Effect of preoperative interventions on outcome following liver resection in a rat model of cirrhosis

Background/Aims: High morbidity and mortality rates in cirrhotic patients undergoing resections for hepatocellular malignancies underscore the need for identifying a therapy that will decrease fibrosis or enhance hepatic regenerative activity in the perioperative period. Thus, in the present study, 104 carbon tetrachloride-induced cirrhotic rats received either saline (untreated cirrhotic controls) or one of the following agents that have been reported to decrease hepatic fibrosis or increase hepatic regeneration; pentoxifylline, ciprofloxacin or a traditional Chinese herbal remedy (TCHR). Twelve additional rats served as healthy, non-cirrhotic controls. Methods: Treatments were administered daily by gavage for 4 weeks followed by a 70% partial hepatectomy. Hepatic fibrosis was documented at the time of surgery by computer-assisted quantitation of collagen content. Liver function and hepatic regenerative activity were documented 24 h post partial hepatectomy by serum bilirubin determinations and a combination of 3[H]-Thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) quantitation, respectively. Results: Compared to untreated cirrhotic controls (8.1±0.7%), fibrosis was significantly reduced in the pentoxifylline- and ciprofloxacin-treated groups (4.6±0.2%, p<0.005 and 5.5±0.6%, p<0.05) but unchanged in the TCHR-treated group (6.6±1.0%). Post-operatively, total serum bilirubin levels were lower in the pentoxifylline (1.40±0.15 mg/dl, p<0.01) and ciprofloxacin (1.87±0.25 mg/dl, p<0.05)-treated groups, but unchanged in the TCHR group (2.20±0.45 mg/dl), when compared to untreated cirrhotic controls (3.00±0.37 mg/dl). Hepatic regenerative activity was also significantly improved in the pentoxifylline-treated group (17.8±2.2 versus 9.9±1.9 DPM/μg DNA in untreated cirrhotic controls, p<0.05), but unchanged in the ciprofloxacin (16.1±1.8 DPM/μg DNA) and TCHR (10.9±1.2 DPM/μg DNA)-treated groups. PCNA protein determinations were in keeping with the 3[H]-Thymidine results. Conclusions: Pre-operative pentoxifylline holds promise as a useful therapeutic intervention for patients with cirrhosis requiring hepatic resection.