A randomized controlled pilot study of Pentoxifylline in patients with non-alcoholic steatohepatitis (NASH)

Abstract

Purpose Tumor necrosis factor-a (TNF-a) is implicated in non-alcoholic steatohepatitis (NASH). Pentoxifylline inhibits TNF-a. We wanted to evaluate the efficacy of Pentoxifylline on NASH patients. Methods Patients with biopsy proven NASH and persistently elevated alanine aminotransferase (ALT) greater than 1.5 times the upper limit of normal were randomized to 3 months of treatment with a step 1 American Heart Association diet and daily exercise with Pentoxifylline or placebo. Liver function tests, serum lipids and TNF-a, Interleukin 6 (IL-6), and plasma hyaluronic acid were measured at baseline, at weeks 6 and 12. Categorical data were analyzed by Fisher's exact test while independent sample t-test and Mann-Whitney test were used for continuous data. Results Eleven patients were randomized into the Pentoxifylline and nine to the placebo group. After 3 months of treatment body mass index (BMI), ALT and aspartate aminotransferase (AST) decreased significantly in both groups. There was no difference between the two groups in reduction of BMI (P = 0.897). There was significantly greater reduction in AST in the Pentoxifylline group (P = 0.038). There was a trend toward lower ALT level (P = 0.065) in the Pentoxifylline group. TNF-a and IL-6 decreased significantly in both groups after treatment, but there was no significant difference between the two groups. Conclusion Three months of Pentoxifylline treatment in combination with diet and exercise results in significantly greater reduction in AST levels in patients with NASH as compared with controls.

Beneficial effects of diacerein on adipokines and pro-inflammatory cytokines involved in diet-induced nonalcoholic steatohepatitis in rats

“…The present findings suggest that modulation of the inflammatory response is a key factor in the progression of NASH, in accordance with previous report supporting the potential clinical utility of a drug with anti-inflammatory effects in patients having predisposing factors of NAFLD and NASH. 19 In the present study, the histopathological changes of the hepatic tissue in the HFHC fed group demonstrated hepatic cell injury, which led to the release of excessive amounts of intracellular hepatic transaminases into the serum. The structural distortion and the functional impairment of the hepatic cells by NASH were associated with increase in insulin level and high insulin resistance.…”

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

“…6). One RCT found no impact on plasma LDL-C, HDL-C and TG [80]. There was no significant publication bias for assessed outcomes (not reported).…”

“…The anti-TNF-α agent pentoxifylline has been evaluated in four RCTs in NASH [78][79][80][81] (three with low risk of bias, two assessing post-treatment histology) (ESM Table 4). …”

Evidence based literature review of clinical management of non-alcoholic fatty liver disease in real world settings

“…4 RCTs have shown that PTX 1200 mg daily appears to improve histology via reduction in steatosis, inflammation, and even fibrosis. [79][80][81][82][83] Further studies are needed to confirm these findings.…”