January 2017 Letters to the Editor 149
JEAN-MARC GORNET, MD this meta-analysis is that the use of NSBBs is not asso-
Hepato-Gastroenterology Department ciated with a significant increase in all-cause mortality in
Saint-Louis Hospital APHP patients with cirrhosis and ascites or refractory ascites.
Paris, France However, the investigators underlined that certainty in
the available estimates was low and concluded with the
References well-known refrain: “further randomised clinical studies
1. Simon M, et al. Clin Gastroenterol Hepatol 2016;14:966–972.
are warranted to evaluate the effects of NSBBs therapy
2. Wils P, et al. Clin Gastroenterol Hepatol 2016;14:242–250.
on patients with cirrhosis and ascites,”7 thus compli-
3. Faubion WA Jr, et al. Gastroenterology 2001;121:255–260.
cating a subject of therapy that already is becoming
4. Lichtenstein GR, et al. Am J Gastroenterol 2012;107:1409–1422.
confused, making it more difficult for a disoriented
gastroenterologist to find an answer to one of the most
Conflicts of interest frequent questions that is being asked about the safety of
The authors disclose no conflicts.
NSBBs: to initiate or not the b-blocker treatment, or to
Most current article continue/discontinue such therapy in patients with
http://dx.doi.org/10.1016/j.cgh.2016.09.016 decompensated cirrhosis? Until future randomized
controlled trials come with convincing arguments, the
b-Blockers in Decompensated Cirrhosis: Baveno VI consensus conference recommendations are a
good guide to NSBB therapy in patients with decom-
More Questions Than Answers pensated cirrhosis: NSBBs can be used in patients with
refractory ascites but dose reduction or discontinuation
Dear Editor:
should be considered when systolic blood pressure is
Thirty–five years ago, the first controlled clinical less than 90 mm Hg, or serum sodium level is less than
study documented that propranolol significantly reduced 130 mEq/L, or in case of renal insufficiency.8
the risk of rebleeding from esophageal varices,1 and
ANCA TRIFAN, MD
since then has been followed up by hundreds of articles
“Gr. T Popa” University of Medicine and Pharmacy
(including randomized controlled trials and meta-
Iasi, Romania
analyses), all showing that nonselective b-blockers
(NSBBs) improve survival in patients with cirrhosis. CAROL STANCIU, MD
Five years ago, Sersté et al2 published an article “St. Spiridon” University Hospital
showing that the use of NSBBs was associated with poor Iasi, Romania
survival in cirrhotic patients with refractory ascites and
suggested that b-blockers should be contraindicated in References
1. Lebrec D, et al. Lancet 1981;317:920–921.
these patients. More recently, Mandorfer et al3 showed
2. Sersté T, et al. Hepatology 2010;52:1017–1022.
that in patients with cirrhosis and spontaneous bacterial
3. Mandorfer M, et al. Gastroenterology 2014;146:1680–1690.
peritonitis, NSBBs reduce transplant-free survival, rec-
4. Krag A, et al. Gut 2012;61:967–969.
ommending in the end that such patients should not
5. Leithead JA, et al. Gut 2015;64:1111–1119.
receive b-blockers. The aforementioned 2 studies sup-
6. Mookerjee RP, et al. J Hepatol 2016;64:574–582.
port the window hypothesis for b-blockers by Krag et al,4
7. Chirapongsathorn S, et al. Clin Gastroenterol Hepatol 2016;
who suggested that NSBBs may be effective and improve
14:1096–1104.
survival only within a narrow clinical window in the
8. de Franchis R. J Hepatol 2015;63:743–752.
course of cirrhosis, and are harmful beyond this window.
The presence of refractory ascites or the development of
spontaneous bacterial peritonitis closes the window. Conflicts of interest
Both of these studies generated significant controversies The authors disclose no conflicts.
among clinicians caring for cirrhotic patients, many of Most current article
them deciding to cease to use NSBBs in patients with http://dx.doi.org/10.1016/j.cgh.2016.09.140
decompensated cirrhosis.
However, in the past 2 years only, some studies have Reply. We thank the authors for their comments
re-opened the window, reporting either no association on our meta-analysis relating to nonselective b-
between the use of NSBBs and increased mortality risk in blockers (NSBB) and survival in patients with
patients with decompensated cirrhosis or even a bene- cirrhosis and ascites.1
ficial effect of such therapy on the survival of these We agree there are many studies showing the bene-
patients.5,6 ficial effect of NSBB in patients with cirrhosis. However,
It is in this context that we expected the recent meta- there is a paucity of randomized controlled trials, which
analysis published by Chirapongsathorn et al7 in Clinical are the gold standard of scientific testing for medications,
Gastroenterology and Hepatology to bring more light to to measure the efficacy and safety of NSBB in cirrhotic
the ongoing debate about the use of NSBBs in cirrhotic patients with ascites. The randomized controlled trials
patients with ascites. The most important conclusion of that demonstrated the benefit of NSBB in decreasing
JEAN-MARC GORNET, MD this meta-analysis is that the use of NSBBs is not asso-
Hepato-Gastroenterology Department ciated with a significant increase in all-cause mortality in
Saint-Louis Hospital APHP patients with cirrhosis and ascites or refractory ascites.
Paris, France However, the investigators underlined that certainty in
the available estimates was low and concluded with the
References well-known refrain: “further randomised clinical studies
1. Simon M, et al. Clin Gastroenterol Hepatol 2016;14:966–972.
are warranted to evaluate the effects of NSBBs therapy
2. Wils P, et al. Clin Gastroenterol Hepatol 2016;14:242–250.
on patients with cirrhosis and ascites,”7 thus compli-
3. Faubion WA Jr, et al. Gastroenterology 2001;121:255–260.
cating a subject of therapy that already is becoming
4. Lichtenstein GR, et al. Am J Gastroenterol 2012;107:1409–1422.
confused, making it more difficult for a disoriented
gastroenterologist to find an answer to one of the most
Conflicts of interest frequent questions that is being asked about the safety of
The authors disclose no conflicts.
NSBBs: to initiate or not the b-blocker treatment, or to
Most current article continue/discontinue such therapy in patients with
http://dx.doi.org/10.1016/j.cgh.2016.09.016 decompensated cirrhosis? Until future randomized
controlled trials come with convincing arguments, the
b-Blockers in Decompensated Cirrhosis: Baveno VI consensus conference recommendations are a
good guide to NSBB therapy in patients with decom-
More Questions Than Answers pensated cirrhosis: NSBBs can be used in patients with
refractory ascites but dose reduction or discontinuation
Dear Editor:
should be considered when systolic blood pressure is
Thirty–five years ago, the first controlled clinical less than 90 mm Hg, or serum sodium level is less than
study documented that propranolol significantly reduced 130 mEq/L, or in case of renal insufficiency.8
the risk of rebleeding from esophageal varices,1 and
ANCA TRIFAN, MD
since then has been followed up by hundreds of articles
“Gr. T Popa” University of Medicine and Pharmacy
(including randomized controlled trials and meta-
Iasi, Romania
analyses), all showing that nonselective b-blockers
(NSBBs) improve survival in patients with cirrhosis. CAROL STANCIU, MD
Five years ago, Sersté et al2 published an article “St. Spiridon” University Hospital
showing that the use of NSBBs was associated with poor Iasi, Romania
survival in cirrhotic patients with refractory ascites and
suggested that b-blockers should be contraindicated in References
1. Lebrec D, et al. Lancet 1981;317:920–921.
these patients. More recently, Mandorfer et al3 showed
2. Sersté T, et al. Hepatology 2010;52:1017–1022.
that in patients with cirrhosis and spontaneous bacterial
3. Mandorfer M, et al. Gastroenterology 2014;146:1680–1690.
peritonitis, NSBBs reduce transplant-free survival, rec-
4. Krag A, et al. Gut 2012;61:967–969.
ommending in the end that such patients should not
5. Leithead JA, et al. Gut 2015;64:1111–1119.
receive b-blockers. The aforementioned 2 studies sup-
6. Mookerjee RP, et al. J Hepatol 2016;64:574–582.
port the window hypothesis for b-blockers by Krag et al,4
7. Chirapongsathorn S, et al. Clin Gastroenterol Hepatol 2016;
who suggested that NSBBs may be effective and improve
14:1096–1104.
survival only within a narrow clinical window in the
8. de Franchis R. J Hepatol 2015;63:743–752.
course of cirrhosis, and are harmful beyond this window.
The presence of refractory ascites or the development of
spontaneous bacterial peritonitis closes the window. Conflicts of interest
Both of these studies generated significant controversies The authors disclose no conflicts.
among clinicians caring for cirrhotic patients, many of Most current article
them deciding to cease to use NSBBs in patients with http://dx.doi.org/10.1016/j.cgh.2016.09.140
decompensated cirrhosis.
However, in the past 2 years only, some studies have Reply. We thank the authors for their comments
re-opened the window, reporting either no association on our meta-analysis relating to nonselective b-
between the use of NSBBs and increased mortality risk in blockers (NSBB) and survival in patients with
patients with decompensated cirrhosis or even a bene- cirrhosis and ascites.1
ficial effect of such therapy on the survival of these We agree there are many studies showing the bene-
patients.5,6 ficial effect of NSBB in patients with cirrhosis. However,
It is in this context that we expected the recent meta- there is a paucity of randomized controlled trials, which
analysis published by Chirapongsathorn et al7 in Clinical are the gold standard of scientific testing for medications,
Gastroenterology and Hepatology to bring more light to to measure the efficacy and safety of NSBB in cirrhotic
the ongoing debate about the use of NSBBs in cirrhotic patients with ascites. The randomized controlled trials
patients with ascites. The most important conclusion of that demonstrated the benefit of NSBB in decreasing
