Hepatoblastoma

GBD 2019 estimated each epidemiological quantity of interest—incidence, prevalence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs)—for 23 age groups; males, females, and both sexes combined; and 204 countries and territories that were grouped into 21 regions and seven super-regions. For GBD 2019, nine countries and territories (Cook Islands, Monaco, San Marino, Nauru, Niue, Palau, Saint Kitts and Nevis, Tokelau, and Tuvalu) were added, such that the GBD location hierarchy now includes all WHO member states. GBD 2019 includes subnational analyses for Italy, Nigeria, Pakistan, the Philippines, and Poland, and 16 countries previously estimated at subnational levels (Brazil, China, Ethiopia, India, Indonesia, Iran, Japan, Kenya, Mexico, New Zealand, Norway, Russia, South Africa, Sweden, the UK, and the USA). All subnational analyses are at the first level of administrative organisation within each country except for New Zealand (by Māori ethnicity), Sweden (by Stockholm and non-Stockholm), the UK (by local government authorities), and the Philippines (by province). In this publication, we present subnational estimates for Brazil, India, Indonesia, Japan, Kenya, Mexico, Sweden, the UK, and the USA; given space constraints, these results are presented in appendix 2. At the most detailed spatial resolution, we generated estimates for 990 locations. The GBD diseases and injuries analytical framework generated estimates for every year from 1990 to 2019.
Diseases and injuries were organised into a levelled cause hierarchy from the three broadest causes of death and disability at Level 1 to the most specific causes at Level 4. Within the three Level 1 causes—communicable, maternal, neonatal, and nutritional diseases; non-communicable diseases; and injuries—there are 22 Level 2 causes, 174 Level 3 causes, and 301 Level 4 causes (including 131 Level 3 causes that are not further disaggregated at Level 4; see appendix 1 sections 3.4 and 4.12 for the full list of causes). 364 total causes are non-fatal and 286 are fatal. For GBD 2019, 12 new causes were added to the modelling framework: pulmonary arterial hypertension, eye cancer, soft tissue and other extraosseous sarcomas, malignant neoplasm of bone and articular cartilage, and neuroblastoma and other peripheral nervous cell tumours at Level 3, and hepatoblastoma, Burkitt lymphoma, other non-Hodgkin lymphoma, retinoblastoma, other eye cancers, and two sites of osteoarthritis (hand and other joints) at Level 4.

Vero (African Green Monkey kidney cells), SW480 (Human colon adenocarcinoma), and HepG2 (Human hepatoblastoma) cells were obtained from American Type Culture Collection (Manassas, VA). A549 (Human lung adenocarcinoma) cells were provided by W. Kallas (Massachusetts General Hospital, Boston, MA). E5 cells are Vero cells stably transfected with HSV ICP4, so they express complementing levels of wild type ICP4 upon HSV-1 infection and were provided by N. DeLuca (University of Pittsburgh School of Medicine, Pittsburgh, PA) [22 (link)]. Vero and E5 cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% calf serum and other cell lines in DMEM supplemented with 10% fetal calf serum. Wild-type HSV-1 strain KOS was provided by D. Knipe (Harvard Medical School, Boston, MA), ICP6- recombinant hrR3 (parental strain KOS) was provided by S. Weller (University of Connecticut Health Center, Farmington, CT) [47 (link)], and ICP4 deletion mutant d120 (parental strain KOS) was provided by N. DeLuca [22 (link)]. Virus stocks were generated from low-multiplicity infections.

Diagnosis groups are described in Table 1; they represent the top 5 indications for pediatric liver transplantation based on data from 2006 to 2016. These groups, in descending order of frequency, are as follows: biliary atresia, acute hepatic necrosis (AHN), metabolic disorders, hepatoblastoma, and autoimmune cirrhosis. Biliary atresia served as the reference group. Different variations of the same general diagnosis category were grouped together; for example, patients listed with alpha-1-antitrypsin deficiency would be placed in the same indication category (metabolic disorders) as patients listed with Wilson's disease.

We included cases of hepatoblastoma identified in the Texas Cancer Registry (TCR) diagnosed at 0–19 years of age for the period 1995–2018. The TCR is one of the largest and most diverse population-based cancer registries with Gold Certification from the North American Association of Central Cancer Registries. We used the International Classification of Disease for Oncology, Third Edition (ICD-O-3) and included cases with a histology code of 8970, as defined by the International Classification of Childhood Cancer, Third Edition (ICCC-3) site group VII for hepatoblastoma. A total of 309 hepatoblastoma cases who fulfilled these criteria were identified in the TCR.
Hepatoblastoma cases were further categorized as localized vs. metastatic using the SEER summary stage variable from the TCR. Variables of interest obtained from the TCR included patient age at diagnosis (infancy defined as age < 1 year), biological sex, and race/ethnicity. We also obtained information on: (1) county of residence at the time of diagnosis; (2) rural vs. urban residence; and (3) residence along the Texas-Mexico Border.

Descriptive statistics were evaluated for hepatoblastoma overall, as well as metastatic hepatoblastoma. We calculated incidence ratios for the entire population over the study period overall and by the following characteristics: infancy, biological sex, race/ethnicity, urban-rural residence, and residence along the Texas-Mexico border. Incidence ratios were age standardized and were calculated per million persons-years using the at-risk population present. To assess trends in hepatoblastoma incidence over time, joinpoint regression was used to calculate annual percent change (APC) in incidence, overall and by ethnicity. To assess factors associated with hepatoblastoma overall and metastatic hepatoblastoma, both crude incidence rate ratios (IRRs) and adjusted IRRs (aIRRs), as well as corresponding 95% confidence intervals (CIs), were estimated using Poisson regression. Joinpoint regresson analyses were conducted using the National Cancer Institute's Joinpoint Regression Program version 4.9.1.0 (9 ). All other analyses were conducted using Stata Version 15 (College Station, TX).