Pentoxifylline in Patients With Nonalcoholic Steatohepatitis
Condition: Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: pentoxifylline (PTX); placebo
Intervention description: 400 mg PO tid; placebo tid
Intervention MeSH terms: Pentoxifylline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Fatty Liver; Nonalcoholic fatty liver disease (NALFD); NAFLD; Nonalcoholic steatohepatitis (NASH); NASH; pentoxifylline

Summary:

      One third of the population in the United States has nonalcoholic fatty liver disease
      (NAFLD). Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, can lead to
      cirrhosis.Currently, there is no proven therapy for patients with NASH. The investigators
      core hypothesis is that therapy of patients with NASH with pentoxifylline (PTX) for one year
      will result in improvement of biochemical parameters of liver disease and hepatic histology.
      The focus of this proposal is on the effectiveness of pentoxifylline (PTX) in improving
      laboratory and tissue parameters of liver disease, parameters of insulin-resistance, and
      levels of cytokines in patients with NASH.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients ages 18 to 70 years.

          -  Liver biopsy compatible with NASH, including presence of steatosis and
             necroinflammatory activity on liver biopsy done during the prior 6 months to study
             enrollment

          -  Daily alcohol intake of <30 g for males and <15 g for females;

          -  Appropriate exclusion of other liver diseases.

          -  Patients with diabetes mellitus type 2 diagnosis as defined by a previous diagnosis of
             DM and current therapy with antidiabetic agents, or by fulfillment of 1997 American
             Diabetic Association (ADA) criteria, may be included if they fulfill the following
             criteria: (i) therapeutic regimen limited to specific oral agents including
             sulfonylureas (e.g. glipizide and glyburide) and/or biguanides (e.g. metformin); (ii)
             stable therapeutic regimen as defined by no changes in oral agents for at least 3
             months; (iii) Hemoglobin A1C (HgbA1C) < 8.5 %.

        Exclusion Criteria:

          -  History of past excessive alcohol drinking (as defined above) for a period longer than
             2 years at any time in the past 10 years.

          -  Current consumption of alcohol >30 g daily for males and >15 g daily for females.

          -  Positive testing for hepatitis B surface antigen, hepatitis C virus antibody, or
             ribonucleic acid (RNA) of hepatitis C virus of deoxyribonucleic acid (DNA) of
             hepatitis B virus.

          -  Patients taking medications known to cause steatosis.

          -  Other causes of liver disease suspected by history, family interview, or laboratory
             testing.

          -  Patients with cirrhosis defined by stage 4 fibrosis on liver biopsy, or if the patient
             shows unequivocal clinical evidence of portal hypertension, such as thrombocytopenia,
             splenomegaly, or esophageal varices.

          -  Patients taking medications of possible benefit in NASH within 3 months prior to the
             liver biopsy. These medications include Vitamin E, Betaine, S-adenosylmethionine
             (SAM-e), thiazolidinediones, and acarbose.

          -  Patients with diabetes mellitus who are on Insulin therapy.

          -  Patients with diabetes mellitus on therapy with thiazolidinediones or
             alpha-glucosidase inhibitors such as acarbose

          -  Hypersensitivity to pentoxifylline or the methylxanthines (caffeine, theophylline,
             theobromine).

          -  History of cerebral or retinal hemorrhage.

          -  Other medical comorbidities (such as cardiac, central nervous system, renal, cancer)
             that would interfere with completion of the study.

          -  Patients taking Theophylline or Coumadin because of potential drug-drug interactions
             with Pentoxifylline.

          -  Pregnant or nursing women.