Short chain fatty acids exchange: Is the cirrhotic, dysfunctional liver still able to clear them?

Abstract

Background & aims: Prebiotics are increasingly used to improve gut integrity. A presumed mechanism of their beneficial action is the synthesis of short chain fatty acids (SCFA: acetate, propionate and butyrate). High systemic concentrations of propionate and butyrate are toxic and can adversely affect the patient. In physiological situations the liver uses propionate and butyrate for energy metabolism. The aim of the present study was to investigate to which extent patients with liver cirrhosis are still able to metabolize portal derived SCFA in the liver.

Methods: Twelve patients with liver cirrhosis and an intrahepatic portosystemic shunt (TIPSS) were studied. Blood was sampled from the femoral artery, portal and hepatic vein. Organ plasma flow was measured. Net release or uptake was calculated by multiplying the arteriovenous differences by plasma flow. SCFA plasma concentrations were measured using LC-MS.

Results: Arterial concentrations were 124+/-12, 8+/-1 and 10+/-1micromol/l for acetate, propionate and butyrate, respectively. The gut produced 32.5+/-13.0, 4.8+/-1.3 and 6.2+/-2.1micromolkgbw(-1)h(-1) of acetate, propionate and butyrate, respectively. Assuming 70% portosystemic shunting, hepatic uptake of propionate and butyrate was 3.1+/-0.9 and 5.2+/-1.4micromolkgbw(-1)h(-1). Hepatic uptake of acetate was non significant (12.1+/-12.3micromolkgbw(-1)min(-1)). As a consequence of shunting, part of total acetate escaped from the splanchnic bed, which equalled 34.9+/-14.7micromolkgbw(-1)h(-1).

Conclusion: The liver of patients with stable cirrhosis is able to use butyrate and propionate, most likely preventing increased systemic concentrations. This suggests that prebiotics can be administered safely, but monitoring butyrate levels may be advisable in patients with diminished liver function.