A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis

OBJECTIVE: There is no effective therapy for patients with primary sclerosi ng cholangitis (PSC). Rats with experimental small bowel bacterial overgrow th develop hepatobiliary injury similar to PSC. The hepatobiliary injury re sults from peptidoglycan-polysaccharide-mediated activation of Kupffer cell s, release of cytokines such as tumor necrosis factor (TNF-alpha), and is p revented by pentoxifylline. Our aims were to assess the safety and effects of pentoxifylline on symptoms and biochemical liver tests in patients with PSC, METHODS: A total of 20 patients with clinical, cholangiographic, and histol ogical features of PSC of varying severity were treated with pentoxifylline sustained release (SR) tablets (400 mg q.i.d.) for less than or equal to 1 yr. Serum alkaline phosphatase, aspartate aminotransferase, and bilirubin were monitored every 3 months for 1 year; serum TNF-alpha and TNF receptor subtypes I and II were assessed at baseline and 1 year. RESULTS: Of 20 patients, 16 tolerated pentoxifylline and completed the stud y. Two patients were withdrawn because of severe nausea, and two patients w ere noncompliant with medication and withdrew. Pentoxifylline did not signi ficantly alter symptoms of fatigue or pruritus, serum liver tests, serum TN F-alpha or TNF receptor levels. CONCLUSIONS: In the current regimen, pentoxifylline alone does not signific antly improve symptoms or liver tests in patients with PSC. (Am J Gastroent erol 2000;95: 2338-2342. (C) 2000 by Am. Coll. of Gastroenterology).