Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury.

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

COVID-19 Vaccine Seroresponse Based on The Timing of The Primary Series; Pre- versus Post-Renal Transplantation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) poses a serious risk to patients with chronic kidney disease (CKD) and renal transplant. While COVID-19 vaccination is recommended before transplant, there are limited data comparing vaccine timing. Our aim is to evaluate serological responses to COVID-19 vaccines pre- and post-renal transplant and the durability of antibody levels. METHODS: We retrospectively evaluated the antibody response of adult renal transplant recipients who had received at least a primary series of the COVID-19 vaccine. The patients were divided into two groups based on the timing; pre- or post-transplant. Antibody titer levels were evaluated at least 4 weeks after vaccination for each group. Titer durability was assessed by calculating the median titer level of individuals. RESULTS: A total of 139 patients were identified between January 2019 and April 2022. Twenty-nine patients were excluded because of previous COVID-19 infection, and 15 patients were excluded each for insufficient vaccine doses and lack of titer data. Forty patients were included for the pre-transplant group and 40 for post-transplant. The number of pre-transplant patients who developed antibodies (39 patients, 97.5%) was significantly greater than the number of post-transplant patients (21 patients, 52.5%) with p < .01. The median post-vaccination titer levels were significantly greater in the pre-transplant group up to 5 months after vaccination (p < .05). The pre-transplant group's titers seemed sustained even after renal transplantation. CONCLUSION: Vaccinating renal transplant patients before transplant results in increased achievement of seroresponse, higher levels of antibody titers, and sustained titers following transplant. Larger and prospective studies are warranted to confirm the findings.

Diagnosis of metastatic fibrolamellar hepatocellular carcinoma by endoscopic ultrasound-guided fine needle aspiration.

The fibrolamellar variant of hepatocellular carcinoma (FL-HCC) is distinguished from other hepatocellular carcinomas (HCC) by its unique clinical and pathologic features. Cytological features for this tumor on fine needle aspiration (FNA) of primary tumors have been described earlier. We present here a unique case of metastatic FL-HCC diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of mediastinal adenopathy. A 32-year-old woman with a history of oral contraceptive use presented with nausea and severe abdominal pain but no ascites or stigmata of cirrhosis. She had a past history of resection of a liver lesion. Serial computed tomography scans revealed mediastinal lymphadenopathy and the patient was referred for endoscopic ultrasound (EUS). A transesophageal EUS-FNA was performed and tissue was collected for cytological evaluation by an on-site pathologist with no knowledge of prior history. Based on morphology correlated with prior history received later, a final diagnosis of metastatic FL-HCC in the retrocardiac lymph node was rendered on the EUS-FNA samples. There are very few reports in the literature where a diagnosis of FL-HCC is rendered at unusual sites. This case highlights that EUS-FNA is a relatively non-invasive, rapid, accurate and effective modality in obtaining tissue from otherwise hard-to-reach areas. It also suggests that metastasis of FL-HCC can be observed in mediastinal nodes and that diagnosis based on cytological features can be rendered even when the tumor is identified at unusual locations.