Recanalization of portal vein thrombosis after pediatric liver transplantation: Efficacy and safety of the transsplenic access.

BACKGROUND: Endovascular management of portal vein thrombosis (PVT) is challenging. Transsplenic access (TSA) is growing as an access option to the portal system but with higher rates of bleeding complications. The aim of this article is to evaluate the efficacy and safety of transsplenic portal vein recanalization (PVR) using a metallic stent after pediatric liver transplantation. MATERIALS AND METHODS: This is a retrospective review of 15 patients with chronic PVT who underwent PVR via TSA between February 2016 and December 2020. Two children who had undergone catheterization of a mesenteric vein tributary by minilaparotomy were excluded from the patency analysis but included in the splenic access analysis. The technical and clinical success of PVR and complications related to the procedure via TSA were evaluated. RESULTS: Thirteen children with PVT were treated primarily using the TSA. The mean age was 4.1 years (range, 1.5-13.7 years), and the most common clinical presentation was hypersplenism (60%). Technically successful PVR was performed in 11/13 (84.6%) children, and clinical success was achieved in 9/11 (81.8%) children. No major complications were observed, and one child presented moderate pain in the TSA (from a total of 17 TSA). The median follow-up was 48.2 months. The median primary patency was 9.9 months. Primary patency in the first 4 years was 75%, and primary assisted patency was 100% in the follow-up period. CONCLUSIONS: Transsplenic PVR is a safe and effective method for the treatment of PVT after pediatric liver transplantation.

Oral findings in children on liver transplantation programming: a scoping review.

OBJECTIVE: To identify oral characteristics found in children with liver disease in programming for liver transplantation. DATA SOURCE: The methodology was written according to PRISMA-ScR. We adopted the methodological framework and recommendations for this type of review by Arksey and O'Malley and the Joanna Briggs Institute. The protocol was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/QCU4W). A systematic search (Medline/PubMed, Scopus, Web of Science, and ProQuest) was conducted to identify studies that met the inclusion criteria: systematic reviews; prospective clinical trials (parallel or crossover group designs); observational studies (cohort, case-control, and cross-sectional studies); clinical case series; and case reports evaluating children with liver disease in preparation for transplantation. The last search was conducted in July 2021, and no restrictions were imposed as to language or year of publication. Studies presenting mixed data with post-transplant evaluation, and studies evaluating not only liver transplantation but also other solid organs were excluded. Screening, inclusion, and data extraction were performed by two reviewers independently. A narrative synthesis was conducted to describe the findings of the study. DATA SYNTHESIS: The bibliographic search identified 830 references. A total of 21 articles were read in their entirety after the inclusion criteria assessment. Finally, after evaluating the exclusion criteria, only 3 studies were considered for the qualitative analysis. CONCLUSIONS: Children with liver disease in preparation for transplantation may present enamel defects, tooth pigmentation, caries, gingivitis, and opportunistic infections such as candidiasis.

Hepatic venous reconstruction of the left lateral segment with emphasis on anomalous hepatic vein in pediatric liver transplantation.

Left lateral segment grafts have become a suitable option in pediatric liver transplantation (PLT). The correlation between hepatic vein (HV) reconstruction and outcome is relevant when assessing the safe use of these grafts. We retrospectively reviewed the medical records prospectively collected from a pediatric living donor liver transplantation database and conducted a comparative analysis of the different left lateral segment graft types according to HV reconstruction. Donor, recipient, and intraoperative variables were analyzed. Post-transplant outcomes included vascular complications such as hepatic vein outflow obstruction, early (≤30 d) and late (>30 d) PVT, hepatic artery thrombosis, and graft survival. From February 2017 to August 2021, 303 PLTs were performed. According to venous anatomy, the distribution of the left lateral segment was as follows: single HV (type I) in 174 (57.4%), close HVs, simple venoplasty for reconstruction (type II) in 97 (32.01%), anomalous hepatic vein (AHV) with a distance between the HVs orifices that allowed simple venoplasty (type IIIA) in 25 (8.26%) and AHV with a distance between the HVs orifices requiring homologous venous graft interposition (type IIIB) in 07 (2.31%) grafts. Type IIIB grafts came from male donors ( p =0.04) and had a higher mean donor height ( p =0.008), a higher mean graft weight, and a higher graft-to-recipient weight ratio, both p =0.002. The median follow-up time was 41.4 months. The overall cumulative graft survival was 96.3%, and comparative graft survival showed no difference (log-rank p =0.61). No hepatic vein outflow obstructions were observed in this cohort study. There was no statistically significant difference in the post-transplant outcomes between the graft types. The venous reconstruction of the AHV with homologous venous graft interposition had similar outcomes in the short and long term.

Oral findings in children on liver transplantation programming: a scoping review / Achados odontológicos em crianças em programação para o transplante hepático: revisão de escopo

Abstract Objective: To identify oral characteristics found in children with liver disease in programming for liver transplantation. Data source: The methodology was written according to PRISMA-ScR. We adopted the methodological framework and recommendations for this type of review by Arksey and O'Malley and the Joanna Briggs Institute. The protocol was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/QCU4W). A systematic search (Medline/PubMed, Scopus, Web of Science, and ProQuest) was conducted to identify studies that met the inclusion criteria: systematic reviews; prospective clinical trials (parallel or crossover group designs); observational studies (cohort, case-control, and cross-sectional studies); clinical case series; and case reports evaluating children with liver disease in preparation for transplantation. The last search was conducted in July 2021, and no restrictions were imposed as to language or year of publication. Studies presenting mixed data with post-transplant evaluation, and studies evaluating not only liver transplantation but also other solid organs were excluded. Screening, inclusion, and data extraction were performed by two reviewers independently. A narrative synthesis was conducted to describe the findings of the study. Data synthesis: The bibliographic search identified 830 references. A total of 21 articles were read in their entirety after the inclusion criteria assessment. Finally, after evaluating the exclusion criteria, only 3 studies were considered for the qualitative analysis. Conclusions: Children with liver disease in preparation for transplantation may present enamel defects, tooth pigmentation, caries, gingivitis, and opportunistic infections such as candidiasis.

RESUMO Objetivo: Identificar características bucais em crianças hepatopatas em programação para o transplante hepático. Fontes de dados: A metodologia foi descrita de acordo com o PRISMA-ScR. Adotamos a estrutura metodológica e recomendações para este tipo de revisão por Arksey e O'Malley e o Instituto Joanna Briggs. O protocolo foi registrado no Open Science Framework (https://doi.org/10.17605/OSF.IO/QCU4W). Uma pesquisa sistemática (Medline/PubMed, Scopus, Web of Science e ProQuest) foi conduzida para identificar estudos que preenchessem os critérios de inclusão: revisões sistemáticas; ensaios clínicos prospectivos (desenhos de grupos paralelos ou cruzados); estudos observacionais (coorte, caso-controle e estudos transversais); séries de casos clínicos; e relatos de casos que avaliam crianças com doenças hepáticas em preparação para o transplante. A última busca foi conduzida em julho de 2021, e não foram impostas restrições quanto ao idioma ou ano de publicação. Foram excluídos estudos que apresentavam dados mistos com avaliação pós-transplante e estudos que avaliavam não só o transplante de fígado, mas também de outros órgãos sólidos. O rastreio, inclusão e extração de dados foram realizados por dois revisores independentemente. Foi conduzida uma síntese narrativa para identificar os resultados do estudo. Síntese dos dados: A pesquisa bibliográfica identificou 830 referências. Foram lidos 21 artigos na íntegra após avaliação dos critérios de inclusão. Finalmente, após a avaliação dos critérios de exclusão, apenas três estudos foram considerados para análise. Conclusões Crianças com doença hepática em preparação para o transplante podem apresentar defeitos de esmalte, pigmentação dentária, cárie, gengivite além de infecções oportunistas como a candidíase.

Pediatric Liver Transplantation: Caregivers' Quality of Life.

Purpose: The survival rate of pediatric patients undergoing liver transplantation has increased considerably. Despite this, the period after transplantation is still complex and poses several challenges to the recipient's family, which is responsible for care management. Recently, more attention has been paid to the impact of this complex procedure on the quality of life of caregivers. Hence, this study is aimed at assessing the quality of life of caregivers of patients who have undergone liver transplantation and the aspects that influence it. Methods: This was an observational and cross-sectional study. From November 2020 to January 2021, short-form-36 questionnaires and additional questions were given to the main caregivers of children and adolescents who underwent pediatric liver transplantation. Results: Thirty-eight questionnaires were completed and the results revealed a lower quality of life in comparison to Brazilian standards, primarily in the mental domains (41.8±14.1 vs. 51.1±2.8; p<0.001). It did not show a significant association with socioeconomic or transplant-related factors, but it did show a negative impact on parents' perception of the child's health. Parents who reported worse health status for their children had a lower mental quality of life (44.1±13.8 vs. 33.3±12.6; p<0.05). Conclusion: The caregivers of transplanted children have a lower quality of life than those of the local population. Psychological assistance should be routinely provided to parents for long-term follow-up to mitigate potential negative effects on the transplanted child's care.

Loss of FOCAD, operating via the SKI messenger RNA surveillance pathway, causes a pediatric syndrome with liver cirrhosis.

Cirrhosis is usually a late-onset and life-threatening disease characterized by fibrotic scarring and inflammation that disrupts liver architecture and function. While it is typically the result of alcoholism or hepatitis viral infection in adults, its etiology in infants is much less understood. In this study, we report 14 children from ten unrelated families presenting with a syndromic form of pediatric liver cirrhosis. By genome/exome sequencing, we found recessive variants in FOCAD segregating with the disease. Zebrafish lacking focad phenocopied the human disease, revealing a signature of altered messenger RNA (mRNA) degradation processes in the liver. Using patient's primary cells and CRISPR-Cas9-mediated inactivation in human hepatic cell lines, we found that FOCAD deficiency compromises the SKI mRNA surveillance pathway by reducing the levels of the RNA helicase SKIC2 and its cofactor SKIC3. FOCAD knockout hepatocytes exhibited lowered albumin expression and signs of persistent injury accompanied by CCL2 overproduction. Our results reveal the importance of FOCAD in maintaining liver homeostasis and disclose a possible therapeutic intervention point via inhibition of the CCL2/CCR2 signaling axis.

Impact of COVID-19 Infection on Children and Adolescents after Liver Transplantation in a Latin American Reference Center.

Background: The COVID-19 infection has received the attention of the scientific community due to its respiratory manifestations and association with evolution to severe acute respiratory syndrome (SARS-CoV-2). There are few studies characterizing SARS-CoV-2 in pediatric immunocompromised patients, such as liver transplanted patients. The aim of this study was to analyze the outcomes of the largest cohort of pediatric liver transplant recipients (PLTR) from a single center in Brazil who were infected with COVID-19 during the pandemic. Methods: Cross-sectional study. Primary outcomes: COVID-19 severity. The Cox regression method was used to determine independent predictors associated with the outcomes. Patients were divided into two groups according to the severity of COVID-19 disease: moderate−severe COVID and asymptomatic−mild COVID. Results: Patients categorized as having moderate−severe COVID-19 were younger (12.6 months vs. 82.1 months, p = 0.03), had a higher prevalence of transplantation from a deceased donor (50% vs. 4.3%, p = 0.02), and had a higher prevalence of COVID infection within 6 months after liver transplantation (LT) (75% vs. 5.7%, p = 0.002). The independent predictor of COVID-19 severity identified in the multivariate analysis was COVID-19 infection <6 months after LT (HR = 0.001, 95% CI = 0.001−0.67, p = 0.03). Conclusion: The time interval of less than 6 months between COVID-19 infection and LT was the only predictor of disease severity in pediatric patients who underwent liver transplantation.

Defining paediatric metabolic (dysfunction)-associated fatty liver disease: an international expert consensus statement.

The term non-alcoholic fatty liver disease (NAFLD), and its definition, have limitations for both adults and children. The definition is most problematic for children, for whom alcohol consumption is usually not a concern. This problematic definition has prompted a consensus to rename and redefine adult NAFLD associated with metabolic dysregulation to metabolic (dysfunction)-associated fatty liver disease (MAFLD). Similarities, distinctions, and differences exist in the causes, natural history, and prognosis of fatty liver diseases in children compared with adults. In this Viewpoint we, an international panel, propose an overarching framework for paediatric fatty liver diseases and an age-appropriate MAFLD definition based on sex and age percentiles. The framework recognises the possibility of other coexisting systemic fatty liver diseases in children. The new MAFLD diagnostic criteria provide paediatricians with a conceptual scaffold for disease diagnosis, risk stratification, and improved clinical and multidisciplinary care, and they align with a definition that is valid across the lifespan.

Pediatric liver transplantation activity in a high-volume program during the COVID-19 pandemic in Brazil.

BACKGROUND: The impact of the COVID pandemic on liver transplant (LT) programs varied among countries. Few data are available about that impact in pediatric liver transplant (PLT) programs. This study aimed at comparing the data of our program in Brazil (2019 vs. 2020). METHODS: Retrospective cohort study. RESULTS: One hundred and seventy-four PLT were performed in the period (93% living donors). Patients were divided into two groups according to the LT date: pre-COVID-19 period (march/2019-February/2020) and COVID-19 period (March/2020-February 2021). In the pre-COVID-19 period, 97 LTs were performed, and 77 LTs were performed in the COVID-19 period. Patients in the COVID-19 period were younger (10.9 months vs. 16 months, p 0.009), had higher PELD scores (15 vs. 14, p 0.04), more ascites (66.2 vs. 51.5%, p 0.03), and more frequently hospitalized before LT (27.3 vs. 17.5%). However, there was no difference in post-LT complications, retransplantation nor survival rates. Six (6.2%) patients from pre-COVID-19 period were COVID positive at a median of 15.5 months (14-17.5), and 6 (7.8%) patients from COVID-19 period were COVID positive at a median of 3 months (20 days-6 months) from LT. There was neither mortality nor complications in those patients. Four (33%) were hospitalized, and one had prolonged intubation. Four (33%) were asymptomatic, 4 (33%) had upper airways symptoms, and the remaining had gastrointestinal symptoms. CONCLUSION: Overall, PLT was not affected during COVID-19 period. Even though patients from COVID-19 period were sicker, there was no significant impact in LT outcomes. All the recipients who tested positive for COVID had a favorable outcome.

Progressive Familial Intrahepatic Cholestasis Associated With USP53 Gene Mutation in a Brazilian Child.

ABSTRACT: A case of low-γ-glutamyltranspetidase cholestasis associated with ubiquitin-specific peptidase 53 (USP53) gene mutation in a Brazilian child is described. Transient jaundice and hypocholia started at the age of 10 days. Liver enzymes, total bilirubin, and total bile acids were elevated at presentation. During follow-up, he developed cholelithiasis treated with cholecystectomy, and an intracranial hemorrhage resolved with full recovery. At last, evaluation at the age of 18 months, he was not jaundiced and had normal liver tests, but experienced from moderate pruritus despite treatment with rifampicin and ursodeoxycholic acid. A genetic study revealed novel homozygous mutations c.1687_1688delinsC p.Ser563Profs∗25 in the USP53 gene. His parents carried the same heterozygous mutation in the USP53 gene.

Impact of hypoxemia on pediatric liver transplantation for hepatopulmonary syndrome.

BACKGROUND: The treatment of choice for patients with cirrhosis and HPS is LT. The clinical manifestations associated with hypoxemia result in limitations and a poor health-related quality of life of affected patients. The present report aims to study the differences in outcomes between patients with PaO2  < 50 mm Hg and those with PaO2  ≥ 50 mm Hg. METHODS: This was a retrospective study of 21 patients under 18 years of age conducted from 2001 to 2018; the patients were divided into 2 groups: G1-PaO2  ≥ 50 mm Hg, 11 patients, and G2-PaO2  < 50 mm Hg, 10 patients. Demographic, clinical, laboratory, and perioperative data; outcome variables; and post-transplant survival were compared between the groups. RESULTS: In total, 2/11 (18.2%) patients in G1 and 8/10 (80%) patients in G2 required supplemental oxygen therapy at home (P = .005). Patients in G2 required prolonged MV (median 8.5 days in G2 vs 1 day in G1, P = .015) and prolonged ICU and hospital stays (P = .002 and P = .001, respectively). Oxygen weaning time was longer in G2 (median 127.5 days) than in G1 (median 3 days; P = .004). One (9.1%) patient in G1 and three (30%) patients in G2 died (P = .22). The survival at 90 months was 90.9% in G1 and 70% in G2 (P = .22). CONCLUSION: The survival between groups was similar. Patients with very severe HPS required a longer MV time, longer ICU and hospital stays, and a longer O2 weaning time than those with mild, moderate, or severe HPS.

Autoimmune Hepatitis: Predictors of Native Liver Survival in Children and Adolescents.

OBJECTIVE: To determine predictors of native liver survival (NLS) in children and adolescents with autoimmune hepatitis (AIH). STUDY DESIGN: The medical records of children and adolescents with AIH were reviewed. A questionnaire was used to collect data on clinical presentation, biochemical and histologic findings, and treatment. RESULTS: A total of 819 patients were included, 89.6% with AIH-1 and 10.4% with AIH-2. The median age (months) at onset was 108 (min 6; max 210; IQR 59). The female sex was predominant (75.8%). The overall survival was 93.0%, with an NLS of 89.9%; 4.6% underwent liver transplantation. The risk of death or liver transplantation during follow-up was 3.2 times greater in patients with AIH-1 (P = .024). Greater levels of aspartate aminotransferase, alanine aminotransferase, serum albumin, platelet, and normal international normalized ratio at the initial presentation were associated with longer NLS (P = .046, P = .006, P < .001, P = .001, and P = .019, respectively). Normal C3 levels was associated with longer NLS (P = .017), with a chance of death or liver transplantation during follow-up being 3.4 times greater in patients with C3 below normal. Death or liver transplantation during follow-up was 2.8 times greater in patients with associated sclerosing cholangitis (P = .046). Complete remission favored NLS (P < .001), with a risk of death or liver transplantation 11.7 times greater for patients not achieving remission. CONCLUSIONS: The best predictors of NLS in children and adolescents with AIH were the AIH-2 subtype, a normal C3 at diagnosis, remission during treatment, and normal a cholangiogram during the disease course.

Evaluation of drug-induced liver injury as etiology for acute liver failure in Brazil.

INTRODUCTION AND OBJECTIVES: Little is known about the etiology of acute liver failure (ALF) in Latin America. The objective of this paper is to investigate the main etiologies of ALF in Brazil, including Drug Induced Liver Injury (DILI) using stringent causality criteria. PATIENTS OR MATERIAL AND METHODS: All the cases of individuals who underwent liver transplantation (LT) in 12 centers in Brazil for ALF were reviewed. When DILI was stated as the cause of ALF, causality criteria were applied on site by the main investigator in order to rule out other etiologies. RESULTS: 325 individuals had ALF mainly for unknown reasons (34%), DILI (27%) and AIH (18%). Reassessment of the 89 cases of DILI, using stringent causality criteria, revealed that in only 42 subjects could DILI be confirmed as the cause of ALF. Acetaminophen (APAP) toxicity (n = 3) or DILI due to herbal and dietary supplements (HDS) (n = 2) were not commonly observed. CONCLUSIONS: Undetermined etiology and DILI are the main causes of ALF in Brazil. However, APAP toxicity and DILI due to HDS are mostly uncommon.

Hepatocellular carcinoma in an adult with Alagille syndrome: case report and literature review.

Alagille syndrome (AS) is an autosomal dominant multisystem disorder which can lead to hepatopathy and the development of focal hepatic lesions. The majority of the hepatic lesions are benign, including regenerative nodules, focal hyperplasia, and adenoma. Hepatocellular carcinoma (HCC) is extremely rare in AS, with very few cases reported in the literature. A 38-year-old man complaining of acute right upper quadrant pain with long-standing diagnosis of Alagille syndrome. On imaging, the patient had a large hepatic mass in the right lobe, with arterial hyperenhancement, washout appearance, and areas of internal hemorrhage. The patient underwent a right hepatectomy and histopathology demonstrated HCC. The patient passed away 3 months after the surgery due to infectious complications. HCC is a rare complication of AS, although rare, it should be considered. This case also emphasizes the need of HCC screening in patients with AS in order to allow an early diagnosis and treatment, which can improve patients' outcome.

Particularities of Autoimmune Hepatitis in Latin America.

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Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Oral health-related quality of life among pediatric liver transplant candidates.

To assess the impact of oral conditions on the oral health-related quality of life (OHRQoL) of pediatric liver transplant candidates. This cross-sectional study included 60 children aged 13 to 48 months who were liver transplant candidates that attended the AC Camargo Cancer Center, São Paulo, Brazil. On the day of oral examinations, the children's mothers were invited to answer two questionnaires; one related to children's OHRQoL using the B-ECOHIS and another related to socioeconomic/demographic characteristics. Thereafter, a single, adequately trained dentist carried out children's oral examinations for gingival inflammation (Silness-Löe index), dental plaque (Green-Vermillion Simplified index), dental caries (dmft index), developmental defects of enamel (DDE index), tooth discoloration, oral mucosal/lip alterations. The data collected also included socioeconomic/demographic characteristics and liver disease. The adjusted Poisson regression model was used to associate children's socioeconomic/demographic characteristics and clinical conditions to the outcome. The adjusted regression model showed that children with untreated caries lesions (RR = 3.35, p < 0.0001) and tooth discoloration (RR = 1.74, p = 0.04) had poorer total B-ECOHIS scores. Dental discoloration and untreated caries lesions had a negative impact on the OHRQoL in pediatric liver transplant candidates.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B.

Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified. Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment. The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc). Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Technical Choices in Pediatric Living Donor Liver Transplantation: The Path to Reduce Vascular Complications and Improve Survival.

Pediatric living donor liver transplantation (PLDLT) is a successful therapeutic option for children with chronic and acute liver disease. After early transplant results, many technical advancements were introduced in the field to reduce the rate of complications and improve survival. The aim of this study is to present the outcomes of 975 primary PLDLTs in 3 periods: initial practice (period 1, 29 patients, January 1995 to December 1999), second period (period 2, 331 patients, January 2000 to December 2009), and third period (period 3 [P3], 615 patients, January 2010 to September 2019). Among the technical refinements introduced in P3 are the use of hyperreduced left lateral segment grafts, abdominal wall prosthetic mesh closure, double hepatic artery anastomosis, and increased use of vascular grafts for portal vein reconstruction. The outcomes included significant reductions of hepatic artery thrombosis (HAT), early portal vein thrombosis (EPVT), and retransplantation, with better patient and graft survival in P3. Additional analyses showed that the factors independently associated with worse 90-day patient survival were HAT, EPVT, and increasing Pediatric End-Stage Liver Disease score. In conclusion, the introduction of technical refinements in P3, in addition to improvements in patient care, determined a reduction in EPVT, HAT, and retransplantation. Consequently, patient and graft survival rates increased in all time points studied.

Comparison of Recommendations for Treatment of Chronic Hepatitis C Virus Infection in Children and Adolescents: A Position Paper of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

OBJECTIVE: This position paper written by the Hepatitis Expert Team of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition aimed to systematically evaluate clinical practice guidelines (CPGs), medical consensus, and position papers on the use of direct-acting antivirals (DAA) to treat chronic hepatitis C virus (HCV) infection in adolescents and children in order to compare recommendations and provide the basis for developing a unified position statement. METHODS: MEDLINE, Cochrane-Library, National Guideline Clearinghouse and select websites of relevant societies/organizations were used to identify CPGs, medical consensus and position papers between 2011-2019. RESULTS: A total of 5 documents were analysed: 3 CPGs, 1 medical consensus, and 1 position paper. All publications were consistent in recommending DAA treatment for adolescents (12-17 years old) with chronic HCV infection. Similarly, all of these publications consistently recommended deferring therapy for children between 3 and 11 years of age until DAA became available as standard of care. Finally, none of the included publications recommended treating children younger than 3 years old. By contrast, there was significant discrepancy across the retrieved documents regarding specific DAA regimens and treatment strategies. CONCLUSIONS: There is strong consensus on treating all adolescents with chronic HCV infection with DAA and on delaying therapy in younger children until these agents are approved for them. Interferon-based therapies should be avoided. Specific recommendations regarding which DAA regimen to use and treatment duration varied significantly. Key stakeholders need to convene to standardize therapeutic strategies at a global level if we are to eradicate HCV in children.