Cure for immune-tolerant hepatitis B in children: is it an achievable target with sequential combo therapy with lamivudine and interferon?

We prospectively studied the HBsAg seroconversion with sequential combination therapy of lamivudine (LAM) and interferon (IFN) in hitherto untreatable 'immune-tolerant' chronic hepatitis B in children. In this case-control study, 28 children with immune-tolerant hepatitis B [HBsAg positive for >6 months with near normal aminotransferase level, minimal/no inflammation in liver histology and high viral load (HBV DNA>10(7) copies/mL)] were treated with LAM alone at 3 mg/kg/day for 8 weeks followed by LAM plus IFN alpha (5 MU/m(2) three times a week) for another 44 weeks. They were compared with 34 untreated children. HBV markers (HBsAg, HBeAg, anti-HBe, quantitative HBV DNA) were carried out at baseline, at the end of therapy and 6 monthly thereafter. The mean age was 5.9 ± 3.2 years and 24 were boys. End therapy response: HBe seroconversion was achieved in 11, and of these, five had complete response (HBsAg clearance), 11 did not respond and six had virologic response (DNA undetectable but no HBe seroconversion). Six months after therapy, 10 of the 11 (91%) originally seroconverted children remained seroconverted while one seroreverted. Six of the 28 (21.4%) children lost HBsAg and they remained HBsAg negative and anti-HBs positive on follow-up. After a mean follow-up of 21.1 ± 11.9 months, the status remained same in the responders but one of the nonresponders HBe seroconverted (39.3%). There were no serious side effects of therapy. It is possible to achieve a cure in more than one-fifth of immune-tolerant children with hepatitis B with the sequential combination of LAM and IFN.

Predictors of outcome in children with acute viral hepatitis and coagulopathy.

The presence of coagulopathy in acute viral hepatitis (AVH) in children raises issues about prognosis and need for liver transplantation. We evaluated factors predicting outcome in such patients and determined the applicability of the paediatric acute liver failure study group (PALFSG) definition of acute liver failure (ALF) of coagulopathy alone in comparison with coagulopathy and encephalopathy. Children with AVH (clinical features, raised transaminases and positive viral serology) with uncorrectable coagulopathy [prothrombin time (PT) > 15 s] with or without hepatic encephalopathy (HE) were enrolled. Comparative analysis was based on (i) outcome: survivors/nonsurvivors and (ii) ALF criteria: group A coagulopathy (PT > 15 s) and encephalopathy and group B coagulopathy (PT > 20 s). We studied 130 children (86 boys, mean age 7.5 ± 4.5 years): 86 recovered and 44 died. Single virus infection was present in 96 (74%), hepatitis A being the commonest (n-69). On multiple stepwise logistic regression analysis, age <3.5 years, serum bilirubin ≥ 16.7 mg/dL, PT ≥ 40.5 s and clinical signs of cerebral oedema were independent predictors of mortality. Mortality increased from 0% with single to 100% with four risk factors. Ninety-seven cases met the PALFSG criteria: group A-79 and group B-18. Group A subjects had higher mortality (55.6%vs 0%) and poorer liver functions (bilirubin 18.1 ± 8.9 vs 13.8 ± 6.9 mg/dL, PT 63.9 ± 35.1 vs 27.2 ± 5.2 s) than group B. PT deteriorated significantly with the appearance and progression of HE. One-third of children with AVH with coagulopathy die without transplantation. Age <3.5 years, bilirubin ≥ 16.7 mg/dL, PT ≥ 40.5 s and signs of cerebral oedema are predictors of poor outcome. Children with encephalopathy and coagulopathy have a poorer outcome than those with coagulopathy alone.

Renal lymphangiomatosis: a rare cause of bilateral nephromegaly.

We report the ultrasound, excretory urography and MR findings in a young child with renal lymphangiomatosis who presented with gradually progressive bilateral flank swelling but who was otherwise asymptomatic. The typical perirenal and parapelvic cysts are visualized as hypoechoic lesions on sonography and hyperintense on T2-weighted HASTE images. T1-weighted image could not delineate the cysts clearly. The renal parenchyma was hyperechoic on sonography, and MRI showed reversal of the normal corticomedullary signal intensity, and confirmed the diagnosis by suggesting the non-parenchymal origin of the cysts.

Crohn's disease: disastrous consequences of late diagnosis.

Chronic and recurrent perianal abscess is an uncommon condition in children. Tuberculosis is thought to be the common etiology for such a presentation in India. We report a case of a child with colonic and perianal disease due to Crohn's disease and emphasize the disastrous complication due to delayed diagnosis.

Natural history and risk factors in fulminant hepatic failure.

BACKGROUND: The natural history of fulminant hepatic failure (FHF) without liver transplantation is not well known. AIMS: To study the natural history and prognostic factors, especially the presence of ascites and spontaneous bacterial peritonitis (SBP), in children with FHF. METHODS: FHF was defined by the onset of encephalopathy within 12 weeks of onset of jaundice. From August 1997 to December 2000, 67 children (< or =12 years) were diagnosed with FHF. Their clinical features, investigations and outcome were noted. Viral markers A to E (IgM, anti-HAV; IgM, anti-HEV, HBsAg, and anti-HCV) were determined by ELISA. SBP was defined by the presence of > or =250 neutrophils with or without a positive culture in ascitic fluid. RESULTS: Mean age of the children was 5.8 years with an almost equal sex distribution. Viral markers were positive in 63 (94%) cases: hepatitis A in 34 (54%), E in 17 (27%), A+E in seven (11%), and B in five (8%). Thirty one children presented with grade I or II encephalopathy and all recovered, whereas 17 of 36 children who had grade III or IV encephalopathy died. Ascites was detected (both clinically and ultrasonically) in 34 (51%) cases, nine (26%) of which had SBP. Overall mortality was 25%. Mortality was higher in those who had ascites than in those who did not (32% v 18%); among those with ascites it was maximum in those who had SBP (78% v 16%). Total serum bilirubin and grade of encephalopathy were significantly higher, serum albumin was significantly lower, and prothrombin time was significantly prolonged in those who died than in those who recovered. CONCLUSION: The natural history of FHF in Indian children depends on age, grade of encephalopathy, ascites, and SBP. SBP depicts worse outcome. In all cases of FHF with ascites, the presence of SBP should be investigated.

Portal hypertension secondary to Langerhans cell histiocytosis.

We report two children, aged 2 and 2 1/2 years, with multisystem Langerhans cell histiocytosis (LCH). Both were administered chemotherapy, with apparently good response. However, hepatic fibrosis and portal hypertension were detected 5 and 1 1/2 years after therapy, respectively. The first child died after a bout of hematemesis. Hepatic fibrosis can proceed despite apparently successful chemotherapy in LCH.

Benign esophageal strictures in infants and children: results of Savary-Gilliard bougie dilation in 107 Indian children.

BACKGROUND: Little information is available regarding the safety and efficacy of dilation of esophageal strictures in children with Savary-Gilliard bougies. This is a report of our experience with this form of dilation in Indian children. METHODS: One hundred seven Indian children age 14 years or younger with benign esophageal strictures underwent dilation. Clinical information including etiology was recorded. Dilation was performed at 2- to 3-week intervals by using Savary-Gilliard bougies under ketamine sedation and was considered adequate if the esophageal lumen could be dilated to 15 mm diameter (12.8 mm in children <5 years of age) with complete relief of symptoms. Subsequently, dilation was performed on an "as needed" basis. RESULTS: Mean age was 4.8 +/- 3.4 years; male to female ratio was 3:1. Fifty-four children had corrosive strictures (acid 34, alkali 20). Noncorrosive strictures were sclerotherapy-induced (23), postsurgical (14), congenital (10), peptic (4), and due to other causes (2). Dilation was successful in all but 3 cases. Corrosive strictures required a significantly higher number of sessions to achieve adequate initial dilation (2.4 +/- 1.9 vs. 1.3 +/- 0.5, p < 0.01). Patients with corrosive strictures also required a higher number of subsequent sessions for recurrence (7.3 +/- 6.5 vs. 0.7 +/- 1.3, p = 0.10). Dilation was also successful in patients with strictures 5 cm or more in length and/or patients with multiple corrosive strictures, although these required a higher number of sessions to achieve adequate dilation (p < 0.05) and also higher number of subsequent sessions for recurrence. Six esophageal perforations occurred during 648 dilation sessions (0.9%); 5 occurred in patients with corrosive strictures. One patient required surgery. CONCLUSIONS: Corrosive injury is the most common cause of benign esophageal strictures in Indian children. Savary-Gilliard bougie dilation is safe and effective, even for long and/or multiple corrosive strictures.

Endoscopic retrograde cholangiopancreatography in the management of pancreaticobiliary disorders in children.

BACKGROUND AND AIM: The role of endoscopic retrograde cholangiopancreatography (ERCP) is not yet fully established in children. The purpose of this study was to assess the use of ERCP in the diagnosis and management of various pancreaticobiliary disorders in children. METHODS: Eighty-four ERCPs were performed over 5.5 years in 72 children with suspected pancreaticobiliary tract disorders with an adult-type duodenoscope. In all cases, indications, procedure time, ERCP findings, complications, patients course and therapeutic intervention (if any) were recorded. RESULTS: The mean (+/- SD) age of these children was 8.8 +/- 3.3 years. Successful cannulation was possible in 70 (97%) cases. Of the 44 cases with suspected biliary tract disease, 14 had a choledochal cyst, 13 had portal biliopathy, two each had CBD stones, primary sclerosing cholangitis and a bile leak, one had biliary ascariasis, eight had a normal cholangiogram, and CBD cannulation failed in two. Eight of the 28 children with suspected pancreatic disorders had chronic pancreatitis, five had pancreatic duct disruption, three had pancreas divisum and the rest had a normal pancreatogram (including all eight children with unexplained abdominal pain). Therapeutic ERCP was performed in 22 children, endoscopic nasobiliary or a nasocystic drain was placed in 16, biliary stenting was conducted in two, pancreatic duct stenting was conducted in three, and minor papilla dilation was conducted in one child. Six children had mild procedure-related complications. CONCLUSION: Endoscopic retrograde cholangiopancreatography is very useful in the treatment of cholangitis, bile leak, pseudocyst and pancreatic fistulae in children. However, its role in unexplained abdominal pain is doubtful.

Non-cirrhotic portal fibrosis in children.

BACKGROUND AND OBJECTIVES: Non-cirrhotic portal fibrosis (NCPF) is an infrequent cause of portal hypertension in children. We report 11 children with NCPF, from among 338 with portal hypertension, seen over 6.5 years. METHODS: The diagnosis was based on patent splenoportal axis on ultrasonography and/or splenoportal venography and liver biopsy showing no evidence of cirrhosis or other diagnosis, in children with portal hypertension. Those with variceal bleed were managed with endoscopic sclerotherapy and/or shunt surgery. RESULTS: The median age was 11 years (range 5 to 14), and 8 were boys. Presentation was with variceal bleed in 6, lump in left upper abdomen in 5 (though all children had splenomegaly) and esophageal varices on endoscopy. The median spleen enlargement was 8.5 cm; 8 also had hepatomegaly. Hypersplenism was present in 7, and two had developed ascites after bleed. Of 6 children presenting with bleed, variceal obliteration was achieved on sclerotherapy (average 5.6 sessions) in 4 while two underwent shunt surgery for associated hypersplenism. After median follow up of 57.5 months (range 12-78) all are alive and well. CONCLUSION: NCPF is an uncommon cause of portal hypertension in Indian children. Presentation with variceal bleed is less common than in adults; sclerotherapy is effective.

Post-biopsy liver cyst: a rare complication of liver biopsy.

Liver biopsy rarely leads to complications in a non-cirrhotic liver. We describe here a case of a biliary cyst of the liver that developed after a liver biopsy. It was successfully treated with surgery.

Celiac disease: clinical features and diagnostic criteria.

Celiac disease (CD) classically presents between 9-18 months of age but in India there is a significant delay in the onset of symptoms (3-4 years) and the age of presentation (6.8-9.2 years). Failure to thrive, anemia, and muscle wasting are more common in children. Symptomatic CD represents the tip of the iceberg. Clinically there may be overt, silent, latent and potential CD. Modified ESPGAN criteria for diagnosis of CD is based on demonstration of characteristic histological changes in small intestinal biopsy while on gluten, and unequivocal clinical improvement when on gluten free diet. However, in developing countries there are several conditions which can give rise to villous atrophy and using it as a diagnostic criteria may lead to overdiagnosis of CD. IgA antigliadin antibody has a high sensitivity (98%) and specificity (90%) for CD and hence, may be an ideal adjunct to modified ESPGAN criteria in the diagnosis of CD in India.