Fk506 Inhibit Liver Regeneration in HOC Model Rat

BackgroundStudies have shown that lymphocytes support hepatic oval cell (HOC)-dependent liver regeneration and FK506（Tacrolimus） is known as an immunosuppressor. Therefore, we studied the role of FK506 in HOC activation and/or proliferation to guide the clinical use of FK506.MethodsThirty male Lewis rats were randomly divided into 4 groups: (A) intervene in activation (n = 8), (B) intervene in proliferation (n = 8), (C) control HOC model (n = 8), and (D) pure partial hepatectomy (PH) (n = 6). The HOC model was established by 2AAF(2-acetylaminofluorene)/PH in groups A to C. FK506 (at a dose of 1 mg/kg/d) was given subcutaneously in group A except on operation day, and not until day 8 post-operation (PO) in group B. Half of the animals were euthanized on days 10 and 14 PO, respectively. The remnant liver was weighed and stained by hematoxylin and eosin and immunohistochemical staining of proliferating cell nuclear antigen and epithelial cell adhesion molecule enabled HOC proliferation analysis.ResultsFK506 intervention exacerbated liver damage and hindered the recovery of the HOC model rat. Weight gain was severely retarded or even negative. Liver weight and the liver body weight ratio were lower than control group. HE and immunohistochemistry showed pooer proliferation of hepatocytes and fewer HOC numbers in group A.ConclusionFK506 inhibited HOC activation by affecting T and NK cells, ultimately blocking liver regeneration. Poor liver regeneration after auxiliary liver transplantation might be associated with the inhibition of HOC activation and proliferation caused by FK506 treatment.     

Rejection and graft outcomes in kidney transplant recipients with and without angiotensin II receptor type 1 antibodies

AimAngiotensin II type 1 receptor antibody (AT1R Ab) is a non-Human Leucocyte Antigen (HLA) antibody that is maybe associated with early severe kidney transplant rejection and worse graft outcomes. This study aimed to assess the association between AT1R Ab and kidney transplant rejection and graft outcomes.MethodsWe performed a retrospective analysis of all adult kidney transplant recipients in an Australian centre who had an AT1R Ab test between 1 January 2015 to 30 June 2020. AT1R Ab positive patients were compared to AT1R Ab negative patients. Primary outcomes were rejection risk, type and histopathological severity scores. Secondary outcomes were 8-week graft function and graft loss.ResultsOf 965 kidney transplants that were performed during the study period, 73 patients had AT1R Ab tested; 16 (22%) were positive and 57(78%) were negative. Positive patients were on average younger and had higher level of donor-specific HLA antibodies. Rejection occurred in 13 (81%) positive patients and 41 (72%) negative patients (P = 0.45). No significant differences in rejection type or severity were found. HLA mismatch and peak panel reactive antibody ≥80%, but not AT1R Ab, independently predicted rejection. Average (132 vs. 177 mmol/L, P = 0.302) and graft loss were not significantly different between groups.ConclusionThe study found no evidence that AT1R Ab is associated with rejection type, severity or worse graft function. Future studies should assess its relationship with graft outcomes to help complement immunological risk assessment and potentially provide therapeutic options to alter outcomes.     

National Trends in Transplantation-Associated Intensive Care Unit Admission in South Korea From 2010 to 2019

BackgroundWe aimed to investigate the mortality and associated factors among patients admitted to the intensive care unit (ICU) after transplantation in South Korea.Materials and MethodsThe South Korean National Health Insurance Service database was used as the data source. All adult patients (age ≥18 years) who were admitted to the ICU for organ transplantation-related causes from January 1, 2010 to December 31, 2019 (10 years) were included. Transplantation-associated ICU admissions were defined as admissions to the ward and ICU after transplantation or to the ICU before transplantation.ResultsA total of 23,994 ICU admissions after transplantation were included in the analysis (mean [SD] age: 52.7 [10.7] years; men: 67.0%; kidney transplantation: n = 9638; liver transplantation: n = 12,196; heart and/or lung transplantation: n = 1829; pancreas or small bowel transplantation: n = 331). Transplantation-associated ICU admissions gradually increased from 1666 in 2010 to 3014 in 2019. The 1-year mortality rates were 21.2%, 12.3%, 4.2%, and 3.0% after heart and/or lung, liver, pancreas or small bowel, and kidney transplantation, respectively. Invasive life support procedures during ICU stay, comorbidities, and older age were potential risk factors for 1-year mortality after transplantation.ConclusionTransplantation-associated ICU admissions gradually increased from 2010 to 2019 in South Korea. The 1-year mortality rate after transplantation was the highest in the heart and/or lung transplantation group, followed by those of the liver, pancreas or small bowel, and kidney transplantation groups.     

Soluble HLA-G levels in heart transplant recipients: Dynamics and correlation with clinical outcomes

PurposeTo describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes.MethodsObservational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden –as assessed by a rejection score–, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years.ResultsSoluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV.Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population.ConclusionsSoluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.