Seronegative autoimmune hepatitis in childhood

Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children,although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis.Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated.The absence of autoantibody positivity,hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease.In general,seronegative autoimmune hepatitis often presents with acute hepatitis,and its treatment and prognosis similar to seropositive autoimmune hepatitis.The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood,and those of which current knowledge is vague.

Cirrhosis and hepatopulmonary syndrome

Hepatopulmonary syndrome(HPS)is characterized as a triad:liver disease,intrapulmonary vascular dilatation and arterial hypoxemia.HPS is reported to be present in 4%to 32%of adult patients with end-stage liver disease and in 9%-20%of children.The pathogenesis of HPS has not been clearly identified.Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram(-)bacteria and endotoxins.This stimulates the release of vasoactive mediators,such as tumor necrosis factor-alpha,heme oxygenase-derived carbon monoxide and nitric oxide.Genetic alterations have not been associated with this syndrome yet;however,cytokines and chemokines have been suggested to play a role.Recently,it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis,which plays an important role in HPS pathogenesis.At present,the most effective and only radical treatment is a liver transplant(LT).Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS.Therefore,it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list.

Biliary atresia and congenital disorders of the extrahepatic bile ducts

Biliary atresia(BA)and choledochal cysts are diseases of the intrahepatic and extrahepatic biliary tree.While their exact etiopathogeneses are not known,they should be treated promptly due to the potential for irreversible parenchymal liver disease.A diagnosis of BA may be easy or complicated,but should not be delayed.BA is always treated surgically,and performing the surgery before the age of 2 mo greatly increases its effectiveness and extends the time until the need for liver transplantation arises.While the more common types of choledochal cysts require surgical treatment,some can be treated with endoscopic retrograde cholangiopancreatography.Choledochal cysts may cause recurrent cholangitis and the potential for malignancy should not be ignored.

Acute-on-chronic liver failure in children

Although various complex definitions of acute-on-chronic liver failure(ACLF)have been suggested in relation to adult patients,there is currently no universal definition of the syndrome in pediatric patients.In simplified terms,ACLF is characterized by the acute deterioration of the liver functions due to the effects of a precipitating factor on the basis of a chronic liver disease.Acute events and underlying liver diseases are very different in children from those seen in adults.Moreover,acute events and underlying chronic liver diseases vary among geographical regions,although it seems that the most common such diseases and acute events are autoimmune hepatitis,Wilson’s disease,and their flares.ACLF is associated with a poor prognosis.While no scoring systems have been developed to predict the prognosis for children with ACLF,modified versions of the Asian Pacific Association for the Study of the liver’s acute-on-chronic liver failure scoring system and the Chronic Liver Failure-Sequential Organ Failure Assessment criteria can be used in children until specific and validated scoring systems are available.Aside from liver transplantation,there is no proven treatment for ACLF.Thus,the early recognition of ACLF prior to the development of extrahepatic organ failure is important.

Inflammatory bowel disease in Turkish children

Background:This study was undertaken to evaluate demographics,clinical manifestations,laboratoryfi ndings and outcomes of children with inflammatory bowel disease(IBD)in Turkey.Methods:We analyzed the medical records of 127 children diagnosed with IBD(under 18 years old)between January 2004 and January 2012 in 8 pediatric gastroenterology centers.Results:Of the 127 patients,90(70.9%)suffered from ulcerative colitis(UC),29(22.8%)from Crohn's disease(CD),and 8(6.3%)from IBD unclassified.The mean age of the 127 patients was 11.6±4.1 years,and 11.8%of the patients were below 5 years old.Of the patients,49.6%were male,and males were more predominant in patients with CD than in those with UC(72.4%vs.42.2%,P=0.008;a male/female ratio of 2.62 in CD,P=0.0016).Approximately one fifth of the patients had extra-intestinal manifestations and 13.3%of the patients had associated diseases.Extraintestinal manifestations and associated diseases were more common in early onset disease[P=0.017,odds ratio(OR)=4.02;P=0.03,OR=4.1].Of the patients,15%had normal laboratory parameters including anemia,high platelet count,hypoalbuminemia,hypoferritinemia,and high sedimentation rate.Area under receiver operation characteristics was used to predict pancolitis in patients with UC.The values of C-reactive protein,sedimentation rate and pediatric ulcerative colitis activity were 0.61(P=0.06),0.66(P=0.01)and 0.76(P=0.0001),respectively.Four(4.4%)patients with UC underwent colectomy,andfi nally two(1.5%,95%confidence interval:0-3.7%)patients died from primary disease or complications.Conclusions:IBD is an increasing clinical entity in Turkey.Features of IBD are similar to those in other populations,but prospective multicenter studies are needed to analyze the true incidence of IBD in Turkish children.