Potential role of TNF alpha blockers in delaying the progression of hepato-renal syndrome.

Hepatorenal syndrome occurs in patients with advanced liver cirrhosis and is associated with functional renal impairment and poor prognosis. These patients present a challenge to physicians and management strategies. Although various pharmacological therapies are available, large randomized controlled trials are required to determine which treatment modality is most effective to improve survival rates along with its dose and duration of treatment. The overproduction of tumor necrosis factor-alpha (TNF-alpha) has been postulated to play a role in progression of this disease, being associated with hyperdynamic circulation and inflammatory process. Moreover, increasing the levels of TNF-alpha during the course of hospitalization is suggested to be associated with increased mortality. Hence the role of TNF-alpha inhibitors, such as pentoxifylline, may prove to be become a new clinical pathway. Various randomized clinical trials have demonstrated a significant reduction in mortality in patients receiving pentoxifylline, in comparison to the control group. This survival rate benefit was associated with decrease in the incidence of hepatorenal syndrome in these patients. We propose a double-blinded trial to test the hypothesis, in which patients with advanced liver disease without evidence of hepatorenal syndrome are recruited. The control group receives the standard management while the case group receives standard management along with TNF-alpha blockers. If the cases develop hepatorenal syndrome at a significant duration later in comparison to the control group, our hypothesis will be confirmed. Our methodology is limited due to costs of TNF-alpha inhibitors in a developing country setup, hence it has only been proposed as a hypothesis. If the recommended trial confirms our hypothesis, we might see favorable outcomes and improved survival rates in patients with decompensated liver diseases.