Clinical & Experimental Cardiology
Open Access

Correction of Oxygen-Nutrient Mismatch Might Account for the Beneficial Effect of Obeticholic Acid in NASH

Gerond Lake-Bakaar^{* *}Correspondence: Gerond Lake-Bakaar, Presbyterian Saint Luke's Medical Center, Denver, Ethiopia, Email:

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Description

The Farnesoid X Receptor (FXR) is a nuclear bile acid receptor involved in bile acid homeostasis, hepatic and intestinal inflammation, liver fibrosis, and cardiovascular disease. Obeticholic Acid (OCA), a potent, selective FXR agonist decreases portal hypertension in animal models of cirrhosis [1,2]. The drug is also effective in the treatment of non-alcoholic steatohepatitis, NASH [3-5]. The two disparate findings might be reconciled by an effect of OCA on hepatic artery flow.

The liver has a unique dual blood supply comprising both a Portal Vein (PV) and a Hepatic Artery (HA). PV blood is nutrient rich and deoxygenated. It lacks myogenic elements for flow control, which is unregulated but accounts for over 80 percent of liver blood supply. By contrast, HA blood is well oxygenated and accounts for 20 percent of liver blood flow. The liver has no mechanisms for matching nutrient delivery via the PV with oxygen supply from the HA.

Thus, chronic excess nutrient delivery via the PV may fail to be matched by oxygen supply from the HA, resulting in relative tissue hypoxia and damage. This potential link between oxygennutrient mismatch and liver disease pathology was first proposed for alcoholic steatohepatitis, ASH by Lautt [6] with chronic excess alcohol exposure. It is of interest that maximum damage in both NASH [7] and ASH [8] is found in zone 3 of the hepatic lobule, where the partial pressure of oxygen is lowest [7]. Furthermore, NASH has been associated with chronic obstructive sleep apnea and intermittent hypoxia. Treatment of intermittent hypoxia in obstructive sleep apnea improves NASH severity [9-11].

Conclusion

The study highlights the potential for drugs that could directly affect blood flow in the HA on ASH, NASH and portal hypertension. Pharmacologically induced increase in HA blood flow will simultaneously increase oxygen delivery to the liver, which could reduce liver damage in ASH and NASH. Similarly, increased HA flow inversely reduces PV flow and pressure via HABR, which might prove an effective way to reduce portal hypertension.

References

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