Role of Valganciclovir in Neonatal Hepatitis with Cytomegalovirus

Abstract

Cytomegalovirus (CMV) is an important cause of neonatal hepatitis. Untreated, though hepatomegaly may spontaneously regress, these children may develop portal hypertension and chronic liver disease. Also, these children can progress to develop biliary atresia. Long term sequelae may be sensorineural deafness and intellectual impairment. Role of ganciclovir and its prodrug valganciclovir for treatment of congenital CMV infection is not completely established. There have been few case series and case reports that have documented resolution of CMV hepatitis on treatment with ganciclovir. However, there is very little literature on role of valganciclovir in neonatal CMV hepatitis. We report for the first time in India, effectiveness of valganciclovir in 3 infants with neonatal hepatitis and CMV. All 3 infants in age group of 2-4 months with neonatal hepatitis and variable CMV viral load were treated with oral valganciclovir (125250 mg/m2/day) for 6 weeks and had clinical improvement and undetectable viral load at the end of therapy. One patient however developed long term sequelae of CMV in form of sensorineural deafness and delayed development. Thus, valganciclovir appears safe and effective in neonatal hepatitis with CMV. However, randomized controlled trials in larger groups are required to determine its efficacy. Introduction Cytomegalovirus (CMV) is the most common cause of congenital infection in humans.1,2 Severe jaundice and granulomatous hepatitis have been established due to neonatal CMV infection.3,4 Isolated neonatal hepatitis with CMV has been reported in literature but response to antivirals has been encouraging.5,6,7,8,9,10 We present 3 infants with neonatal hepatitis and associated CMV and their response to valganciclovir. Case 1: A 21⁄2 months old boy presented with jaundice and clay-colored stools since birth. Baby was born at 34 weeks by caesarean section in view of premature labour, had a birth weight of 1.75 kg and was put in neonatal intensive care unit (NICU) for 7 days. On examination, weight was 2.75 kg, length was 47 cms and head circumference was 35 cms. He had hepatosplenomegaly and umbilical hernia. Other systems were normal. Investigations are depicted in Table 1. Liver biopsy showed balloon degeneration of hepatocytes with multinucleated giant cells without inclusion bodies. In view of CMV infection, child was started on oral Valganciclovir (250 mg/m2/dose BD for 21 days, and then 125 mg/m2/dose BD for 21 days) following which liver function tests improved at end of 6 weeks (Bilirubin = 1.2 mg/dl, SGPT = 62 IU/L, Total proteins = 6.1 gm/dl, Albumin = 3.8 gm/dl), CMV viral load was undetectable. At 8 months of age, child is asymptomatic. Case 2: A 3-month-old girl was referred in view of jaundice. There were no clay-colored stools. She was born at 9 months gestation with birth weight of 2.75 kg and had achieved milestones appropriately for age. On examination, weight was 4 kg, length was 60 cms. She had with jaundice with massive hepatosplenomegaly with umbilical hernia. Other systems were normal. Investigations are depicted in Table 1. Liver biopsy showed distorted architecture with moderate inflammation and intracellular cirrhosis. The child was treated with valganciclovir for 6 weeks. At end of 6 weeks, the child had no jaundice. Case 3: A 31⁄2 months old boy born at full term presented with jaundice and clay-colored stools since 1 month of age. The patient had convulsions on Day 2 of life and required NICU stay for 7 days and was on oral phenobarbitone for the same. Mother had fever at 7 months of gestation. Child was investigated at 1 month of age and was found to have direct hyperbilirubinemia [(Bilirubin = 7.3 gm/dl, direct bilirubin = 2.3 gm/dl)] and CMV IgM was positive. Since jaundice did not resolve, child was referred for further management. On examination, at 31⁄2 months of age, weight was 5 kg, length was 63.5 cm and there was splenohepatomegaly with jaundice. Investigations are depicted in Table 1. His vision appeared impaired and fundus examination was normal though visual evoked potential was suggestive of retinal damage. MRI brain showed delayed cortical maturation. EEG was normal. In view of persistent neonatal hepatitis, child was Address for Correspondance: Dr Ramya Uppuluri, Department of Pediatric Hematology, Oncology and BMT, Apollo Specialty Hospital, 320, Padma Complex, Anna Salai, Chennai, 600035 India. Email: ramya.december@gmail.com ©2021 Pediatric Oncall ARTICLE HISTORY Received 9 January 2020 Accepted 29 July 2021