Mathieu Duché

Risk of gastrointestinal bleeding during adolescence and early adulthood in children with portal vein obstruction

OBJECTIVE To estimate the risk of bleeding during adolescence and early adulthood in a group of children with portal vein obstruction who had not undergone an effective treatment beforehand. STUDY DESIGN Children (n = 44) were followed up from age 12 years to a mean age of 20 years (range, 15-34 years). Actuarial risk of bleeding, related to previous occurrence of gastrointestinal bleeding and to pattern of varices at age 12, was calculated yearly. RESULTS Twenty-four children presented with gastrointestinal bleeding after age 12, and 20 did not bleed. The overall actuarial probability of bleeding was 49% at age 16 and 76% at age 24. Probability of bleeding at age 23 was higher in children who had bled before age 12 than in children who had not bled (93% vs 56%; P =.007). Probabilities of bleeding at age 18 and at age 23 were 60% and 85%, respectively, in patients who had grade II or III esophageal varices at age 12. The 9 children without varices or with grade I varices only on endoscopy did not bleed between the ages of 12 and 20 years. CONCLUSIONS Children with portal vein obstruction have a >50% risk of bleeding during adolescence; the pattern of varices on endoscopy at age 12 may have a prognostic value.

Prognostic Value of Endoscopy in Children With Biliary Atresia at Risk for Early Development of Varices and Bleeding

BACKGROUND & AIMS Biliary atresia is the most common cause of childhood cirrhosis. We investigated prospectively the development of portal hypertension in 139 children with biliary atresia, the risk of gastrointestinal (GI) bleeding in the first years of life, and associations between endoscopic patterns of varices and risk. METHODS Children with clinical or ultrasonographic signs of portal hypertension underwent upper GI endoscopy examinations (n = 125, median age of 13 months). Information was recorded about esophageal varices and grade, red wale markings on the variceal wall, gastric varices along the cardia, and portal hypertensive gastropathy. A second endoscopy examination was performed in 64 children after a mean interval of 51 months to study their progression or regression. RESULTS At the first endoscopy examination, 88 of 125 children had esophageal varices, including 74 who were younger than 2 years. Grade II and III varices, red markings, gastric varices, and signs of gastropathy were present in 29, 30, 24, and 27 children, respectively. At the second endoscopy examination, progression, stability, and regression of endoscopic signs were observed in 37, 18, and 9 of the 64 children, respectively. Twenty-eight children had GI bleeding at a median age of 17 months. Multivariate analysis showed that red markings, and most importantly gastric varices, were independent factors associated with bleeding. CONCLUSIONS Children with biliary atresia have a high risk of portal hypertension in the first years of life. Spontaneous regression of varices is rare. Children with a combination of esophageal varices and red markings and/or gastric varices along the cardia should receive primary prophylaxis of bleeding.

Prophylactic endoscopic sclerotherapy of large esophagogastric varices in infants with biliary atresia

BACKGROUND Esophageal varices-related GI bleeding occurs frequently and early in life in children with biliary atresia and it may be life threatening. OBJECTIVE We report the results of prophylactic sclerotherapy in 13 infants with biliary atresia and large varices. PATIENTS Mean age was 13 months, mean weight was 8.2 kg, mean total serum bilirubin was 258 mumol/L, and mean prothrombin time was 78%. Esophageal varices were grade III (11 patients) or II (2 patients), with red signs in all infants and gastric varices in 12. None had GI bleeding. INTERVENTION Sclerotherapy was performed with the patient under continuous intravenous octreotide therapy in 7 infants. RESULTS In 8 children a complete or almost complete eradication of varices was obtained; none of these children bled later, 4 underwent liver transplantation, 3 are alive without liver transplantation, and 1 died of sepsis after 9 months awaiting liver transplantation. In 4 children a partial eradication was obtained and liver transplantation was performed. None of these children bled. One other child bled to death after 2 sessions of sclerotherapy. LIMITATIONS Four ulcers and 2 stenoses occurred in 6 children with no octreotide versus no ulcer and 1 stenosis in 7 children receiving octreotide. CONCLUSION These results (1) indicate that primary prevention of GI bleeding by sclerotherapy of esophageal varices is technically feasible and fairly effective in infants with biliary atresia and large varices, even in those with end-stage liver disease, (2) suggest that decreasing the risk of bleeding may allow liver transplantation under better conditions, and (3) further suggest that octreotide associated with sclerotherapy lowers the rate of complications.

Experience With Endoscopic Management of High-Risk Gastroesophageal Varices, With and Without Bleeding, in Children With Biliary Atresia

BACKGROUND & AIMS Biliary atresia, the most common cause of childhood cirrhosis, increases the risks for portal hypertension and gastrointestinal bleeding. We report the results from a single-center study of primary and secondary prophylaxis of bleeding in children with portal hypertension and high-risk varices. METHODS We collected data from 66 children with major endoscopic signs of portal hypertension, including grade 3 esophageal varices or grade 2 varices with red wale markings and/or gastric varices, treated consecutively from February 2001 through May 2011. Thirty-six children (mean age, 22 mo) underwent primary prophylaxis (sclerotherapy and/or banding, depending on age and weight). Thirty children (mean age, 24 mo) who presented with gastrointestinal bleeding received endoscopic treatment to prevent a relapse of bleeding (secondary prophylaxis). RESULTS In the primary prophylaxis group, a mean number of 4.2 sessions were needed to eradicate varices; no bleeding from gastroesophageal varices was observed after eradication. Varices reappeared in 37% of children, and 97% survived for 3 years. In the secondary prophylaxis group, a mean number of 4.6 sessions was needed to eradicate varices. Varices reappeared in 45%, and 10% had breakthrough bleeding; 84% survived for 3 years. There were no or only minor complications of either form of prophylaxis. CONCLUSIONS Endoscopic therapy as primary or secondary prophylaxis of bleeding appears to be well tolerated and greatly reduces the risk of variceal bleeding in children with biliary atresia and high-risk gastroesophageal varices. However, there is a risk that varices will recur, therefore continued endoscopic surveillance is needed.

Percutaneous Endoscopic Gastrostomy for Continuous Feeding in Children with Chronic Cholestasis

BACKGROUND Malnutrition associated with chronic cholestasis in children often requires continuous enteral feeding through a nasogastric tube, which may be poorly tolerated. METHOD Percutaneous endoscopic gastrostomy was performed in five children (age range, 20 months to 13 years) with severe cholestasis (Alagille syndrome in four; biliary atresia in one) and severe malnutrition (mean weight, -2.6 standard deviations; mean height, -2.7 standard deviations) who were awaiting liver transplantation. The pull-through technique was used in patients under general anesthesia, and the button was set within 2 months. RESULTS Minor wound infection required antibiotic therapy in one patient. In the four children with Alagille syndrome, enteral feeding by means of percutaneous endoscopic gastrostomy was used until liver transplantation for a mean period of 14 months with a mean weight gain of 350 g/mo and a mean height gain of 0.53 cm/mo. Seventeen months to 3 years, 3 months after liver transplantation, all four children were alive and in good clinical condition with normal readings in liver function tests. The technique had to be discontinued in the child with biliary atresia because of secondary occurrence of ascites, gastric intolerance, and refractory wound infection. CONCLUSION Percutaneous endoscopic gastrostomy may be a valuable alternative to nasogastric tube for nutritional support in children with cholestasis and mild portal hypertension.

Primary Prophylaxis of Variceal Bleeding in Children and the Role of MesoRex Bypass–Summary of the Baveno VI Pediatric Satellite Symposium

Approaches to the management of portal hypertension and variceal hemorrhage in pediatrics remain controversial, in large part because they are not well informed by rigorous clinical studies. Fundamental biological and clinical differences preclude automatic application of approaches used for adults to children. On April 11‐12, 2015, experts in the field convened at the first Baveno Pediatric Satellite Meeting to discuss and explore current available evidence regarding indications for MesoRex bypass (MRB) in extrahepatic portal vein obstruction and the role of primary prophylaxis of variceal hemorrhage in children. Consensus was reached regarding MRB. The vast majority of children with extrahepatic portal vein obstruction will experience complications that can be prevented by successful MRB surgery. Therefore, children with extrahepatic portal vein obstruction should be offered MRB for primary and secondary prophylaxis of variceal bleeding and other complications, if appropriate surgical expertise is available, if preoperative and intraoperative evaluation demonstrates favorable anatomy, and if appropriate multidisciplinary care is available for postoperative evaluation and management of shunt thrombosis or stenosis. In contrast, consensus was not achieved regarding primary prophylaxis of varices. Although variceal hemorrhage is a concerning complication of portal hypertension in children, the first bleed appears to be only rarely fatal and the associated morbidity has not been well characterized. Conclusion: There are few pediatric data to indicate the efficacy and safety of pharmacologic or endoscopic therapies as primary prophylaxis or that prevention of a sentinel variceal bleed will ultimately improve survival; therefore, no recommendation for primary prophylaxis with endoscopic variceal ligation, sclerotherapy, or nonspecific beta‐blockade in children was proposed. (Hepatology 2016;63:1368–1380)

Progression to high-risk gastroesophageal varices in children with biliary atresia with low-risk signs at first endoscopy.

Objectives: Biliary atresia carries a risk of bleeding because of portal hypertension. Our goal was to define the factors associated with the emergence of endoscopic signs carrying a high risk of bleeding in children who did not display these signs at the first upper gastrointestinal endoscopy. Methods: From 1989 to 2013, a total of 225 children with low-risk signs at the first endoscopic examination underwent ≥2 upper gastrointestinal endoscopic examinations. The emergence of high-risk gastroesophageal varices was observed in 76 children in the 10 years following the first endoscopic examination. A survival study using the occurrence of high-risk varices as an event was performed to identify factors related to the emergence of these varices and to describe the probability of their emergence in 2 groups of children ages older than 18 months and 18 months or younger at the time of the first endoscopy. Results: High total serum bilirubin concentration, young age, and high number/grade of esophageal varices at the first endoscopy were significantly related to the emergence of high-risk varices. The probability of the emergence of high-risk signs was higher and these signs appeared faster in infants 12 months of age or younger and/or when the first endoscopic examination displayed >1 grade 1 or grade 2 varices. Progression to high-risk varices was also related to bilirubinemia in children older than 18 months at the first endoscopy. Conclusions: The results allow defining a program of repeat endoscopies to detect high-risk varices and to discuss endoscopic primary prophylaxis of bleeding or hasten liver transplantation when these signs are found.

Portal hypertension in children: High-risk varices, primary prophylaxis and consequences of bleeding

BACKGROUND & AIMS Primary prophylaxis of bleeding is debated for children with portal hypertension because of the limited number of studies on its safety and efficacy, the lack of a known endoscopic pattern carrying a high-risk of bleeding for all causes, and the assumption that the mortality of a first bleed is low. We report our experience with these issues. METHODS From 1989 to 2014, we managed 1300 children with portal hypertension. Endoscopic features were recorded; high-risk varices were defined as: grade 3 esophageal varices, grade 2 varices with red wale markings, or gastric varices. Two hundred forty-six children bled spontaneously and 182 underwent primary prophylaxis. The results of primary prophylaxis were reviewed as well as bleed-free survival, overall survival and life-threatening complications of bleeding. RESULTS High-risk varices were found in 96% of children who bled spontaneously and in 11% of children who did not bleed without primary prophylaxis (p<0.001), regardless of the cause of portal hypertension. Life-threatening complications of bleeding were recorded in 19% of children with cirrhosis and high-risk varices who bled spontaneously. Ten-year probabilities of bleed-free survival after primary prophylaxis in children with high-risk varices were 96% and 72% for non-cirrhotic causes and cirrhosis respectively. Ten-year probabilities of overall survival after primary prophylaxis were 100% and 93% in children with non-cirrhotic causes and cirrhosis respectively. CONCLUSION In children with portal hypertension, bleeding is linked to the high-risk endoscopic pattern reported here. Primary prophylaxis of bleeding based on this pattern is fairly effective and safe. LAY SUMMARY In children with liver disease, the risk of bleeding from varices in the esophagus is linked to their large size, the presence of congestion on their surface and their expansion into the stomach but not to the childs age nor to the cause of portal hypertension. Prevention of the first bleed in children with high-risk varices can be achieved by surgery or endoscopic treatment, and decreases mortality and morbidity.

Survey on Clinical Practice of Primary Prophylaxis in Portal Hypertension in Children

ABSTRACT Primary prophylaxis in portal hypertension in children is controversial, because there are few studies documenting its efficacy on the risk of bleeding. Twenty-eight centres out of the 38 we contacted returned a completed questionnaire about their clinical practices. More than 75% of the centres use endoscopy to screen patients diagnosed with portal cavernoma, biliary atresia, cystic fibrosis, and other fibrotic chronic liver diseases with suspected portal hypertension. In cases of grade 2 varices with red marks and grade 3 varices >90% of centres perform sclerotherapy or endoscopic variceal ligation. Noncardioselective beta-blockers were used by approximately 20% of centres. In conclusion, despite the absence of scientific recommendations there is a tacit consensus concerning the need to screen children with clinical signs of portal hypertension, and to provide primary prophylaxis in cases of endoscopic patterns of high-risk varices.

The efficacy of surgical shunts to treat severe portal hypertension after a Kasai procedure for biliary atresia

BACKGROUND To assess the outcome of patients with biliary atresia (BA) who underwent a surgical shunt (SS) for severe portal hypertension (PH) following a Kasai procedure. METHODS We collected and analyzed the data and outcomes of patients with BA who underwent SS for severe PH following a Kasai procedure between 1974 and 2014, focusing on complications related to the procedure, overall survival (OS), and transplant-free survival (TFS). RESULTS SS was performed at a median age of 5.5 years [2-13.5] in 38 patients. Conjugated bilirubin level (cBL) was ≤20 μmol/l in 24 patients at time of SS. Median follow-up was 15 years [1-32]. OS at 5 and 10 years was 91% and 87% respectively. TFS at 5 and 10 years was 84% and 70% respectively. Long-term complications included hepatic encephalopathy in 9 patients, and hepatopulmonary syndrome in 3. At last follow-up, 10/14 patients without LT and 18/ 24 who had a delayed LT at a median delay of 11 years [1.5-22] were alive. CONCLUSION Surgical shunt for severe portal hypertension in biliary atresia may delay the need for liver transplantation. However complications are indications for transplantation. LEVEL OF EVIDENCE Type of study: Therapeutic. Level of evidence III.