LETTERS TO THE EDITORS 309
suggest – that healing of even mild oesophagitis is clinically important, we would have to argue for a population-wide screening with endoscopy and PPI maintenance therapy in all patients with oesophagitis, which is clearly not feasible. ACKNOWLEDGEMENT Declaration of personal and funding interests: The author has received financial support in the form of speaker’s fees, consultation fees and research funding from AstraZeneca and Nycomed (formerly ALTANA Pharma).
REFERENCES 1 Tan VPY, Wong BCY. A false sense of security; symptom control does not predict healing of oesophagitis on proton pump inhibitors. Aliment Pharmacol Ther 2009; 30: 307–8. 2 Labenz J, Armstrong D, Zetterstrand S, et al. Clinical trial: factors associated with resolution of heartburn in patients with reflux oesophagitis: results from the EXPO study. Aliment Pharmacol Ther 2009; 29: 959–66. 3 Cheung TK, Wong WM, Wong NY, et al. Symptom resolution does not predict healing of erosive esophagitis in Chinese. Digestion 2007; 75: 128–34. 4 Kahrilas PJ, Falk GW, Johnson DA, et al. Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. Aliment Pharmacol Ther 2000; 14: 1249–58. 5 Richter JE, Kahrilas PJ, Johanson J, et al. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Am J Gastroenterol 2001; 96: 656–65.
A. D E G O T T A R D I & J. -C . G A R C I A - P A G A N Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, IDIBAPS and Ciberehd, Barcelona, Spain. E-mail:
[email protected] doi:10.1111/j.1365-2036.2009.04029.x
Aliment Pharmacol Ther 30, 307–313 ª 2009 Blackwell Publishing Ltd
6 Castell DO, Kahrilas PJ, Richter JE, et al. Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol 2002; 97: 575–83. 7 Schmitt C, Lightdale CJ, Hwang C, et al. A multicenter, randomized, double-blind, 8week comparative trial of standard doses of esomeprazole (40 mg) and omeprazole (20 mg) for the treatment of erosive esophagitis. Dig Dis Sci 2006; 51: 844–50. 8 Labenz J, Armstrong D, Lauritsen K, et al. Esomeprazole 20 mg versus pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study. Aliment Pharmacol Ther 2005; 22: 803–11. 9 Labenz J, Nocon M, Lind T, et al. Prospective follow-up data from the ProGERD study suggest that GERD is not a categorial disease. Am J Gastroenterol 2006; 101: 2457–62. 10 Ronkainen J, Aro P, Stroskrubb T, et al. High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: a Kalixanda study report. Scand J Gastroenterol 2005; 40: 275–85.
Does debugging the portal system decrease pressure? SIRS, Bacteria and their products (DNA, endotoxin and cytokines) may contribute not only to deteriorate hyperdynamic circulation, but also to increase hepatic vascular resistance in cirrhotic patients, promoting by this way a further increase in portal pressure. Bacterial infections have been proposed as triggers for variceal bleeding and have been shown to be associated with a poor prognosis.1 As a consequence, whether antibiotics may contribute to ameliorating portal pressure in cirrhosis has been a matter of debate. Indeed, three studies had previously evaluated this issue (Table 1). Only two of them showed the effects of
310 L E T T E R S T O T H E E D I T O R S
Table 1. Synopsis of studies on the effects of antibiotics on the HVPG Data on placebo group
Effect of treatment on HVPG Antibiotic
Placebo
Antibiotic
No
)2.4 mmHg
N.A.
Norfloxacin 400 mg b.d. for 4 weeks
Albillos et al.2
14 (but only 6 with clinically relevant portal hypertension) 37*
Yes
)0.8 mmHg
)0.5 mmHg
Kemp et al.3
16
Yes
)2.7 mmHg
)2.9 mmHg
Vlachogiannakos et al.5
28
No
)3.1 mmHg
N.A.
Norfloxacin 400 mg b.d. for 4 weeks Norfloxacin 400 mg b.d. for 4 weeks Rifaximin 1200 mg ⁄ d for 4 weeks
Author Rasaratnam et al.4
Number of patients
N.A., Not available. * Data shown of the 18 patients with elevated Lipopolysacaride binding protein.
placebo on hepatic venous pressure gradient (HVPG) and the effect was completely equivalent to that of norfloxacin.2, 3 In a third study,4 a nonsignificant trend to reduce HVPG was observed. However, this study did not evaluate the effect of placebo on HVPG and less than half of the patients had clinically significant portal hypertension (HVPG > 10 mmHg). A recent study published in Alimentary Pharmacology and Therapeutics5 provides novel data testing the possible efficacy of antibiotics in lowering portal pressure. The investigators treated for 1 month patients with decompensated alcoholic cirrhosis with rifaximin, a nonsystemically absorbed antibiotic, and observed a significant decrease in plasma endotoxin levels, which directly correlated with a significant drop in HVPG. The authors concluded that intestinal decontamination with rifaximine might represent a therapeutic approach in the prevention of complications of portal hypertension. The major drawback of this study was the absence of a control group. Indeed, similar effect on HVPG was observed in the two studies that had data on the effect of norfloxacin and placebo on HVPG, thus highlighting the importance of excluding other possible factors biasing the results like, for example, alcohol abstinence. The potential interest of these findings was further faded by the absence of follow-up data on the outcome of their patients during the study period. Therefore, these results should be considered preliminary and need to be confirmed. We must wait for additional studies with appropriate design and sample size to define clearly the possible role of antibiotics to improve the hemodynamic disturbances of cirrhotic patients.
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LETTERS TO THE EDITORS 311
ACKNOWLEDGEMENTS Declaration of personal and funding interests: The writing of this paper was funded in part by the Swiss National Science Foundation, the EASL Sheila Sherlock Fellowship. Ciberehd is funded by Instituto de Salud Carlos III.
REFERENCES 1 Goulis J, Armonis A, Patch D, et al. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage. Hepatology 1998; 27: 1207–12. 2 Albillos A, de la Hera A, Gonzalez M, et al. Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology 2003; 37: 208–17. 3 Kemp W, Colman J, Thompson K, et al. Norfloxacin treatment for clinically significant
J. VLACHOGIANNAKOS, N. VIAZIS & D. KARAMANOLIS 2nd Department of Gastroenterology, Evangelismos Hospital, Athens, Greece. E-mail:
[email protected] doi:10.1111/j.1365-2036.2009.04046.x
portal hypertension: results of a randomised double-blind placebo-controlled crossover trial. Liver Int 2009; 29: 427–33. 4 Rasaratnam B, Kaye D, Jennings G, et al. The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial. Ann Intern Med 2003; 139: 186–93. 5 Vlachogiannakos J, Saveriadis AS, Viazis N, et al. Intestinal decontamination improves liver haemodynamics in patients with alcohol related decompensated cirrhosis. Aliment Pharmacol Ther 2009; 29: 992–9.
Does debugging the portal system decrease pressure? Authors’ reply SIRS, We would like to thank the authors for their interest in our study.1, 2 Although we agree that our results are preliminary, we believe that our data give further evidence that bacteria and bacterial products deteriorate liver haemodynamics in cirrhotics. It is true that a placebo group is lacking from our study, but our data strongly support the efficacy of antibiotics in reducing HVPG. The beneficial role of intestinal decontamination is also supported by the significant reduction in endotoxin levels that was directly correlated with the drop in HVPG. Furthermore, it is worth noting that instead of norfloxacin, for the first time, we used rifaximin - a highly efficient and safe antibiotic with a broad spectrum of action and minimal intestinal absorption. We believe that our results could not have been biased by other factors, like for example, continued alcohol consumption, as all our patients were regularly followed-up at the outpatient clinic, where they had prolonged periods of documented alcohol abstinence. As regards follow-up data on the outcome of our study population during the study period, it should be mentioned that all our patients were alive at the end of the 28 days. Regular admissions were necessary for endoscopic ligation of the varices in six patients and treatment of ascites in three patients. The authors comment on the two previous studies that found no advantage of norfloxacin over placebo in reducing HVPG; however, the results of these studies have to be viewed with skepticism, as they have included a small number of patients with various aetiologies of cirrhosis.3, 4 Finally, we agree that our data support the need for additional studies, which would further investigate the efficacy of long-term antibiotic administration in the prevention of portal hypertension complications. ACKNOWLEDGEMENT Declaration of personal and funding interests: None.
Aliment Pharmacol Ther 30, 307–313 ª 2009 Blackwell Publishing Ltd
