(1) Background: Acute cholangitis during the first year after Kasai hepatoportoenterostomy (HPE) has a negative impact on patient and native liver survival. There are no consistent guidelines for the definition, treatment, and prophylaxis of cholangitis after HPE. The aim of this study was to develop definition, treatment, and prophylaxis guidelines to allow for expeditious management and for standardization in reporting. (2) Methods: the Delphi method, an extensive literature review, iterative rounds of surveys, and expert panel discussions were used to establish definition, treatment, and prophylaxis guidelines for cholangitis in the first year after HPE. (3) Results: Eight elements (pooled into two groups: clinical and laboratory/imaging) were identified to define cholangitis after HPE. The final proposed definitions for suspected and confirmed cholangitis are a combination of one element, respectively, two elements from each group; furthermore, the finding of a positive blood culture was added to the definition of confirmed cholangitis. The durations for prophylaxis and treatment of suspected and confirmed cholangitis were uniformly agreed upon by the experts. (4) Conclusions: for the first time, an international consensus was found for guidelines for definition, treatment, and prophylaxis for cholangitis during the first year after Kasai HPE. Applicability will need further prospective multicentered studies.

Background: The global pandemic caused by novel Coronavirus SARS-CoV-2 disease (COVID-19) is a major threat to the general population and for patients with pre-existing chronic conditions. We report data concerning SARS-CoV-2 infection in children with chronic liver disease (CLD).Methods: A literature review using the online database PubMed was performed to summarize available findings on the association between pre-existing liver disease and COVID-19 infection in children.Results: Children with COVID-19 have preserved effector and immunosuppressive components resulting in a milder disease compared to adults. The most common hepatic manifestation is an elevation of hepatic transaminases. Liver damage may be directly caused by viral infection of liver cells, by medications or by the chronic hypoxia seen in COVID-19 patients. A multicenter study reported that the majority of children with a CLD remained healthy during the outbreak. Similarly, studies reported that children on immunosuppressive treatment, including patients with autoimmune liver disease (AILD) and liver transplantation (LT), maintained good health during the outbreak without experiencing major complications even if infected with COVID-19.Conclusion: COVID-19-related liver injury presents with a mild elevation of transaminases, although its clinical significance is unclear. Children with CLD, including those with AILD and post-LT, do not have an increased risk for severe disease course of SARS-CoV-2 infection with little or no liver dysfunction. These data highlight the necessity to ensure normal standards of care while adhering to national Covid-19 guidelines, and particularly to maintain immunosuppressive medication to prevent relapse or rejection. Further research is required to evaluate the differences in clinical course between immunosuppressed adults and children and in particular whether asymptomatic infection is a concern.

Acute liver failure (ALF) is a rare but potentially fatal disease in children. The etiology is multifactorial, including infection, autoimmune, and genetic disorders, as well as indeterminate hepatitis, which has a higher requirement for liver transplantation. Activation of the innate and adaptive immune systems leads to hepatocyte-specific injury which is mitigated by T regulatory cell activation. Recovery of the native liver depends on activation of apoptotic and regenerative pathways, including the integrated stress response (ISR; e.g., PERK), p53, and HNF4α. Loss-of-function mutations in these pathways cause recurrent ALF in response to non-hepatotropic viruses. Deeper understanding of these mechanisms will lead to improved diagnosis, management, and outcomes for pediatric ALF.

Although trough levels of immunosuppressive drugs are largely used to monitor immunosuppressive therapy after solid organ transplantation, there is still no established tool that allows for a validated assessment of functional degree of immunosuppression or the identification of clinically relevant over- or under-immunosuppression, depending on graft homeostasis. Reliable non-invasive markers to predict biopsy proven acute rejection (BPAR) do not exist. Literature data suggest that longitudinal measurements of immune markers might be predictive of BPAR, but data in children are scarce. We therefore propose an observational prospective cohort study focusing on immune monitoring in children after liver transplantation. We aim to describe immune function in a cohort of children before and during the first year after liver transplantation and plan to investigate how the immune function profile is associated with clinical and laboratory findings. In an international multicenter prospective approach, children with end-stage liver disease who undergo liver transplantation are enrolled to the study and receive extensive immune monitoring before and at 1, 2, 3, 4 weeks and 3, 6, 12 months after transplantation, and whenever a clinically indicated liver biopsy is scheduled. Blood samples are analyzed for immune cell numbers and circulating levels of cytokines, chemokines and factors of angiogenesis reflecting immune cell activation. Statistical analysis will focus on the identification of trajectorial patterns of immune reactivity predictive for systemic non-inflammatory states, infectious complications or BPAR using joint modelling approaches. The ChilSFree study will help to understand the immune response after pLTx in different states of infection or rejection. It may provide insight into response mechanisms eventually facilitating immune tolerance towards the graft. Our analysis may yield an applicable immune panel for non-invasive early detection of acute cellular rejection, with the prospect of individually tailoring immunosuppressive therapy. The international collaborative set-up of this study allows for an appropriate sample size which is otherwise difficult to achieve in the field of pediatric liver transplantation.