, somatostatin, and 0-adrenergic blockers. Especially, the oral administration of Isosorbide-5-rnononitrate, a preterentia] venous dilator with prolonged biological activity and no hepatic metabo]ism, caused a significant reduction in portal pressure in patients with cirrhosis. This was due in part to a decrease in hepatic vascular resistance. Hcwever, the indications for and against such therapies are not standardized and the problems caused by both hemodynamic evaluation of the response to treatment and selection of responders are still unresolved. Methods: Doppler ultrasonography(real time B-scan imaging and pulsed Doppler ultrasonographic study) represents a valuable and non-invasive method for the study nf portal hemodynamics in patients with liver cirrhosis. Twenty patients(16 males, aged 51+6) had hemo- dynamic measurements in the baseline condition Liefore and 1 day, l week, 3 weeks, aind 5 weeks after oral administration of propranolol and Isosorbide-S-Mononitrate, respectively by Doppler ultrasonography. Results: Diameter, maximal ve]ocity, cross sectional area, mean velcicity, blood flow vo]ume of porta] system were significantly reduced after drug administration(p--0,001). But the congestion index was not decreased statistically. Blood flov, volume difference between the portal vein and the sum of splenic vein and superior mesenteric vein(P-SS) was significantly reduced after drug administration(p<0.001). Conslusions: The oral adrainistration of propranolo] and Isosorbide- 5-Mononitrate achieved an effective reduction in portal hypertension with cirrhosis. When pharmacologic treatment of portal hypertension is contemplated, Doppler u]trasonography would appear to be of considerable interest because of its availability, noninvasivity and repeatability.(Korean J Gastroenterol 1996; 28:241-250)

산화 질소 억제제가 문맥 고혈압 쥐의 혈역학 변화에 미치는 영향

장병익,김태년,김필영,정문관 영남대학교 의과대학 1999 Yeungnam University Journal of Medicine Vol.16 No.2

Background: Nitric oxide, a vasodilator synthesized from L-arginine by vascular endothelial cells, accounts for the biological activity of endothelium derived relaxing factor Previous studies demonstrated that nitric oxide inhibitor, N"-Nitro-L-Arginine(NNA) diminished the hyperdynamic splanchnic and systemic circulation in portal hypertensive rats. The present study was done to determine the role of nitric oxide in the development of hyperdynamic circulations in the prehepatic portal hypertensive rat model produced by partial portal vein ligation. Methods: The portal hypertensive rats were divided into water ingestion group and NNA ingestion group. After partial portal vein ligation. NNA ingestion group and water ingestion group received NNA, 1me/kg/day and plain water through the mouth for 14 days, respectively. Cardiac output, mean arterial pressure, organ blood flow and porto-systemic shunting were measured by radioisotope labeled microsphere methods. Vascular resistances were calculated by standard equation. Results: There were significant decreases in mean arterial pressure, increases in cardiac output and cardiac index, and decreases in total systemic and splanchnic vascular resistance in portal hypertensive rats compared to normal control group(p<0.01). Compared to the water ingestion group, significantly increased mean arterial pressure with decreased cardiac output and cardiac index were developed in the NNA ingestion group. Total systemic and splanchnic vascular resistance were significantly increased in the MNA ingestion group compared to water ingestion group(p<0.05). But, there was no significant difference in portal pressure between the two groups. Conclusion: The hemodynamic results of this study indicate that hyperdynamic circulation in prehepatic portal hypertensive rat model was attenuated by ingestion of NNA. Nitric oxide may play an important role in the development of hyperdynamic circulation with splanchnic vaodilation in chronic portal hypertension.

Recent Advances in the Pathogenesis and Clinical Evaluation of Portal Hypertension in Chronic Liver Disease

Kotani Kohei,Kawada Norifumi 거트앤리버 소화기연관학회협의회 2024 Gut and Liver Vol.18 No.1

In chronic liver disease, hepatic stellate cell activation and degeneration of liver sinusoidal endothelial cells lead to structural changes, which are secondary to fibrosis and the presence of regenerative nodules in the sinusoids, and to functional changes, which are related to vasoconstriction. The combination of such changes increases intrahepatic vascular resistance and causes portal hypertension. The subsequent increase in splanchnic and systemic hyperdynamic circulation further increases the portal blood flow, thereby exacerbating portal hypertension. In clinical practice, the hepatic venous pressure gradient is the gold-standard measure of portal hypertension; a value of ≥10 mm Hg is defined as clinically significant portal hypertension, which is severe and is associated with the risk of liver-related events. Hepatic venous pressure gradient measurement is somewhat invasive, so evidence on the utility of risk stratification by elastography and serum biomarkers is needed. The various stages of cirrhosis are associated with different outcomes. In viral hepatitis-related cirrhosis, viral suppression or elimination by nucleos(t)ide analog or direct-acting antivirals results in recompensation of liver function and portal pressure. However, careful follow-up should be continued, because some cases have residual clinically significant portal hypertension even after achieving sustained virologic response. In this study, we reviewed the current and future prospects for portal hypertension.

Effect of Propranolol on Portal Pressure and Systemic Hemodynamics in Patients with Liver Cirrhosis and Portal Hypertension: A Prospective Study

( Ki Tae Suk ),( Moon Young Kim ),( Dong Hun Park ),( Kyu Hong Kim ),( Ki Won Jo ),( Jin Hon Hong ),( Jae Woo Kim ),( Hyun Soo Kim ),( Sang Ok Kwon ),( Soon Koo Baik ) 대한소화기기능성질환·운동학회 2007 Gut and Liver Vol.1 No.2

Background/Aims: Propranolol can prevent variceal bleeding by ameliorating portal hypertension. We conducted this study to determine the effect of propranolol on portal hypertension and the optimal required dose in Korean cirrhotic patients. Methods: This study prospectively evaluated 50 patients with cirrhosis who exhibited variceal bleeding. The hepatic venous pressure gradient (HVPG), portal venous flow, heart rate (HR), and blood pressure were assessed both at baseline and at 3 months after the treatment. The initial dose of propranolol (20 mg) was subsequently adjusted until the target HR was reached. Patients in whom HVPG reduced by >20% or to less than 12 mmHg were defined as responders. Results: Propranolol significantly (p<0.01) reduced the HVPG (-21±26%, mean±standard deviation), portal venous flow (-25±21%), HR (-20±13%), and blood pressure (-3±13%). Twenty-nine patients were responders, and the optimal required dose was 154.4 mg. The main complication was dizziness (24%), but this was not serious enough to require medication withdrawal. Conclusions: Propranolol is safe and effective at reducing portal pressure in Korean cirrhotic patients. An effective improvement in portal hypertension requires the dose to be increased until the target HR is reached. (Gut and Liver 2007;1:159-164)

Surgery versus Radiofrequency Ablation in the Treatment of Very Early or Early Stage Hepatocellular Carcinoma Patients with Portal Hypertension

( Seheon Chang ),( Jihyun An ),( Ju Hyun Shim ),( Ha Il Kim ),( Sangyoung Yi ),( Jonggi Choi ),( Gwang Hyeon Choi ),( Danbi Lee ),( Kang Mo Kim ),( Young-suk Lim ),( Han Chu Lee ),( Young-hwa Chung ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Surgical resection is not universally recommended in hepatocellular carcinoma (HCC) patients with established portal hypertension, even in single small cases. Radiofrequency ablation (RFA) is a formal alternative in treating such patients. A number of studies have concluded that portal hypertension should not be a contraindication for hepatic resection. We aimed to compare prognostic outcomes of surgical resection versus RFA in patients with solitary ablatable HCC and portal hypertension. Methods: This retrospective study included 189 resected or ablated patients who had a subclinical single HCC ≤3 cm and clinical signs of portal hypertension. All patients had well-preserved liver function with 105 (55.6%) and 84 (44.4%) primarily receiving surgery and RFA, respectively. Overall and recurrence-free survivals were compared between the two subsets, and clinical factors related to survival endpoints were identified in the entire set. Results: The number of patients belonging to BCLC 0 stage was 45 (42.9%) and 55 (65.5%), respectively in the resection and ablation groups (P<0.05). The mean count of platelet before treatment was greater in the resection group (81.7±13.8K vs.71.7±19.3K; P<0.05). During the median follow-up of 6.2 years, tumor recurrence and mortality from any cause were noted in 62 (59.0%) and 27 (25.7%) patients; and 50 (59.5%) and 26 (31.0%), respectively in the resection and ablation groups. The respective 5-year cumulative rates of recurrence- free and overall survivals were 40.6% and 82.9% versus 33.6% and 76.2% in the corresponding groups (Ps=NS). In multivariate Cox model adjusted for other confounders, resection and RFA was comparable in terms of risk of recurrence and death (Ps=NS). Conclusions: Our data indicate that guidelines-based RFA treatment can be justified as a primary option for compensated patients with single small HCC and portal hypertension, even though a tumor is resectable.

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension

( Kwang Yong Shim ),( Young Woo Eom ),( Moon Young Kim ),( Seong Hee Kang ),( Soon Koo Baik ) 대한내과학회 2018 The Korean Journal of Internal Medicine Vol.33 No.3

The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

Ultrasonography for Noninvasive Assessment of Portal Hypertension

( Hitoshi Maruyama ),( Osamu Yokosuka ) 대한간학회 2017 Gut and Liver Vol.11 No.4

Portal hypertension is a major pathophysiology in patients with cirrhosis. Portal pressure is the gold standard to evaluate the severity of portal hypertension, and radiological intervention is the only procedure for pressure measurement. Ultrasound (US) is a simple and noninvasive imaging modality available worldwide. B-mode imaging allows broad applications for patients to detect and characterize chronic liver diseases and focal hepatic lesions. The Doppler technique offers real-time observation of blood flow with qualitative and quantitative assessments, and the application of microbubble- based contrast agents has improved the detectability of peripheral blood flow. In addition, elastography for the liver and spleen covers a wider field beyond the original purpose of fibrosis assessment. These developments enhance the practical use of US in the evaluation of portal hemodynamic abnormalities. This article reviews the recent progress of US in the assessment of portal hypertension. (Gut Liver 2017;11:464-473)

Non-cirrhotic portal hypertension in an ankylosing spondylitis patient

Park, Sukki,Lee, Ji Hyun,Choi, Joon Sul,Kim, Hyun Woo,Shim, Beom Jin,Choi, Won Kyu,Kim, Sang Hyun Yeungnam University College of Medicine 2018 Yeungnam University Journal of Medicine Vol.35 No.1

Idiopathic non-cirrhotic portal hypertension (INCPH) is a disease with an uncertain etiology consisting of non-cirrhotic portal hypertension and portal pressure increase in the absence of liver cirrhosis. In INCPH, patients exhibit normal liver functions and structures. The factors associated with INCPH include the following: Umbilical/portal pyremia, bacterial diseases, prothrombic states, chronic exposure to arsenic, vinyl chloride monomers, genetic disorders, and autoimmune diseases. Approximately 70% of patients present a history of major variceal bleeding, and treatment relies on the prevention of complications related to portal hypertension. Autoimmune disorders associated with INCPH are mainly systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. To the best of our knowledge, a case of ankylosing spondylitis (AS) associated with INCPH has not been reported thus far. Therfore, we report our experience of a patient with AS accompanied by INCPH, who showed perisplenic varices with patent spleno-portal axis and hepatic veins along with no evidence of cirrhosis on liver biopsy, and provide a brief literature review.

문맥압항진증의 병태 생리

권소영 ( So Young Kwon ) 대한간학회 2012 Postgraduate Courses (PG) Vol.2012 No.-

Portal hypertension is a serious complication of liver cirrhosis leading to the development of ascites and esophageal varices. Anatomical lesions are largely responsible for the elevated portal pressure and contribute approximately for 70% of the increased intrahepatic vascular resistance. The remaining 30% are dynamic component of the elevated portal pressure. The hepatic stellate cells play a central role in the regulation of sinusoidal resistance. Nitric oxide is a key factor in the splanchnic and intrahepatic hemodynamic abnormalities in portal hypertension. The comprehensive mechanism of pathophysiology of the portal hypertension is essential for the understanding of pharmacological therapy.

폐동맥 고혈압으로 발현한 선천성 간문맥 형성부전의 증례 보고

전수령,이활,천정은,김우선,김인원,연경모 대한영상의학회 2007 대한영상의학회지 Vol.57 No.5

Congenital absence of the portal vein (CAPV) is a rare malformation in which intestinal and splenic venous flow bypasses the liver and drains directly into the systemic circulation via a congenital portosystemic shunt. We describe two cases of CAPV presenting as pulmonary hypertension that were initially suspected as primary pulmonary hypertension. However, subsequent ultrasonography and CT detected the absence of a portal vein and the presence of a portosystemic shunt. Pulmonary hypertension is a recognized complication of liver disease and portal hypertension. However, these two cases illustrate that CAPV may result in pulmonary hypertension without liver disease or portal hypertension. 선천성 간문맥형성부전은 문맥혈류가 간을 우회하여 문맥-체정맥 단락을통해 대정맥으로 직접 배출되는 드문 기형이다. 저자들은 일차성 폐동맥고혈압으로 진단되었다가 초음파 및 전산화단층촬영을 통해 문맥의 형성부전 및 선천성 문맥-체정맥 단락을 비침습적으로 발견해 냄으로써, 이로 인한 이차성 폐동맥 고혈압이 발생하였음을 밝힐 수 있었던 증례를 2예 보고하고자 한다.