The pulmonary features of pulmonary arterial hypertension (PAH) are well described in the medical literature. In recent years, the extrapulmonary features of PAH have gained greater attention as physicians seek to manage PAH using a multidisciplinary approach. A more comprehensive view of PAH recognizes it as a multiorgan disease that involves, for example, the systemic circulation, central nervous system, and skeletal muscles. 

Nickel and colleagues, in a study published in Pulmonary Circulation, described the liver abnormalities typically present in PAH. PAH often results in right-sided heart failure, which leads to passive venous congestion and causes congestive hepatopathy. We will examine in greater detail how PAH causes hepatopathy and describe some of its main clinical features. 

How PAH Affects the Liver 

PAH can be described as the precapillary component of pulmonary hypertension. It is defined as an increase in the mean pulmonary arterial pressure in the absence of an increase in pulmonary venous pressure. 

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Nickel et al wrote, “There is a bidirectional intricate relationship between the liver, heart, and lung.” Therefore, dysfunction in any one organ can easily impact another. In the case of PAH, its link to the liver is largely a result of its impact on the right ventricle – congestive right-sided heart failure results in circulatory injury in the liver. This results in the condition known as congestive hepatopathy. In addition, the liver suffers from ischemic injury due to poor cardiac output in PAH.

Read more about PAH etiology

Fortea and colleagues, in a study published in the International Journal of Molecular Sciences, described the features of congestive hepatopathy in detail. In their paper, Fortea et al juxtapose the unique resilience of the liver to initial ischemic damage with its vulnerability to congestion. The liver’s resilience to ischemic damage stems from its dual blood supply – the hepatic artery and the hepatic portal vein; its vulnerability to congestion arises from its lack of a robust system to deal with pressure surges and the lack of valves in the hepatic veins. 

This means that pressure surges in PAH due to congestive heart failure can cause significant liver damage. Fortea and colleagues wrote, “The resulting congestion produces liver damage through several pathogenic mechanisms: (1) shear stress promotes fibrogenesis and sinusoidal ischemia by the activation of hepatic stellate cells and by a decrease in nitric oxide production from endothelial cells; (2) decreased portal and arterial inflow aggravates hepatic ischemia.” 

Nickel et al stated, “The liver is a central organ of carbohydrate, fat, and protein metabolism.” This is the reason why patients with PAH often have abnormal concentrations of circulating lipids. In addition, the liver plays a major role in glucose metabolism; PAH patients who have liver damage can show signs of poor glucose control even in the absence of a diagnosis of diabetes mellitus. 

How does all of this manifest itself in liver function tests? Nickel and colleagues wrote that “hepatic venous congestion from chronic heart failure is mainly characterized by cholestatic liver enzyme elevation (increased bilirubin and alkaline phosphatase), and gamma-glutamyl transferase and hypoalbuminemia.” Cholestasis can occur as a result of obstructed hepatic bile flow into the gallbladder, causing the accumulation of bile acids in the liver. In ischemic hepatitis, a rapid rise in serum aminotransferases and lactate dehydrogenase more than 10 times the upper limits of normal can be observed. 

If hepatic congestion results in liver pathology, a relief in congestion can lead to an improvement in cholestatic chemistry. This is most clearly observed in patients who respond well to medical heart failure therapy and those who undergo heart transplantation in cases of end-stage heart failure. 

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What are the common physical signs that can be observed in congestive hepatopathy caused by PAH? Fortea and colleagues wrote, “Physical examination may often show hepatomegaly and signs of heart failure, including hepatojugular reflux, peripheral edema, and ascites.”

Ascites is a frequent finding in patients with PAH, and it does not necessarily indicate that cardiac cirrhosis has already developed. Instead, it is typically caused by pressure on the sinusoidal network. A study demonstrated that up to 57% of patients with congestive hepatopathy had ascites with no relation to the extent of liver fibrosis. 

A Broader View of PAH 

Considering the significant impact that PAH can have on the liver, it makes sense to closely monitor it and ensure optimal hepatic health when managing PAH. An escalation in PAH severity will make its mark on liver parameters; likewise, a relief in pressure can improve liver function test results. 

“Despite its significant impact on mortality and a close relationship to right-sided hemodynamics, liver dysfunction in PAH patients is likely underreported in clinical trials and large registries,” Nickel and colleagues wrote. “This is certainly a component of the PAH field that will require more detailed research to better understand the relationship between PAH and liver dysfunction.”

Indeed, a renewed appreciation of the impact of PAH on liver dysfunction may result in renewed interest among researchers to investigate new ways to protect the liver in PAH and reduce liver-related pathologies. This is important because “there is no specific therapy of congestive hepatopathy” and “management of the underlying cardiac disease is the mainstay of treatment,” according to Fortea et al. 


Nickel NP, Galura GM, Zuckerman MJ, et al. Liver abnormalities in pulmonary arterial hypertensionPulm Circ. Published online October 21, 2021. doi:10.1177/20458940211054304

Fortea JI, Puente Á, Cuadrado A, et al. Congestive hepatopathyInt J Mol Sci. 2020;21(24):9420. doi:10.3390/ijms21249420