Decoding hepatorenal tyrosinemia type 1: Unraveling the impact of early detection, NTBC, and the role of liver transplantation.

Hepatorenal tyrosinemia type 1 (HT-1) is a rare autosomal recessive disease that results from a deficiency of fumaryl acetoacetate hydrolase (FAH), a critical enzyme in the catabolic pathway for tyrosine. This leads to the accumulation of toxic metabolites such as fumaryl and maleylacetoacetate, which can damage the liver, kidneys, and nervous system. The discovery of 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC or nitisinone) has significantly improved the management of HT-1, particularly when initiated before the onset of symptoms. Therefore, newborn screening for HT-1 is essential for timely diagnosis and prompt treatment. The analysis of succinyl acetone (SA) in dried blood spots of newborns followed by quantification of SA in blood or urine for high-risk neonates has excellent sensitivity and specificity for the diagnosis of HT-1. NTBC combined with dietary therapy, if initiated early, can provide liver transplant (LT) free survival and reduce the risk of hepatocellular carcinoma (HCC). Patients failing medical treatment (eg, due to non-adherence), and who develop acute liver failure (ALF), have HCC or evidence of histologically proven dysplastic liver nodule(s), or experience poor quality of life secondary to severe dietary restrictions are currently indicated for LT. Children with HT-1 require frequent monitoring of liver and renal function to assess disease progression and treatment compliance. They are also at risk of long-term neurocognitive impairment, which highlights the need for neurocognitive assessment and therapy.

Visceral Fat Indices: Do They Help Differentiate Crohn's Disease and Intestinal Tuberculosis in Children?

BACKGROUND AND AIMS: Crohn's disease [CD] and intestinal tuberculosis [ITB] are often difficult to differentiate. Mesenteric fat hypertrophy is a feature of CD. We evaluated the utility of fat indices (visceral fat [VF] and subcutaneous fat [SF]) in differentiating CD and ITB in children. METHODS: Symptomatic children diagnosed to have CD or ITB based on recommended criteria were enrolled. Clinical, anthropometric, and laboratory details were noted. Abdominal fat was measured on computed tomography in supine position at the level of L4 vertebrae. VF and SF area was measured separately by a radiologist, blinded to the diagnosis. The sum of VF and SF was taken as total fat [TF]. VF/SF and VF/TF ratios were calculated. RESULTS: Thirty-four (age 14 years [10.8-17.0], 14 boys) children were recruited: 12 had CD [seven boys, age 13.0 years] and 22 had ITB [seven boys, age 14.5 years]. VF area was higher in CD compared to ITB (18.34 cm2 [15.62-40.01] vs 6.48 cm2 [2.65-21.96]; p = 0.012). The SF and TF area was similar in ITB and CD. The ratios of VF/SF (0.82 [0.57-1.5] vs 0.33 [0.16-0.48]; p = 0.004) and VF/TF (0.45 [0.36-0.60] vs 0.25 [0.13-0.32]; p = 0.004) were significantly higher in CD. On comparing CD and ITB in boys and girls separately, the difference was significant for boys but not for girls. A VF/SF ratio of 0.609 predicted CD with a good sensitivity [75%] and specificity [86.4%] [area under the curve 0.795, 95% confidence interval 0.636-0.955; p = 0.005]. CONCLUSION: The VF/SF ratio is a simple, non-invasive, objective parameter to differentiate CD and ITB in children, particularly boys. Larger studies are needed to validate this in girls.

Gastrointestinal bleeding due to pseudoaneurysms in children.

Radiological embolization is the treatment of choice in adults with visceral artery pseudoaneurysm (PSA) and gastrointestinal bleeding, but pediatric data is scanty. We analyzed the etiology, clinical presentation, and outcome of radiological intervention in children with PSA of celiac (CA) or superior mesenteric artery (SMA) branches. Electronic records of children with PSA of CA or SMA branches were reviewed and data on clinical and laboratory profile, radiological intervention, and outcome was recorded. Eleven children with PSA (5 boys, 11 [7-17] years) were studied. Etiology was liver abscess (n 4), abdominal trauma (n 3), pancreatitis (n 3), and indeterminate in 1 case. Ten (91%) patients were symptomatic: abdominal pain (10, 91%), hematemesis/melena (9, 81%), and Quincke's triad (1, 9%). One child with pancreatic pseudocyst was diagnosed incidentally on imaging. Doppler ultrasound identified PSA only in 3 cases, while computed tomography angiography (CTA) picked all cases. Children with liver abscess, trauma, and unknown etiology had PSA from CA (right hepatic artery 7, left hepatic artery 1). Of the 3 pancreatitis cases, 2 had PSA from SMA (inferior pancreatico-duodenal artery and ileal branch) and 1 from CA (left gastric artery). Radiological embolization was done in 9 (81%) cases (coil 6, glue 2, both 1), without any complications or failure. One case resolved spontaneously and 1 died pre-intervention. Nine intervened cases were asymptomatic in follow-up [6 (1-24) months].Conclusion: Liver abscess, trauma, and pancreatitis are causes of PSA of CA and SMA branches in children. A majority present with gastrointestinal bleeding and are identified on CTA. Radiological embolization was safe with 100% success. What is Known: • Pseudoaneurysm of visceral artery is an uncommon cause of gastrointestinal bleeding. • Endoluminal intervention is an established and efficacious treatment modality in adults and preferred over surgery. What is New: • Liver abscess, abdominal trauma and pancreatitis are common causes of celiac artery and superior mesenteric artery branch pseudoaneurysm in children and computed tomography angiography has high sensitivity in identifying these pseudoaneurysms. • Minimally invasive radiological angio-embolization, in the hands of trained radiologists, is a safe and successful modality of treatment in children.

Efficacy of amitriptyline in pediatric functional abdominal pain disorders: A randomized placebo-controlled trial.

BACKGROUND AND AIM: Amitriptyline improves symptoms in functional abdominal pain disorders (FAPD) in adults with variable results in pediatric studies. The study aims to evaluate the efficacy of amitriptyline in pediatric FAPD. METHODS: In this open-label trial, children (≤ 18 years) diagnosed as FAPD based on ROME IV criteria were randomized to amitriptyline or placebo for 12 weeks. Post-treatment improvement of pain and quality of life (QOL) from the baseline were compared between the two groups. RESULTS: The mean age of 149 children (amitriptyline 75, placebo 74) was 11.3 ± 3.5 years (79 boys). There was a significant difference in pain improvement in terms of reduction in scores for intensity (3.4 vs 0.9), frequency (3.6 vs 0.6), duration (3.5 vs 0.9), and QOL (2.3 vs 0.9) between amitriptyline and placebo group (P < 0.001 in all). Responders (> 50% reduction) in pain was seen in 76% in amitriptyline compared with 14.9% in the placebo group (P < 0.001). On multivariate analysis, the use of amitriptyline was the only factor predictive of response (odds ratio 24.1, 95% confidence interval: 9.1-64.6, P < 0.001). Minor adverse events were comparable between the groups (25.3% vs 13.5%, respectively, P = 0.07). Eighty-nine percent of children (24/27) who had extended treatment duration (6.8 ± 1.8 months) had pain improvement. After discontinuation of amitriptyline, 70% had sustained response over a mean follow up of 15.84 ± 5.6 months. CONCLUSIONS: A 3-month trial of amitriptyline gives sustained relief of pain in two-thirds of children with FAPD. The safety profile of the drug and its efficacy necessitate more frequent use in the clinical settings.

Chelation therapy in liver diseases of childhood: Current status and response.

Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson's disease (WD), one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine. D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation. Trientine, an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects. The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD. Indian childhood cirrhosis is related to excessive copper ingestion, rarely seen in present era. D-Penicillamine is effective in the early part of this disease with reversal of clinical status. Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias. There are strict chelation protocols during bone marrow transplant. The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy. Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.

Pediatric non-cirrhotic portal hypertension: Endoscopic outcome and perspectives from developing nations.

Non-cirrhotic portal hypertension (NCPH) forms an important subset of portal hypertension in children. Variceal bleed and splenomegaly are their predominant presentation. Laboratory features show cytopenias (hypersplenism) and preserved hepatic synthetic functions. Repeated sessions of endoscopic variceal ligation or endoscopic sclerotherapy eradicate esophageal varices in almost all cases. After variceal eradication, there is an increased risk of other complications like secondary gastric varices, cholangiopathy, colopathy, growth failure, especially in extra-hepatic portal vein obstruction (EHPVO). Massive splenomegaly-related pain and early satiety cause poor quality of life (QoL). Meso-Rex bypass is the definitive therapy when the procedure is anatomically feasible in EHPVO. Other portosystemic shunt surgeries with splenectomy are indicated when patients present late and spleen-related issues predominate. Shunt surgeries prevent rebleed, improve growth and QoL. Non-cirrhotic portal fibrosis (NCPF) is a less common cause of portal hypertension in children in developing nations. Presentation in the second decade, massive splenomegaly and patent portal vein are discriminating features of NCPF. Shunt surgery is required in severe cases when endotherapy is insufficient for the varices. Congenital hepatic fibrosis (CHF) presents with firm palpable liver and splenomegaly. Ductal plate malformation forms the histological hallmark of CHF. CHF is commonly associated with Caroli's disease, renal cysts, and syndromes associated with neurological defects. Isolated CHF has a favourable prognosis requiring endotherapy. Liver transplantation is required when there is decompensation or recurrent cholangitis, especially in Caroli's syndrome. Combined liver-kidney transplantation is indicated when both liver and renal issues are present.

Peritoneal Lymphomatosis Masquerading as Pyoperitoneum in a Teenage Boy.

A 16-year-old boy presented with 1 month of fever, abdominal pain, and distension. The ascitic tap drained pus-like fluid, and ultrasonography showed diffuse thickening of the omentum and mesentery with echogenic ascites. A diagnosis of pyoperitoneum due to peritoneal tuberculosis with secondary infection was suspected, and antitubercular therapy was started elsewhere, but there was no improvement. Computed tomography of the abdomen revealed enhancing soft-tissue thickening in the retroperitoneum, extending into the mesentery and encasing the superior and inferior mesenteric vessels. The ascitic fluid appearance deceptively resembled pus, but further analysis revealed atypical lymphocytes. Omental and bone marrow biopsies confirmed Burkitt lymphoma. Awareness of this rare presentation is imperative for making a correct diagnosis.