LINKED CONTENT
This article is linked to Nayagam et al papers. To view these articles, visit https://doi.org/10.1111/apt.16708 and https://doi.org/10.1111/apt.16751
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.
Familial amyloid polyneuropathy, a lethal genetic disease caused by aggregation of variant transthyretin, induces progressive peripheral nerve deficits and disability. Diflunisal, a nonsteroidal ...anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro.
To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy.
International randomized, double-blind, placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinically detectable peripheral or autonomic neuropathy at amyloid centers in Sweden (Umeå), Italy (Pavia), Japan (Matsumoto and Kumamoto), England (London), and the United States (Boston, Massachusetts; New York, New York; and Rochester, Minnesota) from 2006 through 2012.
Participants were randomly assigned to receive diflunisal, 250 mg (n=64), or placebo (n=66) twice daily for 2 years.
The primary end point, the difference in polyneuropathy progression between treatments, was measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS+7) which ranges from 0 (no neurological deficits) to 270 points (no detectable peripheral nerve function). Secondary outcomes included a quality-of-life questionnaire (36-Item Short-Form Health Survey SF-36) and modified body mass index. Because of attrition, we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data.
By multiple imputation, the NIS+7 score increased by 25.0 (95% CI, 18.4-31.6) points in the placebo group and by 8.7 (95% CI, 3.3-14.1) points in the diflunisal group, a difference of 16.3 points (95% CI, 8.1-24.5 points; P < .001). Mean SF-36 physical scores decreased by 4.9 (95% CI, -7.6 to -2.2) points in the placebo group and increased by 1.5 (95% CI, -0.8 to 3.7) points in the diflunisal group (P < .001). Mean SF-36 mental scores declined by 1.1 (95% CI, -4.3 to 2.0) points in the placebo group while increasing by 3.7 (95% CI, 1.0-6.4) points in the diflunisal group (P = .02). By responder analysis, 29.7% of the diflunisal group and 9.4% of the placebo group exhibited neurological stability at 2 years (<2-point increase in NIS+7 score; P = .007).
Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life. Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for familial amyloid polyneuropathy.
clinicaltrials.gov Identifier: NCT00294671.
Autoimmune liver diseases (AILDs) are a group of conditions where immune-mediated liver damage can lead to the need for transplantation. Collectively, they account for almost a quarter of all liver ...transplants. Outcomes in terms of graft and patient survival for all liver transplants have improved markedly over decades with improvements in patient selection, surgical techniques and longer-term care and this is also seen in patients with AILDs. The current five- and ten-year survival rates post-transplant in autoimmune disease are excellent, at 88% and 78%, respectively. A key factor in maintaining good outcomes post liver transplant for these autoimmune conditions is the immunosuppression strategy. These patients have increased the rates of rejection, and autoimmune conditions can all recur in the graft ranging from 12 to 60% depending on the population studied. Immunosuppressive regimens are centred on calcineurin inhibitors, often combined with low dose corticosteroids, with or without the addition of antimetabolite therapy. There is no clear evidence-based immunosuppressive regimen for these conditions, and a tailored approach balancing the individuals’ immunological profile against the risks of immunosuppression is often used. There are disease-specific considerations to optimised graft function including the role of ursodeoxycholic acid in both primary biliary cholangitis and primary sclerosing cholangitis and the role and timing of colectomy in primary sclerosing cholangitis in inflammatory bowel disease patients. However, unmet needs still exist in the management of AILDs post liver transplantation particularly in building the evidence base for optimal immunosuppression as well as mitigating the risk of recurrent disease.
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•Collectively, autoimmune liver diseases (AILDs) represent a significant requirement for organs in liver transplant programs. Long-term outcomes for these patients have improved, with excellent one- and five-year survival (90% and 70%, respectively).•As well as the transplant indications seen in other forms of chronic liver disease, there are unique indications for transplantation seen in AILDs such as recurrent cholangitis in primary sclerosing cholangitis.•Furthermore, there are also special considerations post liver transplantation in these conditions. All forms of AILD can recur post transplantation, and there is an increased risk of rejection. In this article, we discuss the need to balance the selection of immunosuppression for long-term optimal graft and patient survival with the complications of these drugs.•Additionally, we highlight prognostic- and disease- specific treatment options for each of the main AILDs after liver transplantation in terms of immunosuppression strategy and any disease modifying therapies.
Summary
Background
Current therapeutic options for autoimmune hepatitis (AIH) are limited by adverse events associated with corticosteroids and thiopurines and the limited evidence base for second‐ ...and third‐line treatment options. Furthermore, current treatment approaches require long‐term exposure of patients to pharmacological agents. There have been significant advances in the understanding of the mechanisms underpinning autoimmunity and an expansion in the available therapeutic agents for suppressing autoimmune responses or potentially restoring self‐tolerance.
Aim
To review the mechanisms and evidence for experimental therapies that are being actively explored in the management of AIH.
Methods
We have reviewed the literature relating to a range of novel therapeutic immunomodulatory treatment strategies and drugs.
Results
Drugs which block B cell‐activating factor of the tumour necrosis factor family (BAFF) and tumour necrosis factor α are currently in clinical trials for the treatment of AIH. Experimental therapies and technologies to increase immune tolerance, such as pre‐implantation factor and regulatory T cell therapies, are undergoing development for application in autoimmune disorders. There is also evidence for targeting inflammatory pathways to control other autoimmune conditions, such as blockade of IL1 and IL6 and Janus‐associated kinase (JAK) inhibitors.
Conclusions
With the range of tools available to clinicians and patients increasing, it is likely that the therapeutic landscape of AIH will change over the coming years and treatment approaches offering lower corticosteroid use and aiming to restore immune self‐tolerance should be sought.
To report baseline features and long-term medical/social outcomes of juvenile autoimmune liver disease, including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), managed in a ...single tertiary center.
Retrospective study of children diagnosed in 2000-2004 with AIH/ASC followed up to date. Patients with abnormal cholangiogram were classified as ASC. Presentation and outcome features were compared.
Eighty-three children were included (42 female, median age 12.1 years 8.5-14.1 years, AIH = 54, ASC = 29). Most (65%) had antinuclear and/or anti-smooth muscle autoantibodies; 6% presented with acute liver failure; 29% had histologic evidence of cirrhosis. The 1999 and simplified International Autoimmune Hepatitis Group criteria failed to diagnose up to 26% of patients with AIH and 48% with ASC, and the proposed the European Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria were accurate. Response to treatment was excellent with 95% achieving normal transaminase levels. During follow-up, 31% had at least 1 relapse episode; 3 patients with AIH developed cholangiopathy and 5 patients with ASC developed progressive bile duct injury. At last follow-up (median of 14.5 years, 10.4-16.8), 99% were alive, 11 underwent transplantation and 1 is listed for transplant. Five-, 10-, and 15-year transplant-free survival rates were 95%, 88%, and 83%; patients with ASC and those relapsing being more likely to require transplant. Social outcome was excellent with 93% in employment/education.
Seamless management of juvenile autoimmune liver disease leads to excellent clinical and social outcomes. Despite good response to immunosuppressive treatment, patients with ASC have a worse prognosis than those with AIH. Diagnostic models developed for adults are unsatisfactory to correctly diagnose juvenile autoimmune liver disease.
Young people (YP) with chronic illness have higher rates of mental health problems than the general population, with psychosocial complexity associated with nonadherence and poorer health outcomes. ...This study aimed to describe the prevalence of anxiety and depression in YP after liver transplantation, with autoimmune liver disease and other chronic liver diseases, identify the factors YP attribute their distress to and the relationship between anxiety/depression, and describe YP's beliefs about their illness and treatment. An electronically administered questionnaire battery was given routinely to YP attending an outpatient liver transition clinic; 187 YP participated, of which 17.7% screened positive for anxiety or depression. There were no significant differences between disease groups. This is significantly higher than the prevalence of common mental health problems in the general adolescent population. Patients most frequently attributed their distress to fatigue, sleep difficulties, financial concerns, problems at work/school, worry, and low self‐esteem. Higher levels of depression and anxiety were significantly associated with specific illness and treatment beliefs but not with perceived understanding of illness or treatment control. In conclusion, the increased prevalence of mental health problems in YP and the intertwined nature of these with their physical health outcomes provide evidence that holistic care should be delivered as standard for this age group. Liver Transplantation 22 1544–1553 2016 AASLD.
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