Effects of Sapropterin on Portal and Systemic Hemodynamics in Patients With Cirrhosis and Portal Hypertension: A Bicentric Double-Blind Placebo-Controlled Study

Abstract

Sapropterin, an oral synthetic analogue of BH4, at the used dose did not reduce portal pressure in patients with cirrhosis. Sapropterin was safe and no serious adverse effects or deleterious systemic hemodynamic effects were observed.

Treating oxidative stress in heart failure: past, present and future

“…Similarly, inhibition of NOS uncoupling, by means of sapropterin treatment, has also been studied in the clinical setting. Several small clinical trials have been performed with oral sapropterin administration in patients ( n = 18–49) with systemic or pulmonary hypertension . However, these trials all failed to demonstrate significant differences in nitric oxide synthesis, oxidative stress, systemic haemodynamics, vascular redox state, or endothelial function.…”

Portal Hypertension and Related Complications: Diagnosis and Management

“…28 However, a benefit could not be confirmed in human trials. 29,30 On the other hand, simvastatin, a 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitor, has been found to increase nitric oxide release in the liver and decrease hepatic sinusoidal resistance in patients with cirrhosis and portal hypertension. [31][32][33] Although no effect on prevention of variceal bleeding has been reported, simvastatin may confer a survival benefit to patients with Child-Pugh class A or B cirrhosis.…”

Sinusoidal communication in liver fibrosis and regeneration

“…Additionally, therapies aimed at controlling KC or HSC activation may also prevent the development of hepatic cirrhosis, probably in part due to the re-activation of proper hepatic crosstalk. To date, various drugs with anti-inflammatory or anti-oxidant properties have shown promising results on fibrosis at the benchside, but limited outcomes in clinical trials [72–76], likely because of unknown effects on cellular communication. Future studies are needed to discover new mechanisms of cellular crosstalk to determine at which stage of cirrhosis progression these interactions occur.…”