Pentoxifylline for Primary Biliary Cirrhosis
Condition: Primary Biliary Cirrhosis
MeSH terms: Liver Cirrhosis; Liver Cirrhosis, Biliary; Fibrosis
Intervention: Pentoxifylline
Intervention description: Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.
Intervention MeSH terms: Pentoxifylline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 76 Years
Healthy volunteers: No
Keywords: biliary cirrhosis

Summary:

      Primary biliary cirrhosis (PBC) is cholestatic liver disease characterized by progressive
      destruction of small bile ducts within the liver that can lead to end stage liver disease and
      all its complications.

      Although ursodeoxycholic acid (UDCA) is associated with increased survival in many patients
      with PBC, there is absence of an adequate response to UDCA in a significant proportion of PBC
      patients.

      Tumor necrosis factor alpha (TNF-alpha) is a cytokine that plays an important role in the
      pathogenesis of PBC. Other fibrosis biomarkers such as tissue metallo proteinase 1 (TIMP-1)
      are associated with progression of liver fibrosis in PBC. Pentoxifylline (PTX) is a
      methylxanthine derivative that inhibits pro-inflammatory cytokines and also has shown
      anti-fibrotic effects in serum of patients with PBC. Furthermore, PTX has well known clinical
      and safety profiles. The main hypothesis of this study is that therapy with pentoxifylline
      (PTX) will result in improvement of liver disease in PBC patients who are incomplete
      responders to UDCA.

      The focus of this proposal is on the effectiveness of PTX in improving laboratory parameters
      of liver disease and levels of cytokines involved in the pathogenesis of the disease in
      patients with PBC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients ages 18 to 76 years.

          -  Established diagnosis of PBC based on at least three of the following criteria:

               -  Detectable anti-mitochondrial antibodies (AMA)

               -  Cholestatic biochemical pattern

               -  Liver biopsy compatible with PBC

               -  Appropriate exclusion of other liver diseases.

          -  Therapy with UDCA at adequate dose (13-15mg/kg/d) for at least six months and evidence
             of suboptimal response defined by alkaline phosphatase levels that did not normalize
             and remain elevated by at least 1.5 times the upper limit of normal.

          -  No history or present hepatic decompensation (e.g. variceal hemorrhage,
             encephalopathy, or poorly controlled ascites).

        Exclusion Criteria:

          -  Findings highly suggestive of liver disease of other etiology.

          -  A score >=10 points on the Revised Scoring System for autoimmune hepatitis (AIH),
             supporting a diagnosis of PBC/AIH overlap.

          -  Patients on steroids (systemic), immunosuppressants, or immunomodulatory agents within
             the previous 6 months.

          -  Patients with clinical or laboratory evidence suggestive of decompensated cirrhosis.

          -  Hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, theobromine).

          -  History of cerebral or retinal hemorrhage.

          -  Other medical comorbidities (such as cardiac, renal, cancer) that would interfere with
             completion of the study.

          -  Patients taking Theophylline or Coumadin because of potential drug-drug interactions
             with PTX. In addition, patients taking low molecular weight heparin preparations.

          -  Pregnant or nursing women.