Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease

Abstract

Background: As an anti-TNF agent that targets inflammatory process directly, Pentoxifylline has been investigated for treatment of NASH in individual studies and pilot trials for years. We summarized the available information and generating hypotheses for future research.

Data sources: Google, Cochrane, MEDLINE, and EMBASE and the Chinese Biomedical data bases for studies restricted to pentoxifylline treatment in humans with NAFLD in all languages until June 2010. Six studies (2 randomized, double-blind, placebo-controlled trials; 4 prospective cohort studies) extracted from 11604 references.

Results: Pentoxifylline-treated patients showed a significant decrease AST (n=37, P=0.01) and ALT (n=50, P=0.03), but no significant effect on IL-6 (n=36, P=0.33) and TNF-α (n=68, P=0.26) compared with Placebo or UDCA-controlled groups. Improvement in one or more histological variables was reported in two trails, only 1 study showed a reduction in of one or two points in fibrosis stage.

Limitations: The trails did not consistently report all of the outcomes of interest. Sample sizes (117 patients totally) were small and only 2 out of 6 studies had a randomized, controlled design.

Conclusion: Pentoxifylline reduce AST and ALT levels and may improve liver histological scores in patients with NALFD/NASH, but did not appear to affect cytokines. Large, prospective, and well-designed randomized, controlled studies are needed to address this issue. Novel therapeutic targets for activation of inflammatory signaling pathways by fat also merit investigation.

Figure 1

Search strategy and results. We use the Fatty liver as the MeSH term and list all known synonyms as free-text, 11604 references were searched totally. Combined search for all MeSH and free-text searches, 132 references were identified. Of these, we excluded 122, because they were animal experiments, nonclinical, or clearly irrelevant. Of the remaining 10 references, 4 were excluded because they did not meet our inclusion criteria. Finally, 6 references were identified (2 randomized trials and 4 prospective cohort studies) in the Figure 1 explained section.

Figure 2

Overall summary of meta-analyses results of treatments of pentoxifylline for NASH. Pentoxifylline-treated patients showed a significant decrease AST (n = 37, P = 0.01) and ALT (n = 50, P = 0.03), but no significant effect on IL-6 (n = 36, P = 0.33) and TNF-α (n = 68, P = 0.26) compared with Placebo or UDCA-controlled groups.