Preoperative Serum IL-12p40 Is a Potential Predictor of Kasai Portoenterostomy Outcome in Infants with Biliary Atresia

The standard-of-care treatment for biliary atresia (BA) is surgical restoration of bile flow by Kasai portoenterostomy. We aimed to study serum interleukin- (IL-) 12p40, a natural antagonist for the proinflammatory IL-12p70, and its relation to surgical outcomes of BA. The study included 75 infants with neonatal cholestasis: BA group (n=25), non-BA cholestasis group (n=30), and neglected BA group (n=20), in addition to thirty healthy neonates serving as controls. IL-12p40 was measured by ELISA in all individuals and a second assessment was performed 3 months postoperatively in the BA group. The surgical outcomes were classified as successful (bilirubin ≤ 2 mg/dl) or failed (bilirubin > 2 mg/dl). IL-12p40 was higher in BA compared to that in the non-BA and control groups (P values were 0.036 and <0.0001, resp.) but comparable to that in the neglected BA group. Preoperative IL-12p40 levels in BA patients were significantly higher in successful Kasai compared with failed Kasai and a cutoff level of 547.47 pg/ml could predict the successful outcome with 87.5% sensitivity and 82.4% specificity. Three-month postoperative IL-12p40 tended to decrease in both the successful and failed groups. In conclusion, preoperative serum IL-12p40 is a potential predictor of Kasai outcome. Serial postoperative measurements may anticipate the failure of an initially successful operation, hence the need for liver transplantation

Biliary Atresia Etiopathogenesis: On the Way to Solve the Mystery

Biliary Atresia (BA) is the most common cause of chronic cholestasis in infants and the most frequent cause for surgery in cholestatic jaundice in this age group. It is a destructive inflammatory obliterative cholangiopathy that affects varying lengths of both intrahepatic and extrahepatic biliary tree. The extensive research in BA aims at three main aspects; a) understanding the etiopathogenesis, b) achieving early diagnosis, and c) improving the outcome of surgical interventions. The improvements in the latter two are largely based on the advances in further understanding and revealing the etiopathogenesis. Till the moment, the exact etiology remains a mystery. Biliatresone, a recently identified toxin that causes BA phenotype in zibrafish may open a new horizon for future studies in humans in an attempt to solve the mystery

Serum YKL-40 (Chitinase-3-Like Protein 1) Compared to APRI and FIB-4 in Predicting Liver Fibrosis in Children with Chronic Hepatitis C

Background: Liver fi brosis is a critical factor for the treatment policy and its outcome in chronic hepatitis C virus (HCV) infection. Although liver biopsy represents the gold standard for evaluating fibrosis, it remains an invasive procedure with inherent risks. Thus, it cannot be performed frequently to monitor therapeutic outcomes specially in the pediatric population. For that, developing a non-invasive test that can predict liver fi brosis represents a growing medical need

Stem cell therapy in children with acute liver failure: The dream could come true

Acute liver failure (ALF) in children is a severe disease with a high mortality rate. The current treatment strategies are still defective, with many cases die when liver transplantation is unavailable. The current protocol of steroids therapy improved the survival rate of hepatitis A virus (HAV)-related ALF. However, there is still a high mortality for non-HAV cases. Stem cell therapy (SCT) has been tried in experimental animals with ALF and in few adult studies with acute-on-chronic liver failure. No previous trials of SCT have been tested in children with ALF. The absence of SCT application in ALF in children could be due to some issues. These could be related to safety, sources, administration route, optimum dosage, efficacy, and survival. It is proposed that could be the future therapy if these obstacles have been well studied and solved

Biliary Atresia: A Challenging Diagnosis

Abstract: Biliary atresia (BA) constitutes about one third of all neonatal cholestasis (NC) and the most common indication (up to 50%) of liver transplantation (LTx) in children. Despite extensive studies, its etiopathogenesis has not been clearly revealed. Treatment is primarily surgical based on reinstitution of bile flow by Kasai portoenterostomy, the success of which is largely dependent on the early diagnosis before 60 days of age. If portoenterostomy is not successful or not performed, LTx is the only life-saving alternative. Accurate diagnosis of BA, particularly distinguishing it from other causes of liver injury in the neonatal period, is challenging as there is a high degree of overlap in clinical, biochemical, imaging, and histological characteristics. There is no single preoperative investigation that enables the diagnosis of BA to be made with certainty. Liver biochemistry assessment, biliary radionuclide excretion scanning, magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous needle liver biopsy, and laparoscopy can all be helpful, but their results are not individually diagnostic. The current review presents an overview of BA with emphasis on the recent diagnostic modalities

Prevalence of Serological Markers of TORCH Infections in Biliary Atresia and Other Neonatal Cholestatic Disorders

Background: Viral infections, congenitally or perinatally acquired, have been associated with neonatal cholestasis. Investigators have suggested a similar link to biliary atresia (BA).&nbsp;&nbsp;Aim: The aim of the current study is to investigate the prevalence of serological markers of congential infections in BA and other neonatal cholestatic disorders.Methods: This retrospective study included 94 patients with confi rmed diagnosis of BA. A nearly comparable number of patients with cholestasis due to causes other than BA (n = 91) were also recruited and termed non-BA group. The data was retrieved from patients’ records. TORCH (toxoplasma, rubella, cytomegalovirus [CMV] and herpes simplex virus [HSV] type 1 and type 2) antibodies (immunoglobulin [Ig] M and IgG) were performed in all the patients using enzyme-linked immunosorbent assay. CMV DNA was detected by polymerase chain reaction (PCR).Results: Both groups were age and sex matched (P&gt;0.05). TORCH IgM antibodies were detedcted in 15.7% of all the study population (8.5% in BA group and 23% in non-BA group), of which CMV was the commonest agent. CMV IgM and CMV DNA by PCR were signifi cantly higher in non-BA group (20.9% and 23% respectively) than in BA group (4.3% and 5.3% respectively). Toxoplasma IgM was positive in only one patient in BA group and rublella IgM was positive only in one patient in the non-BA group. HSV- 1 IgM was found in a total of 4 patients; 3 in BA group and one in non-BA group while HSV-2 IgM was negative in all the patients. CMV infection was the sole incriminated agent in 13 patients (CMV hepatitis), while it was associated with other etiologies such as pregressive familial intrahepatic cholestasis (5 of 29 patients), and intrahepatic biliary paucity (3 of 14 patients). Liver transaminases, prothrombin time and the frequency of&nbsp; growth failure were signifi cantly higher in non-BA group.Conclusions: TORCH IgM antibodies were detedcted in 8.5% of BA and in 23% of non-BA group, of which CMV was the commonest agent. In addition to CMV hepatitis, CMV infection was associated with other causes of neonatal cholestasis. For that, all cases with neonatal cholestasis should be thoroughly evaluated for other causes, even in cases with demonstrable CMV infection.</p

Preoperative Serum IL-12p40 Is a Potential Predictor of Kasai Portoenterostomy Outcome in Infants with Biliary Atresia

The standard-of-care treatment for biliary atresia (BA) is surgical restoration of bile flow by Kasai portoenterostomy. We aimed to study serum interleukin-(IL-) 12p40, a natural antagonist for the proinflammatory IL-12p70, and its relation to surgical outcomes of BA. The study included 75 infants with neonatal cholestasis: BA group (n = 25), non-BA cholestasis group (n = 30), and neglected BA group (n = 20), in addition to thirty healthy neonates serving as controls. IL-12p40 was measured by ELISA in all individuals and a second assessment was performed 3 months postoperatively in the BA group. The surgical outcomes were classified as successful (bilirubin ≤ 2 mg/dl) or failed (bilirubin &gt; 2 mg/dl). IL-12p40 was higher in BA compared to that in the non-BA and control groups (P values were 0.036 and &lt;0.0001, resp.) but comparable to that in the neglected BA group. Preoperative IL-12p40 levels in BA patients were significantly higher in successful Kasai compared with failed Kasai and a cutoff level of 547.47 pg/ml could predict the successful outcome with 87.5% sensitivity and 82.4% specificity. Three-month postoperative IL-12p40 tended to decrease in both the successful and failed groups. In conclusion, preoperative serum IL-12p40 is a potential predictor of Kasai outcome. Serial postoperative measurements may anticipate the failure of an initially successful operation, hence the need for liver transplantation