Etiology and outcome of neonatal cholestasis: an experience in a tertiary center of Bangladesh

Abstract

Background Neonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh. Results Out of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes. Conclusion BA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.

Neonatal Cholestasis: an update

“…PFIC is a group of autosomal recessive disorders that show progressive intrahepatic cholestasis. Among all cholestatic infants, only 1 (1.2%) case of PFIC was found in Mahmud et al 9 and Nahid et al study. 18 PFIC-1 is caused by mutation in the FIC1 gene and is the original Byler disease described in the descendants of an Amish American family.…”

“…), and are labeled as having the so-called fetal/embryonic form. Mahmud et al 9 (37.5%) and Nahid et al 18 (31.6%) stated that BA was the most common etiology of NC of Bangladeshi children. These infants may appear jaundiced at birth and and remain so.…”

“…Out of 19 cholestatic TORCH infections, CMV (68.4%) were the most commonest followed by CMV with herpes-simplex virus (HSV) co-infection (21.1%) and Toxoplasmosis (10.5%) among Bangladeshi infants. 9 Obtaining a good maternal history and discussing with the obstetrician and neonatal intensive care team about placental abnormalities can help with directing the workup for an infection. 1,4 Figure 10 CMV hepatitis (Picture was taken with permission).…”

“…Out of 80 cholestatic infants, Two (2.5%) cases of galactosemia were found in a study of Bangladeshi infants. 9 A deficiency of the enzyme galactose-1-phosphate uridyl transferase results in defective metabolism of galactose (Figure 12). Newborn screening for galactosemia is performed in most countries, thus identifying the majority of infants before they become symptomatic.…”

“…It is crucial to rapidly identify infants who have medically treatable forms of cholestasis as well as those causes amenable to surgical intervention (Table 7). 4,9,10 Kasai's PE consists of removal of the atretic extrahepatic tissue and a Roux-en-Y jejunal loop anastomosis to the hepatic hilum. PE may be considered successful if serum bilirubin normalizes after surgery.…”