Predictors and management of post-banding ulcer bleeding in cirrhosis: A systematic review and meta-analysis

Background and Aims

Post-banding ulcer bleeding (PBUB) is an understudied complication of oesophageal varices endoscopic band ligation (EBL). This systematic review with meta-analysis aimed at: (a) evaluating the incidence of PBUB in patients with cirrhosis treated with EBL in primary or secondary prophylaxis or urgent treatment for acute variceal bleeding and (b) identifying predictors of PBUB.

Methods

We conducted a systematic review of articles in English published in 2006–2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were made in eight databases including Embase, PubMed and Cochrane Library. Random-effects meta-analysis was used to determine the incidence, mean interval and predictors of PBUB.

Results

Eighteen studies (9034 patients) were included. The incidence of PBUB was 5.5% (95% CI 4.3–7.1). The mean time for it to occur was 11 days (95% CI 9.94–11.97). Model for End-stage Liver Disease (MELD) score (OR 1.162, 95% CI 1.047–1.291) and EBL done in emergency setting (OR 4.902, 95% CI 2.99–8.05) independently predicted post-ligation ulcer bleeding. Treatment included drugs, endoscopic procedures and transjugular intrahepatic portosystemic shunt. Refractory bleeding was treated with self-expandable metallic stents or balloon tamponade. Mortality was on average 22.3% (95% CI 14.1–33.6).

Conclusions

Patients with high MELD score and receiving EBL in an emergency setting are more prone to develop PBUB. Prognosis is still poor and the best therapeutic strategy to address remains to be ascertained.     

Prognosis in patients with cirrhosis and mild portal hypertension

Objective. Sixty to 70% of upper gastrointestinal bleeding episodes in patients with cirrhosis are caused by oesophageal varices. Prophylaxis is indicated in patients with varices and a hepatic venous pressure gradient (HVPG) above 12 mmHg. The study of the natural history of patients with lower HVPG has been sparse. In this study, long-term survival and the risk of complications in mild portal hypertension were analysed. Material and methods. Sixty-one patients with cirrhosis and HVPG below 10 mmHg were included in the study. Data were collected from medical files and National Patient Registries. Variceal bleeding, hepatic encephalopathy and death related to cirrhosis were registered. Thirty-nine patients were graded as Child class A, 19 as class B and 3 as class C. Median survival time was 11 years. Results. Twenty-eight patients (46%) developed one or more complications: variceal bleeding in 10 (16%) and hepatic encephalopathy in 18 patients (30%). Twenty-three patients (38%) died from complications of cirrhosis. Two patients (3%) died from variceal bleeding, another two (3%) from gastrointestinal bleeding of unidentified source. Survival rate was significantly decreased compared with that in the background population. Conclusions. The frequency of complications in patients with mild portal hypertension is considerable, and guidelines for follow-up or medical prophylaxis are warranted. The risk of bleeding from oesophageal varices is low and bleeding-related deaths rare.     

Comparative efficacy of emergency endoscopic sclerotherapy for active variceal bleeding due to cirrhosis of the liver, non-cirrhotic portal fibrosis and extrahepatic portal venous obstruction

Patients with continued variceal bleeding due to portal hypertension (n = 202) were treated by endoscopic injection sclerotherapy after resuscitation. Portal hypertension was due to hepatic cirrhosis in 123, non-cirrhotic portal fibrosis (NCPF) in 49 and extrahepatic portal venous obstruction (EHO) in 30 patients. Polidocanol 1% was injected intravariceally. An adequate sclerotherapy was carried out in 97% of patients. Immediate haemostasis was achieved in 177 (88%) patients. Rebleeding occurred in 31 (17.5%) of 177 patients. By reinjection of varices, definitive control of bleeding occurred in 160 (79%) patients. There was no significant difference in terms of immediate control of bleeding in patients with different aetiologies of portal hypertension and hepatic functional status (Child's grade). Rebleeding episodes were lower in patients with EHO than cirrhosis of the liver and NCPF. Similarly, the Child's status significantly influenced the recurrence of bleeding which was lower in Child's A than B and B than C. The in-hospital mortality was 18.6%. This was also significantly related to Child's status and aetiology of portal hypertension. Minor complications occurred in 10.4% of patients. It is concluded that endoscopic sclerotherapy as the first line of treatment is an effective and technically feasible procedure for the control of active variceal bleeding, regardless of the cause of portal hypertension. Furthermore, the results were influenced by the aetiology of portal hypertension and hepatic functional status.     

Does the measurement of portal flow velocity have any value in the identification of patients with cirrhosis at risk of digestive bleeding?

Abstract: Upper gastrointestinal bleeding is a leading cause of death in patients with liver cirrhosis. In most cases haemorrhage originates from oesophageal varices or from congestive gastropathy, and the evaluation of the bleeding risk is based on oesophagogastroduodenoscopic data. The aim of this prospective study was to determine whether the measurement of portal flow velocity by Duplex-Doppler, compared with endoscopic data, can help in detecting patients with cirrhosis at risk of bleeding. One hundred and seventy-three patients underwent endoscopy to ascertain the size of the varices and the severity of congestive gastropathy. For each patient maximal portal flow velocity measurements were obtained. No difference in portal flow velocity was observed between patients with or without oesophageal varices or congestive gastropathy. During a 2-year observation period, 27 patients (15.6%) had at least one episode of acute digestive bleeding. Stepwise multiple logistic regression analysis demonstrated a correlation between oesophageal varices and congestive gastropathy endoscopic grading and the incidence of bleeding; only the former was entered into the final regression equation (p>0.001). No relationship between the max portal flow velocity value and incidence of bleeding was found. This study shows that portal flow velocity is unrelated to the degree of the endoscopic abnormalities in patients with liver cirrhosis and that it has no value in the identification of patients with cirrhosis at risk of upper gastrointestinal bleeding.     

Long-term follow up of a randomized, controlled trial on prophylactic sclerotherapy of small oesophageal varices in liver cirrhosis

BACKGROUND: In order to evaluate the prophylactic impact of sclerotherapy of small varices in patients with cirrhosis and no endoscopic signs suggesting risk of haemorrhage, a randomized clinical trial was performed. METHODS: Seventy-one hospitalized patients met the inclusion criteria of diagnosis of cirrhosis with no previous bleeding and small varices. Due to exclusion criteria of: gastroduodenal ulcers (n = 5), diverticulosis (n = 1), hepatic insufficiency (n = 10), hepatocellular carcinoma (n = 4), death before randomization (n = 6), age over 70 (n = 1) and denial of consent to participate in the study (n = 1), 43 patients could be randomized, 21 for sclerotherapy and 22 for the control group. Two patients (one in each group) were lost to follow up, and another patient, although not lost, refused sclerotherapy after randomization. Ethanolamine oleate was used as the sclerosing agent. All patients were followed up for a mean time of 60 months, initially every 2 months for the first 2 years and clinical and endoscopic controls were performed each 6-12 months thereafter. RESULTS AND CONCLUSIONS: During the first 2 years clinical assessment showed that there were five bleedings in the sclerotherapy group and none in the control group, but mortality was similar in both groups. Long-term follow up continued to show a higher prevalence of bleeding in the sclerotherapy group but that mortality was not different from the control group.     

Case of chronic schistosomiasis mansoni with portal hypertension

The patient was a 30‐year‐old male from Guinea, who had been living in Japan for 10 years. He was diagnosed as having chronic active schistosomiasis mansoni with portal hypertension. Ultrasonography of the liver showed wide high‐echo bands in the hilus of the portal vein, and its central and peripheral branches. Selective splenic arteriography demonstrated enlargement of the portal vein trunk and amputation of large peripheral branches of portal vein. On peritoneoscopy, the liver surface showed medium‐sized block‐like formations separated by irregular linear septa with mild to moderate depression, and many tiny white structures were observed on the liver surface. On magnifying peritoneoscopy, some irregular abnormal veins were observed, and normal peripheral branches of the portal vein were almost diminished on the liver surface. Wide white structures assumed to be thickened medium‐sized branches of the portal vein were also observed on the deeper part of the liver surface. Histological examination of the liver biopsy specimens revealed broad collagenous fibrosis of the portal area with slight infiltration of eosinophils, a few schistosomal ova, diminishing of the peripheral branches of the portal vein and dilatation of abnormal vessels in some portal tracts.     

Repeated endoscopic sclerotherapy of oesophageal varices due to non-cirrhotic portal fibrosis using intravariceal polidocanol

Forty patients with variceal bleeding due to non-cirrhotic portal fibrosis have been treated by repeated endoscopic injection sclerotherapy using intravariceal polidocanol (1%). This has decreased re-bleeding as evidenced by a decrease in mean bleeding risk factor (BRF) and transfusion requirement; difference between presclerotherapy and postsclerotherapy parameters were significant ( P < 0.001). Low doses of polidocanol (mean 13.2 ml per session) were effective in the obliteration of varices. The mean sclerotherapy sessions required for obliteration were 8.04 (s.d. = 2.24). Complications were infrequent. Cumulative survival for 4 years was 92.5%. Based on these results endoscopic sclerotherapy is recommended for managing variceal bleeding due to non-cirrhotic portal fibrosis and is a reasonable alternative to surgery.     

Percutaneous transhepatic catheterization of the portal venous system

During recent years, percutaneous transhepatic catheterization of the portal venous system has become the most accurate procedure for investigation of the portal system. The procedure can be performed under local analgesia, is relatively simple, and complications are rare. The success rate is high, approximately 90%, especially when the liver hilum is localized by ultrasonography prior to catheterization. The free portal pressure can be measured. Selective catheterization of all portal tributaries can be performed. The indications are: portography in patients with cirrhosis of the liver and portal hypertension for delineation of collateral vein systems including gastro-oesophageal varices; visualization of veins that may be used for portosystemic shunt operations; postoperative control of shunt patency; diagnosis of portal and hepatic vein thrombosis; localization of stenosis in the portal vein system; pre-operative evaluation of patients with tumours in the biliary tract and pancreas; obliteration of bleeding oesophageal varices; and verification and localization of endocrine pancreatic tumours making curative resection possible. Further, transhepatic catheterization of the portal system may be used in research on the development of portal hypertension, collateral veins, variceal bleeding, and for haemodynamic, metabolic and pharmacologic studies in the gastrointestinal tract.     

Non-cirrhotic portal fibrosis (idiopathic portal hypertension): experience with 151 patients and a review of the literature

BACKGROUND: Non-cirrhotic portal fibrosis (NCPF), the equivalent of idiopathic portal hypertension in Japan and hepatoportal sclerosis in the United States of America, is a common cause of portal hypertension in India. The clinical features, portographic and histological findings, and management of 151 patients with non-cirrhotic portal fibrosis are presented. METHODS: The disease is diagnosed by the presence of unequivocal evidence of portal hypertension in the definite absence of liver cirrhosis and extrahepatic portal vein obstruction (EHPVO). Retrospective analysis of records of 151 patients with NCPF was analyzed for the clinical presentation, physical findings, laboratory tests, radiological and histological findings, and for the outcome of treatment. RESULTS: The disease is characterized by massive splenomegaly with anemia, preserved liver function and benign prognosis in a majority of patients. Splenoportovenography (SPV) showed massive dilatation of the portal and splenic veins, and the presence of collaterals. Twenty-four (15.9%) patients showed evidence of natural/spontaneous shunts (splenorenal 15, umbilical nine) on SPV; these patients had a lower incidence of variceal bleeding. Liver histology demonstrated maintained lobular architecture, portal fibrosis of variable degree, sclerosis and obliteration of small-sized portal vein radicles, and subcapsular scarring with the collapse of the underlying parenchyma. Piecemeal or hepatocytic necrosis was absent in all histology specimens. Three patients showed nodular transformation along with abnormal liver functions, and may represent late manifestation of NCPF where features are similar to those seen in patients with incomplete septal cirrhosis. In the initial part of the study, surgery (side-to-side lieno-renal shunt) was the preferred modality of treatment, however, endoscopic sclerotherapy or variceal ligation has now become the preferred first line of management of variceal bleeding. CONCLUSIONS: The epidemiological and clinical features of NCPF have more similarity to IPH than has previously been documented. The development of spontaneous shunts tends to protect these patients from variceal bleeding.     

Endoscopic variceal ligation is a sufficient procedure for the treatment of oesophageal varices in patients with hepatitis C liver cirrhosis: comparison with injection sclerotherapy

AIMS: Endoscopic variceal ligation (EVL) is a recently developed alternative to endoscopic injection sclerotherapy (EIS) for the treatment of oesophageal varices. Endoscopic variceal ligation and EIS were compared in an attempt to clarify the efficacy and safety of EVL for patients with cirrhosis due to hepatitis C. METHODS: Endoscopic variceal ligation was performed in 60 patients and EIS in 30. Varices were eradicated in all patients by EVL and 87% (26 out of 30) by EIS. RESULTS: There was no significant difference between EVL and EIS in relation to the incidence of bleeding and the 5 year survival rate after treatment. There were no severe complications except mild substernal pain after EVL, while pulmonary embolism occurred in one patient receiving EIS. CONCLUSIONS: Endoscopic variceal ligation is a safe and effective technique for eradicating oesophageal varices in patients with hepatitis C cirrhosis.     

Mixed connective tissue disease associated with idiopathic portal hypertension and chronic thyroiditis

We report a patient with mixed connective tissue disease (MCTD) associated with idiopathic portal hypertension (IPH) and chronic thyroiditis. The patient was a 68-year-old Japanese woman who was admitted to our hospital for treatment of bleeding esophageal varices. She had previously exhibited Raynaud's phenomenon and had had arthritis for about 30 years. She also had had high titers anti-U1 of ribonucleoprotein (RNP) anti-single strand-DNA autoantibodies for 2 years, and had been diagnosed with MCTD 1 year previously. The bleeding from esophageal varices was successfully stopped by endoscopic injection sclerotherapy. Results of laboratory examinations, imaging examinations, and laparoscopy, including liver biopsy, indicated that the esophageal varices were caused by portal hypertension due to IPH. The patient also had a diffusely firm and enlarged goiter and hypothyroidism, and she exhibited anti-thyroid microsomal antibodies and anti-thyroglobulin antibodies, she was diagnosed as having a complication of chronic thyroiditis. This association of MCTD, IPH, and chronic thyroiditis is quite rare and provides a unique opportunity to observe immunological involvement in the pathogenesis of IPH.     

内镜治疗与断流术治疗门静脉高压的效果比较

目的比较内镜治疗与断流术对门静脉高压的治疗效果。方法收集2010年1月-2012年1月沈阳军区总医院101例肝硬化合并食管胃底静脉曲张破裂出血患者的临床资料,其中内镜下联合治疗53例(内镜组),断流术治疗48例(断流术组),比较两组患者肝功能、脾亢变化以及术后再出血率和并发症情况。计量资料采用均数±标准差(x±s)表示,计数资料采用例数或百分率表示,两组间比较计量资料采用t检验,计数资料采用χ2检验。结果内镜组术后肝脏储备功能较术前变化不明显(P值均0.05);断流术组术后白蛋白水平与术前比较下降,差异均有统计学意义(t=2.512,P0.05);内镜组术后白细胞、血小板与术前相比变化不明显(P值均0.05),断流术组术后白细胞、血小板与术前相比升高,差异均有统计学意义(P值均0.05);两组术后累计再出血率比较3个月7.5%和6.2%(χ2=0.066,P0.05),6个月7.5%和8.3%(χ2=0.021,P0.05)及1年9.4%和8.3%(χ2=0.038,P0.05);两组术后并发症发生率分别为24.5%和50%,差异有统计学意义(χ2=7.040,P0.05)。结论肝硬化门静脉高压内镜联合治疗与断流术相比,内镜治疗对患者损伤小,术后肝功能变化不明显,术后并发症发生率低;对肝硬化食管胃底静脉曲张破裂出血合并脾功能亢进明显的患者,可行断流术。     

肝硬化门静脉高压食管胃静脉曲张出血的防治指南

正1概述门静脉高压症是指由各种原因导致的门静脉系统压力升高所引起的一组临床综合征,其最常见病因为各种原因所致的肝硬化。门静脉高压症基本病理生理特征是门静脉系统血流受阻和(或)血流量增加,门静脉及其属支血管内静力压升高并伴侧支循环形成,临床主要表现为腹水、食管胃静脉曲张(gastroesophageal varices,GOV)、食管胃静脉曲张破裂出血(esophagogastric variceal bleeding,EVB)和肝性脑病等,其中     

Management of rectal varices in portal hypertension

Rectal varices are portosystemic collaterals that form as a complication of portal hypertension, their prevalence has been reported as high as 94% in patients with extrahepatic portal vein obstruction. The diagnosis is typically based on lower endoscopy (colonoscopy or sigmoidoscopy). However, endoscopic ultrasonography has been shown to be superior to endoscopy in diagnosing rectal varices. Color Doppler ultrasonography is a better method because it allows the calculation of the velocity of blood flow in the varices and can be used to predict the bleeding risk in the varices. Although rare, bleeding from rectal varices can be life threatening. The management of patients with rectal variceal bleeding is not well established. It is important to ensure hemodynamic stability with blood transfusion and to correct any coagulopathy prior to treating the bleeding varices. Endoscopic injection sclerotherapy has been reported to be more effective in the management of active bleeding from rectal varices with less rebleeding rate as compared to endoscopic band ligation. Transjugular intrahepatic portsystemic shunt alone or in combination with embolization is another method used successfully in control of bleeding. Balloon-occluded retrograde transvenous obliteration is an emerging procedure for management of gastric varices that has also been successfully used to treat bleeding rectal varices. Surgical procedures including suture ligation and porto-caval shunts are considered when other methods have failed.     

Pathogenesis of varices in schistosomal portal hypertension

Patients with schistosomiasis and portal hypertension have significantly lower levels of hydroxyproline in their saphenous veins and anterior rectus sheaths than do individuals without schistosomal hepatic fibrosis. The stomach of patients with schistosomal portal hypertension demonstrates an increased number of lymphatics by lymphangiography. The disrupted lymph node architecture in these patients could be partially responsible for dilation, tortuosity, and retrograde lymph flow in the gastric lymphatics. These histological and lymphangiographic findings could be attributed to the effect of venous and lymphatic hypertension. A postmortem histological examination of the esophagus of patients with decompensated schistosomal portal hypertension revealed edema of the entire esophageal wall with lymphatic dilation and tortuosity. Based upon these data, we suggest that the varices that develop in patients with schistosomal portal hypertension occur as a consequence of an increased portal venous pressure together with acquired lymphangectasia as well as an intrinsic weakness of the walls of the portosystemic venous channels.     

《肝硬化门静脉高压食管胃静脉曲张出血的防治指南》解读

正肝硬化门静脉高压并发食管胃静脉曲张破裂出血(esophageal gastric variceal bleeding,EVB)是临床常见的危急症之一。尽管近10年来药物及内镜治疗成绩显著,但其6周内病死率达15%~20%,肝功能Child-Pugh C级合并EVB患者病死率高达30%~40%[1-2]。2008年中华医学会肝病学分会、消化内镜分会及消化病学分会(称为"三个学会")首次制订了我国《肝硬     

Management of portal hypertension based on portal hemodynamics

Portal hypertension is most commonly caused by chronic liver disease. As liver damage progresses, portal pressure gradually elevates and hemodynamics of the portal system gradually change. In normal liver, venous returns from visceral organs join the portal trunk and flow into the liver (hepatopetal blood flow). As portal pressure increases due to liver damage, congestion of some veins of the visceral organ occurs (blood flow to and from). Finally, the direction of some veins (the left gastric vein in particular) of the visceral organ change (hepatofugal blood flow) and develop as collateral veins (portosystemic shunt) to reduce portal pressure. Therefore, esophagogastric varices serve as drainage veins for the portal venous system to reduce the portal pressure. In chronic liver disease, as intrahepatic vascular resistance is increased (backward flow theory) and collateral veins develop, adequate portal hypertension is required to maintain portal flow into the liver through an increase of blood flow into the portal venous system (forward flow theory). Splanchnic and systemic arterial vasodilatations increase the blood flow into the portal venous system (hyperdynamic state) and lead to portal hypertension and collateral formation. Hyperdynamic state, especially around the spleen, is detected in patients with portal hypertension. The spleen is a regulatory organ that maintains portal flow into the liver. In this review, surgical treatment, interventional radiology, endoscopic treatment, and pharmacotherapy for portal hypertension (esophagogastric varices in particular) are described based on the portal hemodynamics using schema.     

Advances in the treatment of portal hypertension in cirrhosis

Non-selective beta-blockers and handling of esophageal varices has been key elements in the treatment of portal hypertension in recent decades. Liver vein catheterization has been essential in diagnosis and monitoring of portal hypertension, but ongoing needs for noninvasive tools has led to research in areas of both biomarkers, and transient elastography, which displays promising results in discerning clinically significant portal hypertension. Novel research into the areas of hepatic stellate cell function and the dynamic components of portal hypertension has revealed promising areas of treatment modalities, targeting intestinal decontamination, angiogenesis, inflammation and oxidative stress. Future studies may reveal if these initiatives lead to developments of new drugs for treatment of portal hypertension.     

Medical treatment of portal hypertension

In this chapter we give a quick review of the rationale for treatment of portal hypertension. The different scenarios for treatment of variceal bleeding will be discussed-that is, primary and secondary prophylaxis of variceal bleeding as well as the treatment of the acute bleeding episode. The role of the pharmacological, endoscopic and derivative treatments in each one of these scenarios will be discussed. Particular attention will be devoted to the potential role of the combination therapy of beta-blockers with isosorbide-5-mononitrate for preventing re-bleeding and to the best approach to patients with intolerance or contraindications to beta-blockers. We also give a rational review of the data comparing sclerotherapy against ligation as well as the potential role of the latter on primary prophylaxis.