Non-cirrhotic portal hypertension versus idiopathic portal hypertension

Portal hypertension occurs in a number of disorders other than cirrhosis and they are collectively called non-cirrhotic portal hypertension (NCPH). The common causes of NCPH include idiopathic portal hypertension (IPH), non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal venous thrombosis (EHPVT). Other causes include schistosomiasis, hepatic venous outflow tract obstruction, veno-occlusive disease and congenital hepatic fibrosis. Patients with IPH and EHPVT present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation and jaundice due to portal biliopathy. The diagnosis is usually made by abdominal ultrasound, upper gastrointestinal endoscopy, normal liver function tests and normal liver histology. Variceal bleeding in NCPH has lower mortality as compared with cirrhosis because of better liver functions in NCPH. Treatment for NCPH includes primary prophylaxis for variceal bleeding and prevention of repeat bleeding using drugs like beta-blockers, endoscopic sclerotherapy and endoscopic band ligation of varices. In patients with uncontrolled variceal bleeding or symptomatic hypersplenism, porto-systemic shunt surgery or splenectomy are required.     

肝硬化合并贲门区曲张静脉破裂出血134例内镜诊疗分析

目的回顾性分析急诊内镜治疗肝硬化合并贲门区曲张静脉破裂出血的疗效。方法以内镜下硬化术、套扎术和组织粘合剂栓塞术等手段治疗134例肝硬化合并贲门区曲张静脉破裂出血。结果 134例中,121例(90.3%)止血成功,内镜下硬化术和组织粘合剂栓塞术的止血率分别为89.8%和95.8%。死亡4例,72 h内病死率为4.5%,原因为失血性休克、肝性脑病和多脏器功能衰竭。胃镜操作过程中未见死亡病例。结论肝硬化合并贲门区曲张静脉破裂出血,以内镜下硬化术和栓塞术治疗可获得较好的近期效果。     

Hepatobiliary fibropolycystic diseases. A clinical and histological review of 51 patients

The clinical, radiological and hepatic histological features of 51 patients with hepatobiliary fibropolycystic disease were reviewed. Many of the patients had more than one of the diseases; the combination of both congenital hepatic fibrosis (CHF) and Caroli's disease was most striking. Twelve patients with CHF (50% male) presented at 6 +/- 2 years of age (mean +/- SEM) with hepatosplenomegaly or variceal bleeding. Their main problems were recurrent variceal bleeds and renal disease. Polycystic kidneys and renal stones were present in 79% and chronic renal failure in 30%. Six of the 8 patients with Caroli's disease were male (75%) and presented later (aged 37 +/- 8 years) with hepatomegaly or cholangitis. Recurrent cholangitis developed in most (7/8) and 2 had polycystic kidneys. Twelve patients had a combination of CHF and Caroli's disease presenting with hepatosplenomegaly, bleeding or cholangitis. As in Caroli's disease, most (83%) were male, but the age of presentation (15 +/- 4 years), and the incidence of polycystic kidneys (42%) and renal failure (8%) was intermediate between CHF and Caroli's disease. In these patients, bleeds always predated cholangitis. Histologically, acute cholangitis was superimposed on the changes of CHF. Adult polycystic liver disease (10 patients) presented later (43 +/- 3 years) in females (90%) with pain, a mass or incidentally; polycystic kidneys were present in 33%. Microhamartomas (10 patients), which were usually incidental findings, were diagnosed latest (50 +/- 6 years). Three choledochal cysts were seen. The hazard of cancer in these diseases was reflected by 2 bile duct cancers and 1 pancreatic cancer (incidence 6%). This study has confirmed that hepatobiliary fibropolycystic diseases form part of a family and are often associated together. However, the diseases are of greatly differing severity and the prognosis in an individual patient is determined by the fibropolycystic diseases present.     

Motion - prophylactic banding of esophageal varices is useful: arguments for the motion.

Variceal hemorrhage is a frequent complication of cirrhosis and is associated with a high mortality rate, especially in patients with decompensated liver disease. Endoscopy is useful in identifying factors that predict a high likelihood of bleeding, including large varices and red colour signs. Endoscopic rubber band ligation has superseded sclerotherapy in the prevention of both recurrent hemorrhage and the first episode of bleeding, because it causes fewer complications and requires fewer sessions to eradicate varices. It has been proven to be more effective than nontreatment in the primary prophylaxis against variceal hemorrhage. There is extensive literature that has found that band ligation is more effective than beta-adrenergic receptor antagonists at preventing the first variceal hemorrhage. There is ongoing debate about the relative merits of these two approaches, but the available evidence supports the conclusion that band ligation is the treatment of choice in the primary prevention of variceal bleeding. Trials of combined medical and endoscopic therapy are eagerly awaited, and the author suspects that it may prove to be more effective than either modality alone.     

经内镜结扎和硬化剂治疗食管静脉曲张和门脉高压性胃病的疗效及预后

目的：观察经内镜结扎和硬化剂治疗食管静脉曲张的疗效及对门脉高压性胃病（PHG）的影响。方法;对92例患者随机分为套扎组（n=43)和硬化剂（n=49),分别在治疗后1－3月和1－3年内复查。观察静脉曲张及PHG的转归情况。结果：1－3月内复查套扎组完成26例,其中食管静脉曲张根除12例,曲张减轻12例,无效2例,PHG加重17例。硬化剂组完成29例,其中静脉曲张根除4例,曲张减轻22例,无效3例,PHG加重11例。1－3年内复查套扎组和硬化剂组的再曲张率及再出血率分别为61．5％、46．7％和44．4％．33．3％。结论：近期套扎治疗在根治静脉曲张方面优于硬化剂注射,但更易诱发和加重PHG。而套扎组和硬化剂组远期均可出现再曲张和再出血。两组比较无差异。     

Primary prophylaxis of variceal bleeding in cirrhosis

Variceal bleeding is the result of portal hypertension, which is a major complication of liver cirrhosis and carries a high mortality rate. Because of the mortality associated with variceal bleeding, strategies for prevention of the first bleed is important. Risk stratification is important in determining those at risk of bleeding from varices and current data suggest that patients with large varices with red signs, severe underlying liver disease and those who have a hepatic venous pressure gradient of greater than 12 mmHg are at high risk of bleeding. Surveillance for varices in patients with cirrhosis is therefore important. The current review evaluates the role of various treatments in the primary prophylaxis of variceal bleeding. The current first choice treatment is non-selective beta-blockers; which is cheap, easy to administer, and reduces the risk of first variceal haemorrhage significantly. Combination of beta-blockers and nitrates looks promising but needs further evaluation. Endoscopic variceal band ligation compares favourably with non-selective beta-blockers in preventing the first bleeding episode in cirrhotic patients and may be an alternative for patients who cannot tolerate, or have contraindications to beta-blockers. The role of monitoring the hepatic venous pressure gradient in those being treated with pharmacological agents, the role of newer drugs such as non-selective beta-blockers with intrinsic alpha-adrenergic activity and angiotensin receptor blockers require further evaluation.     

Endoscopic variceal ligation vs. propranolol for prevention of first variceal bleeding: a randomized controlled trial

OBJECTIVES: Data in the literature regarding the role of endoscopic variceal ligation for the prevention of first variceal bleeding in cirrhotic patients are controversial. To further explore this issue we have compared ligation and propranolol treatment in a prospective randomized study. METHODS: Sixty patients with cirrhosis and oesophageal varices with no history but at high risk of bleeding were randomized to ligation treatment (30 patients) or propranolol (30 patients). Patients were followed for approximately 27.5 months. RESULTS: Variceal obliteration was achieved in 28 patients (93.3%) after 3+/-1 sessions. The mean daily dose of propranolol was 60.3+/-13.3 mg. Two patients (6.7%) in the ligation group and nine patients (30%) in the propranolol group developed variceal bleeding (P = 0.043). The actuarial risks of variceal bleeding at 2 years were 6.7% and 25%, respectively. On multivariate analysis, propranolol treatment and grade III varices turned out to be predictive factors for the risk of variceal bleeding. Mortality was not different between the two groups. There were no serious complications due to ligation. Propranolol treatment was discontinued in four patients because of side effects. CONCLUSIONS: Variceal ligation is a safe and more effective method than propranolol treatment for the prevention of first variceal bleeding in cirrhotic patients with high-risk varices.     

Carvedilol in the Treatment of Portal Hypertension

Variceal bleeding is a major event in the natural history of end-stage liver disease with a subsequent high mortality rate. Non-selective β-blockers are currently the drugs of choice for preventing first variceal bleeding. Endoscopic rubber band ligation of high risk varices features as a first line option if cirrhotic patients cannot tolerate β-blockers. Despite adequate β-blockade, some patients may still present with variceal bleeding. The effect of carvedilol, a non-selective β and α-1 receptor-blocker, on lowering portal pressure has been investigated in several clinical trials and found to be superior to propranolol in both acute and chronic hemodynamic studies. Recently, carvedilol has also been compared with band ligation for primary prophylaxis against variceal bleeding with equivalent results to band ligation. Patient tolerance to carvedilol in advanced liver disease remains a source of concern. This review examines the place of carvedilol as an alternative to the currently recommended pharmacological therapy in prophylaxis against variceal bleeding.     

Detachable endoloop vs. elastic band ligation for bleeding esophageal varices

BACKGROUND: Variceal bleeding is a serious complication with a mortality rate that ranges from 20% to 50%. Patients who have variceal hemorrhage usually are treated by endoscopic injection sclerotherapy or elastic band ligation to eradicate the varices. Endoloop ligation is a newly developed technique for achieving hemostasis and variceal eradication. This study compared endoloop ligation with elastic band ligation in patients with acute esophageal variceal bleeding. METHODS: Fifty patients with acute esophageal variceal bleeding were recruited: 25 were treated by elastic band ligation and 25 by endoloop ligation. RESULTS: Although the number of patients in whom bleeding recurred during a follow-up period of 6 months was smaller in the endoloop group (12%) vs. the band group (28%), this difference was not statistically significant. Furthermore, no statistically significant difference was found between the two groups with respect to the number of patients in whom variceal eradication was achieved, the number of treatment sessions required for variceal eradication, or the frequency of variceal recurrence. The total cost for variceal obliteration by endoloop ligation was 342 dollars per patient, whereas, the total cost of variceal eradication by elastic band ligation was 356 dollars per patient. The endoloop had certain technical advantages over band application: a better field of vision, tighter application, good results with junctional varices, and a lack of strain exerted by the device on the endoscope. CONCLUSIONS: Endoloop ligation is a promising new technique for management of patients with bleeding esophageal varices.     

Do we need endoscopic sclerotherapy of oesophageal varices or the last turn off the light

For the primary prophylaxis of variceal bleeding endoscopic band ligation has been shown to be as effective as non-selective beta-blockers (carvedilol), but variceal injection sclerotherapy is not generaly recommended in this setting because of higher rate of complications and lower effect in reducing either bleeding or mortality. Endoscopic management of acutely bleeding gastroesophageal varices includes injection sclerotherapy, rubber band ligation, and variceal obturation with tissue adhesives. Variceal injection sclerotherapy remains a quick, simple and cheap technique for the control of active bleeding from esophageal varices, but is associated with more rebleeding than variceal band ligation, which is now preferred also for lower rate of complications. Endoscopic sclerotherapy has increasingly been replaced by ligation also in secondary prophylaxis of variceal bleeding. The studies showed that band ligation can eradicate varices in fewer sessions, re-bleeding and complications were fewer in comparison with variceal injection sclerotherapy. Because of the reduced efficacy, severe complications, and the high mortality associated with using conventional sclerosants in acute bleeding gastric varices, the technique of injecting tissue adhesives has been studied, described and used despite numerous complications. Endoscopic injection sclerotherapy of esophageal varices remains usable as an oldest method in arresting of this hemorrhage only in rare cases when the band ligation is not available.     

Congenital hepatic fibrosis in Indian children

BACKGROUND: Congenital hepatic fibrosis (CHF) is an uncommon cause of portal hypertension in children. So far, there is no report of this from the subcontinent. We have studied the clinical spectrum of CHF in North Indian children. METHODS: Fifteen children were diagnosed with CHF on the basis of their liver histology over a period of 6.5 years. Their clinical details were recorded. Oesophagogastroduodenoscopy and abdominal ultrasonography were performed in all cases. All siblings were examined clinically; and ultrasonography, endoscopy and liver biopsy were performed if there was firm hepatomegaly. Children with variceal bleeding were managed by endoscopic sclerotherapy. The median age of these children was 8 years with a male to female ratio of 1.5:1. RESULTS: Only one sibling (of 33) was diagnosed as having CHF. The predominant presentations were variceal bleeding in six, abdominal distension in seven and incidental detection of organomegaly in two. Hepatomegaly was present in all patients and splenomegaly in all but one. Liver function and renal function tests were normal in all children, except for a raised serum alkaline phosphatase in six. Two children had associated renal cysts, two had choledochal cysts, one each had Caroli's disease and biliary atresia and two children had portal vein thrombosis. Variceal obliteration was achieved in five children after an average 4.8 sclerotherapy sessions and one required a mesocaval shunt. On follow up (median 41 months, range 1-80 months) all are doing well. CONCLUSIONS: Congenital hepatic fibrosis is mainly sporadic in India and associated renal lesions are uncommon. Endoscopic sclerotherapy is effective in controlling variceal bleed and the prognosis is universally good in the absence of renal diseases.     

Cerebral and splenic infarctions after injection of N-butyl-2-cyanoacrylate in esophageal variceal bleeding

Variceal bleeding is the most serious complication of portal hypertension,and it accounts for approximately one fifth to one third of all deaths in liver cirrhosis patients.Currently,endoscopic treatment remains the predominant method for the prevention and treatment of variceal bleeding.Endoscopic treatments include band ligation and injection sclerotherapy.Injection sclerotherapy with N-butyl-2-cyanoacrylate has been successfully used to treat variceal bleeding.Although injection sclerotherapy with N-butyl-2-cyanoacrylate provides effective treatment for variceal bleeding,injection of N-butyl-2-cyanoacrylate is associated with a variety of complications,including systemic embolization.Herein,we report a case of cerebral and splenic infarctions after the injection of N-butyl-2-cyanoacrylate to treat esophageal variceal bleeding.     

Variceal and other portal hypertension related bleeding

Variceal bleeding is one of the commonest and most severe complications of liver cirrhosis. Even with the current best medical care, mortality from variceal bleeding is still around 20%. When cirrhosis is diagnosed, varices are present in about 30–40% of compensated patients and in 60% of those who present with ascites. Once varices have been diagnosed, the overall incidence of variceal bleeding is in the order of 25% at two years. Variceal size is the most useful predictor for variceal bleeding, other predictors are severity of liver dysfunction (Child–Pugh classification) and the presence of red wale marks on the variceal wall. The current consensus is that every cirrhotic patient should be endoscopically screened for varices at the time of diagnosis to detect those requiring prophylactic treatment. Non-selective beta-adrenergic blockers (NSBB) and endoscopic band ligation (EBL) have been shown effective in the prevention of first variceal bleeding. The current recommendation for treating acute variceal bleeding is to start vasoactive drug therapy early (ideally during the transferral or to arrival to hospital, even if active bleeding is only suspected) and performing EBL. Once bleeding is controlled, combination therapy with NSBB + EBL should be used to prevent rebleeding. In patients at high risk of treatment failure despite of using this approach, an early covered-TIPS within 72 h (ideally 24 h) should be considered. Data on management of gastric variceal bleeding is limited. No clear recommendation for primary prophylaxis can be done. In acute cardiofundal variceal bleeding, vasoactive agents together with cyanoacrylate (CA) injection seem to be the treatment of choice. Further CA injections and/or NSBB may be used to prevent rebleeding. TIPS or Balloon-occluded retrograde transvenous obliteration when TIPS is contraindicated may be used as a rescue therapy.     

Pediatric non-cirrhotic portal hypertension:Endoscopic outcome and perspectives from developing nations

Non-cirrhotic portal hypertension(NCPH) forms an important subset of portal hypertension in children. Variceal bleed and splenomegaly are their predominant presentation. Laboratory features show cytopenias(hypersplenism) and preserved hepatic synthetic functions. Repeated sessions of endoscopic variceal ligation or endoscopic sclerotherapy eradicate esophageal varices in almost all cases. After variceal eradication, there is an increased risk of other complications like secondary gastric varices, cholangiopathy, colopathy, growth failure,especially in extra-hepatic portal vein obstruction(EHPVO). Massive splenomegaly-related pain and early satiety cause poor quality of life(QoL). Meso-Rex bypass is the definitive therapy when the procedure is anatomically feasible in EHPVO. Other portosystemic shunt surgeries with splenectomy are indicated when patients present late and spleen-related issues predominate. Shunt surgeries prevent rebleed, improve growth and QoL. Non-cirrhotic portal fibrosis(NCPF) is a less common cause of portal hypertension in children in developing nations.Presentation in the second decade, massive splenomegaly and patent portal vein are discriminating features of NCPF. Shunt surgery is required in severe cases when endotherapy is insufficient for the varices. Congenital hepatic fibrosis(CHF)presents with firm palpable liver and splenomegaly. Ductal plate malformation forms the histological hallmark of CHF. CHF is commonly associated with Caroli's disease, renal cysts, and syndromes associated with neurological defects.Isolated CHF has a favourable prognosis requiring endotherapy. Liver transplanta-tion is required when there is decompensation or recurrent cholangitis, especially in Caroli's syndrome. Combined liver-kidney transplantation is indicated when both liver and renal issues are present.     

Feasibility and potential benefit of maintenance endoscopic variceal ligation in patients with unresectable hepatocellular carcinoma and acute esophageal variceal hemorrhage: a controlled trial.

BACKGROUND: Patients with unresectable hepatoma and acute esophageal variceal bleeding have extremely high rates of recurrent bleeding and mortality. This controlled study evaluates the feasibility and potential benefit of maintenance endoscopic variceal ligation in these patients. METHODS: Patients with unresectable hepatoma and acute esophageal variceal bleeding underwent emergent endoscopic variceal ligation. After hemostasis, patients were randomized to undergo maintenance or esophageal variceal ligation (EVL) as necessary (demand ligation). RESULTS: Fifty-four patients underwent maintenance EVL and 55 demanded EVL. One or more subsequent EVL session could be performed in only 30 patients (55.6%) in the maintenance group (actual maintenance ligation). Logistic regression analysis found that hepatic function determines the feasibility of maintenance ligation (Child-Pugh's A+B vs. C, OR 23.00: 95% CI [5.26, 100.66]). The survival and recurrent bleeding rates were similar in both groups. A subgroup analysis of patients with Child-Pugh's A and B hepatic reserve in both the maintenance EVL group (n = 24) and demand EVL group (n = 25) was performed to assess the potential benefit of maintenance ligation. Maintenance ligation reduced the rate of recurrent bleeding compared with demand ligation (p = 0.043). Cox regression showed that portal vein thrombosis and tumors in both hepatic lobes were also factors together with EVL that determined recurrence of bleeding. Survival was similar in both groups. CONCLUSIONS: Maintenance ligation is feasible in patients with unresectable hepatoma and variceal hemorrhage if they have a good hepatic reserve. Maintenance ligation might lower the rate of recurrent bleeding in this subgroup of patients.     

Treatment of variceal bleeding

Opinion statement Mortality due to variceal bleeding secondary to portal hypertension has decreased significantly in the past 2 decades. Endoscopic therapy has been the mainstay of treatment for acute variceal bleeding. Variceal banding ligation has superceded injection sclerotherapy as the most popular treatment modality for acute bleeding. Multiple banding ligators are widely used with high success in restoring hemostasis. The combination of banding and sclerotherapy may be useful in preventing the early recurrence of varices and rebleeding after initial obliteration of varices. Selective vasoactive agents such as somatostatin analogs also improve the outcome of patients. Radiologic shunting has proven to be an effective salvage procedure when endoscopic treatments fail and may be a good intermediate-stage therapy while the patient is waiting for liver transplantation.     

Caroli's disease in congenital hepatic fibrosis and infantile polycystic disease

ABSTRACT— Two of three patients with infantile polycystic disease and all three patients with congenital hepatic fibrosis revealed multiple gross cystic dilatation of the intrahepatic biliary tree, referred to as Caroli's disease. All three patients with congenital hepatic fibrosis showed recurrent cholangitis related to coexisting Caroli's disease, and two of them died of sepsis following cholangitis. There were several common morphologic findings in the intrahepatic biliary tree of macroscopic and microscopic levels in infantile polycystic disease and congenital hepatic fibrosis with Caroli's disease: 1. irregular, non-obstructive dilatation of the duct lumen; 2. bulbar protrusion of the duct wall into the lumen; and 3. bridge formation of the duct wall across the lumen. These ductal changes might be caused by a combination of uneven and disproportionate overgrowth of biliary epithelia and their supporting connective tissue. This pathogenetic mechanism might be operative along the entire intrahepatic biliary system in this disease group, and involvement of the smaller levels in early life might result in infantile polycystic disease and congenital hepatic fibrosis and simultaneous or possibly later involvement of the larger levels in Caroli's disease.     

A commonsense approach to esophageal varices

Variceal hemorrhage is one of the most serious complications of portal hypertension and cirrhosis and is associated with a mortality of at least 20% at 6 weeks, despite improvements in therapy over the last decade. Variceal hemorrhage predisposes cirrhotic patients to worsening hepatic decompensation, infection, or renal insufficiency, which contribute to mortality. Providing primary prophylaxis against first variceal hemorrhage, general management of an acute bleeding episode, and treatment after variceal hemorrhage--mainly prevention of rebleeding--are equally important components of care for the cirrhotic patient who has gastroesophageal varices. This article describes a practical approach to the management of cirrhotic patients who have gastroesophageal varices.     

Pattern of upper gastrointestinal haemorrhage in northern India—An endoscopic study of 316 patients

Three hundred and sixteen patients with acute upper gastrointestinal haemorrhage were studied prospectively and consecutively. The most frequent cause was variceal bleeding due to portal hypertension (36%), followed by peptic ulceration (24%) and gastric erosions (19%). Variceal haemorrhage tended to be severe and had a high individual mortality rate. Associated acute mucosal lesions with portal hypertension were strikingly less frequent when compared with the experience from the West. Seven per cent of patients died of bleeding alone and an equal number of an associated systemic disorder or complication. Splenomegaly was present in all patients with a variceal haemorrhage due to non-cirrhotic portal hypertension. However, in patients with portal hypertension due to cirrhosis splenomegaly was present in 63%. Endoscopy altered the clinical diagnosis in 13.2% of patients. Based on previous experience oesophago-gastro-duodenal endoscopy has been a useful tool in the management of acute upper gastrointestinal haemorrhage.     

Congenital hepatic fibrosis

We report the clinical features of 7 men (mean age 22 years, range 7-53 years) with congenital hepatic fibrosis (CHF). Five patients presented with variceal bleeding and/or hepatosplenomegaly due to portal hypertension. Cholangitis was the presenting symptom in the other 2 cases. Diagnosis was established by histological examination of a surgical wedge biopsy (4 patients) or needle biopsy (3 patients). A portal-systemic shunting was performed in 6 patients, three times prophylactically. None of the 5 survivors developed chronic hepatic encephalopathy. Recurrent bouts of cholangitis with septicemia and hepatic abscesses were a major complication in 5 patients with a fatal outcome in 2 cases. Six patients had associated small and large cysts in the cortex of both kidneys, compatible with adult-type polycystic disease. One patient developed terminal renal insufficiency. In 3 patients kidney function remained normal at a mean follow-up time of 7.5 years (range 1-18 years). In 2 families (4 cases) an autosomal dominant inheritance of renal disease was suggested. This study demonstrates that CHF is a rare cause of portal hypertension in late childhood and in adults. Cholangitis is a severe and frequently fatal complication. Association with a variety of congenital renal abnormalities is very frequent. However, the association with adult-type polycystic disease as reported in 4 cases is very rare.