Effects of propranolol on gastric mucosal perfusion and serum gastrin level in cirrhotic patients with portal hypertensive gastropathy

Gastric mucosal hyperemia associated with elevated serum gastrin level has been suggested in cirrhotic patients with portal hypertensive gastropathy (PHG). Clinical evidence has shown that these patients may benefit from propranolol administration. The aim of this study was to investigate effect of propranolol on gastric mucosal perfusion and serum gastrin level in cirrhotic patients with portal hypertensive gastropathy. Gastric mucosal perfusion was assessed by laser Doppler flowmetry. Measurements were performed under basal conditions and after observer-blind administration of propranolol (30–60 mg/day,N=9) or placebo (N=9) for seven days. Placebo had no effect on either gastric mucosal perfusion or serum gastrin level. In contrast, propranolol administration significantly decreased both antrum gastric mucosal perfusion (from 0.88±0.28 to 0.73±0.26 V,P<0.05) and corpus gastric mucosal perfusion (from 0.94±0.35 to 0.78±0.25 V,P<0.05). However, this drug had no effect on serum gastrin level. We conclude that chronic propranolol administration in cirrhotic patients with portal hypertensive gastropathy may reduce gastric mucosal perfusion without changing serum gastrin level.     

Assessment of portal hemodynamics by ultrasound color Doppler and laser Doppler velocimetry in liver cirrhosis.

BACKGROUND: Color Doppler is a noninvasive method for assessing portal hemodynamics. Laser Doppler velocimetry is useful in assessment of microcirculatory abnormalities in portal hypertensive gastropathy (PHG). AIMS: To study portal hemodynamics by color Doppler and gastric mucosal blood flow (GMBF) by laser Doppler velocimetry in patients with cirrhosis. METHODS: Twenty-eight patients with cirrhosis of liver (24 men) and 10 healthy subjects (7 men) were studied. Portal venous blood flow (PVBF) and portal flow velocity (PFV) were assessed by color Doppler at the level where the hepatic artery crosses the portal vein, and GMBF was measured by laser Doppler velocimetry. RESULTS: PVBF (379.5 [102.9] mL/min), PFV (5.3 [1.1] cm/sec) and GMBF (3.5 [0.8] volts) were significantly lower in patients with cirrhosis than in controls. PVBF and PFV were significantly lower in patients in Child class B and C than those in class A. Patients with ascites had significantly lower PVBF, PFV and GMBF than those without; values were also lower in patients with PHG than in those without. History of bleeding had no relation with PVBF and PFV. GMBF showed good correlation with PVBF (r=0.58, p<0.001) and with PFV (r=0.48, p<0.01). CONCLUSIONS: In cirrhosis of liver, PVBF, PFV and GMBF are significantly lower, and the changes increase with increasing severity of liver disease.     

Increased gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy.

To characterize gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy, 34 cirrhotics with this lesion and 24 noncirrhotics were studied by reflectance spectrophotometry and laser-Doppler flowmetry during endoscopy. A significant correlation was observed between the hemoglobin content of the gastric mucosa, measured by reflectance spectrophotometry, and the serum hemoglobin concentration both in cirrhotics (r = 0.72) and in noncirrhotics (r = 0.87). IHb ratio (hemoglobin content of gastric mucosa divided by blood hemoglobin concentration) was higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001), whereas the oxygen content of the gastric mucosa was similar in both groups. This pattern indicates that cirrhotics with portal hypertensive gastropathy have increased gastric perfusion without congestion. Gastric blood flow estimated by laser-Doppler was significantly higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001). In cirrhotic patients, gastric areas with cherry red spots showed a significantly higher IHb ratio than areas with a mosaic or scarlatina pattern (P < 0.05). The magnitude of changes in gastric perfusion and the endoscopic severity of portal hypertensive gastropathy had no relationship with the degree of portal hypertension or the azygos blood flow.     

Portal hypertension and portal hypertensive gastropathy in patients with liver cirrhosis: a haemodynamic study

BACKGROUND/AIM: The relationships between the levels of portal hypertension and the morphologic alterations of gastric mucosa in patients with liver cirrhosis--generally described as portal hypertensive gastropathy--are poorly defined. PATIENTS: In total, 62 patients with cirrhosis of different aetiologies, were examined by endoscopy and measurement of portal hypertension by hepatic venous pressure gradient. RESULTS: Portal hypertensive gastropathy was observed in 49 cases; six patients showed gastric antral vascular ectasia always associated with gastric lesions described as severe portal hypertensive gastropathy with different localizations. Hepatic venous pressure gradient showed severe portal hypertension in 37 cases, and averaged 17.7 +/- 4.3 mmHg. It was much higher in patients with severe lesions (p=0.0004). Hepatic venous pressure gradient in patients with endoscopic signs of isolated antral gastropathy was lower (p=0.04) than in those with isolated lesions in body-fundus. No relationship was found between hepatic function, as assessed by the Child-Pugh score, and portal hypertensive gastropathy. CONCLUSIONS: The present data suggest that the severity of portal hypertensive gastropathy is related to portal hypertension, but portal hypertension is not the sole determinant of the occurrence of endoscopic abnormalities of gastric mucosa. The derangement of liver function does not appear to play any role in the occurrence of portal hypertensive gastropathy.     

Treatment of bleeding from portal hypertensive gastropathy by portacaval shunt

Portal hypertensive gastropathy is a vascular disorder of the gastric mucosa distinguished by ectasia of the mucosal capillaries and submucosal veins without inflammation. During 1988 to 1993,12 patients with biopsy-proven cirrhosis (10 alcoholic, 2 posthepatitic) were evaluated and treated prospectively by portacaval shunt for active bleeding from severe portal hypertensive gastropathy. Eleven patients had been hospitalized for bleeding three to nine times previously, and one was bleeding uncontrollably for the first time. Requirement for blood transfusions ranged from 11 to 39 units cumulatively, of which 8 to 30 units were required specifically to replace blood lost from portal hypertensive gastropathy. Admission findings were ascites in 9 patients, jaundice in 8, severe muscle wasting in 10, hyperdynamic state in 9. Child's risk class was C in 7, B in 4, A in 1. Ten of the 12 patients had previously received repetitive endoscopic sclerotherapy for esophageal varices, which has been reported to precipitate portal hypertensive gastropathy. Eight patients had failed propranolol therapy for bleeding. Portacaval shunt was performed emergently in 11 patients and electively in 1, and permanently stopped bleeding in all by reducing the mean portal vein—inferior vena cava pressure gradient from 251 to 16 mm saline. There were no operative deaths, and two unrelated late deaths after 13 and 24 months. During 1 to 6.75 years of follow-up, all shunts remained patent by ultrasonography, the gastric mucosa reverted to normal on serial endoscopy, and there was no gastrointestinal bleeding. Recurrent portal-systemic encephalopathy developed in only 8% of patients. Quality of life was generally good. It is concluded that portacaval shunt provides definitive treatment of bleeding portal hypertensive gastropathy by eliminating the underlying cause, and makes possible prolonged survival with an acceptable quality of life.     

Effect of transjugular intrahepatic portosystemic shunt formation on portal hypertensive gastropathy and gastric circulation

OBJECTIVES: The aim of this study was to investigate the effect of a transjugular intrahepatic portosystemic shunt (TIPS) on portal hypertensive gastropathy (PHG) and gastric hemodynamics. METHODS: A total of 16 patients with cirrhosis and portal hypertensive gastropathy were prospectively studied. Of these, 12 patients underwent TIPS for esophageal varices and four for refractory ascites. Gastric mucosal blood flow (GMBF) was assessed by laser Doppler flowmeter, and total blood flow (TBF) in submucosa and mucosa by near-infrared endoscopy. Portal venous pressure was obtained by a transducer during the TIPS procedure. The severity of portal hypertensive gastropathy was classified as none, mild, or severe. The examinations were performed before and 2 wk after the procedure. RESULTS: TIPS significantly reduced portal venous pressure. PHG improved in all four patients with severe PHG and in five of 12 patients with mild PHG after treatment. Gastric mucosal blood flow increased from 49.0 to 55.6 ml/min/100 g after TIPS. In contrast, TBF decreased from 0.35/s to 0.27/s after treatment. Liver function tests showed no significant changes before and after the procedure. CONCLUSIONS: It is considered that TIPS may have a beneficial effect on PHG at least for a short time. The mechanism by which PHG improves may be closely related to the improvement of the injured gastric perfusion in cirrhotic patients with PHG.     

The natural history of portal hypertensive gastropathy in patients with liver cirrhosis and mild portal hypertension

BACKGROUND: Portal hypertensive gastropathy is a potential cause of bleeding in patients with liver cirrhosis. Studies on its natural history have often included patients submitted to endoscopic or pharmacological treatment for portal hypertension. PATIENTS AND METHODS: A total of 222 cirrhotic patients with mild degree of portal hypertension (i.e., with no or small varices at entry, without previous gastrointestinal bleeding and medical, endoscopic, or angiographic treatment) were followed up with upper endoscopy every 12 months for 47 +/- 28 months. RESULTS: Upon enrollment 48 patients presented portal hypertensive gastropathy (43 mild and 5 severe) and the presence of esophageal varices was the only independent predictor of the presence of this gastric lesion at multivariate analysis. The incidence of portal hypertensive gastropathy was 3.0% (1.1-4.9%) at 1 yr and 24% (18.1-29.9%) at 3 yr, while the progression was 3% (1-6.9%) at 1 yr and 14% (4.2-23.8%) at 3 yr. The presence of esophageal varices and the Child-Pugh class B or C at enrollment were predictive of the incidence of portal hypertensive gastropathy, while only Child-Pugh class B or C was correlated with the progression from mild to severe, at multivariate analysis. During follow-up 16 patients bled from portal hypertensive gastropathy (9 acutely and 7 chronically) and one patient died of exsanguination from this lesion. CONCLUSIONS: The natural history of portal hypertensive gastropathy is significantly influenced by the severity of liver disease and severity of portal hypertension. Acute bleeding from portal hypertensive gastropathy is infrequent but may be severe.     

Hepatic arterial buffer response in patients with advanced cirrhosis

Hepatic arterial buffer response (HABR) is considered an important compensatory mechanism to maintain perfusion of the liver by hepatic arterial vasodilation on reduction of portal venous perfusion. HABR has been suggested to be impaired in patients with advanced cirrhosis. In patients with hepatopetal portal flow, placement of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal venous liver perfusion. Accordingly, patients with severe cirrhosis should have impaired HABR after TIPS implantation. Therefore, the aim of this study was to investigate the effect of TIPS on HABR as reflected by changes in resistance index (RI) of the hepatic artery. A total of 366 patients with cirrhosis (Child-Pugh class A, 106; class B, 168; class C, 92) underwent duplex Doppler ultrasonographic examination with determination of RI and maximal flow velocity in the portal vein before and 1 month after TIPS placement. Portosystemic pressure gradient was determined before and after TIPS placement. In 29 patients with hepatofugal portal blood flow, RI was significantly lower than in 337 patients with hepatopetal flow (0.63 plus minus 0.02 vs. 0.69 plus minus 0.01; P <.001). TIPS induced a significant decrease of the RI in patients with hepatopetal flow (RI, 0.69 plus minus 0.01 before vs. 0.64 plus minus 0.01 after TIPS; P =.001) but not in patients with hepatofugal flow (RI, 0.63 plus minus 0.02 before vs. 0.63 plus minus 0.02 after TIPS; NS). This response was not dependent on the Child-Pugh class. In conclusion, our results suggest that some degree of HABR is preserved even in patients with advanced cirrhosis with significant portal hypertension.     

Portal hypertensive colopathy in patients with liver cirrhosis

AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with liver cirrhosis over a 6-year period. The main cause of liver cirrhosis was post-viral hepatitis (68%) related to hepatitis B (6%) or C (62%) infection. All patients underwent upper gastrointestinal endoscopy to examine the presence of esophageal varices, cardiac varices, and congestive gastropathy, as well as a full colonoscopy to observe changes in colonic mucosa. Portal hypertensive colopathy was defined endoscopically in patients with vascular ectasia, redness, and blue vein. Vascular ectasia was classified into two types: type 1, solitary vascular ectasia; and type 2, diffuse vascular ectasia. RESULTS: Overall portal hypertensive colopathy was present in 31 patients (66%), including solitary vascular ectasia in 17 patients (36%), diffuse vascular ectasia in 20 patients (42%), redness in 10 patients (21%) and blue vein in 6 patients (12%). As the Child-Pugh class increased in severity, the prevalence of portal hypertensive colopathy rose. Child-Pugh class B and C were significantly associated with portal hypertensive colopathy. Portal hypertensive gastropathy, esophageal varices, ascites and hepatocellular carcinoma were not related to occurrence of portal hypertensive colopathy. Platelet count was significantly associated with portal hypertensive colopathy, but prothrombin time, serum albumin level, total bilirubin level and serum ALT level were not related to occurrence of portal hypertensive colopathy. CONCLUSION: As the Child-Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. A colonoscopic examination in patients with liver cirrhosis is indicated, especially those with worsening Child-Pugh class and/or decreasing platelet count, to prevent complications such as lower gastrointestinal bleeding.     

Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification

Objective This study primarily aimed to investigate the short-term effects of partial splenic embolization (PSE) on the Child-Pugh score and identify predictive factors for changes in the score caused by PSE. The secondary aim was to analyze changes in various parameters at one month postoperatively using these identified factors. Methods Between September 2007 and December 2019, 118 patients with cirrhosis and hypersplenism underwent PSE at our hospital. Testing was conducted preoperatively and at one month after PSE. Results Overall, the Child-Pugh score was not significantly changed postoperatively. The Child-Pugh score before PSE was identified as the strongest independent predictor of ameliorated and deteriorated Child-Pugh scores after PSE. Higher pretreatment Child-Pugh scores were correlated with higher posttreatment amelioration rates of the score. A significant decrease in the portal vein diameter and a significant increase in the common hepatic artery diameter were evident at the same level postoperatively in 64 patients with Child-Pugh class A (group A) and in 54 patients with Child-Pugh class B or C (group B/C) preoperatively. According to Murray''s Law, PSE resulted in decreased portal venous flow and increased hepatic arterial flow, suggesting a hepatic arterial buffer response (HABR) induced by the procedure. Despite equivalent splenic infarction rates and similar posttreatment changes in hepatic hemodynamics, PSE significantly increased the Child-Pugh score of group A; however, the procedure significantly decreased the score of group B/C. Conclusion Considering original portal venous-hepatic arterial hemodynamics, PSE is expected to produce HABR-mediated hepatic functional improvements in cirrhosis patients with Child-Pugh class B/C.     

Classification of gastric lesions associated with portal hypertension

Abstract There are two gastric mucosal lesions which commonly occur in patients with portal hypertension; one is portal hypertensive gastropathy and the other is gastric varices. These lesions occasionally cause fatal haemorrhage. Several classifications for these lesions have been proposed, but none of them have been evaluated prospectively. We consider it better to classify portal hypertensive gastropathy into three stages including non-specific redness, specific mosaic pattern and red spots. Gastric varices may be classified according to form, location and mucosal lesions. Prospective trials are needed to obtain more practical evidence for the accurate classification of these gastric lesions.     

肝硬化患者门静脉高压性胃病发病因素的研究

背景：门静脉高压性胃病是肝硬化患者上消化道出血的原因之一．但其发病机制目前尚不完全清楚。目的：探讨肝硬化患者门静脉高压性胃病的发生与肝硬化分级、食管胃底静脉曲张程度、腹水量和胃肠激素血管活性肠肽（VIP）水平的关系。方法：45例肝硬化患者行胃镜检查观察食管胃底静脉曲张程度和胃黏膜改变．行腹部B超检查观察腹水量，同时检测血清白蛋白、总胆红素、胆碱酯酶、凝血酶原时间等肝功能指标和血浆VIP水平。结果：Child—Pugh A、B、C级肝硬化患者、不同程度食管胃底静脉曲张患者以及不同程度腹水患者之间的门静脉高压性胃病发生率均无显著差异（P〉0．05）。但肝硬化伴门静脉高压性胃病患者的血浆VIP水平较无门静脉高压性胃病者显著升高（P〈0．001）。结论：门静脉高压是门静脉高压性胃病的必要条件，而其他因素．如血浆VIP水平与门静脉高压性胃病的发生也有一定关系。     

Effect of early propranolol administration on portal hypertensive gastropathy in cirrhotic rats

AIM： To investigate any protective effect of early propranolol administration in the development of portal hypertensive gastropathy in cirrhotic rats. METHODS： For the development of liver cirrhosis and portal hypertensive gastropathy, 60 rats underwent ligation of the left adrenal vein and complete devascularization of the left renal vein, followed by phenobarbital and carbon tetrachloride （CCl4） administration. After two weeks of CCl4 administration, the rats were randomly separated into two groups. In group A, propranolol was continuously administered intragastrically throughout the study, whereas in group B normal saline （placebo） was administered instead. Hemodynamic studies and vascular morphometric analysis of gastric sections were performed after complete induction of cirrhosis. RESULTS： Vascular morphometric studies showed higher numbers of vessels in all mucosal layers in the control group. Statistical analysis revealed a significantly higher total vascular surface in the control group compared to the propranolol group, but with no statistically significant difference between the mean vascular surfaces between the groups. Our study clearly shows that the increased mucosal blood flow is manifested by a marked increase of vessel count. CONCLUSION： Early propranolol＇s administration in portal hypertensive cirrhotic rats seems to prevent intense gastric vascular congestion that characterizes portal hypertensive gastropathy.     

Findings of Portal Hypertensive Gastroenteropathy Using Infrared Electronic Endoscopy

Abstract: The aim of this study was to ascertain how and in what form portal hypertensivive gastroenteropathy affects the submucosal vasculature using an infrared electronic endoscope (IREE), which is capable of visualizing the submucosal vasculature. Subjects were 46 patients with liver cirrhosis (19 in Child-Pugh class A, 21 in B, and 6 in class C). In 37 of 46 patients, the submucosal vasculature of the stomach was visualized using IREE and morphologic features were studied in relation to the severity of portal hypertensive gastropathy (PHG; none, mild and severe). In the remaining 9 patients, the submucosal vasculature of the rectum and sigmoid colon was observed with IREE. IREE images of blood vessels of the gastric submucosa demonstrated withered branch-like vessels (35.1%), multiple dotted or spotted stains at terminations of branches (32.4%), vascular ectasia-like circular stains (11%) and dilated tortuous venules of relatively large caliber around the cardia and in the upper region of the stomach (18.8%). This feature around the cardia was observed more frequently in patients with complications of gastric varices (55.6%). In relation to the severity of PHG, the incidence of withered branch-like vessels was significantly higher in the severe gastropathy group than in the non-gastropathy group. Dotted or spotted stains were most frequently observed in the severe gastropathy group. Visual examination of the colorectal mucosa with IREE noted withered branch-like vessels in 7 of 9 cases. In 3 of 9 patients, dilated venules were seen running in the anorectal submucosa and joining the rectal varices. In conclusion, morphological changes due to congestion were found in portal hypertensive gastroenteropathy using IREE in submucosal venules of relatively large caliber and even in the venous plexus in the vicinity of the muscularis mucosa. (Dig Endosc 1999; 11: 144–149)     

Impaired gastric mucosal energy metabolism in congestive gastropathy in cirrhotic patients

To clarify the characteristics of congestive gastropathy, we investigated gastric mucosal hemodynamics and energy metabolism in cirrhotic patients, using a reflectance spectrophotometry system and high performance liquid chromatography. The index of the gastric mucosal blood volume of cirrhotic patients with esophageal varices was significantly higher, and the index of gastric mucosal blood oxygenation significantly lower, than those in controls, thus indicating congestion and hypoxia in the gastric mucosa. Energy charge levels in the gastric mucosa of cirrhotic patients with esophageal varices were also significantly decreased. The energy charge level showed a strong linear correlation with the index of mucosal blood oxygenation in the antral (r=0.996,P<0.01) and body (r=0.994,P<0.01) mucosa of the stomach. These findings suggest that congestive gastropathy in a portal hypertensive state causes hypoxia in the gastric mucosa, leading to a mucosal energy deficit that may increase mucosal susceptibility to aggressive factors.     

Breakdown of mucosal defences in congestive gastropathy in cirrhotics

ABSTRACT— The gastric mucus-bicarbonate barrier, the first line of mucosal defence, has been evaluated in patients with congestive gastropathy and cirrhosis of the liver. Fourteen cirrhotic patients of both sexes (Child's class A or B), with or without oesophageal varices, but with endoscopic signs of congestive gastropathy, and a matched group of healthy controls were studied. The amount of luminal mucoproteins, a Mucoprotective Index as a qualitative assessment of mucus secretion and the output of gastric bicarbonate were determined in basal conditions. In patients with congestive gastropathy a significant (p<0.01) reduction in all the above parameters was observed, suggesting a substantial impairment of the gastric mucus-bicarbonate barrier. Whether this is an independent phenomenon or a consequence of altered local microcirculation remains to be determined.     

肝硬化非常见侧支循环临床特点研究

目的 探讨肝硬化患者门体循环之间非常见侧支循环形成的临床特点及意义。方法 对临床确诊为肝硬化的患者运用64排螺旋CT和三维血管成像结合电子胃镜检查,观察其门体循环之间非常见侧支循环的形成。结果 ①700例肝硬化患者中118例(16.86%)存在非常见侧支循环,依次为脾肾静脉分流、胃肾静脉分流、椎旁静脉分流、腹膜后静脉分流、胃脾分流和心膈角静脉分流。②非常见侧支循环形成与肝硬化Child-Pugh分级相关(P<0.01)。③与常见侧支循环形成组比较,非常见侧支循环组较少出现重度食管和(或)胃底静脉曲张、重度门静脉高压性胃病及大量腹水(P<0.01)。④非常见侧支循环组中肝性脑病和慢性血氨升高的发生率高于常见侧支循环组(P<0.01)。结论 ①肝硬化患者中非常见侧支循环并不"非常见";②非常见侧支循环形成与肝功能Child-Pugh分级有关;③非常见侧支循环形成可缓解门静脉高压引起的相关并发症,但增大了肝性脑病和慢性血氨升高的发病率。     

Vasopressin plus oxygen vs vasopressin alone in cirrhotic patients with portal-hypertensive gastropathy: Effects on gastric mucosal haemodynamics and oxygenation

The effects of vasopressin plus oxygen and vasopressin alone on gastric mucosal perfusion and oxygenation were studied using reflectance spectrophotometry and laser Doppler velocimetry in 23 cirrhotic patients with portal-hypertensive gastropathy. The measurements were performed under basal conditions and after double-blinded administration of placebo (n= 7), vasopressin (0.3 U/min; n= 8) or vasopressin (0.3 U/min) plus nasal oxygen (4 L/min; n= 8). No significant effects on gastric mucosal haemodynamics and oxygenation were observed after placebo. In contrast, vasopressin and vasopressin plus oxygen induced a similar reduction in haemoglobin content (-26 ± 2 and -21 ± 4%, respectively P < 0.01) and laser Doppler signal (-23 ± 2 and -22 ± 2%, respectively, P < 0.01). Although each treatment induced a significant reduction in oxygen saturation (-21 ± 2 and -7 ± 1%, respectively P < 0.01), the effect was less pronounced in patients receiving the combination than in those receiving vasopressin alone (P < 0.01). These data suggest that vasopressin and vasopressin plus oxygen reduce gastric mucosal hyperaemia and that the oxygen supplement partially protects against gastric mucosal hypoxia during vasopressin infusion in cirrhotic patients with portal-hypertensive gastropathy.