Letters to the Editors
Letter: probiotics vs. lactulose for minimal hepatic encephalopathy therapy – authors’ reply S. Shukla*, T. C. Mahl* & S. Guha† *Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA. † Gastroenterology, Hepatology, and Nutrition, UTH-Medical School and Health Science Center, Houston, TX, USA. E-mail: [email protected] doi:10.1111/apt.12700
SIRS, We thank Dr Ding and colleagues for the interest in our paper.1, 2 Their updated appraisal of the current literature comparing the effects of lactulose with probiotics in minimal hepatic encephalopathy (MHE) is a useful addition to the current knowledge of the efficacy of these agents. The authors conclude that probiotics may be a better therapeutic option compared with lactulose for the treatment of MHE, due to a lower adverse effect profile and similar efficacy. Although these data are useful, several aspects related to the nature of the probiotic agents need consideration. Probiotics may appear safer than lactulose. However, experience with these agents is limited compared with the longer duration of experience with lactulose. Furthermore, before probiotics can be recommended as the pre-
Letter: low risk of colorectal cancer in a Greek cohort of inflammatory bowel disease patients J. Kountouras, C. Zavos, D. Chatzopoulos, S. A. Polyzos, G. Deretzi, C. Simeonidou, N. Grigoriadis, E. Vardaka, C. Kountouras, E. Loli, J. Moschos, G. Kouklakis & P. Katsinelos Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. E-mail: [email protected] doi:10.1111/apt.12689
SIRS, Casta~ no-Milla et al.’s systematic review and meta1 analysis concluded that the risk of patients with ulcerative colitis (UC) developing colorectal cancer (CRC) has decreased steadily, though the extent and duration of the
Aliment Pharmacol Ther 2014; 39: 996-1002 ª 2014 John Wiley & Sons Ltd
ferred treatment option for MHE, other aspects need consideration. Firstly, the types and dosages of probiotics used in trials have been variable and it is currently unclear which specific species, strain, dose and regimen is most efficacious. Secondly, once treatment with probiotics is initiated, the duration and end point of treatment remain unclear; most of the available probiotics are expensive and can add significantly to the treatment cost for patients. Thirdly, cirrhotics often receive antibiotics such as rifaximin or cephalosporins for prophylaxis of overt HE or spontaneous bacterial peritonitis. The interactions between these agents and probiotics are not known. Future research should focus on these aspects to better elucidate how probiotics best fit into the treatment algorithm for MHE.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Ding X, Zhang F, Wang Y. Letter: probiotics vs. lactulose for minimal hepatic encephalopathy therapy. Aliment Pharmacol Ther 2014; 39: 1000. 2. Shukla S, Shukla A, Mehboob S, et al. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther 2011; 33: 662–71.
disease increase this risk. Concerning the limitations of their analysis, the authors mentioned the different CRC incidences according to the geographical area. In this regard, contrary to the data from other countries, the incidence of CRC in Greek inflammatory bowel disease (IBD) patients appears to be low,2, 3 although there is, as yet, no possible explanation of this observation. We aimed to provide an explanation of the aforementioned low CRC incidence through potential molecular-based ethnic differentiations. In a pilot study,4 we examined colonic biopsy specimens by immunohistochemistry obtained by endoscopy, from Greek patients with Crohn’s disease (CD) and UC stained for anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins. Bax overexpression was observed in 62% of CD patients and 50% of UC patients. Moreover, Bcl-2 protein was overexpressed in 25% of CD and in 50% of UC patients. These preliminary results suggest a possible
1001
Letters to the Editors existence of a balance between cell pro-apoptotic and anti-apoptotic mechanisms in UC, indicated by Bax and Bcl-2 overexpression in 50% of the patients, and a greater propensity for pro-apoptotic mechanisms in CD, indicated by Bax and Bcl-2 overexpression in 62% and 25% of the patients, respectively, thereby reflecting a coherent apoptotic process that might explain, at least in part, the low incidence of CRC development in Greek IBD patients. Our additional series5 also indicates a possible existence of a balance between cell proliferation (indicated by Ki-67 increased expression) and apoptosis (indicated by Bax overexpression), thereby providing an equilibrium between cell apoptosis and proliferation, and this again might partly explain the low oesophageal adenocarcinoma incidence in Greece, which is among the lowest in the world (3.5 per 100 000 person-years).
REFERENCES 1. Casta~ no-Milla C, Chaparro M, Gilbert JP. Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 645–59. 2. Triantafillidis JK, Emmanouilidis A, Manousos ON, et al. Ulcerative colitis in Greece: clinicoepidemiological data, course, and prognostic factors in 413 consecutive patients. J Clin Gastroenterol 1998; 27: 204–10. 3. Kountouras J, Kouklakis G, Zavos C, et al. Apoptosis, inflammatory bowel disease and carcinogenesis: overview of international and Greek experiences. Can J Gastroenterol 2003; 17: 249–58. 4. Kountouras J, Zavos C, Chatzopoulos D. Apoptosis and apoptosis-related proteins in inflammatory bowel disease. Apoptosis 2004; 9: 657–8. 5. Chatzopoulos D, Kyrgidis A, Kountouras J, Zavos C, Molyvas E, Venizelos I. Bax upregulation may provide a rationale for the low incidence of esophageal adenocarcinoma in a Greek cohort of patients with Barrett’s esophagus. Hepatogastroenterology 2007; 54: 705–9.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None.
1002
Aliment Pharmacol Ther 2014; 39: 996-1002 ª 2014 John Wiley & Sons Ltd
Letter: probiotics vs. lactulose for minimal hepatic encephalopathy therapy – authors’ reply S. Shukla*, T. C. Mahl* & S. Guha† *Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA. † Gastroenterology, Hepatology, and Nutrition, UTH-Medical School and Health Science Center, Houston, TX, USA. E-mail: [email protected] doi:10.1111/apt.12700
SIRS, We thank Dr Ding and colleagues for the interest in our paper.1, 2 Their updated appraisal of the current literature comparing the effects of lactulose with probiotics in minimal hepatic encephalopathy (MHE) is a useful addition to the current knowledge of the efficacy of these agents. The authors conclude that probiotics may be a better therapeutic option compared with lactulose for the treatment of MHE, due to a lower adverse effect profile and similar efficacy. Although these data are useful, several aspects related to the nature of the probiotic agents need consideration. Probiotics may appear safer than lactulose. However, experience with these agents is limited compared with the longer duration of experience with lactulose. Furthermore, before probiotics can be recommended as the pre-
Letter: low risk of colorectal cancer in a Greek cohort of inflammatory bowel disease patients J. Kountouras, C. Zavos, D. Chatzopoulos, S. A. Polyzos, G. Deretzi, C. Simeonidou, N. Grigoriadis, E. Vardaka, C. Kountouras, E. Loli, J. Moschos, G. Kouklakis & P. Katsinelos Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. E-mail: [email protected] doi:10.1111/apt.12689
SIRS, Casta~ no-Milla et al.’s systematic review and meta1 analysis concluded that the risk of patients with ulcerative colitis (UC) developing colorectal cancer (CRC) has decreased steadily, though the extent and duration of the
Aliment Pharmacol Ther 2014; 39: 996-1002 ª 2014 John Wiley & Sons Ltd
ferred treatment option for MHE, other aspects need consideration. Firstly, the types and dosages of probiotics used in trials have been variable and it is currently unclear which specific species, strain, dose and regimen is most efficacious. Secondly, once treatment with probiotics is initiated, the duration and end point of treatment remain unclear; most of the available probiotics are expensive and can add significantly to the treatment cost for patients. Thirdly, cirrhotics often receive antibiotics such as rifaximin or cephalosporins for prophylaxis of overt HE or spontaneous bacterial peritonitis. The interactions between these agents and probiotics are not known. Future research should focus on these aspects to better elucidate how probiotics best fit into the treatment algorithm for MHE.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Ding X, Zhang F, Wang Y. Letter: probiotics vs. lactulose for minimal hepatic encephalopathy therapy. Aliment Pharmacol Ther 2014; 39: 1000. 2. Shukla S, Shukla A, Mehboob S, et al. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther 2011; 33: 662–71.
disease increase this risk. Concerning the limitations of their analysis, the authors mentioned the different CRC incidences according to the geographical area. In this regard, contrary to the data from other countries, the incidence of CRC in Greek inflammatory bowel disease (IBD) patients appears to be low,2, 3 although there is, as yet, no possible explanation of this observation. We aimed to provide an explanation of the aforementioned low CRC incidence through potential molecular-based ethnic differentiations. In a pilot study,4 we examined colonic biopsy specimens by immunohistochemistry obtained by endoscopy, from Greek patients with Crohn’s disease (CD) and UC stained for anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins. Bax overexpression was observed in 62% of CD patients and 50% of UC patients. Moreover, Bcl-2 protein was overexpressed in 25% of CD and in 50% of UC patients. These preliminary results suggest a possible
1001
Letters to the Editors existence of a balance between cell pro-apoptotic and anti-apoptotic mechanisms in UC, indicated by Bax and Bcl-2 overexpression in 50% of the patients, and a greater propensity for pro-apoptotic mechanisms in CD, indicated by Bax and Bcl-2 overexpression in 62% and 25% of the patients, respectively, thereby reflecting a coherent apoptotic process that might explain, at least in part, the low incidence of CRC development in Greek IBD patients. Our additional series5 also indicates a possible existence of a balance between cell proliferation (indicated by Ki-67 increased expression) and apoptosis (indicated by Bax overexpression), thereby providing an equilibrium between cell apoptosis and proliferation, and this again might partly explain the low oesophageal adenocarcinoma incidence in Greece, which is among the lowest in the world (3.5 per 100 000 person-years).
REFERENCES 1. Casta~ no-Milla C, Chaparro M, Gilbert JP. Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 645–59. 2. Triantafillidis JK, Emmanouilidis A, Manousos ON, et al. Ulcerative colitis in Greece: clinicoepidemiological data, course, and prognostic factors in 413 consecutive patients. J Clin Gastroenterol 1998; 27: 204–10. 3. Kountouras J, Kouklakis G, Zavos C, et al. Apoptosis, inflammatory bowel disease and carcinogenesis: overview of international and Greek experiences. Can J Gastroenterol 2003; 17: 249–58. 4. Kountouras J, Zavos C, Chatzopoulos D. Apoptosis and apoptosis-related proteins in inflammatory bowel disease. Apoptosis 2004; 9: 657–8. 5. Chatzopoulos D, Kyrgidis A, Kountouras J, Zavos C, Molyvas E, Venizelos I. Bax upregulation may provide a rationale for the low incidence of esophageal adenocarcinoma in a Greek cohort of patients with Barrett’s esophagus. Hepatogastroenterology 2007; 54: 705–9.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None.
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Aliment Pharmacol Ther 2014; 39: 996-1002 ª 2014 John Wiley & Sons Ltd
