Influence of Probiotics Administration Before Liver Resection in Liver Disease
Influence of Probiotics Administration Before Liver Resection in Liver Disease
Surgical resection is one of the curative treatment modalities for HCC. Limits are
 postoperative septic and liver functional complications related to an increase in bacterial
 translocation and systemic endotoxemia. Bacterial translocation is a passage of bacteria and
 bacterial degradation products from the intestine to the portal circulation. The endotoxemia
 secondary to bacterial translocation, stimulates endothelial production of nitric oxide (NO).
 NO is also a potent inducer of membrane instability, responsible for an increase in the
 permeability of the vascular endothelium and intestinal mucosa, possibly contributing to a
 worsening of bacterial translocation.

 Probiotics are live microorganisms which when administered in adequate amounts, provide a
 health benefit on the host ((Health and Nutritional Properties of Probiotics in Food
 Including Powder Milk with Live Lactic Acid Bacteria - Cordoba Argentina October 2001). Data
 from experimental and clinical literature show a significant effect of probiotics on the
 improvement of liver function and a decrease in infectious complications in patients with
 chronic liver disease. The proposed study would evaluate the effect preventive and
 therapeutic in a population of surgical patients, in whom the intestinal portal and hepatic
 inflammation promotes postoperative complications.
The aim of this study is to evaluate the effect of the administration of probiotics on
 intestinal barrier function in patients with chronic liver disease (fibrosis stage F3 or F4)
 operated for hepatocellular carcinoma.

 After hepatectomy, kinetic of endotoxemia have been studied previously and the evolution will
 be summarized by the area under the plasma concentration versus time curve (AUC) of
 circulating endotoxin levels measured before surgery and at 5 different times analysis after
 hepatectomy. At 12 hours, portal hypertension and its consequences on gut permeability
 (impaired barrier function, bacterial translocation) are highest with peak of circulating
 endotoxins. The decreasing of endotoxemia curve is observed between the 2nd and 3rd day (end
 of liver regeneration and early liver architectural reorganization). On the 5th day, persist
 measurable but not deleterious to liver restructured and theoretically functional rates.

 Then the main criterion to demonstrate the effectiveness of a diet enriched with probiotics
 is the AUC of circulating levels of endotoxins ((pg/ml) using the Limulus amebocyte lysate
 (LAL) assay) observed for each patient. Endotoxin levels were analysed on samples of
 peripheral blood. The two arms of equal size will be considered significantly different when
 compared to the AUC of circulating levels of endotoxin if the null hypothesis (AUC is the
 same for both arms) is rejected in favor of the alternative hypothesis (AUC differs between
 the two arms - Wilcoxon test)

 In order to estimate the sample size to distinguish between the two hypotheses with
 sufficient power, the median AUC in arm without probiotics be used to form two groups of
 patients in each arm. Thus, half of the patients without probiotics have a higher median AUC
 arms. Then, this proportion may be compared to the proportion of patients with probiotics
 have an AUC greater than the median of the group without probiotics.

 The secondary endpoints are:

 -  Evaluation of systemic inflammation by assay of inflammatory cytokines

 -  IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFNa, TNFa

 -  CRP

 -  Leukocyte count

 -  The post-operative liver function monitored in the usual manner

 -  Standard Liver function tests between J1 and J5 (Bilirubin, prothrombin, ammonia)

 -  Indocyanine green clearance with measuring retention rates at 15 minutes between J1 and
 J3

 -  Monitoring of overall postoperative complications and specifically liver failure and
 infectious complications at 3 months.
Inclusion Criteria:

 -  Agreement signed by the patient

 -  Diagnosis of HCC confirmed

 -  Diagnosis of liver disease (score F3 or F4) confirmed

 -  Indication of surgical resection confirmed and validated by a specialist
 multidisciplinary assessment meeting of gastrointestinal oncology

 -  Patient operable (no indication against anaesthesiological)

 -  Resectable tumor lesion (surgical expertise)

 -  Laboratory tests and endoscopy: No suspicion of severe portal hypertension with
 bleeding risk

 Exclusion Criteria:

 -  Patient not willing, at risk of default of compliance, or patient can not be monitored
 regularly

 -  Antibiotic extended or terminated for less than 1 month, may limit the effects of
 taking probiotics.

 -  Inflammatory Bowel Disease, which could skew the results expected by taking probiotics
 results.