A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis.
OBJECTIVE
There is no effective therapy for patients with primary sclerosing cholangitis (PSC). Rats with experimental small bowel bacterial overgrowth develop hepatobiliary injury similar to PSC. The hepatobiliary injury results from peptidoglycan-polysaccharide-mediated activation of Kupffer cells, release of cytokines such as tumor necrosis factor (TNF-alpha), and is prevented 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 histological features of PSC of varying severity were treated with pentoxifylline sustained release (SR) tablets (400 mg q.i.d.) for < or = 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 study. Two patients were withdrawn because of severe nausea, and two patients were noncompliant with medication and withdrew. Pentoxifylline did not significantly alter symptoms of fatigue or pruritus, serum liver tests, serum TNF-alpha or TNF receptor levels.


CONCLUSIONS
In the current regimen, pentoxifylline alone does not significantly improve symptoms or liver tests in patients with PSC.
Bharucha
A E
AE
Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Jorgensen
R
R
Lichtman
S N
SN
LaRusso
N F
NF
Lindor
K D
KD
D000284:Administration, Oral; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002758:Cholangiography; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage / Q000627:therapeutic use*; D010865:Pilot Projects; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin; D010431:Pentoxifylline