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Subclinical rejection (SCR) is a common injury in protocol biopsy after pediatric liver transplantation (pLT), but its effect on the recipient is not clearly understood. We herein investigated the incidence and risk factors involved in SCR and analyzed the relationship between SCR and allograft fibrosis (AF).We retrospectively reviewed the biopsy results from 507 children between May 2013 and May 2019, and 352 patients underwent protocol biopsy two years after pLT, 203 underwent protocol biopsy five years after pLT, and 48 underwent protocol biopsy both two and five years after pLT.The incidence of SCR in the five-year group was higher than that in the two-year group (20.2%vs.13.4%, respectively, P = 0.033). The number of patients with mild and moderate SCR in the 5-year group was also higher than that in the 2-year group(P = 0.039). Logistic regression analysis showed that acute rejection before liver biopsy and cadaver liver transplantation (DDLT) were independent risk factors for SCR in the two groups, and that the incidence and severity of AF in protocol biopsies at both periods in the SCR group were higher than those in the non-SCR group (P0.05).The incidence and severity of SCR increased with the prolongation of protocol biopsy time. We postulate that acute rejection and DDLT are independent risk factors for SCR after transplantation. As the occurrence of SCR also augmented the incidence and severity of AF. This article is protected by copyright. All rights reserved.

Hepatic ischemia/reperfusion injury (IRI) is tissue damage resulting from return of the blood supply to the tissue after a period of ischemia or lack of oxygen. Much of the morbidity associated with liver transplantation and major hepatic resections is, in part, due to IRI. Both innate immunity and autophagy play important roles in hepatic IRI. With regard to innate immunity, one factor that plays a key role is NOD1, an intracellular pattern recognition receptor. NOD1 has recently been shown to be associated with autophagy, but the mechanisms involved with this process remain obscure. This relationship between NOD1 and autophagy prompted us to examine the role and potential mechanisms of NOD1 in regulating autophagy as related to hepatic IRI. We found that NOD1 was upregulated during hepatic IRI and was associated with an activation of the autophagic signaling pathway. Moreover, levels of Atg5, a critical protein associated with autophagy, were decreased when NOD1 was inhibited by NOD1 small interfering RNA. We conclude that NOD1 appears to exert a pivotal role in hepatic IRI by activating autophagy to aggravate hepatic IRI, and Atg5 was required for this process. The identification of this novel pathway, that links expression levels of NOD1 with Atg5-mediated autophagy, may provide new insights for the generation of novel protective therapies directed against hepatic IRI.

AIM To compare the immunogenicity of two modified hepatitis B virus (HBV) vaccination schedules in liver transplant recipients. Hepatitis B immunoglobulin (HBIG) in combination with nucleoside/nucleotide analogs (NUCs) is the recommended prophylaxis for preventing HBV recurrence following liver transplantation (LT). However, HBIG treatment is expensive. Active immunization with hepatitis B vaccine would be a preferable alternative prophylaxis to replace HBIG treatment. However, the overall response rate to standard vaccination (given at months 0, 1 and 6) is relatively low in immune-compromised patients. METHODS Two cohorts of 114 subjects were immunized with recombinant HBV vaccine containing S-antigen. The patients in the rapid schedule group were immunized with 40 μg HBV vaccine at months 0, 1, 2 and 3, and with 20 μg at months 4, 5 and 6. The patients in the accelerated schedule group were immunized with 40 μg of HBV vaccine at days 0, 7, 14 and 28, and 20 μg at months 2, 3 and 4. RESULTS The overall response rate was 16.7% (19/114) and all responders discontinued HBIG injection and only one patient developed HBV recurrence. The response rate was 24.6% (14/57) and 8.8% (5/57) in the rapid vaccination and the accelerated vaccination schedules, respectively (P = 0.024). CONCLUSION HBV vaccination may induce endogenous anti-HBs to replace HBIG in selected patients. Vaccination schedules may influence vaccine response, and individual optimization may improve response rate to HBV vaccination.