破译 HCV 相关肝纤维化范围内微生物易位的机制

Primary clinical patients with chronic HCV infection divided into 2 groups according to liver fibrosis stage.

• INCLUSION CRITERIA:

  1. All age greater than 18 male or female
  2. Capacity to provide written informed consent
  3. Evidence of HCV RNA in 2 serum samples at least 6 months apart.
  4. All HCV genotypes
  5. Liver biopsy in the last 2 years prior to enrollment showing Ishak fibrosis score of either 0-1 or 5-6. An alternative to liver biopsy will be a Fibroscan study performed in the 6 months prior to study enrollment showing a score of either kPa <7 or above 13.
  6. Child-Pugh score less than or equal to 6
  7. Prior to each liver biopsy and portal vein cannulation procedure, blood will be drawn for CBC, PT/INR & acute care panel.

EXCLUSION CRITERIA:

1. Pregnant women or females at child bearing age not taking measures to prevent pregnancy during the period of study

2. Patients currently on treatment for hepatitis C

3. Clinical, serologic or histopathologic evidence supporting other etiologies of chronic liver disease besides HCV

4. Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy etc.)

5. Cross sectional liver imaging study from the past 6 months showing a focal lesion suspicious of hepatocellular carcinoma and/or alpha-fetoprotein level greater than 200 ng/mL.

6. Patients with active bacterial, viral or fungal, systemic or localized infection.

7. Antibiotic treatment 30 days prior to study enrollment

8. History of chronic inflammatory diseases of the bowel (Crohn s disease, Ulcerative colitis and celiac disease)

9. History of congestive heart failure of moderate to severe degree.

10. History of non-cirrhotic portal hypertension or portal vein thrombosis

11. Patients with severe allergic reactions to iodine contrast, which cannot be controlled by premedication with antihistamines and steroids.

12. EXCLUSION CRITERIA FOR MRI:

    12.1 Subjects with contraindication to MRI scanning. These contraindications include but are not limited to the following devices or conditions:

    <TAB>a. Implanted cardiac pacemaker or defibrillator

    <TAB>b. Cochlear Implants

    <TAB>c. Ocular foreign body (e.g. metal shavings)

    <TAB>d. Embedded shrapnel fragments

    <TAB>e. Central nervous system aneurysm clips

    <TAB>f. Implanted neural stimulator

    <TAB>g. Medical infusion pumps

    <TAB>h. Any implanted device that is incompatible with MRI.

    12.2 Unsatisfactory performance status as judged by the referring physician such that the subject could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would include unstable angina and dyspnea at rest.

    12.3 Subjects requiring sedation for MRI studies.

    12.4 Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.).

    12.5 Pregnant or lactating women.

    12.6 Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination.

    12.7 For Gadolinium based and SPIO MRI Use:

    <TAB>a. History of severe allergic reaction to these contrast agents despite the use of premeditation with an anti-histaminic and cortisone.

    <TAB>b. eGFR < 60 ml/min/1.73m^2

13. Absolute neutrophil count below 1000/mm^3, Hemoglobin level below 10.0 g/dl or platelet count lower than 70,000/mm^3.

14. INR greater than or equal to 1.5, PTT greater than or equal to 1.3 times control and/or any known history of disease associated with increased bleeding diathesis.

15. Serum creatinine greater than or equal to 2.0 mg/dl unless the measured creatinine clearance is greater than 60 mL/min