|Year : 2016 | Volume
| Issue : 3 | Page : 397-399
Neonatal hepatitis with herpes simplex
Rishika Sakaria1, Ira Shah2, Sushmita Bhatnagar3
1 Department of Pediatrics, Seth G S Medical College and B J Wadia Hospital for Children, Mumbai, Maharashtra, India
2 Pediatric Liver Clinic, B J Wadia Hospital for Children, Mumbai, Maharashtra, India
3 Department of Pediatric Surgery, B J Wadia Hospital for Children, Mumbai, Maharashtra, India
|Date of Web Publication||17-May-2016|
1/B Saguna, 271/B St. Francis Road, Vile Parle (W), Mumbai - 400 056, Maharashtra
Source of Support: None, Conflict of Interest: None
We report two cases of neonatal hepatitis with herpes simplex virus (HSV) infection. Whether the HSV infection was the cause of hepatitis, or merely associated with it is not clear. While, in the first case, resolution could not be achieved despite high-dose antiviral treatment with acyclovir and liver transplant had to be advised; in the second case, there was complete resolution of the disease without antiviral therapy. Role of acyclovir in these children needs further assessment.
Keywords: Antiviral therapy, herpes simplex, neonate, viral hepatitis
|How to cite this article:|
Sakaria R, Shah I, Bhatnagar S. Neonatal hepatitis with herpes simplex. Med J DY Patil Univ 2016;9:397-9
| Introduction|| |
Neonatal jaundice has been reported many times in medical literature and has varied etiology ranging from infections to congenital malformations.  Neonatal herpes simplex virus (HSV) infection is rare but associated with severe morbidity and mortality rates.  The infection most commonly occurs in the intrapartum period, but it may also occur in the intrauterine or postpartum period.  HSV infection in neonates causing hepatitis has been seldom reported, and it represents a broad spectrum of disease ranging from mild aminotransferase elevation to fulminant liver failure and death. ,,
We report two cases of neonatal hepatitis with HSV infection. Whether the HSV infection was the cause of hepatitis, or merely associated with it is not clear. While, in the first case, resolution could not be achieved despite high-dose antiviral treatment with acyclovir and liver transplant had to be advised; in the second case, there was complete resolution of the disease without antiviral therapy.
| Case Reports|| |
A 1½-month-old girl presented with clay colored stool since birth and jaundice since 15 days. Mother had no antenatal complications, and the baby was born at full-term. She was on exclusive breast feeds. On examination, she had jaundice, hepatomegaly, weight was 3.5 kg (3 rd centile), total length was 51 cm (3 rd centile), and head circumference was 38 cm (50 th centile). Her hemoglobin was 14.6 g/dl, white blood cell count was 11,900 cells/cumm, platelets were 369,000/cumm, bilirubin was 14.6 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) was 130 IU/L, serum glutamic-pyruvic transaminase (SGPT) was 248 IU/L, gamma-glutamyl transferase (GGTP) was 64, total proteins were 5.9 g/dl, albumin was 3.8 g/dl, globulins were 2.1 g/dl, and alkaline phosphatase was 1369 IU/L. Ultrasound (USG) abdomen was normal. Echocardiography was normal. Her TORCH titers are depicted in [Table 1]. Hepatobiliary iminodiacetic acid (HIDA) scan showed normal extraction of tracer by the liver but no excretion into intestines after 24 h. Her intraoperative cholangiogram showed no biliary atresia, and liver biopsy showed giant cell hepatitis. Sweat chlorides, thyroid function tests, and urine organic acids were normal. Her ophthalmological evaluation and hearing assessment were normal. She was started on acyclovir (80 mg/kg/day) at 2½ months of age in view of 4 fold rise in HSV immunoglobulin G (IgG) following which her bilirubin decreased to 8 mg/dl (direct = 4.7 mg/dl). However, bilirubin again increased to 13.2 mg/dl at 5 months of age in spite of HSV IgG. Child was found to have marked elevation of cytomegalovirus (CMV) IgG at 5 months of age [Table 1]. However, parents refused antivirals for the same. She continued to remain jaundiced, and at 8½ months of age (weight of 6.7 kg), she was advised liver transplant.
A 3-month-old girl presented with jaundice and clay-colored stools since 15 days. She was born full-term, and there were no antenatal or postnatal complications. Her milestones were normal for age. On examination, weight was 4.3 kg (<3 rd centile), length was 54 cm (<3 rd centile), and head circumference was 39.5 cm (10 th centile). She had icterus and hepatosplenomegaly. Investigations showed hemoglobin 9.4 g%, white cell count of 27,700/cumm (61% polymorphs, 39% lymphocytes), platelets of 336,000/cumm, bilirubin of 6.3 mg/dl (direct = 3.5 mg/dl), SGOT of 324 IU/L, SGPT of 218 IU/L, alkaline phosphatase of 1736 IU/L, GGTP = 40 IU/L, total proteins 7.6 g/dl, and albumin = 4.5 g/dl. HIDA scan showed preserved hepatic extraction with no biliary drainage after 24 h. TORCH titers showed positive HSV IgM (1.23) and CMV IgM (1.71). Thyroid function tests and echocardiography were normal. Ultrasound abdomen showed hepatosplenomegaly. Liver biopsy showed giant cell hepatitis with no CMV inclusion bodies and no bile stasis. The child was started on multivitamins in cholestatic doses. A repeat HIDA scan after 20 days showed improved biliary drainage. On follow-up at 11 months of age, weight was 7.2 kg, there was no jaundice or hepatosplenomegaly, bilirubin was 0.6 mg/dl, SGOT = 54 IU/L, SGPT was 31 IU/L, and albumin was 3.8 suggestive of complete resolution.
| Discussion|| |
Neonatal giant cell hepatitis is a rare disease associated with a wide range of etiological factors. Infectious diseases are the most common cause and include generalized bacterial sepsis, viral agents, toxoplasmosis, syphilis, listeriosis, and tuberculosis. Viral hepatitis may be due to CMV, rubella virus, herpes simplex, HHV-6, varicella, coxsackievirus, echovirus, reovirus 3, parvovirus B19, HIV, enteroviruses, paramyxovirus, and hepatitis A, B, or C.  Association of neonatal hepatitis has also been seen with hypopituitarism.  HSV infection in a neonate may be acquired during the intrauterine, intrapartum, or postpartum period. Clinically, neonatal HSV infection can occur as:
The highest rates of mortality and morbidity are seen with disseminated infections.  The clinical outcome in herpetic neonatal hepatitis depends on the time of initiation of antiherpetic therapy. While resolution can be obtained with acyclovir in cases detected early with minimal liver damage, in cases with substantial hepatic destruction, liver transplant is the only lifesaving measure. ,, In the above cases, there were no perinatal complications. Mothers had no symptoms of HSV infection. The liver function tests were markedly elevated; there was associated hepatomegaly with both the cases showing obstruction to bile drainage on HIDA scan. Liver biopsy confirmed giant cell hepatitis. In the first case, there was a four-fold rise in HSV titers, and in the second case, HSV IgM was positive suggestive of acute HSV infection. While TORCH infections can also cause hepatitis in neonates, the association of positive HSV IgM titers with hepatitis in the two cases could not be ascertained and also whether HSV was congenital or acquired could not be determined.
- Localized infection (limited to skin, eyes, and mouth),
- Central nervous system involvement (encephalitis), and
- Disseminated infection involving several organs.
In the first case, the patient was treated with high-dose acyclovir. Studies into the role of acyclovir in treating herpetic hepatitis have suggested the benefit of early acyclovir treatment in patients with herpetic infections, whereas a delay in treatment has been associated with increased mortality. ,, While the patient did respond initially to the treatment as evidenced by a drop in bilirubin levels, this drop was not sustained, and the bilirubin levels increased again in spite of the HSV titers becoming negative. Hence, the patient had to be advised liver transplant. In the second case, the patient was treated with only multivitamin medications, and she showed complete resolution without antiherpetic medication. In both the patients, we could not perform HSV polymerase chain reaction due to nonavailability.
| Conclusion|| |
In children with neonatal cholestasis, HSV infection may be associated. Role of acyclovir in these children needs further assessment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shorter RG, Baggenstoss AH, Logan GB. Neonatal hepatitis. AMA J Dis Child 1959;98:359-69.
Abuhasna SD, Shihab ZM, Al Niyadi SM, Tatari HM, Al Jundi AH, Atwa KH. Neonatal herpes simplex fulminant hepatitis successfully treated with acyclovir. J Clin Neonatol 2012;1:87-90.
White JC, Magee SR. Neonatal herpes infection: Case report and discussion. J Am Board Fam Med 2011;24:758-62.
Benador N, Mannhardt W, Schranz D, Braegger C, Fanconi S, Hassam S, et al.
Three cases of neonatal herpes simplex virus infection presenting as fulminant hepatitis. Eur J Pediatr 1990;149:555-9.
Pilorget H, Estoup C, Mariette JB, Fourmaintraux A. Neonatal herpes simplex hepatitis with favorable outcome after treatment with acyclovir. Arch Pediatr 1994;1:822-5.
McGoogan KE, Haafiz AB, González Peralta RP. Herpes simplex virus hepatitis in infants: Clinical outcomes and correlates of disease severity. J Pediatr 2011;159:608-11.
Hicks J, Barrish J, Zhu SH. Neonatal syncytial giant cell hepatitis with paramyxoviral-like inclusions. Ultrastruct Pathol 2001;25:65-71.
Reiterer EE, Zenz W, Deutsch J, Preisegger KH, Simbrunner J, Borkenstein MH. Congenital hypopituitarism and giant cell hepatitis in a three month old girl. Klin Padiatr 2002;214:136-9.
Kesson AM. Management of neonatal herpes simplex virus infection. Paediatr Drugs 2001;3:81-90.
Spivak W, Grand RJ. General configuration of cholestasis in the newborn. J Pediatr Gastroenterol Nutr 1983;2:381-92.
Shah SS, Aronson PL, Mohamad Z, Lorch SA. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics 2011;128:1153-60.
Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L, Gruber WC, et al.
Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics 2001;108:230-8.