Hepatic Venous Pressure Gradient Response in Non-Selective Beta-Blocker Treatment—Is It Worth Measuring?

Abstract

# AbstractPurpose of Review To review the evidence supporting the assessment of hepatic venous pressure gradient (HVPG) response to non-selective beta-blockers (NSBB). Recent Findings HVPG response to NSBB reduces the risks of variceal bleeding, hepatic decompensation due to ascites and its complications, and, finally, mortality. In hemodynamic non-responders to NSBB, their effectiveness is suboptimal, although there is increasing evidence for non-hemodynamic effects. Carvedilol may be a good treatment option for patients with nonresponse to conventional NSBB, as it is more potent in decreasing HVPG. Furthermore, hemodynamic non-responders may also benefit from (the addition of) other HVPG-lowering drugs that are in clinical development, and, depending on the setting, complimentary or alternative treatment strategies. Summary Clinical benefits of HVPG response have been established throughout a broad spectrum of advanced chronic liver disease (ACLD) severity, ranging from compensated patients without varices but with clinically significant portal hypertension (CSPH) to subjects with a history of bleeding and/or non-bleeding hepatic decompensation. HVPG-guided NSBB therapy facilitates personalized medicine in patients with ACLD and portal hypertension. Since the clinical use of HVPG measurement is limited by its invasiveness and its availability is mostly restricted to academic centers, the development of non-invasive surrogates of HVPG response is of high clinical relevance.

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon‐Free Therapy

“…(13) This recommendation is primarily based on studies evaluating the HVPG response to nonselective beta-blockers (NSBB). (15) However, there is also limited evidence from patients with HVPG ≥ 12 mm Hg due to alcoholic liver disease (ALD) who were advised to abstain from alcohol (HVPG decrease cutoff ≥ 15%), (16) or patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH) treated with simtuzumab or placebo (HVPG decrease cutoff ≥ 20%). (17) Besides variceal (re-)bleeding, HVPG response to conventional NSBB ± vasoactive drugs has been shown to decrease the risks of occurrence/worsening of ascites and its complications.…”

“…(15) In addition, some studies even reported (trends toward) a decrease in hepatic encephalopathy (HE), a decompensating event that is less closely linked to PH. (15) However, conventional NSBB have completely different modes of action, as compared with etiological therapies or other treatments that primarily act by decreasing intrahepatic resistance. (18,19) HVPG is currently not accepted as a surrogate endpoint for the accelerated approval of medical therapies for PH by regulatory authorities, because there is limited evidence supporting its use as a surrogate endpoint for other treatments than NSBB.…”

“…However, nearly two thirds of patients with CSPH before antiviral therapy had an HVPG decrease ≥ 10% after achieving SVR to IFN‐free regimens, which denotes a clinically meaningful decrease according to the Baveno VI chapter on the impact of etiological therapy . This recommendation is primarily based on studies evaluating the HVPG response to nonselective beta‐blockers (NSBB) . However, there is also limited evidence from patients with HVPG ≥ 12 mm Hg due to alcoholic liver disease (ALD) who were advised to abstain from alcohol (HVPG decrease cutoff ≥ 15%), or patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH) treated with simtuzumab or placebo (HVPG decrease cutoff ≥ 20%) .…”

“…However, there is also limited evidence from patients with HVPG ≥ 12 mm Hg due to alcoholic liver disease (ALD) who were advised to abstain from alcohol (HVPG decrease cutoff ≥ 15%), or patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH) treated with simtuzumab or placebo (HVPG decrease cutoff ≥ 20%) . Besides variceal (re‐)bleeding, HVPG response to conventional NSBB ± vasoactive drugs has been shown to decrease the risks of occurrence/worsening of ascites and its complications . In addition, some studies even reported (trends toward) a decrease in hepatic encephalopathy (HE), a decompensating event that is less closely linked to PH .…”

Editorial: pressure to close the therapeutic window of non‐selective beta blockers?

“…Most previous studies stratified patients by disease stage ( eg refractory ascites) or clinical context (severe alcoholic hepatitis, spontaneous bacterial peritonitis [SBP] or acute‐on‐chronic liver failure) . However, even within these patient groups, there is considerable heterogeneity regarding the presumed benefit of NSBBs ( eg primary/secondary prophylaxis and hepatic venous pressure gradient response), but also regarding the haemodynamic reserve, which may determine the safety of NSBBs. For instance, NSBB treatment may be safe in consistently normotensive patients diagnosed with SBP, while the situation may differ in patients with severe hypotension and/or organ dysfunction ( eg acute kidney injury).…”