A randomized trial to assess whether portal pressure guided therapy to prevent variceal rebleeding improves survival in cirrhosis

Villanueva, Càndid; Graupera, Isabel; Aracil, Carles; Alvarado, Edilmar; Miñana, Josep; Puente, Ángela; Hernández‐Gea, Virginia; Ardèvol, Alba; Pavel, Oana; Colomo, Alan; Concepción, Mar; Poca, María; Torras, Xavier; Reñé, Josep Maria; Guarner, Carlos

doi:10.1002/hep.29056

Cited by 73 publications

(75 citation statements)

References 36 publications

(146 reference statements)

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“…There is evidence that addition of NSBB or NSBB alone -besides their effect on bleeding prevention -reduce mortality [36][37][38][39][40] compared to band ligation as sole rebleeding prophylaxis. This beneficial effect on survival is most prominent in patients who show adequate reduction of portal pressure with NSBB [41]. Unfortunately, it has not yet been evaluated whether hemodynamic nonresponders profit from further application of NSBB in the setting of rebleeding prophylaxis or not [42].…”

Section: Prevention Of Rebleeding Depending On Stage and Aetiology Ofmentioning

confidence: 99%

Treatment of Oesophageal Varices in Liver Cirrhosis

Sauerbruch

2018

Digestion

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Background: The development of cirrhosis with resultant portal hypertension can lead to oesophageal varices at a rate of 7% per annum. Bleeding from varices happens when the portal pressure is ≥12 mm Hg and can threaten life. Summary: Eliminating the aetiology of cirrhosis is a pivotal step to prevent the formation of varices. In patients with established varices, primary prophylaxis with non-selective beta blockers (NSBB) may slow down the progression of varices and prevent the first variceal bleed. NSBB, similar to other agents such as renin/angiotensin blockers, statins, and rifaximin, may have the additional advantage of blunting inflammatory stimuli, which can contribute to the progression of varices. Variceal band ligation is an alternative for primary bleeding prophylaxis with excellent results. Any acute variceal bleed should be managed with band ligation after careful resuscitation. Early pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) in decompensated cirrhotic patients is very effective in controlling the bleeding and improves survival. Secondary prophylaxis against further variceal bleeding using NSBB and band ligation is recommended in most other patients. TIPS may be considered in appropriate patients as a secondary prophylaxis against recurrent variceal bleed. Future research should be directed towards the prevention of varices and targeting inflammation to reduce cirrhotic complications. Key Messages: Treatment strategies depend on the stage the patient is at along the natural history of varices: NSBB or band ligation for primary prophylaxis; band ligation or early TIPS for acute bleed; and a combination of NSBB + band ligation or TIPS for secondary prophylaxis (Fig. 1).

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Section: Prevention Of Rebleeding Depending On Stage and Aetiology Ofmentioning

confidence: 99%

Treatment of Oesophageal Varices in Liver Cirrhosis

Sauerbruch

2018

Digestion

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“…The hepatic venous pressure gradient (HVPG; wedge hepatic venous pressure [HVP] minus free HVP) is the pressure difference across the liver and has been reported as a surrogate indicator of the severity of portal hypertension. In patients with cirrhosis, high HVPG increases mortality and risks of complications related to portal hypertension, such as esophageal varices, ascites, or hepatic encephalopathy . In the surgical setting, patients with cirrhosis with increased HVPG are at an increased risk of postoperative liver dysfunction after hepatectomy .…”

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confidence: 99%

“…In patients with cirrhosis, high HVPG increases mortality and risks of complications related to portal hypertension, such as esophageal varices, ascites, or hepatic encephalopathy. (7)(8)(9) In the surgical setting, patients with cirrhosis with increased HVPG are at an increased risk of postoperative liver dysfunction after hepatectomy. (10) At our institution, we routinely measure preoperative HVPG to help assess the severity of portal hypertension in adult-to-adult LDLT recipients.…”

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confidence: 99%

Predictive Value of Hepatic Venous Pressure Gradient for Graft Hemodynamics in Living Donor Liver Transplantation

et al. 2019

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The hepatic venous pressure gradient (HVPG) measurement is known to correlate with the severity of portal hypertension in patients with liver cirrhosis. This retrospective study investigated the clinical value of preoperative measurement of HVPG in patients who underwent adult‐to‐adult living donor liver transplantation (LDLT) and its predictive value for hepatic hemodynamics after graft reperfusion. For this study, 75 patients who underwent adult‐to‐adult LDLT were divided into 2 groups (HVPG <16 mm Hg or HVPG ≥16 mm Hg) to investigate the correlation between preoperative HVPG and characteristics and surgical outcomes of the patients, including portal vein flow (PVF) and hepatic artery flow (HAF) after graft reperfusion. In total, 35 (46.7%) patients had an HVPG ≥16 mm Hg. These patients had significantly higher international normalized ratio values, serum creatinine levels, and Model for End‐Stage Liver Disease scores compared with the 40 patients with HVPG <16 mm Hg. They also had higher rates of variceal bleeding, encephalopathy, and intractable ascites as well as lower serum albumin levels and platelet counts compared with those patients with HVPG <16 mm Hg. Portal inflow modulation (PIM) was frequently performed in the patients with HVPG ≥16 mm Hg compared with those with HVPG <16 mm Hg. No significant differences in surgical outcomes after LDLT were found between these 2 groups except for postoperative ascites. Preoperative HVPG showed a positive correlation with PVF and a negative correlation with HAF after graft reperfusion (false discovery rate [FDR] P = 0.08 and FDR P = 0.08, respectively). In linear regression analyses, preoperative HVPG was independently associated with PVF after graft reperfusion. In conclusion, our findings indicate that preoperative HVPG is associated with hepatic hemodynamics after graft implantation in LDLT. HVPG as a routine preoperative evaluation may be helpful for surgical planning of PIM.

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“…The HVPG response to β‐blocker therapy can also be determined with a single haemodynamic study, where responders (about 50%‐60%) are identified by decrease ≥10% from baseline after the acute administration of iv propranolol (0.15 mg/kg). As for the chronic response of HVPG, these patients have a lower incidence of decompensation and death …”

Section: Introductionmentioning

confidence: 99%

Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis

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Lozano

Alonso

et al. 2019

Liver International

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Background In cirrhosis, a decrease in hepatic venous pressure gradient (HVPG) > 10% after acute iv propranolol (HVPG response) is associated with a lower risk of decompensation and death. Only a part of patients are HVPG responders and there are no accurate non‐invasive markers to identify them. We aimed at discovering metabolomic biomarkers of HVPG responders to propranolol. Methods Sixty‐six patients with cirrhosis and HVPG ≥ 10 mm Hg in whom the acute HVPG response to propranolol was assessed, were prospectively included. A targeted metabolomic serum analysis using ultrahigh‐performance liquid chromatography coupled to mass spectrometry was performed. Different combinations of 2‐3 metabolites identifying HVPG responders (HVPG reduction > 10%) were obtained by stepwise logistic regression. The best of these model (AUROC, Akaike criterion) underwent internal cross‐validation and cut‐offs to classify responders/non‐responders was proposed. Results A total of 41/66 (62%) patients were HVPG responders. Three hundred and eighty‐nine metabolites were detected and 177 were finally eligible. Eighteen metabolites were associated to the HVPG response at univariate analysis; at multivariable analysis, a model including a phosphatidylcholine (PC(P‐16:0/22:6)) and a free fatty acid (20:2(n‐6), eicosadienoic acid) performed well for HVPG response, with an AUROC of 0.801 (0.761 at internal validation). The cut‐off 0.629 was the most efficient for overall classification (49/66 patients correctly classified). Two cut‐off values allowed identifying responders (0.688, PPV 84%) and non‐responders (0.384, NPV 82%) with undetermined values for 17/66 patients. Clinical variables did not add to the model. Conclusions The combination of two metabolites helps at identifying HVPG responders to acute propranolol. It could be a useful non‐invasive test to classify the HVPG response to propranolol.

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A randomized trial to assess whether portal pressure guided therapy to prevent variceal rebleeding improves survival in cirrhosis

Cited by 73 publications

References 36 publications

Treatment of Oesophageal Varices in Liver Cirrhosis

Treatment of Oesophageal Varices in Liver Cirrhosis

Predictive Value of Hepatic Venous Pressure Gradient for Graft Hemodynamics in Living Donor Liver Transplantation

Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis

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