The management of childhood liver diseases in adulthood

doi:10.1016/j.jhep.2016.11.013

Journal of Hepatology

Volume 66, Issue 3, March 2017, Pages 631-644

https://doi.org/10.1016/j.jhep.2016.11.013 Get rights and content

Summary

An increasing number of patients with childhood liver disease survive into adulthood. These young adults are now entering adult services and require ongoing management. Aetiologies can be divided into liver diseases that develop in young adults which present to adult hepatologists i.e., biliary atresia and Alagille syndrome or liver diseases that occur in children/adolescents and adults i.e., autoimmune hepatitis or Wilson’s disease. To successfully manage these young adults, a dynamic and responsive transition service is essential. In this review, we aim to describe the successful components of a transition service highlighting the importance of self-management support and a multi-disciplinary approach. We will also review some of the liver specific aetiologies which are unique to young adults, offering an update on pathogenesis, management and outcomes.

Introduction

The number of patients with childhood liver diseases surviving into adulthood has increased over the last 20 years. Diseases once thought to be only in the domain of paediatric hepatologists are increasingly seen in adult clinics. Greater awareness and expertise is therefore required amongst adult hepatologists to manage this unique cohort and their disease spectrum. In addition, one of the key barriers for a successful transition from paediatric to adult care is an inexperience or a lack of knowledge in treating childhood diseases [1], [2].

The number of patients with childhood liver diseases surviving into adulthood is increasing. Adult hepatologists need to be familiar with the management of these diseases.

One of the important developments in health care services for young adults is the setup of sensitive and responsive transition services. Transition services across all disciplines in medicine play an important role in ensuring the health of young adults is maintained through a holistic approach and supportive environment. The importance of transition services cannot be understated. Even without ill health, young adults (18–24 years old) are a high-risk cohort with higher mortality rates compared to 12–17 year olds and higher rates of substance misuse and suicide [3]. Add in the presence of a chronic illness that goes hand in hand with the necessity of regular medication intake and the situation becomes even more precarious. Developmentally appropriate care for young adults remains key.

A sensitive and responsive transition service is required to manage young adults with liver disease.

This article will highlight the important components of a successful transition service, the multi-disciplinary approach and the successful outcomes that are possible. We will also review the liver aetiologies that develop in young children but will present to adult hepatologists as well as the aetiologies that occur in children/adolescents and adults concentrating on the practical management of these patient cohorts.

Section snippets

Aims of transition care

There is a need to emphasise that the terms ‘transition’ and ‘transfer’ are not synonymous. Transfer only refers to the change in location where care will be delivered, change in health care provider or both [4], [5]. Therefore, transfer, is but a component of transition. Transition, on the other hand is not a single event but a purposeful, planned process of moving adolescents and young adults with chronic medical and physical conditions from a child centre to an adult-orientated health care

Timing of transition

During the transition process, the responsibility of health care moves from the parent or carer to the patient ideally at a pace which is suitable for all. The first stage of transition in the shared management model begins approximately at 10 years of age and involves the introduction of the concept of transition [7], [8]. Over the following years, a slow process ensues of engaging and preparing these young children in becoming independent young adults [7], [9]. The patient essentially swaps

Self-management

Self-management support is an important strategy which empowers young adults to participate in their care.

Patients require more than just information and therefore, the development of self-management skills are integral to the successful transition of patients [13]. Self-management support encourages the individual to actively participate in the care of their everyday symptoms relating to their medical treatments in addition to maintaining their general health and preventing progression of

Transition team members and key objectives

Three major categories appear to be integral to every transition service: 1) building and supporting self-management; 2) engagement with the receiving team; and 3) guidance of patients and families [17]. Yet, there is no single accepted model for transition or the constituents of a transition team [18]. A nurse coordinator (transplant and non-transplant), dedicated paediatric and adult hepatologists, specialist social workers and a clinical psychologist are all integral members of a transition

The importance of transition services

Transition services need to be holistic and adopt a multi-disciplinary approach. Successful transition services aim to improve adherence and long-term outcomes.

Much of the literature in this regard is derived from transplantation services. Studies performed in adolescent transplant recipients provide information which is transferable to adolescents with chronic liver disease. Current data suggests that up to one-third of adolescents are non-adherent with medication and their clinic visits,

Biliary atresia

Biliary atresia (BA) is a progressive sclerosing, inflammatory cholangiopathy of unknown aetiology. Affecting between 1/5000–1/19,000 newborns, this rare disease usually presents within the first three months of life with conjugated hyperbilirubinaemia and cholestasis [40]. BA is classified anatomically according to the level of the most proximal biliary obstruction, the most common form being type 3 (>90%) (Fig. 2) [40]. Twenty percent of patients with BA demonstrate anatomical variants

Autoimmune hepatitis and autoimmune sclerosing cholangitis

Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver disease characterised by high serum transaminases, high immunoglobulin G (IgG) levels, detectable autoantibodies and histologically by the presence of interface hepatitis [84]. AIH is a rare condition both in adults and children, with a reported incidence of 0.4 and 3.0/100,000 children [85], [86].

Children vs. adults

Subtle differences are observed in paediatric patients presenting with AIH. Nearly two-thirds of patients in childhood have type 1 AIH

Conclusion

Liver diseases once thought to be unique to paediatric hepatologists are now presenting to adult hepatologists. Subtleties and awareness in the management of specific diseases are therefore required. Adult hepatology training curriculums need to incorporate and stress a greater emphasis on young adults with liver disease. The management of young adults with childhood liver diseases requires a multi-disciplinary approach. Engagement of young adults and promotion of self-management are key

Conflict of interest

The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Authors’ contributions

DJ and MH wrote and edited the article. NG, MS, MD and FD edited and provided expert opinion.

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This study analyzed the results of a transition program in a patient population with a rare liver disease of pediatric onset.
Data were collected on the clinical course of an adolescent population with a rare disease of pediatric onset and enrolled in a transition program between 1994 and 2022.
A total of 238 adolescents (including 34 having undergone a liver transplant on enrolling in the program) were included. Eight patients were lost to follow-up before the first transition consultation and 16 families requested follow-up in an adult hepatology department closer to their home. Overall, 214 initial transition consultations were carried out; 29 patients were subsequently lost to follow-up and 13 switched center. Overall, 15.4 % of the patients enrolled in our program were lost to follow-up. Five adult patients underwent a liver transplantation during this 28-year period. Overall mortality was 3.2 %, graft survival was 91.5 %, and posttransplant survival was 92 %. In total, the current active file represents 183 patients with a median age of 24.3 years (18–51) and a median follow-up period of 5.8 years (6 months to 28 years).
The implementation of a transition program to adult medicine for adolescents with a rare liver disease should follow the recommendations but must be adapted in line with local practice conditions. This process requires close collaboration between the pediatric and adult medicine teams based on a mutual desire to constantly improve practices and enhance knowledge.
Optimization of the transition process of youth with liver disease in adulthood: A position paper from FILFOIE, the French network for paediatric and adult rare liver diseases
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Regular use of questionnaires may be useful for evaluating self-management skills (Table 1) that should be acquired prior to transitioning to adult services. Another strategy is the creation of a health care passport, listing the patient's medical history, medications and other health related information, prepared in combination with the young adult and health care team [7]. Educational sessions and support groups scheduled to discuss their diseases, treatment rationale, dosing regimen and outcomes may also be useful.
Transition describes a progressive and highly coordinated process encompassing the transfer of a young patient from paediatric care to the adult-care system. Transfer of medical care for an adolescent to adult services is a complex and challenging task requiring close collaboration of both the paediatric and adult-care providers. It must take into account the medical, psychosocial and educational needs of the young adult. The Transition Working Group of the French Network for Rare Liver Diseases (FILFOIE) proposes recommendations and tools designed to optimise the transition process of adolescents and young adults with chronic liver disease from child-based to adult-based healthcare services, focusing on three key time points: preparation before the transfer, the transfer process to the adult service, and finally reception and follow-up within the adult-care service.
Prognostic markers at adolescence in patients requiring liver transplantation for biliary atresia in adulthood
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Age at KP, and early post-operative resolution of jaundice are well known predictors of short-term BA NLS, and although some studies4,8,10,12,15,16 have surprisingly shown an association of these parameters with long-term BA NLS, it would seem more appropriate to explore predictive variables that are distant from the KP time-period. Transition services incorporate a multidisciplinary team, ensuring the health of young people is maintained through a holistic approach and supportive environment.17 Depending on individual readiness, transition is a process that can begin from 12 years of age, through to adult services.
In patients with biliary atresia (BA), the rate of native liver survival (NLS) to adulthood has been reported as 14–44% worldwide. Complications related to portal hypertension (PHT) and cholangitis are common in adulthood. For those requiring liver transplantation (LT), the timing can be challenging. The aim of this study was to identify variables that could predict whether young people with BA would require LT when they are >16 years of age.
This study was a single-centre retrospective analysis of 397 patients who underwent Kasai portoenterostomy (KP) between 1980–96 in the UK. After KP, 111/397 (28%) demonstrated NLS until 16 years of age. At final follow-up, 67 showed NLS when >16 years old (Group 1) and 22 required LT when >16 years old (Group 2). Laboratory, clinical and radiological parameters were collected for both groups at a median age of 16.06 years (13.6–17.4 years).
The need for LT when >16 years old was associated with higher total bilirubin (hazard ratio 1.03, p = 0.019) and lower creatinine (hazard ratio 0.95, p = 0.040), at 16 years, on multivariate analysis. Receiver-operating characteristic curve analysis demonstrated that a total bilirubin level of ≥21 µmol/L at 16 years old (AUROC = 0.848) predicted the need for LT when >16 years old, with 85% sensitivity and 74% specificity. Cholangitis episode(s) during adolescence were associated with a 5-fold increased risk of needing LT when >16 years old. The presence of PHT or gastro-oesophageal varices in patients <16 years old was associated with a 7-fold and 8.6-fold increase in the risk of needing LT, respectively.
BA in adulthood requires specialised management. Adult liver disease scoring models are not appropriate for this cohort. Bilirubin ≥21 µmol/L, PHT or gastro-oesophageal varices at 16 years, and cholangitis in adolescence, can predict the need for future LT in young people with BA. Low creatinine at 16 years also has potential prognostic value.
Patients with biliary atresia commonly require liver transplantation before reaching adulthood. Those who reach adulthood with their own liver are still at risk of needing a transplant. This study aimed to identify tests that could help clinicians predict which patients with biliary atresia who reach the age of 16 without a transplant will require one in later life. The study found that the presence of bilirubin ≥21 µmol/L, lower creatinine levels, and a history of portal hypertension or gastro-oesophageal varices at 16 years, as well as cholangitis in adolescence, could predict the future likelihood of needing a liver transplant for young people with biliary atresia.
Autoimmune hepatitis — update on clinical management in 2017
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Moreover, a relapse after withdrawal of steroids in a patient with unconfirmed diagnosis strongly argues in favour of autoimmune hepatitis. Since the number of patients with childhood chronic liver diseases surviving into adult age increases, hepatologists are increasingly faced with challenges of paediatric-to-adult care transition [64]. Therefore, special considerations in paediatric AIH become more important to adult hepatology practitioners.
Autoimmune hepatitis (AIH) is a progressive immune mediated liver disease of unknown origin. Key diagnostic features include hypergammaglobulinemia/elevated serum-IgG, characteristic circulating autoantibodies, periportal hepatitis with interface activity on liver biopsy and the exclusion of hepatotropic viruses. However, the diagnosis is challenging in cholestatic and severe presentations. It can be difficult to differentiate AIH from drug-induced liver injury. Although many patients initially respond to standard immunosuppressive therapy, a significant proportion experiences intolerable side effects or insufficient treatment response. This underlines the need for effective alternative treatment options, which are still very limited and based on rather poor evidence. This review summarises core aspects of the clinical management of AIH with focus on recent achievements and unmet needs.
Decreased health-related quality of life in children and adolescents with autoimmune hepatitis
2019, Jornal de Pediatria
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The clinical presentation of AIH is highly variable in children, ranging from acute hepatitis to an insidious onset with progressive fatigue, intermittent jaundice, anorexia, and weight loss.4 The primary goal of immunosuppressive treatments is to improve clinical manifestations and laboratory findings.1,4 A common treatment is prednisone, which may lead to side effects such as hypertrichosis, weight gain, and linear growth restriction; these effects may affect self-image and negatively influence emotional health, thus jeopardizing the health-related quality of life (HRQOL) in children and adolescents with AIH.4
The objective of this study was to evaluate the health-related quality of life in children and adolescents with autoimmune hepatitis.
A cross-sectional assessment with the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) was completed for 80 patients with autoimmune hepatitis and 45 healthy controls. Demographic data, prednisone dose, disease remission state, disease severity, and abdominal pain were also evaluated.
Based on the child self-reports, physical, emotional, school, and total scores were significantly lower in autoimmune hepatitis patients when compared with controls (p < 0.05). Based on the parental reports, only the physical and total scores were significantly lower in autoimmune hepatitis patients versus controls (p < 0.05). Further analysis in autoimmune hepatitis patients with abdominal pain in the last month revealed significantly lower physical, social, and total median scores (p < 0.05). No differences were observed based on disease remission state or disease severity (p > 0.05). Autoimmune hepatitis patients who received a prednisone dose below 0.16 mg/kg/day at the time of the interview showed significantly higher physical scores than those who received a dose similar to or above 0.16 mg/kg/day (87.5 [50–100] vs. 75 [15.63–100], p = 0.006).
Reduced scores in the physical, emotional, and school domains were observed in pediatric autoimmune hepatitis patients compared to control patients. Abdominal pain and corticosteroid dose negatively influenced the health-related quality of life in children and adolescents with autoimmune hepatitis.
Avaliar a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune (HAI).
Foi concluída uma avaliação transversal com o Inventário Pediátrico de Qualidade de Vida 4.0 (PedsQL 4.0) para 80 pacientes com hepatite autoimune e 45 controles saudáveis. Os dados demográficos, a dose de prednisona, o estado de remissão da doença, a gravidade da doença e dor abdominal também foram avaliados.
Com base nos autorrelatos das crianças, os escores físico, emocional, escolar e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Com base nos relatos dos pais, apenas os escores físico e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Uma análise adicional em pacientes com hepatite autoimune com dor abdominal no mês passado revelou escores médios físico, social e total significativamente menores (p < 0,05). Nenhuma diferença foi observada com base no estado de remissão da doença ou na gravidade da doença (p > 0,05). Os pacientes com hepatite autoimune que receberam uma dose de prednisona abaixo de 0,16 mg/kg/dia no momento da entrevista mostraram escores físicos significativamente maiores que os que receberam uma dose semelhante ou acima de 0,16 mg/kg/dia [87,5 (50-100) em comparação com 75 (15,63-100), p = 0,006].
Escores reduzidos nos domínios físico, emocional e escolar foram observados em pacientes pediátricos com hepatite autoimune em comparação com pacientes do grupo de controle. Dor abdominal e dose de corticosteroide influenciaram negativamente a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune.
Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK
2018, The Lancet
This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63 000 preventable deaths over the next 5 years, is to be addressed.

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ReviewThe management of childhood liver diseases in adulthood

Summary

Introduction

Section snippets

Aims of transition care

Timing of transition

Self-management

Transition team members and key objectives

The importance of transition services

Biliary atresia

Autoimmune hepatitis and autoimmune sclerosing cholangitis

Children vs. adults

Conclusion

Conflict of interest

Authors’ contributions

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Clin Gastroenterol Hepatol

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Gastroenterology

Growing up and moving on: transition from pediatric to adult care

Pediatr Transplant

National survey of adult transplant hepatologists on the pediatric-to-adult care transition after liver transplantation

Liver Transpl

Chronic illness in adolescents: transfer or transition to adult services?

J Paediatr Child Health

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Pediatr Transplant

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Review
The management of childhood liver diseases in adulthood