The role of proinflammatory cytokines in the pathogenesis of portal hypertension is unclear.
In this study, a team of investigators from London, England, evaluated whether tumor necrosis factor alpha (TNF-alpha) mediates circulatory disturbances in alcoholic hepatitis (AH).
They also assessed the acute and short term effect of a single infusion of infliximab on portal and systemic hemodynamics.
The team studied 10 patients with severe biopsy proven AH.
They measured cardiovascular hemodynamics, hepatic venous pressure gradient (HVPG), and hepatic and renal blood flow. Measurements were taken before, 24 hours after infliximab, and prior to hospital discharge.
The researchers found that serum bilirubin, C reactive protein, and white cell count were significantly reduced. They also determined that plasma levels of interleukin (IL)-6 and IL-8 were reduced after treatment.
The team found that of the 10 patients, 9 were alive at 28 days.
Overall, mean HVPG decreased significantly after 24 hours, with a sustained reduction observed prior to discharge.
Furthermore, mean arterial pressure and systemic vascular resistance increased significantly. This was mirrored by a reduction in cardiac index prior to discharge.
The team found that hepatic and renal blood flow also increased significantly.
|Serum bilirubin, C reactive protein, and white cell count were significantly reduced.|
Dr Mookerjee's team concluded, "Anti-TNF-alpha treatment in AH patients produces a highly significant, early, and sustained reduction in HVPG, possibly through a combination of a reduction in cardiac output and intrahepatic resistance".
"In addition, there was a reduction in hepatic inflammation and improved organ blood flow, suggesting an important role for TNF- in mediating the circulatory disturbances in AH".