Abstract
Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model.Methods: Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured in-vivo. Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed.Results: Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model.Conclusion: In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.
Highlights
Liver cirrhosis is the common end-stage of chronic liver diseases
Animals were randomized into a group that underwent intestinal manipulation (IM) or median laparotomy (LAP)
Animals presenting with ascites as a clinical sign of Acute decompensation (AD) prior to IM or LAP were excluded from the experiment
Summary
Liver cirrhosis is the common end-stage of chronic liver diseases. Acute decompensation (AD) such as variceal bleeding, refractory ascites, hepatorenal syndrome, or hepatic encephalopathy can develop and define advanced stages (Angeli et al, 2018). AD may precipitate acute-on-chronic liver failure (ACLF), a distinct syndrome recently characterized in the CANONICand PREDICT-study (Moreau et al, 2013; Gustot et al, 2015; Trebicka et al, 2019, 2020a,b). Even though there has been substantial progress in the fields of hepatology and surgery in managing patients with cirrhosis, surgery-associated AD and mortality remains high and correlates with severity of liver disease (Friedman, 2010; de Goede et al, 2012). Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model
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