portal obstruction is the single most common etiology of portal hypertension in children , representing roughly 50% of all cases in the majority of series .
the causes of portal vein obstruction fall into one of following categories : perinatal events ( umbilical catheterization , omphalitis , and dehydration ) , congenital malformations outside the portal vein ( abernethy malformation ) , thrombophilic states ( deficiency of protein - c , s or antithrombin - iii , etc . ) , tumors , abdominal infections , and a category where the etiology is unknown [ 1 , 2 ] .
portal obstruction in children is usually detected early in the first decade , because of splenomegaly , gastrointestinal bleeding , or both .
development of esophageal varices is almost universal , and the actuarial risk of bleeding reaches 76% at 24 years of age .
probability of bleeding is directly correlated with the size of varices as seen on endoscopy , from the absence of bleeding episode in children without varices or with grade i varices , to 85% prevalence of bleeding in patients with grade ii or iiii varices , as reported by lykavieris et al . .
of note , this study showed that varices tended to increase in size over the years instead of disappearing , defying the classical concept of spontaneous improvement as children grow - up .  
variceal bleeding is generally well tolerated , owing to normal function of the liver ; however , the main concern in the management is to reduce the recurrence of episodes .
endoscopic therapy works by physical obliteration of esophageal varices and has shown excellent results , with a 90% rate of success in the long - term control of bleeding .
it usually represents the first approach due to its relative simplicity , low frequency of immediate complications , and widespread availability .
the high rate of success has led to ample use of this technique ; however , an increase of long - term complications is usually observed , as bleeding from ectopic varices , low - grade encephalopathy , hepatopulmonary syndromes , further development of hypersplenism , and cholestasis secondary to portal cholangiopathy . particularly challenging
is the management of cholestasis ; this syndrome has been described in 6% of patients with portal vein obstruction , especially after long - term followup [ 6 , 7 ] , and it is the consequence of dilated peribiliary venous plexus ( cavernoma ) in the wall of biliary ducts ( figure 1 ) . affected patients exhibit high levels of ggt and bilirubin , with dilated bile ducts ( mainly intrahepatic ) as seen on the abdominal ultrasound .
biopsy samples show different degrees of fibrosis and even biliary type of cirrhosis , with a pattern indistinguishably from primary sclerosing cholangitis in some cases .
complete resolution can be achieved with surgical decompression of the portal system by means of a portosystemic or a meso - rex shunts . in rare cases
congenital hepatic fibrosis ( chf ) is part of a spectrum of fibropolycystic diseases , in which the pathological hallmark is the presence of ductal plate malformation .
it combines biliary dysplasia , perilobular fibrosis , and renal polycystic disease in different patterns , giving rise to a wide diversity of clinical manifestations observed throughout the years .
two different forms have been described in association with renal disease : autosomic recessive ( arpkd ) and dominant ( adpkd ) polycystic kidney diseases . in arpkd ,
clinical signs of renal disease can be observed during the first years , appear later , or remain subclinical .
findings of portal hypertension become evident , generally in the first years of life , usually in the form of variceal bleeding and hypersplenism .
it has been estimated that 25% of affected individuals develop clinically significant portal hypertension , with a trend toward increased frequency with increasing age .
interestingly , children with portal hypertension were younger than the mean age of the whole cohort , suggesting that a particular subset of patients is at risk of developing this complication , probably related to specific still unknown genetic or environmental factors .
adpkd patients , in contrast with arpkd , tend to present later in life with progressive renal disease and less liver involvement . however , because variceal bleeding can occur as early as age 4 , screening relatives of the index case ( most commonly an adult with multiple renal cysts ) by regular ultrasounds have been recently advocated .
chf has also been reported as part of other rare syndromes , such as nephronopthisis ( with end - stage renal disease within 5 to 10 years ) , jeune syndrome ( lung and thoracic hypoplasia ) , meckel - gruber syndrome ( encephalocele and polydactily ) , ivemark syndrome ( interstitial fibrosis leading to renal failure ) , chronic diarrhea related to enterocolitis cystic superficialis and intestinal lymphangiectasia , and others . in all cases ,
accompanying liver findings include ductal plate malformation , fibrosis , and biliary cysts in different combinations .  
patients with congenital hepatic fibrosis characteristically have well - preserved liver function ; they behave as those with portal vein obstruction , with regard to the risk and tolerance to bleeding
. moreover , cavernomatous transformation of the portal vein and abnormal intrahepatic branching have been described in chf patients , suggesting that anomalies in the development of portal veins are part of the spectrum of liver disease in this condition [ 13 , 14 ] .
given the relatively benign liver disease , management recommendations for children with chf - related portal hypertension are based on endoscopic eradication of varices .
however , the frequent need for kidney transplantation in children with arpkd leads to perform a surgical portosystemic shunt before the transplant surgery .
successful shunt facilitates abdominal surgery and avoids varices bleeding that could represent a risk for the transplanted organ . for the rare patients with repeated acute or chronic cholangitis , who develop cirrhosis , or for those with pulmonary complications , liver transplantation is a potential therapeutic option .
decision about when ( and if ) to combine it with kidney transplantation should be considered on a case - by - case evaluation .
this disease affects 1 in 15000 to 1 in 20000 newborns and constitutes the main indication for liver transplantation in children .
current treatment strategy includes the kasai portoenterostomy operation , followed by liver transplantation in cases of its failure or later complications from cirrhosis .
children with biliary atresia tend to develop varices very early , with an estimated risk of bleeding of 15% before the age of two .
when associated with high bilirubin levels , it portends a poor prognosis , and constitutes an indication to proceed to transplantation as soon as possible , owing to the more than tenfold rise in the risk of death when conjugated bilirubin levels are over 10  mg% . even in anicteric patients
, there is a considerable risk of bleeding , highlighting their tendency to suffer from severe portal hypertension , probably related to the intense fibrosis as is observed at the time of portoenterostomy , and the diffuse compromise of intrahepatic portal vein described in some .
cholangitis , a frequent complication after portoenterostomy , can be responsible for thrombophlebitis of the portal system , accelerating the development of portal hypertension .
bleeding can be predicted in patients with large varices , associated red signs , presence of gastric varices , and portal hypertensive gastropathy ( figure 2 ) .
recent data supports the implementation of prophylactic sclerotherapy or banding to prevent the first hemorrhage .
sclerotherapy would be preferred over rubber band ligation owing to size constraints faced in little children .  
approximately 5% of cystic fibrosis patients develop liver cirrhosis before adolescence . like other cholestatic type of cirrhosis
, it is characterized by a high degree of portal hypertension , with preserved synthetic function for many years [ 22 , 23 ] . as the management of lung disease continues to improve
, liver disease is becoming a major determinant of the outcome , being the third most common cause of death .
it has been estimated that nearly 60% of cirrhotic patients experimented an episode of variceal bleeding before the second decade of life , contributing to the 10 to 20% of deaths in the cystic fibrosis group as a whole .
data coming from recent cohort studies show that liver disease in cystic fibrosis patients poses a special threat to their wellbeing and survival .
this is not only related to the complications of cirrhosis itself ; affected children tend to have higher shwachman scores and worse pulmonary function suggesting a synergistic effect between liver and lung disease [ 22 , 25 ] .
in fact , improvement in the severity of respiratory disease is well documented after liver transplantation in many of those patients [ 24 , 26 ] .
altogether , approaching a child suffering from variceal bleeding in the context of cystic fibrosis should be tailored to each specific case .
endoscopic treatment should be offered to all , being especially useful in the context of acute hemorrhage .
however , concern remains over the long - term endoscopic treatment due to the need for multiple anesthetics procedures , and the possible development of pulmonary complications from portal hypertension itself . in patients with
relatively well - preserved liver and lung functions , a selective portocaval shunt ( or a tips , when feasible ) could offer many years of benefit without compromising the outcome [ 23 , 27 ] .
patients with advanced liver disease , or severe and refractory bleeding , with good pulmonary function are probably best managed with liver transplantation [ 24 , 26 , 28 ] .
results of combined liver - lung transplantation are currently not encouraging ; hence waiting for advanced lung disease before deciding to go for liver transplantation does not seem to be advisable .
this presinusoidal type of portal hypertension is produced by intimal thickening of small intrahepatic portal vein radicles .
the clinical picture resembles that of prehepatic portal vein obstruction but with a patent ( an even , dilated ) portal vein on ultrasound .
well - tolerated variceal bleeding and hypersplenism have been reported in this syndrome mainly described in asian patients .
recent reports coming from western - country children surviving from acute leukemia treated with 6-thioguanin highlights the alleged toxin exposure as one of the possible causes of the endothelial damage .
chronic hepatitis associated to hbv or hcv infection can rarely present in the first two decades of life with a picture of portal hypertension secondary to cirrhosis .
children exhibit better responses rates to antiviral treatment ; thereby there is better control of complications , including those of cirrhosis [ 3234 ] . 

appropriate treatment with immunosuppressive drugs usually results in control and regression of fibrosis in most patients . a small percentage , however , progresses to decompensated cirrhosis and hemorrhagic complications ; these should be managed in a staggered manner according to the medium - term prognosis of the disease , from endoscopic treatment to liver transplantation in end - stage patients . 

it is the most common indication for liver transplantation from metabolic diseases in the western hemisphere .
although some improvement of liver function tests has been reported with the use of ursodeoxycholic acid , at the present , there is no effective treatment for this condition , and management of affected patients is restricted to the complications of ongoing cirrhosis , using the same principles described for other etiologies . 

budd - chiari syndrome encompasses a series of different causes producing obstruction to the hepatic venous outflow .
these patients tend to present with hepatomegaly and ascitis rather than with variceal hemorrhage , but those developing secondary cirrhosis can experiment bleeding from esophageal varices .
management is very complex , strongly influenced by the clinical picture ( acute versus chronic ) , etiology , and extent of the liver damage .
in contrast with portal vein obstruction , most budd - chiari patients have an associated thrombophilic state that has to be accurately investigated and treated .
avoiding the morbidity and mortality associated with the first bleed from esophageal varices is the rationale behind primary prophylaxis .
clear recommendations exist for the adult population , but unfortunately this is not the case for pediatric patients .
application of such strategy should comply with two premises : correct identification of the population  at risk  and availability of an effective treatment . in spite of many efforts , achieving the first goal
has been elusive , owing to the heterogeneity of the population with portal hypertension in pediatric ages .
stratifying patients at risk according to specific etiologies could be the best way to manage this problem .
regarding the second goal , the absence of controlled randomized trials in primary prophylaxis of esophageal varices bleeding in children makes any recommendation problematic and debatable .
low number of patients and difficulties in recruitment are major obstacles to the realization of such studies , as seen with the use of propranolol in children , which is in strong contrast to the adult population .
a group of expert analyzed possibilities on primary prophylaxis of variceal hemorrhage in children , concluding that future research should focus on the natural history , diagnosis of varices , prediction of variceal bleeding , and explore therapeutic efficacy of different protocols .  
currently , it remains intuitive to offer endoscopic obliteration to patients with high - risk varices who had never bled , preferably by band ligation .
endoscopic examination should be only offered to patients when decision to proceed with sclerotherapy or banding has already been taken in advance [ 5 , 20 ] .
data in children with cirrhosis secondary to biliary atresia showed that esophageal varices developed very early in life in 70% of them .
in addition , endoscopic signs indicating a high risk of mediate bleeding were found in 30% of those with esophageal varices .
another recent study , on a similar population , showed that grade ii - iii varices developed with similar frequency after failed and successful portoenterostomy , but , following failed portoenterostomy , esophageal varices were encountered significantly earlier .
the authors recommended that after failed portoenterostomy surveillance should start early , for example , at six months of age .  
there are different approaches in the care of children at risk for esophageal varices bleeding among pediatric gastroenterologists , most of them based on personal preferences and local expertise rather than strong evidence .
in addition , attitudes from parents could be different from those of physicians ; a high percentage of them would accept an endoscopy to be carried out in their children if a prophylactic treatment can avoid bleeding or even to establish the current risk of bleeding in the absence of treatment .  
acute bleeding is the most feared complication of portal hypertension , with an associated mortality up to 20% , mainly in patients with affected liver function . as a consequence ,
focus on treatment has been directed to the control of hemorrhagic episodes , reaching a rate of success higher than 90% in recent years .
volume resuscitation initiated without delay , should restore hemoglobin levels to around 8  g% , and insure good perfusion of vital organs with plasma expanders .
overzealous use of volume / plasma expanders should be avoided , however , because of the theoretical risk of rebound portal hypertension and rebleeding .
antibiotics directed at the intestinal flora should be part of the treatment from the beginning , as well as vasoactive drugs , preferably by the intravenous route . among many drugs tested in adult patients
, octreotide has been the most widely used in children , at a dose of 1 - 2  ug / kg by bolus over 20 minutes , followed by continuous infusion at 2  ug / kg / h , maintained for 2 to 5 days .
its use in this setting has been advocated to promote easier and safer endoscopic procedures .
once stabilized , patients should be treated by direct approach of the varices , either with band ligation or sclerosant injection .
both treatments are highly effective in controlling the acute episode , and the choice of one particular method depends on the local expertise and other technical issues . in a general sense , endoscopic variceal ligation is preferred in most cases , owing to its simplicity and lower rate of complications , but sclerotherapy is probably easier to implement during active bleeding , and is the best option in small children [ 45 , 46 ] . ideally , the operator should master both techniques and have all appropriate tools available during the procedure . despite the high rate of success achieved with these approaches : in 5 to 10% of cases bleeding
can not be controlled , and rescue therapy is needed , usually after the failure of a second attempt by endoscopy .
this rescue therapy involves a surgical option , or a radiological approach ( tips ) , when feasible . once again , both procedures are equally effective , but when used in an emergency scenario their results are less satisfactory .
tips has the advantage of avoiding a laparotomy , but its availability is limited to specialized services and is not suitable for small children , especially in cases of portal vein obstruction or biliary atresia , which are the main causes of variceal hemorrhage among pediatric patients .
the choice of the surgical technique , on the other hand , depends on the medium - term prognosis of the disease .
shunting procedures are preferred in patients with relatively well - preserved liver function , like those with portal vein obstruction , congenital hepatic fibrosis , or compensated cirrhosis .
once the first bleeding has occurred , there is a substantial risk for rebleeding in the next years ; consequently , eradication of esophageal varices becomes a logical goal .
endoscopic variceal ligation and sclerotherapy have been reported to be equally successful in achieving this .
variceal ligation is usually preferred because of its reported simplicity , lesser number of sessions needed , and a safer profile when compared to sclerotherapy [ 45 , 46 ] .
both techniques are complementary and have been used even in primary prophylaxis with good results [ 5 , 20 ] . an observational study in children with portal hypertension , of several different etiologies , showed a benefit of secondary prophylaxis in avoiding esophageal varices bleeding . in this study ,
in contrast , a large study including mainly adolescents did not find differences between propranolol and endoscopic ligation in the recurrence of bleeding .
longer followup of endoscopic treatments is available , showing recurrence of esophageal varices in 40% of the patients , with a tendency to worsening of gastric varices , portal hypertensive gastropathy , and rising incidence of ectopic varices , all of them representing a more difficult problem to solve .
progression of the spleen size and late incidence of complications like portal cholangiopathy in patients with portal obstruction , formerly considered a rare entity , affect children quality of life . moreover , for these complications endoscopic treatments are clearly unsuitable . in those cases , or when hemorrhagic episodes are refractory to other treatments , surgery becomes the only option .  
total portosystemic shunts are those more than 10  mm in diameter , constructed between the main veins of the portal system and the inferior vena cava .
they provide excellent control of hemorrhages and ascitis , but at the high cost of encephalopathy , and are rarely used in children .
partial shunts comprises portocaval or mesocaval anastomoses of 8  mm in diameter or less , allowing part of the portal flow to reach the liver sinusoids , and thus reducing the risk of systemic complications without losing efficacy for the prevention of further bleeding .
this type of shunts has been widely used in children employing the internal jugular vein as a graft , with excellent results [ 53 , 54 ] .
selective shunts are constructed by the anastomoses of the splenic vein to the left renal vein , thereby decompressing gastroesophageal varices through the short gastric veins ( distal splenorenal shunt ) , and maintaining portal perfusion to the liver .
surgical shunts have gained renewed interest in the management of portal hypertension in children with good liver function , in view of better results obtained with the refinement of surgical techniques driven by the development of liver transplantation programs , and the emergence of nonhemorrhagic complications after successful eradication of esophageal varices . the mesenteric - left portal vein bypass ( rex shunt )
is constructed between the superior mesenteric vein and the recessus of rex at the level of intrahepatic left branch of portal vein .
originally developed to treat patients who have portal vein thrombosis after liver transplantation , it was extended immediately to the treatment of children with extrahepatic portal vein obstruction , allowing them for the first time to reach a real  cure  for their disease .
in fact , when successful , it can restore the normal flow to the liver with normalization of hematological tests .
availability of this technique is promoting a change of paradigm in the treatment of portal vein obstruction , towards an early indication of surgery , before progressive fibrosis of the main portal vein branches precludes the feasibility of such anastomoses .
the percentage of children with portal obstruction who can benefit for a meso - rex shunt is still unknown .  
recent data coming from pediatric series , albeit small in number of patients , have reproduced the rates of success obtained in adult patients , making tips a good option even in small children and expanding indications to postransplant portal hypertension , and children with portal vein obstruction with a favorable anatomy .
future studies will clarify the role of this therapy in the management of pediatric portal hypertension .
treatment of hemorrhagic complications from portal hypertension in children has its own specificities because of the different etiologies involved , and the natural history of these disorders compared to adults ( table 1 ) .
, considerable progress has been achieved in the last years , mainly derived from better control of bleeding from esophageal varices .
longer followup , however , uncovers new complications for which endoscopic treatment is inappropriate , promoting a renewed interest on surgical approaches . as a general principle , management of portal hypertension in children rests on two main characteristics : the etiology of the portal hypertension and the age of the patient .
 portal hypertension in children represents a particular diagnostic and management challenge for several reasons : ( 1 ) treatment outcomes should be evaluated in relationship with a long - life expectancy , ( 2 ) pediatric patients with portal hypertension constitute an heterogeneous population , both in terms of individual characteristics and diversity of liver diseases ; making comparison between treatment outcomes very difficult , ( 3 ) application of techniques and procedures developed in adult patients ( v.gr . 
 tips ) face size limitations in small children , and ( 4 ) absence of data from well - controlled trials in children forces pediatric specialists to adapt results obtained from adult cohorts suffering from diseases such as hcv and alcoholic cirrhosis . despite those limitations , substantial progress in the treatment of children with portal 
 hypertension has been achieved in recent years , with better outcomes and survival . 
 two main factors influence our therapeutic decision : age of the patient and etiology of the liver disease . therefore , diagnosis and treatment of complications of portal hypertension in children need to be described taking such factors into consideration . 
 this paper summarizes current knowledge and expert opinion . 