Anshu Srivastava

Progressive Familial Intrahepatic Cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare disorders which are caused by defect in bile secretion and present with intrahepatic cholestasis, usually in infancy and childhood. These are autosomal recessive in inheritance. The estimated incidence is about 1 per 50,000 to 1 per 100,000 births, although exact prevalence is not known. These diseases affect both the genders equally and have been reported from all geographical areas. Based on clinical presentation, laboratory findings, liver histology and genetic defect, these are broadly divided into three types-PFIC type 1, PFIC type 2 and PFIC type 3. The defect is in ATP8B1 gene encoding the FIC1 protein, ABCB 11 gene encoding BSEP protein and ABCB4 gene encoding MDR3 protein in PFIC1, 2 and 3 respectively. The basic defect is impaired bile salt secretion in PFIC1/2 whereas in PFIC3, it is reduced biliary phospholipid secretion. The main clinical presentation is in the form of cholestatic jaundice and pruritus. Serum gamma glutamyl transpeptidase (GGT) is normal in patients with PFIC1/2 while it is raised in patients with PFIC3. Treatment includes nutritional support (adequate calories, supplementation of fat soluble vitamins and medium chain triglycerides) and use of medications to relieve pruritus as initial therapy followed by biliary diversion procedures in selected patients. Ultimately liver transplantation is needed in most patients as they develop progressive liver fibrosis, cirrhosis and end stage liver disease. Due to the high risk of developing liver tumors in PFIC2 patients, monitoring is recommended from infancy. Mutation targeted pharmacotherapy, gene therapy and hepatocyte transplantation are being explored as future therapeutic options.

Encephalopathy assessment in children with extra-hepatic portal vein obstruction with MR, psychometry and critical flicker frequency

BACKGROUND & AIMS Mild cognitive and psychomotor deficit has been reported in patients with extra-hepatic portal vein obstruction. This prospective study was done to ascertain the presence of minimal hepatic encephalopathy by neuropsychological testing and its correlation with diffusion tensor imaging derived metrics, T1 signal intensity, brain metabolites in (1)H magnetic resonance spectroscopy, blood ammonia and critical flicker frequency in patients with extra-hepatic portal vein obstruction. METHODS Neuropsychological tests, critical flicker frequency, blood ammonia, diffusion tensor imaging, T1 signal intensity and (1)H magnetic resonance spectroscopy were determined in 22 extra-hepatic portal vein obstruction and 17 healthy children. Bonferroni multiple comparison post hoc analysis was done to compare controls with patient groups. RESULTS Based on neuropsychological tests, 7/22 patients had minimal hepatic encephalopathy, and significantly increased Glx/Cr ratio, blood ammonia, mean diffusivity and globus pallidus T1 signal intensity with decreased critical flicker frequency in comparison to controls and in those without minimal hepatic encephalopathy. Cho/Cr, mI/Cr ratio and fractional anisotropy were unchanged in patient groups compared to controls. A significant inverse correlation of neuropsychological test with mean diffusivity, Glx/Cr ratio and blood ammonia and a positive correlation among mean diffusivity, blood ammonia and Glx/Cr ratio was seen. CONCLUSIONS Extra-hepatic portal vein obstruction is a true hyperammonia model with porto-systemic shunting and normal liver functions that results in minimal hepatic encephalopathy in one-third of these children. Hyperammonia results in generalized low grade cerebral edema and cognitive decline as evidenced by increased Glx/Cr ratio, mean diffusivity values and abnormal neuropsychological tests.

Acute on chronic liver disease in children from the developing world: recognition and prognosis.

Objectives: A subset of children with chronic liver disease (CLD) decompensate following an acute insult; however, data for children are not readily available. The present study aims to characterize the clinical presentation, etiology, outcome, and determinants of short-term mortality in children with an acute hepatic insult superimposed over CLD. Patients and Methods: Children of acute on chronic liver disease (ACLD) were grouped as acute on chronic liver failure (ACLF) and non-ACLF. ACLF was defined as per the definition proposed by Asian Pacific Association for the Study of Liver. The acute insult, etiology of CLD, and clinical and laboratory parameters at admission along with 3-month outcome were assessed. Receiver operating curve (ROC) was plotted to measure the performance of pediatric end-stage liver disease (PELD) score in predicting the 3-month mortality. Results: Of the 36 children with ACLD (median age 9.5; range 3–15 years), 17 fulfilled ACLF criteria and 19 non-ACLF. CLD was diagnosed for the first time in 86% children during their presentation with a superimposed acute insult. Wilson disease and autoimmune liver disease were the most common underlying etiology. Acute insult was caused by hepatitis E virus (HEV) in 27 (75%) children and hepatitis A virus (HAV) in 10 (28%). The 3-month mortality of ACLF group was significantly higher than that of non-ACLF group (59% vs 11%, P = 0.001). PELD score of >25.5 predicted death, with a sensitivity of 100% and specificity of 83.3%. Conclusions: Superinfection with hepatotropic viruses on CLD in children manifests as ACLD: ACLF and non-ACLF. Hepatitis E virus is the most common superinfection in the population studied. The mortality in ACLF is 5 times higher than that in the non-ACLF group. PELD score is useful in differentiating likely survivors and nonsurvivors.

Autoimmune liver disease in children

Autoimmune liver disease (AILD) in children progresses to cirrhosis and liver failure if not diagnosed and managed in time. We prospectively analyzed our patients with liver disease for autoimmune etiology and their outcome with treatment.

Prevalence, human leukocyte antigen typing and strategy for screening among Asian first-degree relatives of children with celiac disease.

Background and Aim:  Data on prevalence, human leukocyte antigen (HLA) typing and small bowel histology among first‐degree relatives of subjects with celiac disease (CD) is scarce. This prospective study evaluated the prevalence and role of HLA DQ2/8 testing in screening of first‐degree relatives of children with CD.

Management of childhood pancreatic disorders: a multidisciplinary approach.

Introduction Data on therapeutic endoscopy and radiologic interventions for the management of childhood pancreatic disorders are relatively limited. This study focuses on the multidisciplinary approach to the management of pancreatitis in children. Patients and Methods Children with pancreatic disorders were studied from January 1992 to May 2001. Acute pancreatitis (AP) was diagnosed by clinical evaluation, serum amylase more than three times normal, and morphologic abnormalities of the pancreas on imaging. Children with recurrent abdominal pain, pancreatic calcification or ductal stones on imaging, and pancreatic ductal changes on endoscopic retrograde cholangiopancreatography (ERCP) were diagnosed with chronic pancreatitis (CP). Patients were treated by gastroenterologists, surgeons, and interventional radiologists. Pancreatic exocrine insufficiency was diagnosed in appropriate settings. Results Fifteen children—6 with AP (posttrauma, 3; gallstone disease, 1; and viral, 1), 7 with CP, and 2 with pancreatic exocrine insufficiency—were diagnosed. Local complications observed in children with AP included pseudocyst in three, and infected acute fluid collection, right-sided pleural effusion, and ascites in one patient each. Complications of AP were managed with percutaneous catheter drainage (n = 3; pseudocyst, 2; infected fluid collection, 1), additional pancreatic duct stenting (n = 2), surgical drainage (n = 1), and octreotide for pleural effusion (n = 1). Signs of CP included abdominal pain (n = 7), obstructive jaundice resulting from lower common bile duct stricture (n = 2), and bleeding from gastroduodenal artery pseudoaneurysm (n = 1). Pancreatic duct stenting relieved pain in one patient, and steel coil embolization arrested bleeding from the pseudoaneurysm. Common bile duct strictures were managed by surgical bypass (n = 2), one of which required preoperative endoscopic bile duct stenting for management of cholangitis. Two other patients with CP required no intervention. Conclusion A multidisciplinary approach of radiologic and endoscopic interventions and surgery are complimentary to each other in achieving successful outcomes of complicated childhood pancreatitis.

Quality of life in children managed for extrahepatic portal venous obstruction.

Objectives: There are no studies on health-related quality of life (HRQOL) in children with extrahepatic portal venous obstruction (EHPVO). The present study evaluated the QOL in children with EHPVO, prevariceal and postvariceal esophageal variceal eradication, and postsurgery in comparison with healthy controls. Methods: Children with EHPVO and variceal bleeding were divided into 3 groups: group A, before variceal eradication (n = 50); group B, after variceal eradication (n = 50); and group C, after surgery (n = 12). Group D comprised healthy children (n = 50). Clinical details and investigations were recorded. The Pediatric Quality of Life Inventory parent-proxy HRQOL questionnaire was used for assessment of QOL. Results: Compared with controls, patients with EHPVO in groups A, B, and C had lower median QOL scores in physical, emotional, social, and school functioning health domains. Esophageal variceal eradication had no significant effect on QOL (median total QOL score pre- and postvariceal eradication of 87.5 vs 86.3). Increasing size of spleen (mild 92.5, moderate 88.2, and severe 76.2; P < 0.001), presence of hypersplenism (90 vs 73.7, P = 0.001), and growth retardation (90 vs 82.5, P = 0.04) caused significant reduction of the total QOL score. On multivariate regression analysis, splenic size and growth retardation were found to be independent predictors that affect the QOL. After surgery, a trend toward improvement in physical, psychosocial, and total QOL scores was present, but it was not significant. Conclusions: Children with EHPVO have a poor QOL that is not affected by variceal eradication. Splenomegaly and growth retardation significantly affect the HRQOL. A trend toward improvement of QOL scores is observed in the postsurgery group.

Effect of a gluten-free diet on growth and small-bowel histology in children with celiac disease in India

Background and Aim:  Follow‐up studies on growth and histological recovery of children with celiac disease (CD) while on a gluten‐free diet (GFD) are lacking from Asia. We therefore assessed the effects of this diet.

Effect of surgical portosystemic shunt on prevalence of minimal hepatic encephalopathy in children with extrahepatic portal venous obstruction: assessment by magnetic resonance imaging and psychometry.

Objective: The aim of this study was to evaluate the effect of surgical portosystemic shunt (PSS) on the prevalence of minimal hepatic encephalopathy (MHE) in patients with extrahepatic portal venous obstruction. Patients and Methods: Forty-two children with extrahepatic portal venous obstruction (17 with surgical PSS, 25 without surgical shunt) and 20 healthy children were evaluated with blood ammonia (BA), psychometry, 1H magnetic resonance spectroscopy, critical flicker frequency (CFF), and diffusion tensor imaging. Serum tumor necrosis factor-α and interleukin-6 were measured in 10 patients and 8 controls. Results: Patients with surgical PSS had significantly higher BA and glutamine/creatine on 1H-MR spectroscopy than those without surgical shunt. Both groups of patients had significantly higher BA and glutamate/creatine than controls. Myoinositol was reduced in patients with surgical PSS. MHE was present in 41% cases with and 32% cases without surgical PSS (p-ns). Raised mean diffusivity on diffusion tensor imaging signifying low-grade cerebral edema was seen only in MHE cases. Patients had significantly higher serum tumor necrosis factor-α and interleukin-6 levels than controls. CFF was abnormal in 5 of 15 patients with MHE. Conclusions: Patients with surgical PSS have significantly higher BA and Glx/creatine than those without surgical PSS. MHE prevalence was higher in surgically shunted than in the nonshunted patients, but the difference was not significant. Cerebral edema is present in patients with MHE. CFF has limited diagnostic utility for MHE in children.

Cow's milk protein allergy: an entity for recognition in developing countries.

Aim:  The aim of this prospective study was to determine cows milk protein allergy (CMPA) cases in a tertiary care hospital in India and to study its clinical presentations and outcome following treatment.