BackgroundHepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-associated macrophages (TAMs) of HCC, and can produce various cytokines—most importantly interleukin (IL)-6—to promote tumorigenesis of HCC. However, the roles of KCs and IL-6 in carcinogenesis in the liver are still unclear.MethodsWe analyzed leukocyte-related peripheral blood data of 192 patients and constructed a mouse model in which the bone marrow was cleared out by irradiation and reconstructed using bone marrow donated from IL-6-deficient mice to further elucidate the hepatic pathological changes in response to toxic challenge and oncogenic gene mutation.ResultsPeripheral monocyte counts and serum IL-6 levels were significantly higher in patients with HCC than in those without HCC. In addition, there was a significant difference in the levels of IL-6 among individuals with different histopathological grades. In mice with selective IL-6 ablation in monocytes/KCs, we observed decreased toxic liver injury, inflammatory infiltration, and systemic inflammation. In Mdr2-deficient mice, which spontaneously developed HCC, the loss of IL-6 in monocytes/KCs resulted in inhibition of IL-6/signal transducer and activator of transcription 3 signaling, decreased serum IL-6 levels, and delayed tumorigenesis.ConclusionsOur findings demonstrate that increased TAM-derived IL-6 had an amplifying effect on the inflammation response, thereby promoting the occurrence and development of HCC.

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To investigate whether postoperative hepatic hemodynamics have an impact on graft function. Using a retrospective cohort with 262 adult living donor liver transplantation (LDLT) recipients, we discussed the relationship between postoperative hepatic hemodynamics and patient outcomes. According to the definition of early allograft dysfunction (EAD), the patients were classified into the EAD group (43 patients) and the non-EAD group (219 patients). In terms of postoperative hemodynamic parameters, there was no significant differences between these 2 groups regarding hepatic artery flow (HAF), hepatic artery velocity (HAV), portal vein flow (PVF), and portal vein velocity (PVV), except for the hepatic artery resistance index (HARI) which was somewhat higher in the EAD group on postoperative day 3 (POD3) (0.70 vs 0.61, P < .05). According to these results, we used a ROC curve and found that a HARI of 0.68 was the cutoff point (with 73.8% sensitivity and 58.3% specificity) for predicting EAD after LDLT. In addition, multivariate analysis showed that fulminant hepatic failure, pretransplant hepatorenal syndrome, and HARI ≥ 0.68 on POD3 were independent risk factors for postoperative EAD. Our results showed that postoperative hemodynamics might influence graft function by altering hepatic artery flow.

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