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.