Pentoxifylline in severe alcoholic hepatitis: A prospective, randomised trial

Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab.
The Journal of the Association of Physicians of India 05/2012; 60(5):20-2.
Source: PubMed


Role of corticosteroids in treatment of severe alcoholic hepatitis (SAH) is controversial. Pentoxifylline (PTX), an inhibitor of TNF, has also been shown to decrease short term mortality in SAH. Aim of this study was to evaluate the effect of PTX on short term mortality, renal and hepatic functions in patients with SAH.
Fifty patients with SAH {Maddrey's Discriminant Function (DF) > or = 32} were prospectively enrolled. Twenty five patients received PTX (400 mg orally, three times a day), and 25 received placebo for 4 weeks. Serum tumor necrosis factor (TNF) was measured in both groups.
Baseline characteristics of the two groups were similar. At 4 weeks, mortality in PTX group was lower than that in controls {20% (5/25) versus 40% (10/25) respectively; p = 0.216; RR 0.5; 95% CI 0.19-1.25}. Renal failure was the cause of mortality in 20% (1/5) patients in PTX group, and 70% (7/10) in controls (p = 0.11). Significant reduction in urea, creatinine, DF and TNF was noted in PTX group. Reduction in TNF did not correlate with reduction in creatinine or DF.
In patients with SAH, PTX leads to a significant improvement in renal and hepatic functions, and a trend towards decreased short term mortality.

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Available from: Sandeep Singh Sidhu, Dec 30, 2013
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    • "Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory activity, which is due in part to its ability to block TNFα (Fernandes et al., 2008; Gonzalez-Espinoza et al., 2012; Turhan et al., 2012). In this regard, pentoxifylline has been found to be clinically efficacious in a number of inflammatory pathologies characterized by increased TNFα production including alcoholic liver disease and rheumatoid arthritis (Queiroz-Junior et al., 2013; Sidhu et al., 2012; Zaitone et al., 2011). Since TNFα is a key mediator of pulmonary toxicity induced by vesicants (Sunil et al., 2011a), we tested the ability of pentoxifylline to mitigate NM-induced lung toxicity. "
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    ABSTRACT: Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. Evidence suggests that macrophages and inflammatory mediators including tumor necrosis factor (TNF)α contribute to pulmonary injury. Pentoxifylline is a TNFα inhibitor known to suppress inflammation. In these studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung injury and inflammation. Exposure of male Wistar rats (250g; 8-10weeks) to NM (0.125mg/kg, i.t.) resulted in severe histolopathological changes in the lung within 3d of exposure, along with increases in bronchoalveolar lavage (BAL) cell number and protein, indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro-inflammatory/cytotoxic (COX-2(+) and MMP-9(+)), and anti-inflammatory/wound repair (CD163(+) and Gal-3(+)) macrophages. Treatment of rats with pentoxifylline (46.7mg/kg, i.p.) daily for 3d beginning 15min after NM significantly reduced NM-induced lung injury, inflammation, and oxidative stress, as measured histologically and by decreases in BAL cell and protein content, and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline, while CD163(+) and Gal-3(+) macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung, however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury, inflammation and oxidative stress induced by vesicants.
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