Non-invasive model predicting clinically-significant portal hypertension in patients with advanced fibrosis

Background and Aims:  Hepatic venous pressure gradient (HVPG) has been established as a predictor for the development of varices, clinical decompensation and death. In the present study, the primary objectives were to determine the diagnostic accuracy of the model developed by using readily-available data in predicting the presence of significant portal hypertension and esophageal varices.
Methods:  This study included a total of 61 consecutive treatment-naive patients with advanced fibrosis (METAVIR F3, F4), established by liver biopsy. All patients underwent subsequent HVPG measurement and upper gastrointestinal endoscopy within 1 week of liver biopsy.
Results:  Seventeen patients (F3, 2/26; F4, 15/35) had clinically-significant portal hypertension (HVPG ≥ 10 mmHg). The Risk Score for predicting significant portal hypertension was 14.2 − 7.1 × log₁₀ (platelet [10⁹/L]) + 4.2 × log₁₀ (bilirubin [mg/dL]). The area under the receiver–operator curve (AUC) curve was 0.91 (95% confidence interval [CI], 0.84–0.98). The optimized cut-off value (Risk Score = −1.0) offered a sensitivity of 88% (95% CI, 62–98%) and a specificity of 86% (95% CI, 72–94%). The AUC of the Risk Score in predicting varices was 0.82 (95% CI, 0.67–0.98). The cut-off had a sensitivity of 82% (95% CI, 48–97%) and a specificity of 76% (95% CI, 62–86%).
Conclusion:  A predictive model that uses readily-available laboratory results may reliably identify advanced fibrosis patients with clinically-significant portal hypertension as well as esophageal varices. However, before accepted, the results of the current study certainly should be validated in larger prospective cohorts.     

Bleeding caused by portal hypertension

Variceal bleeding is one of the dreaded complications of portal hypertension. Patients who have suspected or proven cirrhosis should undergo diagnostic upper endoscopy to detect medium and large gastro-esophageal varices. Patients with medium and large gastro-esophageal varices should be treated with non-selective beta-blockers (propranolol or nadolol), and these agents should be titrated to a heart rate of 55 beats per minute or adverse effects. If there are contraindications to or if patients are intolerant to beta-blockers, it is appropriate to consider prophylactic banding therapy for individuals with medium-to-large esophageal varices. When patients who have cirrhosis present with GI bleeding, they should be resuscitated and receive octreotide or other vasoactive agents. Endoscopy should be performed promptly to diagnose the source of bleeding and to provide endoscopic therapy (preferably banding). The currently available treatment for acute variceal bleeding provides hemostasis in most patients. These patients, however, are at significant risk for rebleeding unless secondary prophylaxis is provided. Although various pharmacological, endoscopic, radiological, and surgical options are available, combined pharmacological and endoscopic therapy is the most common form of secondary prophylaxis. TIPS is a radiologically placed portasystemic shunt, and if placed in suitable patients, it can provide effective treatment for patients with variceal bleeding that is refractory to medical and endoscopic therapy.     

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.     

Unusual sites of upper gastrointestinal variceal bleeding

When patients with portal hypertension bleed from varices, these are most commonly located in the esophagus and gastric fundus. However, varices can develop anywhere in the upper or lower gastrointestinal tract. Oftentimes if an active upper gastrointestinal bleeding site is not evident at the time of endoscopy, bleeding is attributed to any esophageal or gastric varices that are present. This supposition may not always be true as illustrated in the two patients presented here. Likewise, the absence of esophagogastric varices in a patient with portal hypertension does not preclude the presence of varices elsewhere. Endoscopic examination of the second and third portion of the duodenum can sometimes be helpful in accurately locating the bleeding site.     

经皮穿脾食管胃底静脉栓塞术治疗血吸虫病上消化道出血

目的探讨经皮穿脾食管胃底静脉栓塞术(PTSVE)在治疗血吸虫病肝硬化上消化道出血中的应用价值。方法以血吸虫病肝硬化门脉高压合并食管胃底静脉曲张破裂出血患者16例(均为食管静脉套扎及硬化治疗术后再次出血患者)为研究对象,其中男12例,女4例。所有病例在X线透视引导下,实施PTSVE术。术后观察手术成功率、并发症发生率,术后1月复查CT,比较患者治疗前后静脉曲张程度。结果 14例(87.50%)患者PTSVE术取得成功,均获有效止血;2例(12.50%)失败;1例术后1周出现腹腔出血。术后1月复查CT,经评估显示患者食道静脉(P0.001)、食道旁静脉(P0.001)和胃底静脉(P0.001)曲张程度均较治疗前明显降低。结论 PTSVE治疗血吸虫病上消化道出血是安全有效的方法,该方法特别适合肝硬化严重,肝裂明显增宽,门静脉主干甚至分支裸露者。     

Isolated gastric varices: splenic vein obstruction or portal hypertension?

The presence of isolated gastric varices without esophageal varices is thought to be highly suggestive of splenic vein obstruction. A review of our radiologic files revealed 14 patients with isolated gastric varices on barium studies performed during the past 10 years. Eight of the 14 patients had adequate clinical and/or radiologic follow-up to suggest the pathophysiology of the varices. Seven had evidence of portal hypertension, and the remaining patient had evidence of splenic vein obstruction. Six patients had signs of upper gastrointestinal (GI) bleeding. Double-contrast upper GI examinations revealed thickened, tortuous fundal folds in 6 patients and a lobulated fundal mass in 2. Thus, most patients with isolated gastric varices have portal hypertension rather than splenic vein obstruction as the underlying cause.     

Ultrasonographic Prediction of Esophageal Varices in Schistosomiasis mansoni

Bleeding from esophageal varices is a common and serious problem in Schistosomiasis mansoni. A simple and accurate method of detection would facilitate measurement of individual and community morbidity and allow institution of preventive measures. An ultrasonographic scoring system grading periportal fibrosis, portal vein diameter, spleen size, and portasystemic anastomoses was evaluated as a predictor of esophageal varices and a past history of upper gastrointestinal hemorrhage in 43 patients with hepatosplenic schistosomiasis. Ultrasonographic variceal score correlated ( r = 0.86, p < 0.001) with the endoscopic variceal grade. Patients with a sonographic score of 5 or greater were highly likely (21 of 23) to have varices of grade II or greater (sensitivity, 91.3%; specificity, 94.7%). Only those with sonographic scores of 5 or greater (15 of 23) had bled from esophageal varices. The ultrasonographic score provided a simple, inexpensive, accurate, and noninvasive means of screening individuals with hepatosplenic schistosomiasis for esophageal varices, and correlated strongly with prior gastrointestinal hemorrhage. It is not known whether a similar score would be useful in hepatic cirrhosis.     

Upper gastrointestinal bleeding in patients with portal hypertension: a reappraisal

The current medical literature states that upper gastrointestinal bleeding in patients with cirrhosis and portal hypertension originates from a variety of sources. Although variceal bleeding has been recognized as the principal source, acute erosive gastritis and peptic ulcer are said to be the bleeding site in a large percentage of cases. In 140 consecutive patients with endoscopically documented esophageal varices who came to our service with upper gastrointestinal hemorrhage, varices were the source of bleeding in approximately 90%, regardless of whether the underlying liver disease was due to alcoholism or not. We conclude that: 1) patients with varices almost always bleed from varices, and 2) the incidence of erosive gastritis and peptic ulcer as a cause of bleeding in this group has been overemphasized.     

多排螺旋CT门静脉成像对门静脉高压食管、胃底静脉曲张的评价

肝硬化失代偿期可引起门静脉高压,食管胃底静脉曲张是门静脉高压的一个严重并发症,其破裂可引起胃肠道大出血,对门静脉高压侧支循环的显示对患者的治疗方式的选择及预后的评估具有重要意义.多排螺旋CT门静脉成像(CTPV)可显示胃底静脉曲张的部位、形态及侧支循环血供的关系,在GEVI型,GV多为LGV或以LGV为主来供应,胃和(或)脾-肾分流较少见,GV的形态多为迂曲型.在GEV2型,GV大部分由PGV和(或)SGV供血,部分病例伴胃和(或)脾-肾分流.IGV型多以PGV和(或)SGV为主要血供,且较多合并胃和(或)脾-肾分流,GEV2和IGV型GV的形态以结节型和瘤型较多.CTPV可显示食管静脉曲张分型与其侧支循环的关系,EV以位于食管黏膜下、食管壁为主时,其血供多为胃左静脉前支优势型;EV为食管管旁静脉曲张为主时,其血供多为后支优势型;EV管壁、黏膜下静脉曲张程度与管旁静脉曲张接近时,其血供多为前后支均衡型.     

Rectosigmoid Varices and Other Mucosal Changes in Patients with Portal Hypertension

A prospective study was performed to evaluate the prevalence of anorectal varices and their clinical significance as well as to study other proctosigmoidoscopic changes in 75 patients with portal hypertension of diverse etiology. Sixty-seven patients (89.3%) had lower gastrointestinal varices with no significant difference (p greater than 0.05) in prevalence between cirrhosis (92.1%), noncirrhotic portal fibrosis (87%), and extrahepatic portal venous obstruction (85.7%). The rectum was the most common site of lower gastrointestinal varices. External anal and sigmoid colonic varices almost always occurred in the presence of rectal and/or internal anal varices. There was no correlation between the presence of rectosigmoid varices and the severity of esophagogastric mucosal changes or portal hypertension. There was no suggestion that esophageal variceal sclerotherapy influenced the presence of anorectal varices. Seven patients (9.3%) had recent hematochezia, including three patients in whom it occurred in the absence of any upper gastrointestinal hemorrhage. Varices were the cause of bleeding in at least five patients. An abnormal mucosal vascular pattern in the form of telangiectasias or spiders was seen, irrespective of etiology of portal hypertension, in nine patients (12%). Hemorrhoids were present in 31 patients (41.3%) with an age-related difference (p less than 0.05) between patients with cirrhosis (55.3%) and extrahepatic portal venous obstruction (21.4%).     

门静脉高压患者胃静脉曲张的内镜识别和分类

背景：肝硬化门静脉高压的出血原因中，食管和（或）胃静脉曲张破裂出血最为常见。胃静脉曲张的发生率较食管静脉曲张低，但再出血率高，出血量大，死亡率亦较高。尽管如此，胃静脉曲张在临床诊治过程中未受到应有的重视。目的：根据内镜下对食管和胃静脉曲张的识别和分类，了解食管和胃静脉曲张的比例。方法：根据Sarin分类，在内镜直视下将114例门静脉高压患者分为单纯食管静脉曲张、胃食管静脉曲张1型（GOV1型）、胃食管静脉曲张2型（GOV2型）、孤立性胃静脉曲张1型（IGV1型）和孤立性胃静脉曲张2型（IGV2型）五种类型。结果：本组患者中单纯食管静脉曲张42例（36．8％），GOV1型40例（35．1％），GOV2型20例（17．5％），IGV1型12例（10．5％），未见IGV2型。结论：半数门静脉高压患者存在胃静脉曲张，临床工作中仅处理食管静脉曲张是很片面的。须努力开展组织黏合剂、球囊闭塞下逆行经静脉栓塞术（B．RTO）或外科分流等治疗：对有条件的患者应鼓励开展肝移植治疗。     

Variceal sclerosis in schistosomotic patients: a 5-year follow-up study

To assess the therapeutic possibilities of injection sclerosis in schistosomotic portal hypertension, a 5-year prospective study was conducted in northeast Brazil, where this parasitosis is endemic. Fifty patients undergoing endoscopy for upper gastrointestinal hemorrhage from rupture of esophageal varices from July through December 1981 were chosen for the study. The 32 consenting patients were submitted to injection sclerotherapy paravariceally, using ethanolamine oleate; the 18 refusing to participate were assigned to the control group. The incidence of rebleeding was 28.1% in the former and 44.5% in the latter, a difference which was not statistically significant (Fisher's test, p = 0.375). Mortality from rupture of esophageal varices was 3.1% in the sclerotherapy group and 27.7% in the control group, a statistically significant difference (Fischer's test, p = 0.017). Since sclerotherapy markedly improved the long-term survival rate of the patients, this procedure is advocated for the treatment of esophageal varices in cases of portal hypertension due to schistosomiasis.     

Chronic oral anticoagulant therapy for extrahepatic visceral thrombosis is safe

Background Patients with hypercoagulability may thrombose visceral veins with resultant portal hypertension, esophagogastric varices, and hemorrhage. The role of chronic oral anticoagulant therapy in such patients is unclear. On the one hand, such patients are prone to significant hemorrhage and thus anticoagulant therapy may seem contraindicated. On the other hand, because the causal pathophysiology is typically hypercoagulability, it would seem rational to treat these patients with chronic anticoagulant therapy in order to both prevent other visceral and systemic thromboses and perhaps, over time, reduce the degree of portal hypertension. Experience and poor prognosis associated with the more common portal hypertension due to hepatic cirrhosis may bias judgment. Methods We retrospectively reviewed the course of chronic oral anticoagulant therapy regarding both the safety and effectiveness using our long-term follow-up of a cohort of seven patients with visceral thrombosis resulting in extrahepatic non-cirrhotic portal hypertension. Results Seven consecutive patients encountered over the past 19 years were observed for 78 patient-years, the first 14 patient-years prior to anticoagulant therapy and the latter 64 patient-years on oral anticoagulant therapy. No patients rethrombosed either visceral or systemic vessels while on oral anticoagulant therapy. There were no fatal or serious hemorrhagic events on oral anticoagulant therapy; in fact, upper gastrointestinal bleeding decreased from 1.2 to 0.2 bleeds/year. The endoscopic grade of esophageal varices decreased in four of five patients who underwent serial endoscopy, and platelet counts increased in all seven patients. Conclusions Chronic oral anticoagulant therapy is safe and not associated with an increase in upper gastrointestinal bleeding in such patients. Additionally, and by inference, perhaps in conjunction with the natural history of portal hypertension, such therapy is possibly effective in reducing portal hypertension in patients with hypercoagulability-induced extrahepatic portal hypertension. Condensed Abstract The safety and role of chronic oral anticoagulant therapy in the long-term management of extrahepatic esophageal varices is unclear. We followed seven patients with hypercoagulability-induced visceral thrombosis for a total of 78 patient-years. Our data show that this was safe, associated with an overall decrease in acute upper gastrointestinal hemorrhagic episodes, and perhaps, in a decrease in portal hypertension.     

Esophageal varices in felty's syndrome. A case report and review of the literature

A case of upper gastrointestinal tract hemorrhage secondary to esophageal varices in a patient with Felty's syndrome prompted a review of the pathogenesis and treatment of this condition. Six previously reported cases of this association were found. The clinical picture is that of long-standing rheumatoid arthritis with severe articular and extraarticular manifestations including splenomegaly, depression of the blood elements, mild liver function abnormalities, portal hypertension without cirrhosis or portal vein obstruction, an elevated splenic blood flow, and a reduction in portal hypertension by simple splenectomy. The presence of portal hypertension with varices may be another indication for splenectomy in patients with Felty's syndrome.     

门-体分流程度评估血吸虫病肝硬化上消化道出血的应用

目的探讨门-体静脉分流程度在评估血吸虫病肝硬化上消化道出血中的应用。方法以金山医院经临床证实的33例血吸虫病肝硬化上消化道出血患者,及29例血吸虫病肝硬化非出血患者为研究对象,对其进行上腹部128层螺旋CT扫描。采用薄层块最大强度投影(TSMIP)、多平面重建(MPR)对门静脉系进行血管重建,对两组患者门-体静脉分流程度进行评分和比较,分析各侧支血管分流程度与血吸虫病肝硬化上消化道出血的关系。结果 33例上消化道出血患者中,侧支血管发生率如下:胃左静脉曲张86.4%、胃短静脉曲张68.2%、食管静脉曲张50.0%、食管旁静脉曲张50.0%、胃底静脉曲张37.9%、胃肾静脉69.7%、脾肾静脉51.5%、腹壁静脉曲张25.8%、网膜静脉曲张15.2%、脾周静脉曲张63.6%、附脐静脉曲张34.8%、腹膜后-椎旁静脉40.9%、肠系膜静脉曲张36.4%。出血组食管静脉、食管旁静脉、胃左静脉和胃底静脉的发生率和分流程度均明显大于非出血组(P值均0.05)。结论 CT门静脉系成像可精确显示各类侧支血管的部位、程度及走向。食管静脉、食管旁静脉、胃左静脉和胃底静脉能较准确地预测血吸虫病肝硬化上消化道出血的风险情况,上述侧支血管分流程度越高,上消化道出血危险性就越大。     

Sugiura procedure in portal hypertensive children

Bleeding from esophageal varices is an important cause of morbidity and mortality in children with portal hypertension. The treatment protocol is planned according to the etiologic factors underlying the portal hypertension, which may be either intrahepatic or extrahepatic. Although portasystemic venous shunt operations were common previously, they are now regarded as nonphysiologic and are rarely used because of their unexpected results and complications. Today, in many centers, endoscopic procedures have become the first-step treatment modality in bleeding esophageal varices. More complicated surgical procedures, such as devascularization procedures in extrahepatic portal hypertension, and liver transplantation in patients with failing liver, should be performed when conservative measures fail. We followed up 69 patients with portal hypertension with endoscopic sclerotherapy in our department. Here we present a retrospective evaluation of the effect of the Sugiura operation on the prognosis of 12 children (6 with extrahepatic and 6 with intrahepatic portal hypertension) who were not responsive to the sclerotherapy program. No rebleeding was seen in 9 of the 12 (75%) patients after the procedure, and the mortality rate in this series was 1 of 12 (8.3%); this patient died of hepatic failure.     

Arterioportal Fistula: A Role for Pre-TIPSS Arteriography and Hepatic Venous Pressure Measurements

A 70-yr-old male presented with massive upper gastrointestinal bleeding secondary to esophageal varices. Because the bleeding was not controlled by sclerotherapy or vasopressin and nitroglycerin, the patient was evaluated for a transjugular intrahepatic portosystemic shunt. Preprocedure arteriography was performed because the etiology of the portal hypertension was uncertain. The arteriogram revealed a hepatic artery to portal vein fistula. Hepatic venous pressure measurements documented an elevated hepatic venous pressure gradient, which diminished dramatically upon embolization of the fistula. Rebleeding from the varices was associated with reestablishment of the fistula via collaterals and elevation of the hepatic venous pressure gradient. The case is presented to establish a role for arteriography prior to transjugular intrahepatic portosystemic shunting, especially in patients with unexplained portal hypertension, and to establish the potential value of hepatic venous pressure measurements in the treatment of arterioportal fistulas.     

Esophageal varices in Felty's syndrome: A case report and review of the literature.

A case of upper gastrointestinal tract hemorrhage secondary to esophageal varices in a patient with Felty's syndrome prompted a review of the pathogenesis and treatment of this condition. Six previously reported cases of this association were found. The clinical picture is that of long-standing rheumatoid arthritis with severe articular and extraarticular manifestations including splenomegaly, depression of the blood elements, mild liver function abnormalities, portal hypertension without cirrhosis or portal vein obstruction, an elevated splenic blood flow, and a reduction in portal hypertension by simple splenectomy. The presence of portal hypertension with varices may be another indication of splenectomy in patients with Felty's syndrome.     

Long term effects of propranolol on portal pressure in cirrhotic patients

Bleeding from varices is a very serious complication in cirrhotic patients, with a mean mortality rate around 30 %. If the portal vein pressure is decreased by pharmacological therapy the varices will not bleed and progressively decrease in size. The portal hypertension in cirrhotic patients develops as a consequence of two mechanisms: the increase of portal inflow and the increase of intrahepatic resistance. The aim of our study was to find out if propranolol can prevent the bleeding from esophageal varices and if it acts by reducing the portal inflow due to splanchnic vasodilatation. The study was initiated in 53 patients with portal hypertension, of whom 14 were withdrawn because of adverse effects of propranolol. Abdominal ultrasonography and Doppler of portal vein system were performed in all subjects. The ultrasonographic parameters were measured before and after a 3-year treatment with propranolol. The patients also underwent endoscopy for evaluation of esophageal varices; the endoscopy was repeated at the end-point of treatment. We noted that propranolol reduced the portal blood inflow and the size of esophageal varices, and that the incidence of hemorrhages by variceal rupture was very low in these patients.