Pentoxifylline/Nonalcoholic Steatohepatitis (NASH) Study: The Effect of Pentoxifylline on NASH

Inclusion Criteria:

1. Subjects must be willing to give written informed consent

2. Diagnosis of steatohepatitis Grade >= 1 (Brunt et al. criteria - Am J Gastroenterology 1999;94(9)2467-74) on biopsy within 6 months prior to entry into protocol

3. No histologic evidence of cirrhosis

4. Persistent ALT elevation (> 1.5 the upper limit normal) over 6 months prior to entryinto study

5. Adult subjects 18-65 years of age of any race or gender

6. Compensated liver disease with the following hematologic, biochemical, and serologicalcriteria on entry into protocol:

• Hemoglobin > 11 gm/dL for females and > 12 gm/dL for males

• White blood cell (WBC) > 2.5 K/UL

• Neutrophil count > 1.5 K/UL

• Platelets > 100 K/UL

• Direct bilirubin, within normal limits

• Indirect bilirubin within normal limits (unless non-hepatitis factors such asGilbert's disease explain indirect bilirubin rise. In such cases total bilirubinmust be < 3.0 mg/dL)

• Albumin > 3.2 g/dL

• Serum creatinine within normal limits

7. Hemoglobin A1c (HgbA1c) < 7%

8. Antinuclear antibodies (ANA) < 1:160

9. Anti-smooth muscle Ab negative

10. Serum hepatitis B surface antigen (HepBsAg) negative

11. Serum hepatitis C antibody (HepC Ab) negative

12. Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) < 45%

13. Alpha-1-antitrypsin level within normal limits

14. Ceruloplasmin level within normal limits

15. Negative pregnancy test (females)

16. Concomitant use of lipid lowering agents at study entry will not exclude patients fromthe study.

Exclusion Criteria:

1. Evidence of decompensated cirrhosis

2. Active gastrointestinal (GI) bleeding

3. Renal failure (creatinine clearance < 80 mL/min)

4. Active alcohol or drug abuse

5. Uncontrolled diabetes (HgbA1c > 7)

6. Current treatment with anti-diabetic medications such as thiazolidinediones ormetformin (stable doses of sulfonylureas are acceptable)

7. Current treatment with anti-TNF alpha medication (i.e. Remicade or Enbrel)

8. Current treatment with vitamin E

9. Alcohol consumption < 20 g/day (males) or < 10 g/day (females) - assessed by onephysician and confirmed with one family member.

10. HIV positive status

11. Any history of cerebral and/or retinal hemorrhage

12. Prior intolerance of pentoxifylline or any other methylxanthine (i.e. caffeine,theophylline, or theobromine)

13. Current use of theophylline

14. Known diagnosis of malignancy

15. Any other conditions which the investigator feels would make the subject unsuitablefor enrollment, or could interfere with the subject completing the protocol