Title: Excellent outcomes in children after haematopoietic stem cell transplantation for hepatitis-associated aplastic anaemia following liver transplantation  

Source: British Journal of Haematology 2026, Jan 12. [E–publication]

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Date of publication: January 2026

Publication type: Article  

Abstract: Hepatitis-associated aplastic anaemia is a rare entity that can sometimes be life-threatening due to its rapid progression to liver failure, necessitating an urgent liver transplantation (LT). Treating severe aplastic anaemia following an LT can be very challenging. While immunosuppressive therapy (IST) has been reported to have some success, the vulnerable state of these patients in addition to the time taken for IST to work makes this a less suitable option for the majority of patients. Haematopoietic stem cell transplantation (HSCT) with matched related donors has been reported as a curative option; there has been less success using alternate donors. Here, we present our experience of predominantly alternate donor HSCT following liver transplantation in an extremely high-risk group of 10 children. Overall survival was 90% at a median of 38 months post-LT. Surviving children have normal blood counts, normal liver function and performance status. No liver-related complications or significant graft versus host disease were encountered. Multiple infective and non-infective post-HSCT complications were successfully treated with excellent multidisciplinary input. Upfront HSCT, even with alternate donors, can be lifesaving if performed in a timely manner, following close liaison between liver transplantation and HSCT teams and with the appropriate multidisciplinary support.

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Title: A vaccine emergency – when to overrule parental refusal of vaccination at birth for prevention of vertical transmission of hepatitis B virus?

Source: Archives of Disease in Childhood 2025, Sep 8. [E–publication]

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Date of publication: September 2025  

Publication type: Review article

Abstract: Hepatitis B virus (HBV) is a potentially chronic infection that can be transmitted from mother to child with the risk of developing cirrhosis, liver failure and hepatocellular carcinoma. There is a safe and effective vaccine to prevent vertical transmission that is recommended to be given as soon as possible after birth and within 24 hours. When a woman with HBV refuses the birth dose of HBV vaccine for her baby, infectious diseases and safeguarding teams are asked to provide urgent opinions on whether this crosses the threshold for triggering child protection mechanisms. We consider a low-infectivity HBV vertical transmission scenario where there is parental refusal of HBV vaccination and focus on ethical arguments for and against overruling parental refusal in the child’s best interests. As an additional resource for clinical and safeguarding teams, we also include the anonymised transcript of the only available UK court judgement to our knowledge that addresses the issue of decline of HBV vaccine to prevent vertical transmission. We propose a dialogue process for managing scenarios where a pregnant woman with HBV has concerns about vaccinating her baby when born, which is the basis of the current UK Health Security Agency guidance.

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Title: Severe hepatitis in pediatric patients: The Severe Hepatitis In Pediatric Patients (SHIPP) registry

Source: Journal of Pediatric Gastroenterology and Nutrition 2025, May 19. [E–publication]

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Date of publication: May 2025 

Publication type: Article 

Abstract: Objectives: Clusters of severe acute hepatitis in children were reported worldwide beginning in October 2021. Although most children recovered, some progressed to liver failure leading to death or liver transplantation. Herein, we characterize the clinical characteristics, and outcomes of this group of children through an international collaborative effort.

Methods: Participation was solicited via a global listserv to pediatric gastroenterologists worldwide. Patients <18 years, alanine aminotransferase >500 U/L, without chronic liver disease or acetaminophen ingestion were eligible. Data were submitted by individual sites into a Research Electronic Data Capture registry created in July 2022.

Results: Two hundred and seven cases were collected, with a peak incidence of 28 in April 2022. The median age was 40 months, 52.7% were male, 63.3% were white, and 44% were Hispanic. At presentation, 80% reported gastrointestinal symptoms followed by fever (27.7%). The median duration of hospitalization was 5.5 days with 51 patients requiring intensive care. Adenovirus serum/whole blood DNA was detected in 28/133 (21%) and seven patients were treated with cidofovir. Liver biopsies, performed in 76 patients revealed portal and lobular inflammation with none identifying a viral etiology. Eleven patients underwent liver transplantation, four were adenovirus positive, all of whom survived. There were four reported deaths.

Conclusions: In this large data set of pediatric patients with severe acute hepatitis, the majority did not have a singular definitive etiology but did recover spontaneously. Continued community surveillance and close cooperation are critical toward understanding the etiology of such clusters in pediatrics.

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Title: Characteristic immune cell interactions in livers of children with acute hepatitis revealed by spatial single-cell analysis identify a possible postacute sequel of COVID-19

Source: Gut 2025, Apr 5. [E–publication]

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Date of publication: April 2025  

Publication type: Article 

Abstract: Background: A rise in paediatric cases of acute hepatitis of unknown origin (AHUO) was observed in 2022, some requiring liver transplantation. A link to adeno-associated virus 2 infection and CD4⁺T-cell mediated disease was reported in cohorts in the UK and USA but does not explain all cases.

Objective: To determine the intrahepatic immune cell interactions in the inflamed liver and a possible contribution of SARS-CoV-2 infection.

Design: Patients with acute non-A non-E hepatitis (10/12 AHUO, 2/12 subacute) during February 2022-December 2022 undergoing liver biopsy were recruited in a European patient cohort. Hepatological, virological, histopathological and highly multiplexed spatial and single-cell analyses of liver biopsies were performed.

Results: Patients were negative for adenoviral and SARS-CoV-2 PCR. Three patients had a positive adenoviral serology and 10/12 patients had a history or serological evidence of SARS-CoV-2 infection. Imaging mass cytometry identified significant intrahepatic immune infiltration with an enrichment of CD8⁺T-cells. The highest CD8 infiltration and concomitant peripheral immune activation were observed in patients with the most severe hepatitis. CD8⁺T-cell infiltration was connected to histomorphological interface hepatitis and bridging necrosis. Cellular neighbourhood analysis indicated disease-associated microanatomic interactions between CX3CR1⁺ endothelial and myeloid cell populations, interacting with effector CD8⁺T-cells suggesting a pathogenic cellular triad. Of note, we detected intrahepatic SARS-CoV-2 antigens in ACE2-expressing cells in the areas with significant pathology in 11/12 samples using several different detection methods. 10/12 patients were treated with corticosteroid therapy and no liver transplantation was required.

Conclusions: We identified a possible manifestation of an immune-mediated postacute sequel to COVID-19 associated with a characteristic immune infiltrate in children with AHUO. COVID-19 testing should be considered in paediatric AHUO.

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Title: Granulocyte transfusions for invasive fungal infections refractory to conventional treatment in pediatric liver transplant recipients with hepatitis-associated aplastic anemia

Source: Pediatric Transplantation 2025, 29 (3): e70061

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Date of publication: March 2025  

Publication type: Case report 

Abstract: Background: Invasive fungal infections (IFI) remain a leading cause of mortality in liver transplant (LTX) patients with neutropenia. Hematopoietic growth factors and granulocyte transfusions (GTx) have been historically used in patients with neutropenia and after hematopoietic stem cell transplantation (HSCT) to treat IFI, but none thus far, in pediatric liver transplant recipients (PLTR).

Methods: We evaluated the safety and effect of GTx for life-threatening IFI, refractory to conventional antifungal treatment, in PLTR with hepatitis-associated aplastic anemia (HAAA) at King’s College Hospital, London. We also conducted a literature review of GTX use in neutropenic pediatric patients with IFI.

Results: Two PLTR with HAAA, Case 1, 9-year-old male and Case 2, 6-year-old male received 6 weeks and 3 weeks of GTx. Both presented with acute liver failure requiring urgent LTX, complicated by bone marrow failure due to HAAA, multiple bacterial infections, and IFI. Case 1 developed invasive pulmonary aspergillosis (IPA), intra-abdominal (IAB) and bloodstream infection (BSI) with Candida guilliermondii and Candida fermentati whilst on four antifungals. Case 2 developed a necrotizing lesion on his arm, confirmed as mucormycosis, and had a BSI with Candida albicans and Candida glabrata whilst on two antifungals. Irradiated ABO group-compatible GTX was used as a bridge to control systemic dissemination of IFI. This provided some control in extremis until definitive treatment and improvement in neutrophil count by HSCT.

Conclusion: These are the first two cases to report the use of GTx in PLTR with bone marrow failure due to HAAA. Both patients tolerated GTx without side effects. We propose the consideration of GTx as adjunctive therapy for life-threatening IFI refractory to conventional antifungals in PLTR with severe neutropenia.

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Title: Update on pediatric hepatitis C infection

Source: Current Gastroenterology Reports 2025, 27 (1): 18  

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Date of publication: February 2025  

Publication type: Review article

Abstract: Purpose of review: Hepatitis C virus (HCV) infections continue to steadily increase in the United States and remain a major public health challenge. This review aims to provide a comprehensive overview of HCV infection in children, focusing on recent advancements in screening, diagnosis, and treatment.

Recent findings: Effective screening strategies, including universal screening of pregnant women and nucleic acid testing for all perinatally exposed infants at 2 to 6 months of age, have been implemented to identify infected individuals early. Direct-acting antiviral agents have revolutionized treatment, offering high cure rates for children of all ages. Despite significant progress, challenges remain in achieving HCV elimination. These include the need for improved access to testing and treatment, as well as ongoing efforts to develop a preventive vaccine. Continued research and implementation of effective strategies are essential to reduce the burden of HCV infection.

Summary: Despite significant progress, challenges remain in achieving HCV elimination. These include the need for improved access to testing and treatment, as well as ongoing efforts to develop a preventive vaccine. Continued research and implementation of effective strategies are essential to reduce the burden of HCV infection.

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Title: Epidemiology and outcomes of alcohol-associated hepatitis in adolescents and young adults

Source: JAMA Network Open 2024, 7 (12): e2452459

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Date of publication: December 2024

Publication type: Retrospective cohort study

Abstract: Importance: Alcohol-associated hepatitis (AH) has high mortality, and rates are increasing among adolescents and young adults (AYAs).

Objective: To define the sex-specific epidemiology of AH in AYAs and the association between female sex and liver-related outcomes after a first presentation of AH.

Design, setting, and participants: A retrospective, population-based cohort study of routinely collected health care data held at ICES from Ontario, Canada, was conducted. Data on AYAs (age, 13-39 years) with first presentation of AH without a history of cirrhosis and/or decompensation from January 1 to December 31, 2022, were included in the analysis.

Exposures: Study year and female sex.

Main outcome and measures: Overall and sex-specific yearly rates of AH were compared using Poisson regression and rate ratios (RRs). Associations between female sex and incident cirrhosis and/or decompensation were evaluated using competing risks regression, and liver-related mortality by sex was evaluated with cumulative incidence functions.

Results: A total of 3340 AYAs with AH were identified. Median age was 33 (IQR, 28-36) years, and the population included 1190 (36%) females and 2150 (64%) males. Rates of AH increased by 8% per year (RR, 1.08; 95% CI, 1.07-1.09), with yearly rates increasing faster among females (RR, 1.11; 95% CI, 1.09-1.12) than males (RR, 1.07; 95% CI, 1.06-1.07). A total of 2374 individuals (71%) were alive without cirrhosis 6 months after AH presentation. Of those, 527 (22%) developed incident cirrhosis and/or decompensation after a median follow-up of 4 (IQR, 2-9) years (37% females vs 29% males; P < .001). After adjustment, female sex was associated with a 47% higher subhazard of cirrhosis and/or decompensation compared with male sex (38%) (subhazard, 1.47; 95% CI, 1.23-1.76; P < .001). The cumulative incidence of liver-related mortality at 10 years was higher among females (11.0%; 95% CI, 8.3%-14.2%) than males (6.9%; 95% CI, 5.4%-8.6%) (P = .01).

Conclusions and relevance: Over the past 2 decades, the rates of AH among AYAs increased significantly, with the greatest increase observed among females. The findings of this study suggest sex-specific interventions to prevent the development of AH and the progression to cirrhosis after an episode of AH are needed.

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Title: Patient source of referral is a key determinant of subsequent retention in care for young chronic hepatitis B patients

Source: Journal of Viral Hepatitis 2025, 3 (2): e14059 

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Date of publication: February 2025

Publication type: Article

Abstract: Hepatitis B elimination objectives can only be realised if new patient linkage to care is matched by long-term patient retention in care. We previously showed in adult chronic hepatitis B (CHB) patients that retention in care was inferior in younger patients and in patients from non-Asian ethnicities. The present study explores further the rates and determinants of loss to follow-up in a cohort of 271 young patients (aged 16-21 years at baseline). 16% of patients were lost to follow-up after a single consultation, and retention in care at 5 and 10 years was 53.7% and 45.9%, respectively. Retention in care was strongly associated with the source of patient referral and was superior for patients referred from the antenatal clinic and those transitioned from paediatric care (68% retention at 5 years for both sources) compared with those from “other” sources (36% at 5 years). In multivariate analyses, patient source of referral and distance of current residence from the Hepatitis Outpatient Clinic were the significant determinants of loss to follow-up. Retention in care may have been promoted by the transition process for those diagnosed in childhood and by the repeated referral from the antenatal clinic of women who had multiple pregnancies during the observation period. Only 20% of asylum seekers and referrals from genitourinary clinics were retained in follow-up at 10 years from baseline. This identifies a group of patients who do not access medical care, cannot benefit from treatment, and who may constitute a long-term public health risk.

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Title: Effectiveness of hepatitis A immunisation after paediatric liver transplantation: a retrospective observational analysis

Source: American Journal of Transplantation 2024, Dec 19. [E–publication]

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Date of publication: December 2024  

Publication type: Retrospective study

Abstract: This retrospective study aimed to investigate the response to hepatitis A virus (HAV) immunisation following liver transplantation. We analysed, 234 vaccination records of 284 children who underwent liver transplantation between January 2003 and July 2021, including annual serological results. Of the 120 HAV-naïve patients, approximately 71% and 83% showed seroconversion after receiving one and two vaccine doses, respectively. The third dose increased the seroconversion rate to 93%. In multivariable logistic regression analysis, the number of vaccine doses and age at first vaccine dose were independently associated with seroconversion. In contrast, additional immunosuppression with mycophenolate mofetil (MMF) was negatively associated with seroconversion. In Cox regression analysis of all 96 seroconverted children, younger age at first vaccination and additional immunosuppression with either MMF or prednisolone were identified as independent risk factors for the early loss of HAV immunity. In summary, HAV immunisation with the three-dose vaccination series is recommended for paediatric liver transplant recipients. Antibody testing and booster vaccinations, if necessary, are recommended, especially for those living in endemic areas or with additional immunosuppressive treatments.

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Title: Feasibility and acceptability of antenatal hepatitis C screening: a pilot study

Source: Canadian Journal of Gastroenterology & Hepatology 2024, Aug 27. [E–publication]

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Date of publication: August 2024

Publication type: Pilot study

Abstract: Introduction: Hepatitis C virus (HCV) is not currently included in the United Kingdom routine antenatal screening program, but the latest guidelines from the Centers for Disease Control and Prevention, American Association for the Study of Liver Diseases, and Infectious Diseases Society of America recommend HCV screening for all pregnant women during each pregnancy. The aim of this study was to collect qualitative data on the feasibility and acceptability of antenatal HCV screening in pregnant women at the time of routine antenatal screening at 12 weeks, to estimate patient knowledge about HCV and identify the prevalence of HCV infection in antenatal women.

Methods: This was a pilot study targeting a single hospital-based antenatal clinic in Birmingham, initially conducted for eight weeks with a further extension of the study period to enhance recruitment to meet the feasibility target of 500 patients. Data collected included demographic and epidemiological details. Pregnant women attending the antenatal unit were given information regarding HCV and antenatal screening for HCV prior to their initial antenatal visit. During the antenatal visit, research nurses provided further information about the study and HCV infection. Consent was obtained for taking part in the study and testing for HCV using blood samples taken at the same time as other routine antenatal screening blood tests. All women who agreed to participate in the study were asked to complete an acceptability and knowledge questionnaire. All women had HCV antibody testing as the primary screening assay. The test result was communicated in writing to the women and their general practitioner. Confirmatory positive antibody tests were followed up with quantitative HCV PCR and genotype analysis. The outcomes of testing were no evidence of HCV infection and evidence of past HCV infection or current HCV infection.

Results: Five hundred and forty-nine women were approached in the antenatal clinic; 30 women refused consent while 29 women were excluded from the study (blood tests not performed after consenting, age less than 18 years, and consent form lost). Four hundred and ninety women were included in the study. The median age of the study population was 29 years (range, 18-46). Knowledge about blood-borne viruses was limited; 75% of women had some understanding about antenatal hepatitis B (HBV) and human immunodeficiency virus (HIV) testing. Previous awareness about hepatitis C was reported by 55%. Ninety-one percent of women found the information they were given about hepatitis C helpful. Ninety-six percent of the women included in this study found the counselling they received about HCV useful and felt that the delivery of this information was carried out in an acceptable manner. Once given information about HCV, 99% felt that universal screening for HCV should be implemented. HCV antibody was negative in 489 women. One patient with a positive HCV antibody (prevalence: 0.2%) had a negative HCV PCR.

Conclusion: Routine antenatal screening for HCV is not currently recommended in the UK. Our study suggests that antenatal HCV screening would be both feasible and acceptable to most pregnant women attending antenatal clinics. Though the awareness of HCV was low, with appropriate counselling and communication, 99% of pregnant women were in favor of antenatal screening for HCV. Antenatal screening would identify HCV-positive mothers and allow follow-up of their infants so that any infected mothers and infants could be offered effective curative therapy and prevent the progression of liver disease. The inclusion of HCV antenatal screening would complete the blood-borne virus profile and enhance the WHO target to eliminate HCV in the UK.

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