Age: 9.0
Sex: F
Vaccine: HEP, HEP
Symptoms: Hepatomegaly, Hepatopulmonary syndrome, Hyperbilirubinaemia, Inappropriate schedule of drug administration, Laboratory test normal
Clinical narrative: This marketed literature report was obtained from a published article and refers a 9-year-old, previously healthy female, who was admitted with 2 weeks of mild, diffuse abdominal pain and 2 days of pronounced scleral icterus. The author reported that she initially presented to an outside institution where she was noted to have marked hepatomegaly. Further examination showed an ill appearing child with a pulse of 144 beats per minute and respiratory rate of 48 breaths per minute. She had a non tender, but distended, abdomen with a firm liver edge palpable 5 cm below the right costal margin. She had non pitting edema in both lower extremities and palmar erythema. Evaluation of her mother's prenatal records revealed that the mother was HBsAg positive during her pregnancy. She was unaware of her diagnosis and denied receiving any further testing or treatment. At the birth hospital, the patient was born full term via Caesarean section due to failure to progress, and was given hepatitis B vaccine (manufacturer unknown) and hepatitis B immune globulin (HBIg) on day 1 of life. She received 3 additional doses of the hepatitis B vaccine (manufacturer unknown) at 3, 5, and 18 months of age. There were no records of an evaluation for hepatitis B infection, including HBsAg and anti-HBs testing after she completed her vaccination series. She was never breastfed. She did not have any other identified risk, either via blood-borne or sexual exposure, for hepatitis B virus infection by history. Laboratory studies during presentation revealed a microcytic anemia (hemoglobin 9.1 g/dL, mean corpuscular volume 76 fL, elevated transarninases (AST 419 U/L, ALT 78 U/L), and hyper bilirubinemia (total bilirubin 5.5 mg/dL). Serum alpha- fetoprotein was markedly elevated at 100 000 ng/mL. Abdominal ultra sound demonstrated a large, right-sided hepatic mass. Contrast-enhanced computed tomography (CT) scan was notable for a nodular liver, a large mixed density mass measuring 15 cm x 12 cm x 18 cm within the right hepatic lobe, multiple smaller hepatic lesions, splenomegaly, and diffuse pulmonary nodules concerning for metastatic disease. The patient underwent open wedge liver biopsy, which revealed a well-differentiated hepatocellular carcinoma (HCC) with active micronodular cirrhosis that was HBsAg positive. Alpha-Fetoprotein immunostaining was positive in the tumor cells. Investigation for an underlying etiology revealed positive serum HBsAg without any detectable hepatitis B surface antibody (anti-HBs). Hepatitis B virus (HBV) DNA was detected in the blood at 100 000 IU/mL and she was hepatitis B envelope antigen (HBeAg) positive. Her HBV genotype was type A with a P 120T surface antigen mutation. Testing was negative for HIV-1, hepatitis C virus, and inherited cholestatic diseases that could predispose her to HCC. The patient rapidly deteriorated post biopsy progressing to multisystem organ failure. She developed respiratory failure requiring endotracheal intubation and had echocardiogram findings consistent with hepato pulmonary syndrome. She developed acute renal failure. Her liver disease decompensated with a total bilirubin increasing to a peak of 16 mg/dL with a predominant direct component, which precluded even palliative treatment of her malignancy. She died on hospital day 16. Final Diagnosis Hepatocellular carcinoma secondary to chronic hepatitis B infection. The authors reported that Mother to child transmission of HBV most often occurs perinatally, but may also occur via transplacental transmission. Vaccine-escape viruses increase the risk of vertical infection, and subsequent complications. In addition to high maternal viral loads, genetic variations in HBV s may facilitate transmission to at risk neonates. These viruses have been described as vaccine escape mutants. Mutations have been identified in the major hydrophilic region of the HBV S protein and have been reported worldwide. The authors reported that the patient developed chronic hepatitis B infection despite receiving adequate immune prophylaxis. This scenario suggests that her virus, with its P120T surface antigen mutation, may have been a vaccine escape mutant. Current guidelines include referring HBsAg-positive pregnant women to specialists for viral load testing, followed by antiviral medication as indicated. Administration of HBIg and hepatitis B vaccination of infants of HBsAg positive mothers should occur ideally within the first 12 hours of life. The infant should receive 3 total doses of the hepatitis B vaccine (4 doses if they weighed <2 kg at the first dose, or if they subsequently receive a combination vaccine) and screening for chronic hepatitis B infection at 9 to 12 months of age with HBsAg and anti-HBs serologies. The optimal timing for serologic testing is 1 to 2 months after completion of the vaccine series in order to avoid detecting HBsAg from the vaccine. In some patients, as in this patient's case, post vaccination serologic testing was not performed. This case clearly demonstrates that serologic testing needs to be a priority, as it was critical for the early diagnosis of chronic hepatitis B infection. Early diagnosis would then trigger periodic screening for complications with laboratory testing of transaminases, a- fetoprotein concentrations, and imaging of the liver, providing opportunities for early intervention. As this case demonstrates, despite the provision of widespread immune prophylaxis and the implementation of screening tools, some neonates remain vulnerable to HBV infection and the significant complications that may follow. Upon internal review the event of Hepatocellular carcinoma secondary to chronic hepatitis B infection was considered to be medically significant. Additional information has been requested.