| Backgroud:Due to the changes in diet and lifestyle, more and more people were suffering from fatty liver disease. Some authors reported that patients with severe steatosis had an increased risk of inflammatory complications after liver resection, however, the exact mechanism remained unclear. This might be attributable to Kupffer cell-mediated inflammation in steatotic livers causing progressive injury.Objective:The aim of this study was to assess the influence of steatosis on hepatocellular recovery after partial hepatectomy(PH) in both a rat model of high-fat diet-induced steatosis and clinical data.Methods:Experimental part:healthy male SD rats were fed with a high-fat diet for8weeks, and then pathological histology of liver was taken to assess the degree of fatty liver. When severe steatosis was successfully induced in a rat model, a70%PH was performed. Rats were killed at6,12,24,48or72hours after liver resection, respectively. The blood and liver tissue were collected for detection. Outcome parameters were hepatocellular injury (ALT, AST in plasma), Kupffer cell-mediated proinflammatory response (IL-6, TNF-a in plasma), antioxidant content and ischemia-reperfusion injury (SOD, MDA in liver), liver regeneration (regeneration rate, histopathology, and Ki-67proliferation rate). Clinical part:A retrospective analysis of338patients who undergoing hepatic resection because of hepatic carcinoma was performed. Their clinical and pathological data were collected for statistical analysis.Results:Experimental part:8weeks high-fat diet induced severe steatosis (>60%hepatocytes affected without inflammation or fibrosis) as confirmed by histopathology. Body weight were higher in the steatosis group (P<0.05). Kupffer cell-mediated proinflammatory response (IL-6, TNF-a in plasma), hepatocellular injury (ALT, AST in plasma) and ischemia-reperfusion injury (SOD, MDA in liver) were increased in both steatosis group and control group after PH. What’s more, hepatocellular injury and Kupffer cell-mediated inflammatory responses were significantly increased in the severe steatosis group at all time points compared with the control group(P<0.05). Ischemia-reperfusion injury were increased in the severe steatosis group compared with the control group at6,12,24h after PH (P<0.05). The regenerative response in control rats was evident at the first6h, peaked at24h and decreased by48h. In contrast, in the steatosis group no regeneration was evident at the first24h after PH, but it was markedly increased at48h and72h. Despite remained relatively high until72h, regeneration in the steatosis group was impaired at each time points as compared with control group except at72h after PH due to this delay by12h in the commencement of regeneration (P<0.05). Clinical part:273cases,44cases and21cases were presented in the control group, mild steatosis group and moderate-to-severe steatosis group, respectively. There was a higher body mass index in the steatosis group(P<0.05). Operative time, blood loss, transfusion rate, postoperative hospital stay and ICU stay were increased in patients of moderate-severe fatty liver group (P<0.05).Conclusion:In experimental part, our study showed that severe steatosis injury the regeneration and liver function after PH. Severe steatosis increased hepatocellular lipid peroxidation and damage in concert with Kupffer cell-mediated proinflammatory responses after70%PH might be one of the reasons. Our results suggested an increased risk of performing extensive partial hepatectomy in the presence of severe steatosis. In clinical part, we found that mild steatosis had less impact on partial hepatectomy. Moderate-to-severe hepatic steatosis was associated with an increased blood loss and perioperative morbidity. In a word, steatosis increased the risk of partial hepatectomy. |
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