Acute hemodynamic response to propranolol predicts bleeding and nonbleeding decompensation in patients with cirrhosis

Abstract

Nonselective beta‐blockers are used as prophylaxis for variceal bleeding in patients with advanced chronic liver disease (ACLD). The acute hemodynamic response to intravenous propranolol (i.e., ≥10% reduction in hepatic venous pressure gradient [HVPG]) is linked to a decreased risk of variceal bleeding. In this study, we aimed to investigate the overall prognostic value of an acute response in compensated and decompensated ACLD. We analyzed the long‐term outcome of prospectively recruited patients with ACLD following a baseline HVPG measurement with an intraprocedural assessment of the acute hemodynamic response to propranolol. Overall, we included 98 patients with ACLD (mean ± SD age, 56.4 ± 11.5 years; 72.4% decompensated; 88.8% varices; mean ± SD HVPG, 19.9 ± 4.4 mm Hg) who were followed for a median of 9.6 (interquartile range, 6.5–18.2) months. Fifty‐seven patients (58.2%) demonstrated an acute hemodynamic response to propranolol that was associated with a decreased risk of variceal bleeding (at 12 months, 3.6% vs. 15% in nonresponder; log‐rank, p = 0.038) and hepatic decompensation (at 12 months, 23% vs. 33% in nonresponder; log‐rank, p = 0.096). On multivariate analysis, the acute response was an independent predictor of first/further hepatic decompensation (adjusted hazards ratio, 0.31; 95% confidence interval [CI], 0.13–0.70; p = 0.005). Importantly, there was a tendency toward a prolonged transplant‐free survival in acute responders compared to nonresponders (34.2; 95% CI, 29.2–39.2 vs. 25.2; 95% CI, 19.8–30.6 months; log‐rank, p = 0.191). Conclusions : Patients with ACLD who achieve an acute hemodynamic response to intravenous propranolol experience a lower risk of variceal bleeding and nonbleeding hepatic decompensation events compared to nonresponders. An assessment of the acute hemodynamic response to intravenous propranolol provides important prognostic information in ACLD.

Diabetes impairs the haemodynamic response to non‐selective betablockers in compensated cirrhosis and predisposes to hepatic decompensation

“…Notably, our clinical study does not provide a mechanistic explanation for the lower efficacy of NSBB in regard to HVPG reduction. NSBB decrease HVPG by ameliorating hyperdynamic circulation and splanchnic vasodilatation, 8,30,31 however, the impact of DM/BMI on these modes of action remains unknown. Nevertheless, it may be speculated that the effects of NSBB therapy may differ in patients with cirrhosis and DM/high BMI, as they may commonly suffer from heart failure with preserved ejection fraction 32 in which betablockaer may have detrimental effects on cardiac function 33 .…”

Nonselective beta-blockers in primary prophylaxis of esophageal variceal bleeding in patients with ascites waitlisted for liver transplantation

“…Hofer et al [24] установили, что острый гемодинамический эффект на внутривенное введение пропранолола у пациентов с ЦП и КЗПГ ассоциируется со значительным снижением риска кровотечений из ВУ и печеночной декомпенсации. Авторы подтвердили наличие различных категорий пациентов при оценке их ответа на терапию НСББ.…”

Austrian consensus on the diagnosis and management of portal hypertension in advanced chronic liver disease (Billroth IV)

“…Moreover, the absence of CSPH identifies patients at low risk for hepatic decompensation, while HVPG values ≥ 16 and ≥ 20 mm Hg indicate a progressively increased risk of short-term mortality in patients undergoing extrahepatic abdominal surgery [ 26 ]. (B1) HVPG decreases to a value of < 12 mm Hg or reductions by ≥ 10–20% in response to acute and chronic NSBB treatment are associated with a reduced incidence of variceal bleeding or other decompensating events and a lower mortality [ 27 – 31 ]. (B1) In clinical trials focusing on the treatment of portal hypertension, HVPG dynamics are an excellent surrogate endpoint [ 27 – 32 ].…”

“…HVPG decreases to a value of < 12 mm Hg or reductions by ≥ 10–20% in response to acute and chronic NSBB treatment are associated with a reduced incidence of variceal bleeding or other decompensating events and a lower mortality [ 27 – 31 ]. (B1)…”