Evaluation of the Effect of Gabexate Mesilate in the Hepatocyte Protection After Liver Resection

Summary

Liver resection have been a primary treatment option for lesions found in the liver. With improvements in surgical technique and perioperative patient management, morbidity and mortality related to liver resection have been greatly reduced. However, many patients with hepatocellular carcinoma have underlying liver disease. Severity of underlying liver disease plays an important role in decision making of resection extent. Therefore, liver failure and decreased liver function following liver resection still remains to be an critical issue.

Postresection liver failure is generally defined by serum total bilirubin greater than 3mg/dL and prothrombin time of less than 50% of normal (INR \>1.7). Pathophysiology of postresection liver failure is not yet well known. However, sepsis after liver resection, small-for-size syndrome (SFSS), and ischemia/reperfusion injury are known to have important roles in persistant liver injury after resection.

After a liver resection, kupffer cells are drastically decreased and innate immunity of the patient is also damaged. This process causes the patient to be vulnerable to infection. In addition, with continuous endotoxin secretion, dysfunction in kupffer cells are triggered and liver regeneration is affected.

Complex mechanisms leading to dysfunctional kupffer cells and apoptosis and necrosis of hepatocytes are mediated by neutrophils, complement, reactive oxygen species, and acute inflammatory cytokines.

Recent studies have reported on many promising effects of the synthetic protease inhibitor, such as Gabexate mesilate. These include antioxidant effect, inhibition of acute inflammatory cytokine reaction, and anticoagulatory property. Based on these effects, synthetic protease inhibitor have gained attention in the role of hepatocyte protection after liver resection.

Currently, there is a report on the hepatocyte protective effects of Gabexate Mesilate on ischemia/reperfusion injury caused by the Pringle maneuver. However, with the advances in surgical technique and equipment, many surgeons now perform liver resection without Pringle maneuver. Therefore, this study was designed to determine effects of Gabexate Mesilate in the liver resection performed without Pringle maneuver.

Conditions

• Liver Disease

Interventions

DRUG

Preoperative Gabexate Mesilate group

Gabexate Mesilate is administered from the preoperative day and continued for 5 days. 300mg of Gabexate Mesilate is mixed with 500cc of 5% dextrose water and administered at 40cc/hr for 12 hours each day.

DRUG

Intraoperative Gabexate Mesilate group

Gabexate Mesilate is administered from the operative day and continued for 5 days. 300mg of Gabexate Mesilate is mixed with 500cc of 5% dextrose water and administered at 40cc/hr for 12 hours each day.

DRUG

hepatectomy with dextrose water

Gabexate Mesilate is not administered. As placebo, 500cc of 5% dextrose water is administered at 40cc/hr for 12 hours

Sponsors & Collaborators

• Yonsei University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-02-24

Primary Completion

2017-02-25

Completion

2017-02-25

Countries

• South Korea

Study Locations