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.

Download full-text


Available from: Sandeep Singh Sidhu, Dec 30, 2013
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Experimental and Molecular Pathology 05/2014; 97(1). DOI:10.1016/j.yexmp.2014.05.009 · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Corticosteroids and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis (SAH), but not to the extent desired. Combining both drugs may lead to better survival, but has not yet been studied. To compare the efficacy of corticosteroids plus pentoxifylline with that of corticosteroids alone in improving survival of SAH patients. Of the 111 patients screened, 70 patients with SAH (Maddrey discriminant function (MDF) ≥ 32) were enrolled. Patients with active infection, bleeding, renal failure, or pancreatitis were excluded. Treatment was given for four weeks to group A (n = 36; prednisolone 40 mg/day plus pentoxifylline 400 mg thrice/day) and group B (n = 34; prednisolone 40 mg/day). Patients were followed up for 6 months. Data are expressed as median (range) or percentage. Baseline characteristics of the two groups were similar (MDF group A 78.5 (36.8-140.9), group B 74.9 (45.6-140.2)). Four-week and six-month survival in groups A and B were not significantly different (four-week 72.2 and 73.5%, respectively, p = 1.00; six-month 30.6 and 23.5%, respectively, p = 0.417). At seven days, 55.6% of patients in group A and 64.7% in group B had a Lille score <0.45 (p = 0.473). Six-month survival was significantly higher for patients with a Lille Score <0.45 than for those with a Lille score ≥0.45 (group A 55.5 vs. 0%, p = 0.0006; group B 36 vs. 0%, p = 0.0304). Biological improvement at 28 days was significant for both groups; however, the difference between the groups was not significant. For patients with severe alcoholic hepatitis, a combination of corticosteroids and pentoxifylline has no additional survival advantage compared with corticosteroids alone.
    Digestive Diseases and Sciences 03/2012; 57(6):1664-71. DOI:10.1007/s10620-012-2097-4 · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The response to injury is one of wound healing and fibrogenesis, which ultimately leads to fibrosis. The fibrogenic response to injury is a generalized one across virtually all organ systems. In the liver, the injury response, typically occuring over a prolonged period of time, leads to cirrhosis (although it should be pointed out that not all patients with liver injury develop cirrhosis). The fact that many different diseases result in cirrhosis suggests a common pathogenesis. The study of hepatic fibrogenesis over the past 2 decades has been remarkably active, leading to a considerable understanding of this process. It has been clearly demonstrated that the hepatic stellate cell is a central component in the fibrogenic process. It has also been recognized that other "effector" cells are important in the fibrogenic process, including resident fibroblasts, bone marrow derived cells, fibrocytes, and even perhaps cells derived from epithelial cells (i.e., through epithelial to mesenchymal transition or EMT). A key aspect of the biology of fibrogenesis is that the fibrogenic process is dynamic; thus, even advanced fibrosis (or cirrhosis) is reversible. Together, an understanding of the cellular basis for liver fibrogenesis, along with multiple aspects of the basic pathogenesis of fibrosis, have highlighted many exciting potential therapeutic opportunities. Thus, while the most effective "anti-fibrotic" therapy is treatment of the underlying disease, in situations in which this not possible, specific anti-fibrotic therapy is likely to not only become feasible, but will soon become a reality. The goal of this review is to highlight the mechanisms underlying fibrogenesis that may be translated into future anti-fibrotic therapies and to review the current state of clinical development.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2013; 11(3). DOI:10.1016/j.cgh.2013.01.005 · 7.90 Impact Factor
Show more