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.

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)

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.

문맥압항진 위병증과 위전정부 혈관확장증

최원혁 ( Won Hyeok Choe ) 대한소화기학회 2010 대한소화기학회지 Vol.56 No.3

Portal hypertensive gastropathy (PHG) is a term used to define the endoscopic findings of gastric mucosa with a characteristic mosaic-like pattern with or without red spots, and a common finding in patients with portal hypertension. These endoscopic findings correspond to dilated mucosal capillaries without inflammation. The pathogenesis of PHG in not well known, but portal hypertension and some humoral factors seem to be crucial factors for its development. Pharmacological (e.g. propranolol), or interventional radiological (such as transjugular intrahepatic portosystemic shunt) procedures may be useful in preventing re-bleeding from PHG. The classic features of gastric antral vascular ectasia (GAVE) syndrome Include red, often haemorrhagic lesions predominantly located in the gastric antrum which can result in significant blood loss. Although the pathogenesis of GAVE is not clearly defined, it seems to be a separate disease entity from PHG, because GAVE generally does not respond to a reduction of portal pressures. Endoscopic ablation (such as argon plasma coagulation) is the first-line treatment of choice. This review will focus on the incidence, clinical importance, etiology, pathophysiology, and treatment of PHG and GAVE syndrome in the setting of portal hypertension. (Korean J Gastroenterol 2010;56:186-191)

간경변증에서의 폐합병증

한슬기,백순구,김문영 대한소화기학회 2023 대한소화기학회지 Vol.82 No.5

Portal hypertension is a clinical syndrome defined by an increased portal venous pressure. The most frequent cause of portal hypertension is liver cirrhosis, and many of the complications of cirrhosis, such as ascites and gastroesophageal variceal bleeding, are related to portal hypertension. Portal hypertension is a pathological condition caused by the accumulation of blood flow in the portal system. This blood flow retention reduces the effective circulation volume. To compensate for these changes, neurotransmitter hormone changes and metabolic abnormalities occur, which cause complications in organs other than the liver. A hepatic hydrothorax is fluid accumulation in the pleural space resulting from increased portal pressure. Hepatopulmonary syndrome and portopulmonary hypertension are the pulmonary complications in cirrhosis by deforming the vascular structure. Symptoms, such as dyspnea and hypoxia, affect the survival and the quality of life of patients. These lung complications are usually underestimated in the management of cirrhosis. This review briefly introduces the type of lung complications of cirrhosis.

간문맥 고혈압에서 문맥 전신성 측부순환의 CT 소견

김호균,심재찬,이성숙 인제대학교 1999 仁濟醫學 Vol.20 No.1

간문맥성 고혈압(Portal hypertension) 환자 48명의 CT 소견을 분석하여 원인을 분류하고, 문맥전신성 측부순환(Portosystemic collaterals)의 종류와 빈도를 파악하며, 이들 소견이 어떻게 보이는지를 알아보고자 하였다. 또한 문맥 고혈압 환자의 문맥전신성 측부순환의 CT소견을 이해함으로써 좀 더 많은 측부순환을 찾을 수 있고, 커진 림프절이나 다른 연부조직 종괴와의 감별에 도움을 줄 수 있을 것이다. Objectives: The purpose of this study is to evaluate the usefulness of CT in detection of portosystemic collaterals in portal hypertension. Mlethods and Materials: Medical records and CT findings of 48 patients with portal hypertension were reviewed. We classified portosystemic collaterals into 10 groups. Results: Liver cirrhosis was the cause of portal hypertension in 44 cases(91.7%), and hepatocellular carcinoma was associated in 12 cases(25.0%). Total 117 cases of portosystemic collaterals were identified. CT showed 33 coronary veins(28.2%), 33 gastroesophageal varices(28.2%), 19 recanalized umbilical veins(16.2%), 14 gastrorenal-splenorenal shunts(12.0%), 5 dilated azygos systems(4.3%), 3 cavernous transformations(2.6%), 3 peripancreatic collaterals(2.6%), 3 perigastric collaterals(2.6%), 2 retroperitoneal-paravertebral collaterals(1.7%), and 2 Caput Medusa(1.7%). Conclusion: CT is useful in the evaluation of portosystemic collaterals in patients with portal hypertension, and it can differentiate the collaterals from enlarged lymph node or soft tissue mass.

사례보고 : 간문맥혈전증을 동반한 특발성 문맥고혈압 환자에서 Protein C, Protein S 결핍 1예

황세나 ( Se Na Hwang ),김도영 ( Do Young Kim ),김민주 ( Min Ju Kim ),전영은 ( Young Eun Chon ),이현정 ( Hyun Jung Lee ),박영년 ( Young Nyun Park ),박준용 ( Jun Yong Park ),안상훈 ( Sang Hoon Ahn ),한광협 ( Kwang Hyub Han ),전재윤 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Portal vein thrombosis (PVT) is an uncommon cause of presinusoidal portal hypertension. Among various hepatoportal disorders, noncirrhotic portal hypertension conditions such as idiopathic portal hypertension (IPH) are considered to have a close relation with PVT. PVT is known to have several predisposing conditions, including infection, malignancies, and coagulation disorders. There is growing interest and recognition that deficiencies in proteins C and S are associated with a hypercoagulable state. These deficiencies are regarded as key factors of systemic hypercoagulability and recurrent venous thromboembolism. We report the case of a 19-year-old male diagnosed as IPH with PVT and combined deficiencies in proteins C and S.