Is primary hepatic angiosarcoma in children an indication for liver transplantation?-A single-centre experience and review of the literature.

PHA in the paediatric population is an extremely rare and aggressive malignant soft tissue neoplasm, with less than 50 cases published worldwide. The prognosis is dismal. If the tumour is unresectable, one treatment option is LT. In this article, the current available literature is reviewed and additionally, three cases of paediatric patients with PHA who underwent LT at Karolinska University Hospital, Sweden, are presented. Based on the literature and our own experience, there is undoubtedly possible good outcome of LT due to PHA. On the contrary, no patients have survived PHA without LT. PHA in paediatric patients should be recommended to LT in selected patients. Effect of modern adjuvant chemo and RT should be evaluated further based on international registry for such rare cases of PHA.

Prevalence of chronic hepatitis C virus infection among childhood cancer survivors in Stockholm, Sweden.

Background: Childhood cancer survivors treated before 1992, when blood donor screening for hepatitis C virus (HCV) infection was introduced, are at risk of transfusion-transmitted HCV infection. A national HCV screening campaign targeting blood transfusion recipients was launched in Sweden in 2007-2010. The aims of this study were to, among adult childhood cancer survivors in Stockholm County, investigate the prevalence of HCV infection, the natural course of infection, treatment outcome and anti-HCV testing frequency before, during and after the screening campaign and finally to actively screen the untested ones. Material and Methods: This was a combined retrospective register based and prospective screening study of adult childhood cancer survivors (n = 686) treated for malignancy in Stockholm before 1992. In the first part, we investigated the prevalence of HCV infection and previous anti-HCV testing, and in the second part, we actively traced and HCV-screened the remaining untested cohort living in Stockholm. Analysis of previous documented anti-HCV tests in medical records, laboratory records, and the national communicable disease registry was performed. In the second part, 231 presumably untested individuals were contacted by mail and offered an anti-HCV test. The natural course of HCV infection and treatment outcome was analyzed for those found to be chronically infected. Results: In total, 235 patients were tested and 11 were HCV-RNA positive. The overall prevalence of chronic HCV infection among the tested childhood cancer survivors was thus 4.7% (95% CI = 2.6-8.2%), which is almost 10 times higher than the national prevalence of 0.5%. Only 12% of the Stockholm cohort were tested during the screening campaign in 2007-2010, while the test uptake using active tracing screening within this study was 40% (p < .001). Conclusion: With today's effective treatment options, active tracing and HCV screening of childhood cancer survivors are recommended.

Prevalence and outcome of post-transfusion hepatitis C acquired at different ages and detected in look-back screening.

OBJECTIVES: The prevalence of hepatitis C virus (HCV) infection in Sweden is estimated to 0.5%. Before 1992, blood transfusion posed a risk of HCV transmission. The primary aim of this study was to estimate anti-HCV prevalence in Stockholm County among individuals receiving blood transfusions 1965-1991. The secondary aim was to study the effect of age at transfusion on the development of liver disease and treatment outcome. MATERIALS AND METHODS: This is a retrospective analysis of individuals found to be anti-HCV tested positive in Stockholm County during a national screening campaign in Sweden 2008-2010. All anti-HCV-positive individuals were also HCV RNA tested. Data on age at transfusion, age at diagnosis, HCV genotype, viral load, fibrosis score, liver histology and antiviral treatment were recorded. RESULTS: Out of 7473, 134 (1.8%) tested individuals were anti-HCV positive and 102 were HCV RNA positive resulting in a prevalence of chronic hepatitis C (CHC) of 1.4%. The rate of advanced liver damage was 18% (10/56). Patients younger than 19 years of age at transfusion were significantly more often started on antiviral treatment compared to adult patients, 65% vs 29% p < .001. No significant correlation was found between treatment outcome and gender or age at transfusion. CONCLUSIONS: In this study, we found an anti-HCV prevalence of 1.8% which is considerably higher than the estimated prevalence in the Swedish general population (0.5%), and patients infected during childhood were more likely to receive antiviral treatment. Additional data on the HCV epidemic in Sweden are needed regarding prevalence and age distribution.

Neonatal Exposure to Hepatitis C Virus Antigens in Uninfected Children Born to Infected Mothers.

OBJECTIVE: Vertical transmission of hepatitis C virus (HCV) infection is uncommon and occurs in approximately 5% of births from HCV-infected mothers. The reason for the low transmission rate is unclear. We aimed to investigate whether there is evidence of HCV exposure also in the noninfected children born to HCV-infected mothers by the presence of a detectable immune response. METHODS: Serum and peripheral blood mononuclear cells from 9 HCV vertically infected children, 32 uninfected children born to HCV infected mothers, and 15 HCV chronically infected mothers, were analyzed. HCV-RNA-negative adults and children were used as controls. HCV-specific T cell responses were analyzed by interferon gamma using an enzyme-linked immunospot assay and 3H-thymidine incorporation assay. HCV antibodies were also analyzed. RESULTS: An HCV-specific T cell response was detected in 73% (11/15) of the HCV-infected mothers, 67% (6/9) of the vertically infected children, 56% (18/32) of the exposed but uninfected children and in 10% and 20% of the control groups, respectively. The 2 groups of HCV-exposed children both had a significantly higher proportion of HCV-specific T cell responders compared to pediatric controls (P = 0.01 and P = 0.02). CONCLUSIONS: HCV-specific immune responses were more common in children born to HCV-infected mothers, regardless of the presence of HCV RNA. We conclude that noninfected children born to HCV-infected mothers may have been exposed to HCV antigens.

Lack of Association Between Interleukin 28B Polymorphism and Vertical Transmission of Hepatitis C.

OBJECTIVES: Single genetic nucleotide polymorphism (rs12979860) near the gene for interleukin 28B (IL28B) is known to be of importance for frequency of spontaneous clearance and treatment outcome in interferon-based therapies in patients with hepatitis C virus (HCV) infection. The aim of the present study was to investigate whether IL28B polymorphism in children and/or their mothers plays a role in vertical transmission of HCV (HCV-VT). METHODS: Plasma samples from 59 infected women, 76 uninfected children born to infected mothers, and 47 children with known vertically transmitted HCV infection, were analysed for IL28B polymorphism and classified by the IL28B genotype (C/C, C/T, and T/T) and by viral genotype. RESULTS: The proportion of children with genotype C/C was the same in the vertically infected (36%, 17/47) and the exposed uninfected children (38%, 29/76). No difference was seen when stratifying for viral genotype. There was no association between mothers' IL28B genotype and the risk of vertical transmission. CONCLUSIONS: Regardless of viral genotype we found no association between IL28B genotype and the risk of HCV-VT. The IL28B genotype CC, which has been shown to be favourable in other settings, was not protective of HCV-VT. Thus, other factors possibly associated with the risk of HCV-VT need to be explored.

Considerable differences in management of cytomegalovirus infection in patients with biliary atresia.

Objectives: Patients with biliary atresia (BA) and ongoing cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy than uninfected patients. Still, there is no consensus on the usefulness of viral testing and antiviral treatment (AVT). This study aims to explore the need for future research on AVT for CMV infection by assessing how CMV infection in BA patients is managed in different centers. Methods: An online questionnaire with 10 questions was offered to participants at an international congress on BA, organized in collaboration with the European Reference Network for rare liver diseases in 2022. Answers to questions were either dichotomic or multiple choices of different numeric intervals. Ongoing CMV infection was defined by detecting cytomegalovirus-immunoglobulin M (CMV-IgM) in serum or cytomegalovirus-deoxyribonucleic acid (CMV-DNA) by polymerase chain reaction in blood or urine. Results: There were 43 respondents from 36 centers in 26 countries. The total number of BA patients per year was between 208 and 380 from centers with 0-5 to >20 BA patients yearly (median 6-10). CMV infection was tested in 27 centers (75%), of which 18 (67%) use AVT. The rate of CMV infection varied between 0%-5% and 40%-50% (median 5%-10%). Willingness to treat the infection did not differ between centers with low and high rates of CMV infection. Conclusions: Most centers test for CMV infection, and a considerable proportion use AVT despite the lack of evidence of its benefits. A future randomized study on treating CMV infection in BA patients is necessary and feasible.

Anti-HCV prevalence and risk factor-based screening for hepatitis C in pregnant women and their partners in Sweden.

BACKGROUND: The hepatitis C virus (HCV) prevalence in Sweden is estimated to be <0.5%, but unclear in pregnant women. The dominating route of transmission is drug use (DU), blood transfusions constituted a risk before 1992. The aim was to examine the anti-HCV prevalence and risk factors for HCV among pregnant women and their partners to evaluate screening strategies. METHODS: Pregnant women and partners in Örebro County and in southern Stockholm were offered HCV-screening when visiting an antenatal clinic in 2013-2016, and completed a questionnaire concerning the country of birth, knowledge of HCV-status and HCV risk factors. RESULTS: In Örebro 2,827 pregnant women and 707 partners, and in Stockholm 1,281 pregnant women and 320 partners participated. Anti-HCV was positive in 34 (0.7%) (25 pregnant women) and the associated risk factors were DU (n = 27), partner with HCV (n = 24) and not born in Sweden (n = 8). HCV RNA was positive in 23 (0.4%), 4 previously unknown and 10 who had been lost to follow-up. The most effective risk factor-based screening model for pregnant women included DU, blood transfusions, born in high prevalence country, partner with HCV, resulting in 538 (13%) pregnant women tested with 96% sensitivity, 87% specificity. CONCLUSIONS: In this study of expecting parents in two Swedish regions, the anti-HCV prevalence was 0.7% and 0.4% were viraemic, of which about 60% were previously unknown or lost to follow-up. Awaiting more studies, including cost-benefit analysis evaluating universal screening, we recommend this improved risk factor-based screening model to identify HCV-infected individuals who need follow-up and therapy.