Elsevier

Journal of Hepatology

Volume 66, Issue 4, April 2017, Pages 849-859
Journal of Hepatology

Grand Rounds
Beta adrenergic blockade and decompensated cirrhosis

https://doi.org/10.1016/j.jhep.2016.11.001Get rights and content

Summary

Non-selective betablockers (NSBBs) remain the cornerstone of medical treatment of portal hypertension. The evidence for their efficacy to prevent variceal bleeding is derived from prospective trials, which largely excluded patients with refractory ascites and renal failure. In parallel to the increasing knowledge on portal hypertension-induced changes in systemic hemodynamics, cardiac function, and renal perfusion, emerging studies have raised concerns about harmful effects of NSBBs. Clinicians are facing an ongoing controversy on the use of NSBBs in patients with advanced cirrhosis. On the one hand, NSBBs are effective in preventing variceal bleeding and might also have beneficial non-hemodynamic effects, however, they also potentially induce hypotension and limit the cardiac reserve. An individualized NSBB regimen tailored to the specific pathophysiological stage of cirrhosis might optimize patient management at this point. This article aims to give practical recommendations on the use of NSBBs in patients with decompensated cirrhosis.

Key point

Non-selective betablockers (NSBBs) represent the cornerstone of pharmacological treatment of portal hypertension.

Section snippets

Clinical scenario 1

A 42-year-old male patient with cirrhosis due to hereditary hemochromatosis with large esophageal varices at endoscopy has been treated with propranolol 120 mg/d for primary prophylaxis of variceal bleeding for 4 years. The patient is undergoing regular phlebotomies to maintain serum ferritin levels of 50–100 μg/L. He presents at the outpatient clinic and reports dizziness and reduced exercise capacity together with weight gain. Edema and new-onset ascites were noted at clinical examination. The

Pathophysiology (Fig. 1)

Both increased intrahepatic vascular (sinusoidal) resistance and increased portal blood flow contribute to the elevated portal pressure in patients with cirrhosis. Clinically significant portal hypertension (CSPH) is defined by a hepatic venous pressure gradient (HVPG) of ⩾10 mmHg. In these patients, porto-systemic collaterals (e.g., esophageal varices) and ascites may develop. Due to progressive splanchnic and peripheral vasodilation, portal hypertension ultimately leads to a hyperdynamic

Diagnostic and prognostic biomarkers

Currently, invasive measurement of HVPG is the only accurate method for diagnosis of portal hypertension [15]. Clinical signs that indicate CSPH are the presence of collaterals on imaging, varices in upper GI endoscopy, or ascites [16]. However, some patients might have CSPH without varices or ascites. Biomarkers such as liver stiffness [17] and spleen stiffness [18] measured by elastography, spleen diameter [19], [20], von-Willebrand factor [21], or simply the platelet count be can used as

Current management with supporting evidence

Endoscopic band ligation is a safe and effective strategy for primary prophylaxis of variceal bleeding in case of intolerance to NSBBs.

Non-selective β-blockers (NSBBs) have been shown to effectively reduce the risk of variceal bleeding [43], [44], [45] and rebleeding [46], [47] due to a reduction of portal pressure. Thus, Baveno VI [16] and AASLD [48] guidelines recommend NSBBs for primary prophylaxis and for secondary prophylaxis (in combination with EBL) of variceal bleeding in patients with

Are NSBBs effective and safe in cirrhotic patients with ascites?

There is no prospective study that assessed the efficacy and safety of NSBBs to prevent variceal bleeding or rebleeding specifically in patients with cirrhosis and ascites. As mentioned previously, most studies on primary and secondary prophylaxis excluded patients with refractory ascites and renal failure. Even if a small number of patients with ascites were included, this does not necessarily imply that NSBBs are as effective and safe in patients with cirrhosis and ascites. We would like to

Therapy beyond guidelines

Based on the currently available data, an individualized NSBB regimen tailored to the specific pathophysiological stage of cirrhosis is likely to be the best strategy to optimize patient management at this point [66]. Treatment recommendations are summarized in Table 2.

Primary prophylaxis: Several studies have demonstrated the superiority of carvedilol over propranolol in reducing portal pressure [63], [67], [68]. However, it is important to point out that carvedilol is also associated with a

Financial support

No financial support was received in relation to this manuscript.

Conflict of interest

T.R. received payments for lectures from Roche, MSD, Boehringer-Ingelheim, and Gore. T.R. received travel support from Gilead, MSD, and Roche. M.M. received honoraria for consulting from Janssen, payments for lectures from Bristol-Myers Squibb, Janssen, Gore, and Roche, as well as travel support from AbbVie, Gilead, MSD, and Roche.

Authors’ contributions

Literature search (T.R., M.M.), concept of the article (T.R., M.M.), extraction of data (T.R., M.M.), drafting of the manuscript (T.R., M.M.), revision for important intellectual content (T.R., M.M.).

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