Immunosuppression minimization is safe and associated with good long-term success in pediatric recipients of liver transplant.

Immunosuppression reduction after liver transplant is an important strategy to mitigate long-term medication side effects. We describe our center's experience with immunosuppression minimization to once-daily calcineurin inhibitor dosing. Success was defined as continuing daily calcineurin inhibitor monotherapy with normal transaminases and no rejection. We performed a retrospective review of eligible children who received a liver transplant between 2009 and 2016, had a surveillance biopsy, and were on twice-daily calcineurin inhibitor monotherapy. Twenty-eight of 51 eligible patients were minimized to daily calcineurin inhibitor with goal 12-hour trough detectable. Nineteen patients (68%) had 1-year success, and 17 (61%) had long-term success at a median follow-up of 5.0 years (interquartile range (IQR): 2.9-6.6). Minimization failure occurred at a median of 0.6 years (IQR: 0.3-1.0) after dose reduction. Patients with long-term success had lower aspartate aminotransferase levels prior to minimization compared to those who failed with a median of 28.0 IU/L (IQR: 20.5-32.0) versus 32.0 IU/L (IQR: 30.0-37.0), p = 0.047. The long-term success group demonstrated a trend toward greater recipients of liver transplant from living donors (53% vs. 18%, p = 0.07). At the time of the last follow-up at a median of 5.0 years (IQR: 2.9-6.1) after surveillance biopsy, most (73%) patients who failed had returned to twice-daily calcineurin inhibitor monotherapy, all had liver enzymes <2 times the upper limit of normal, and there were no patient deaths or graft losses. In conclusion, immunosuppression minimization is safe in pediatric recipients of liver transplant and should be considered to reduce long-term medication side effects and improve patient quality of life. Future studies are necessary to follow long-term outcomes and develop biomarkers to predict minimization success.

Acute-on-chronic liver failure before liver transplantation does not impact post-transplant survival in children with biliary atresia.

Acute-on-chronic liver failure (ACLF) occurs in children with biliary atresia (BA) awaiting liver transplantation (LT). However, data on transplant outcomes in ACLF are limited. Our aim was to characterize ACLF and determine its effect on transplant outcome and resource utilization. Using a linkage of the Scientific Registry of Transplant Recipients and Pediatric Health Information System, we identified children with BA between 3 months and 18 years at the time of listing who received a transplant from 2003 to 2018 and were hospitalized while waiting. ACLF was defined by the presence of at least 1 extra-hepatic organ failure during a pre-LT hospitalization. In all, 1044 patients (58% female, median age at listing 7.0 months IQR 5.0-14.0) were included. Thirty-four percent (351/1044) of the patients had at least 1 ACLF hospitalization. Patients with ACLF had longer waitlist times (114 [54-231] vs. 81 [35-181] days, p < 0.001), and were more likely to be listed as Status 1 (8% vs. 4%, p = 0.02). Pre-LT resource utilization was significantly higher in ACLF patients. There were no differences in mortality at 30 days (ACLF 3% vs. No ACLF 2%, p = 0.17), 90 days (ACLF 3% vs. No ACLF 2%, p = 0.24), 1 year (ACLF 3% vs. No ACLF 2%, p =0.23), 3 years (ACLF 4% vs. No ACLF 3%, p = 0.58), or 5 years (ACLF 5% vs. No ACLF 4%, p = 0.38) after LT. ACLF status was not associated with increased post-transplant mortality (adjusted HR 1.51, 95% CI 0.76-3.0, p =0.25). ACLF is an important morbidity in children with BA awaiting LT as it is associated with higher resource utilization and longer waitlist times. Further studies are needed to help understand the spectrum of ACLF and better prioritize critically ill children awaiting LT, as our study shows successful post-LT outcomes in children with BA and ACLF.

Neonates with acute liver failure have higher overall mortality but similar posttransplant outcomes as older infants.

Neonatal acute liver failure (ALF) carries a high mortality rate; however, little data exist on its peritransplant hospital course. This project aimed to identify factors associated with outcomes in neonates with ALF using large multicenter databases. Patients with International Classification of Diseases, Ninth Revision/International Classification of Diseases, Tenth Revision codes for liver failure (2004-2018) from linked Pediatric Health Information System and Scientific Registry of Transplant Recipients databases were assigned to two groups: neonates aged ≤30 days or older infants aged 31-120 days at admission. Billing data were used to assign diagnoses and assess patient comorbidities (sepsis, extracorporeal membrane oxygenation, total parenteral nutrition, intensive care unit, and cardiac/renal/respiratory failure). Statistical analysis included Kaplan-Meier survival curve analysis and univariate and multivariate analyses with the Cox proportional hazards model. We identified 1807 neonates and 890 older infants. Neonates had significantly lower survival to 90 days ( p = 0.04) and a lower rate of liver transplantation (2.0% vs. 6.4%; p < 0.001). Common risk factors associated with death or transplant were present between groups: diagnosis, respiratory failure, cardiac failure, and renal failure. Among neonates versus older infants who received a transplant, there was no significant differences in posttransplant lengths of stay (median 38 vs. 32 days; p = 0.53), posttransplant mortality (15% vs. 11%; p = 0.66), or graft loss (9.7% vs. 8.1%; p = 0.82). We present the largest multicenter study on peritransplant outcomes in neonatal ALF and show similar risk factors for death or transplant in neonates compared with older infants. Despite lower transplantation rates, neonates demonstrate similar posttransplant outcomes as older infants. Further studies are needed to better risk stratify neonates eligible for transplant and improve outcomes.

Natural history and management of refractory autoimmune hepatitis.

Content available: Author Interview and Audio Recording.

Donor quality of life after living donor liver transplantation: a review of the literature.

Living donor liver transplantation (LDLT) provides a source for transplant in the setting of the deceased donor organ shortage. Seeing as living donors do not derive any medical benefit from the procedure, fully understanding the impact of donation on donor health-related quality of life (HRQOL) is essential. A systematic search of the MEDLINE database was performed from 2008-2020, using relevant Medical Subject Headings. Articles were evaluated for study design, cohort size and follow-up time and excluded if they contained significant methodological flaws. A total of 43 articles were included: 20 (47%) were cross-sectional and 23 (53%) were longitudinal. The mean number of donors per study was 142 (range:8-578) with follow-up ranging from 12-132 months. Forty-two unique HRQOL metrics were implemented across the 43 studies, the majority of which were questionnaires. Of the 31 studies that used the Medical Outcomes Study Short Form 36 questionnaire, 9.1% of donors reported physical QOL did not return to pre-LDLT levels for at least 2 years after donation. Mental QOL remained stable or improved after LDLT, with mean mental composite scores increasing from 50 to 52 at 3 months post-LDLT in one study. The predicted probability of poor sexual desire decreased at 1-year post-LDLT (male: 0.08, female: 0.26) relative to pre-LDLT (male: 0.44, female: 0.76; P<0.001) and three months post-LDLT (male: 0.35, female 0.69; P=0.001). Forty percent of donors found LDLT to be financially burdensome at 3 months and 19% at 2 years post-LDLT. Female gender and obesity were consistent predictors of worse HRQOL. Laparoscopy-assisted donor hepatectomy was associated with shorter hospitalizations than open donor hepatectomy (10.3 vs. 18.3 days, P=0.02). No studies used the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) measures of HRQOL. Our review demonstrates that LDLT can have a long-lasting negative impact on physical QOL in 9.1% of donors and can cause both sexual dysfunction and significant financial strain. Future studies should consider using standardized and extensively validated patient reported outcomes measures, such as PROMIS, in order to directly compare outcomes across studies and gain further insight into the impact of LDLT on D-HRQOL.

ARPC1B Mutation Manifesting as Recurrent Hematemesis With Metaplasia.

ARPC1B is important in the maintenance and assembly of the ARP2/3 complex. Loss of this complex due to ARPC1B mutation results in impairment of actin polymerization and subsequent defects in chemotaxis, cell migration, and DNA repair. Individuals with this rare mutation present in infancy and have abnormal innate and adaptive immune responses. They develop immune-mediated inflammatory disease with associated platelet defects, eosinophilia, rashes, and bowel disease. Recurrent gastrointestinal hemorrhage has been described in known cases. Here, we report a case with endoscopic and histologic findings in a patient with this rare mutation.

The need for support services for family carers of people with motor neurone disease (MND): views of current and former family caregivers a qualitative study.

PURPOSE: Family carers provide the majority of home-based care for people with motor neurone disease (MND). Carers' need for, and use of, support services are not fully understood; this study aimed to explore, from a qualitative perspective, the views of current and former family carers of people with MND. METHODS: A qualitative study was undertaken in Northwest England, using narrative interviews with current (18) and former (10) carers of a family member with MND. An optional longitudinal element involving diary completion was offered to the current carers. Data were analyzed using a thematic framework approach. RESULTS: Carer's needs vary, but encompass the provision of information and training, availability of respite care, counselling, and access to trained paid-for carers. CONCLUSIONS: There is need for a range of support services to be made available from which carers can select those most appropriate for them. Some support services are not always available for carers of this client group. There is a need for carers to access greater manual handling and training for physical care. Without sufficient support, carer burden can be overwhelming which may impact on the place of care of the patient and ultimately has implications for health and social care services.

Social services homecare for people with motor neurone disease/amyotrophic lateral sclerosis: why are such services used or refused?

Many patients with the terminal condition motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) do not access social service homecare, which may have implications for the location of end-of-life care. We aimed to identify factors related to uptake of such care in MND/ALS. A case note review of patients at a UK MND/ALS clinic (N = 97) provided data concerning disease onset and severity, demographic variables and care received. Narrative interviews with people with MND/ALS (N = 24) and family carers (N = 18) explored their perspectives on social services homecare. Quantitative analyses highlighted the role of increasing disease severity and age for social services homecare uptake. However, qualitative findings revealed a number of barriers delaying the uptake of such care. 'Internal' issues focused on retaining control and normality within the home. 'External' issues arose from limited understanding of the disease amongst service providers and lack of awareness of service entitlement amongst patients and carers. Multiple factors are implicated in the uptake of social services homecare. Uncertainties surrounding service entitlement must be addressed, including the simplification of bureaucratic procedures and clarification of the roles of health and social care professionals. Service providers need a greater awareness of the nature of the disease and their role in its management.

Experiences of dying, death and bereavement in motor neurone disease: a qualitative study.

OBJECTIVES: to explore the experiences of people with Motor Neurone Disease (MND), current and bereaved carers in the final stages of the disease and bereavement period. METHODS: a qualitative study using narrative interviews was used to elicit accounts from 24 people with MND and 18 current family carers and 10 former family carers. RESULTS: the needs of patients and carers are not being adequately met in the final stages of MND and there appears a need for increased, co-ordinated support from palliative care services. The use of advance care planning tools is regarded as beneficial for patients and carers, but health professionals demonstrate a limited understanding of them. Anxiety and distress in patients, carers and bereaved carers is heightened during this period. Carer burden is excessive and may exacerbate patient distress and desire for hastening death. CONCLUSION: this study has identified a number of issues people with MND and their carers face in the final stages of the illness, indicating some ways in which health, social and palliative care services could be improved or co-operate more effectively in order to better meet their needs.

From symptom onset to a diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND): experiences of people with ALS/MND and family carers - a qualitative study.

Our objectives were to explore the personal perspectives of the diagnostic experience for people with ALS/MND and their family carers identifying issues that could impact positively or negatively on these experiences. We conducted a qualitative study with face-to-face interviews to capture experiences from 24 people with ALS/MND and 18 current family carers. Ten former family carers were also interviewed. The diagnostic experience was fraught with difficulties. There was failure to recognize the significance of some symptoms by patients, carers and primary and secondary care health professionals, which ultimately delayed diagnosis. Delivery of the diagnosis was frequently unsatisfactory despite international guidelines on the subject. Immediate post-diagnosis support often compared negatively to that provided for people with cancer. In conclusion, this study has identified a need for a more streamlined and empathetic diagnostic pathway for people with ALS/MND. Improvements to medical curricula are required to increase awareness of the condition and reduce the likelihood of diagnostic delays resulting from a failure to recognize the need for a neurological referral. Greater public awareness of the illness is also needed. Furthermore, delivery of the diagnosis should more closely adhere to established guidelines.