Wei-Ju Su

High-Titer Antibody to Hepatitis B Surface Antigen Before Liver Transplantation Can Prevent De Novo Hepatitis B Infection

Objective: De novo hepatitis B virus (HBV) infection is defined as infection occurring in HBV surface antigen (HBsAg)–negative patients who become HbsAg positive after organ transplantation. We assessed the incidence and risk factors of de novo HBV infection in pediatric liver transplant recipients. Patients and Methods: From 1996 to 2006, 71 Taiwanese children with non-HBV-related liver diseases underwent orthotopic liver transplantation (OLT) at the National Taiwan University Hospital. All of the surviving recipients were tested regularly for liver function, serum levels of immunosuppressant, HBsAg, titers of antibodies to hepatitis B surface antigen (anti-HBs), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis C virus (anti-HCV). HBV vaccination histories and the anti-HBs titers before OLT were recorded. No regular prophylaxis was given. Results: Fifty-nine patients (33 girls and 26 boys) were followed up for a median of 4.4 years (range 1.0–10.0). Of those, 36 (61.0%) received allografts from anti-HBc-positive and HBsAg-negative donors. De novo HBV infection was found in 9 (15.3%) patients after OLT, 8 of whom received allografts from HBsAg-negative and anti-HBc-positive donors. Forty-eight (81.4%) patients received 3 or more doses of HBV vaccine before OLT. Pre-OLT anti-HBs titers were available for 49 recipients. Of the 9 de novo HBV-infected recipients, 8 had anti-HBs titers <200 mIU/mL. No graft loss or fulminant hepatitis was noted. Conclusions: In the absence of adequate prophylaxis, the incidence of de novo HBV infection in pediatric OLT recipients is 15.3%. An anti-HBs titer of >200 mIU/mL before OLT may be sufficient to prevent de novo HBV infection in HBsAg-negative recipients.

Effect of Age on the Incidence of Acute Hepatitis B After 25 Years of a Universal Newborn Hepatitis B Immunization Program in Taiwan

BACKGROUND Raising concerns about the waning immunity of cohorts receiving hepatitis B virus (HBV) vaccination in infancy persuaded us to identify the changing incidence of acute hepatitis B (AHB) in children and young adults. METHODS Data on AHB surveillance through the National Notifiable Disease Surveillance System from July 2001 to June 2009 were collected and described. Cases were divided into 2 cohorts according to their birth year: before or after the universal newborn HBV vaccination program. Age-specific incidence was compared for the 2 birth cohorts with diagnosis at age 15-24 years. RESULTS In total, 2226 patients with AHB were identified. AHB rates varied by age; the highest rates occurred among unvaccinated individuals aged 25-39 years (2.33/100 000). Due to breakthrough HBV infection from mother-to-infant transmission, vaccinated infants (0.78/100 000) had higher rates than those aged 1-14 years (0.04/100 000), who had the lowest rates. The incidence in vaccinated birth cohorts was significantly lower than in unvaccinated birth cohorts among patients 15-24 years old, with an adjusted-relative risk of 0.42. CONCLUSIONS Implementation of universal-at-birth HBV immunization programs has effectively reduced the occurrence of AHB among adolescents and young adults in Taiwan for >25 years, making infants and the 25-39-year-old cohort additional targets for preventing AHB.

Clinical Course of De Novo Hepatitis B Infection After Pediatric Liver Transplantation

The characteristics of hepatitis B virus (HBV) in vaccinated children who acquire de novo HBV infections after orthotopic liver transplantation (OLT) remain largely unknown. The aim of this study was to explore HBV mutants in pediatric OLT recipients with de novo HBV infections. In all, 50 recipients underwent OLT between December 1997 and October 2005, and they were regularly checked for HBV serum markers from November 2005 to April 2009. Before OLT, all were hepatitis B surface antigen (HBsAg)–negative and under the coverage of the universal infant HBV vaccination program. Those who became HBsAg‐positive after OLT were diagnosed with de novo HBV infection. HBV viral loads and full‐length genome sequencing were determined when the diagnosis of de novo HBV infection was established. Nine patients (9/50, 18%) acquired de novo HBV infections after OLT. None had graft loss or fulminant hepatitis. Five cleared HBsAg, and 4 of the 5 even recovered with antibody to hepatitis B surface antigen (anti‐HBs) formation. The other 4 were persistently HBsAg‐positive. Mutations in the major S gene (681 base pairs) were discovered in 8 (88.9%) of the de novo HBV–infected children. Six of them harbored mutations within the “a” determinant region (codons 124‐147), whereas the other 2 had mutations outside this region. These 2 cleared HBsAg and recovered with anti‐HBs formation. HBV DNA levels were not different between those who cleared HBsAg and those who did not. In conclusion, surface mutants are frequent among pediatric liver transplant recipients with de novo HBV infections, but their clinical relevance requires further study. Liver Transpl 16:215–221, 2010.

Pancreaticobiliary Anomalies is the Leading Cause of Childhood Recurrent Pancreatitis

BACKGROUND/PURPOSE To explore the etiology, age and gender distribution, complications, and prognosis of recurrent pediatric pancreatitis. METHODS Between 1993 and 2005, 92 children were hospitalized at the National Taiwan University Hospital with pancreatitis. Only 25 diagnosed with recurrent pancreatitis, based on two or more episodes of pancreatitis, elevated serum amylase and/or lipase levels > or = 3 times the upper limit of normal, radiographic evidence, and clinical symptoms, were enrolled. RESULTS A total of 85 episodes of pancreatitis in 25 patients (16 girls, 9 boys; mean age, 9.5 +/- 4.4 years; 3.4 +/- 1.9 episodes per person) were documented. The recurrence rate of pediatric pancreatitis was 27.2%. Recurrent pancreatitis was associated with pancreaticobiliary structural anomalies (n = 7), biliary stones or sludge (n = 4), hyperlipidemia (n = 3), pseudopapillary tumor of the pancreas (n = 2), trauma (n = 2), hypoxic encephalopathy with recurrent bacteremia and sepsis (n = 1), and idiopathic (n = 6). The age and gender distribution according to etiologies were not different (p = 0.301 for age, p = 0.137 for gender). Complications included cholangitis or cholestasis (16%), pancreatic necrosis (16%), pseudocyst formation (12%), shock (8%), hemorrhagic pancreatitis (4%), and diabetes mellitus (4%). No patient died of recurrent pancreatitis. Long-term morbidity after recurrent pancreatitis presented as gout, diabetes mellitus, non-alcoholic steatohepatitis, and chronic pancreatitis. CONCLUSION For children who suffer from recurrent pancreatitis, pancreaticobiliary structural anomalies should be considered first.

Low Seroprevalence of Parvovirus B19 in Taiwanese Children and Young Adults

BACKGROUND This study aimed to evaluate the prevalence of parvovirus B19 antibodies in children and young adults aged=30 years old in Taiwan. METHODS Stored serum samples from healthy volunteers aged 1-29 years in Taipei were randomly selected and tested for antiparvovirus B19 immunoglobulin G by enzyme immunoassay. RESULTS A total of 277 serum samples were tested. The overall seroprevalence of parvovirus B19 in Taiwanese children and young adults was 23.1% (64/277) in 2004. The positive rate increased slightly with age; it ranged from 15.0% in those aged 1-4 years to 30.8% in those aged 25-29 years (trend test, p=0.01). The age-adjusted anti-B19 immunoglobulin G seropositive rate was slightly higher in males (27.8%) than in females (18.8%; adjusted odds ratio: 0.56; 95% confidence interval: 0.32-0.99). CONCLUSION Most children and young adults in Taipei City are not immune to parvovirus B19, suggesting that no parvovirus B19 epidemic has occurred in the last few decades.

Breakthrough Hepatitis B Virus (HBV) Infection From Mother-to-Infant Transmission Is the Key Problem Hindering HBV Eradication

TO THE EDITOR—We greatly appreciate the editorial commentary by Schwarz [1], which provided a comprehensive overview of the impact of our study on the universal hepatitis B virus (HBV) vaccination program in Taiwan [2]. It was pointed out that the 8 infants who were born to mothers positive for HBV e antigen (HBeAg) and some of the infants born to HBeAg-negative mothers developed acute HBV infection in the first year of life. We would like to clarify the details about these infants who developed acute hepatitis B in infancy. As shown in Supplementary Table 2 in our article [2], 13 infants with acute hepatitis B, also known as perinatal HBV infection, included 5 who were born to HBeAg-positive mothers and received HBV immunoglobulin (HBIG); 3 who were born to HBV-carrying mothers with an unknown HBeAg status, of whom 1received HBIG; and 5 who were born to HBV-carrying, HBeAg-negative mothers and did not receive HBIG. According to Taiwan’s HBV immunization policy, HBIG was given to infants of HBeAg-positive mothers within 24 hours after birth, in addition to 3 doses of HBV vaccine at 0, 1, and 6 months. Among mothers who were HBeAg negative but HBV surface antigen (HBsAg) positive or who did not adhere to instructions to undergo screening for serum HBsAg and HBeAg, HBIG was not given to their infants, and only 3 doses of HBV vaccine were given. The need to change current Taiwan HBIG policy to prevent breakthrough perinatal HBV infection remains under debate. Chen et al found that, among children who were born to HBeAg-negative mothers and received HBIG versus those who were born to HBeAg-negative mothers and did not received HBIG, the rate of chronic HBV infection did not differ (0.14% vs 0.29%; P = .65) [3]. Similar rates of antibodies against HBV core protein (0.99% vs 1.88%; P = .19) were noted among children who were born to HBeAg-negative mothers and did or did not receive HBIG [3]. This suggests that adding HBIG cannot significantly reduce the total infection (ie, acute and chronic infection) rate. On the other hand, a high rate (9.26%) among children born to HBeAg-positive mothers who received full coverage by HBIG and HBV vaccine were HBsAg positive. The data indicated that HBIG plus HBV vaccination could not completely prevent mother-to-infant HBV transmission. It is also known that infants born to HBeAgnegative, HBsAg-positive mothers were prone to develop fulminant hepatitis, although overall infection rates were low [3, 4]. The studies mentioned above may also pertain to the infants with perinatal HBV infection in our study [2], who might become chronically infected with HBV even though HBIG was given to them regardless of their mothers’ HBeAg status, although the chance of chronic infection is very small. The cost-effectiveness of giving HBIG to HBeAg-negative, HBsAgpositive mothers requires further confirmation. More clinical information about and follow-up of vaccinated subjects born to high-risk mothers are needed to delineate this important issue and to develop strategies to eradicate HBV infection.