Rapid change of liver stiffness after variceal ligation and TIPS implantation

Abstract

Liver stiffness (LS) as measured by transient elastography is widely used to screen for liver fibrosis. However, LS also increases in response to pressure changes like congestion but no data on portal pressure are available. We study here the effect of rapid portal pressure changes on LS. Therefore, LS was assessed directly prior and after ligation of esophageal varices ( n = 11) as well as transjugular intrahepatic portosystemic shunt (TIPS) implantation in patients with established cirrhosis ( n = 14). Additionally, we retrospectively analyzed changes in LS and variceal size in patients with sequential gastroscopic monitoring and LS measurements ( n = 14). To study LS and portal pressure in healthy livers, LS (µFibroscan; Echosens, Paris, France) and invasive pressures (Powerlab, AD Instruments, New Zealand) were assessed in male Wistar rats after ligation of single liver lobes. Ligation of esophageal varices caused an immediate and significant increase of LS from 40.3 ± 19.0 to 56.1 ± 21.5 kPa. Likewise, LS decreased significantly from 53.1 ± 16.6 to 43.8 ± 17.3 kPa after TIPS placement, which correlated significantly with portal pressure ( r = 0.558). In the retrospective cohort, the significant LS decrease from 54.9 ± 23.5 to 47.9 ± 23.8 kPa over a mean observation interval of 4.3 ± 3 mo was significantly correlated with a concomitant increase of variceal size ( r = -0.605). In the animal model, LS and portal pressure increased significantly after single lobe ligation without changes of arterial or central venous pressure. In conclusion, rapid changes of portal pressure are a strong modulator of LS in healthy and cirrhotic organs. In patients with stable cirrhosis according to the model for end-stage liver disease (MELD), a decrease of LS may be indicative for enlarging varices. NEW & NOTEWORTHY Liver stiffness (LS) immediately increases after variceal ligation while it decreases after transjugular intrahepatic portosystemic shunt (TIPS) implantation due to portal pressure changes. LS and portal pressure rapidly increase after single lobe ligation in Wistar rats without changes of arterial or central venous pressure. Collateral formation may be one cause for a transient decrease in LS in the absence of other confounders. Such pressure changes should be considered when interpreting LS in clinical practice.

The Importance of Transaminases Flare in Liver Elastography: Characterization of the Probability of Liver Fibrosis Overestimation by Hepatitis C Virus-Induced Cytolysis

“…Also, serum transaminase concentrations (mostly ALT) have been linked to the histological grading of necroinflammatory activity, and, as expected, patients with elevated ALT generally show higher activity scores [28,29]. These concepts should be taken into consideration for a critical evaluation of liver elastography results as it has been proven that stiffness values are influenced by tissue congestion and inflammation, rather than the mere degree of collagen deposition (i.e., fibrosis) [30,31]. Therefore, it is safe to assume, as, in the case of our study, that hepatic congestion and inflammation can affect LSM, and that serum transaminase levels can be used to quantify the amount of ongoing damage.…”

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post–liver transplant patient

“…Similarly, factors that increase mean arterial pressure, such as vasopressors or aerobic exercise, increase LS measurements in both animal and human models . Changes in portal venous flow, as in the setting of pharmacologic effect on hepatic hemodynamics, transjugular intrahepatic portosystemic shunt (TIPS) placement or variceal ligation, also affect LS . For example, in a group of 14 patients undergoing TIPS placement, LS decreased by 9.2 kPa on average, whereas in a group of 11 patients undergoing esophageal ligation, LS increased by roughly 16 kPa post‐ligation …”

Transjugular Intrahepatic Portosystemic Shunt: A Possible Risk Factor for Direct‐Acting Antiviral Treatment Failure in Patients With Hepatitis C?

“…Even though the reasons for treatment failure are manifold, we hypothesize that TIPS placement could be a possible contributing factor. From a pathophysiological point of view, a TIPS placement reduces portal pressure by shunting blood from the portal to the hepatic vein, leading to sustained changes in hepatic perfusion and biomechanical properties, such as tissue stiffness, (8) including an intrahepatic retrograde flow toward the TIPS as also seen in this cohort. All our patients received a sofosbuvir-based treatment regimen, a prodrug that is activated intrahepatically.…”

“…(6) Although the primary aim of this intervention is to decrease portal pressure, it has also a profound effect on hepatic hemodynamics, including an increase in hepatic arterial perfusion (7) and changes on tissue stiffness. (8) An unusual case of repeated DAA therapy failures in a patient who had previously been treated with a TIPS led us to analyze our clinical database for a possible association between TIPS and DAA failure in a structured way.…”