The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)-and hepatitis B e antigen-positive pregnant women with HBV DNA 7.5 log 10 IU/mL. The mothers received no medication (control group, n 5 56, HBV DNA 8.22 6 0.39 log 10 IU/mL) or TDF 300 mg daily (TDF group, n 5 62, HBV DNA 8.18 6 0.47 log 10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 6 0.93 versus 8.10 6 0.56 log 10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P 5 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P 5 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio 5 0.10, P 5 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P 5 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for 3 months (3.23% versus 14.29%, P 5 0.0455), a lesser extent of postpartum elevations of ALT (P 5 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P 5 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (HEPATOLOGY 2015;62:375-386) D espite the 75%-90% reduction of chronic hepatitis B viral (HBV) infection following universal infant immunization, active/passive immunoprophylaxis has not eradicated mother-toinfant HBV transmission. [1][2][3][4] Approximately 10% of chronic HBV infections cannot be prevented.5-7 The major risks of chronic HBV infection in the immunization era are maternal hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positivity and high maternal viral load.5-9 Moreover, after immunoprophylaxis, children with HBV infection have a higher risk of developing hepatocellular carcinoma. 10,11 To achieve the goal of global eradication of HBV infection, better strategies aimed at interrupting Abbreviations: ALT, alanine aminotransferase; anti-HBs, antibody to hepatitis B surface antigen; D0, day 0, initiation of TDF treatment (baseline); D1M, 1 month after TDF treatment; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; P0, at partum; PXM, X months postpartum; SNR, signal-to-noise ratio; TDF, tenofov...

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Universal vaccination significantly decreased the HBV carrier rate and infection rate among children and adolescents born since the program began. By decreasing the carrier pool, continuation of the national HBV immunization program should prevent HBV infection in the children of Taiwan, and, subsequently, adults as well.

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To assess the contribution of hepatitis C virus (HCV) in liver disease in Taiwan, antibody to HCV (anti-HCV) was studied by radioimmunoassay in 392 patients with chronic liver disease and in 440 healthy adults and 444 subjects at risk. The anti-HCV prevalence was 0.95% in 420 volunteer blood donors, 90% in 100 hemophiliacs, and 81% in 58 parenteral drug abusers. Anti-HCV was present in 6 (7.7%) of 78 hepatitis B surface antigen (HBsAg)-positive and 28 (65%) of 43 HBsAg-negative patients with chronic hepatitis, 3 (10%) of 31 HBsAg-positive and 13 (43%) of 30 HBsAg-negative cirrhotics, and 7 (17%) of 42 HBsAg-positive and 15 (63%) of 24 HBsAg-negative patients with hepatocellular carcinoma (HCC). An outbreak of non-A, non-B hepatitis revealed 18% of 57 patients to be positive for anti-HCV, and in 29 patients with posttransfusion hepatitis prospectively followed, 7 (24%) developed anti-HCV. Thus, HCV infection appears to play a relatively minor role in HBsAg-positive liver disease in Taiwan but is strongly associated with HBsAg-negative chronic liver disease and HCC. The infection is extremely common in hemophiliacs and parenteral drug abusers.

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Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have now transformed treatment for HCV infection. Since the launch in 2016 of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on treatment of adults, who bear the greatest burden of morbidity and mortality of HCV related chronic liver disease. There has been much less attention paid to addressing response to HCV in children and adolescents, in part because of the lack of data to inform specific paediatric management practices and policy. In this review, we summarize current knowledge on epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden in children aged 1 to 19 years is 0•15% and 3•5 (3•1-3•9) million, respectively. HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir, ledipasvir and ribavirin have now received regulatory approval and guidelines recommend their use in adolescents ages >12 years with HCV infection. Key actions to address the current policy gaps and achieve treatment scale-up comparable to that in adults include: establishment of a testing and treatment access campaign targeted at children and adolescents; fast-track evaluation of pangenotypic regimens and accelerated approval of paediatric formulations. Research gaps that need to be addressed include age-specific seroprevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agenda.

Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease and associated morbidity and mortality worldwide. Vertical and early childhood transmission are the main routes of HBV transmission globally, responsible for most chronic infectionsincluding in adults who bear the greatest burden of morbidity and mortality. Universal infant and birth dose hepatitis B immunization is the key preventative strategy for global elimination of HBV infection, and has been highly effective in reducing new vertical infections. Global progress on HBV testing and treatment, however, has been slow in adults and children. In this review, we summarize current knowledge on epidemiology, natural history, and treatment of chronic HBV infection in adolescents and children, highlighting key differences from the experience with adults, and conclude with key actions to address current policy gaps. The estimated global prevalence in children aged 5 years or less is 1.3%. Most children are in the "high replication, low level of inflammation" infection phase with normal or only minimally raised aminotransferases; cirrhosis and hepatocellular carcinoma are rare. Although entecavir is approved and recommended for children 2 to <18 years, and tenofovir for those 12 to < 18 years, a conservative approach to treatment initiation is currently recommended. Key actions to address current policy gaps include: validation of non-invasive tests for liver disease staging; additional immunopathogenesis studies in HBV infected children, and long-term follow-up of children on nucleoside analogue regimens to inform guidance on when to start treatment; evaluation of different treatment strategies for children with high levels of replication; and establishment of paediatric treatment registries and international consortia to promote collaborative research.