218 Although a strong rationale remains for the use of anti-TNF therapy in alcoholic hepatitis, there is also a theoretical basis for minimizing

TNF inhibition, because it plays a role in liver regeneration as well as apoptosis.219 Thus, in light of the poor clinical outcomes observed in the largest of the infliximab trials and the etanercept study, the use of these parenteral TNF inhibitors should be confined to clinical trials, and recommendations regarding specific therapy will need to await the results of these trials. There are no substantive clinical data comparing the use of steroids or nutrition to specific anti-TNF therapies. Although it is assumed that each Veliparib datasheet of these different treatments may operate via independent mechanisms, there are only minimal data regarding the comparative benefit of sequential therapies or combined approaches. One study tested the use of pentoxifylline in 29 patients with severe AH (MDF > 32) who did not respond to steroids based on a drop in bilirubin level after 1 week of prednisolone treatment. Compared to previously treated patients (who were continued on steroids despite lack of bilirubin response), there was no improvement in 2-month survival, thus arguing against a two-step strategy with MAPK Inhibitor Library an early switch to pentoxifylline.220 Several older studies had examined the role of anabolic steroids with nutritional interventions

(based on the presumption that both interventions acted via a similar mechanism, i.e., correction of protein calorie malnutrition).221 One pilot study evaluated the role of steroids in combination with enteral nutrition in 13 patients with severe AH, and found an overall mortality of 15%—possibly an improvement from expected.222 With the advent of new therapies, it is necessary to reconsider the risk-benefit

ratio of medical treatment. It has been suggested that it may be possible to use less toxic therapies at a lower threshold of disease severity.223 However, the exact role of these new therapies, and IKBKE the threshold for their use, is still undefined. Many other therapeutic interventions have been studied in alcoholic hepatitis, but have not been able to show convincing benefit, including trials of antioxidants (vitamin E, silymarin, combination antioxidants), antifibrotics (colchicine), antithyroid drugs (propylthiouracil [PTU]), promoters of hepatic regeneration (insulin and glucagons), anabolic steroids (oxandrolone and testosterone), as well as calcium channel blockers (amlodipine), polyunsaturated lecithin, and a number of complementary and alternative medicines (reviewed in O’Shea and McCullough224). In addition to medical treatment directed at the underlying pathophysiologic abnormalities, several studies have tested other aggressive interventions in patients with AH, such as a molecular adsorbent recirculating system.