- Email: [email protected]
Is There a Role for Sequential in Sequential Anti–H. pylori Therapy?
1930
CORRESPONDENCE
1. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, Macintosh D, Panaccione R, Wolf D, Pollack P. Human anti-tumor necrosis factor monoclonal antibody (Adalimumab) in Crohn’s disease: the CLASSIC-I Trial. Gastroenterology 2006;130:323–333. 2. van Deventer SJH. Transmembrane TNF-alpha, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn’s disease. Gastroenterology 2001;121:1242–1246. 3. Schreiber S, Khaliq-Kareemi M, Lawrance I, Hanauer S, McColm J, Bloomfield R, Sandborn W. Certolizumab pegol, a humanized antiTNF pegylated Fab= fragment, is safe and effective in the maintenance of response and remission following induction in active Crohn’s disease: a phase III study (PRECiSE) (abstr). Gut 2005; 54:A82. 4. Will M, Nikolaus S, Freitag S, Arpe N, Krawczak M, Schreiber S. Placebo response in the therapy of Crohn’s disease: a comprehensive analysis of primary data from 733 patients from 13 randomized, controlled trials. (abstr) Gastroenterology 2005;128: A48. 5. Nesbitt AM, Henry AJ. High affinity and potency of the pegylated FAB= fragment CDP870 - a direct comparison with other anti-TNF agents. Am J Gastroenterol 2004;99:S253. 6. Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D, Wagner C. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 2002;301:418 – 426. doi:10.1053/j.gastro.2006.03.050
Is There a Role for Sequential in Sequential Anti–H. pylori Therapy? Dear Sir: Recently, Francavilla et al1 reported excellent results with sequential therapy for H pylori infection in children. Similar results have been reported in adults.2–5 Is there something special about sequential administration of the components of therapy? The mucosal surface area of the stomach is very large such that there are a tremendous number of bacteria present (in the range of 107 to 1011), which increases the likelihood that a few naturally resistant mutants are always present. The initial use of antibiotics associated with a low rate of spontaneous mutation to a resistant phenotype or to rapidly reduce the total number of bacteria with a drug with low or absent resistance potential (eg, bismuth) would have theoretical advantages over concomitant therapy.6 It has become clear that the success rates of 7 or 10 days of standard triple therapy (a proton pump inhibitor plus 2 antibiotics) are now typically below 80% and that the outcome can be improved on average about 12% by increasing the duration to 14 days.7 These low cure rates were confirmed in the comparative studies of sequential and triple therapy.2–5 However, sequential therapy is not sequential administration of triple therapy, rather it is a quadruple therapy containing 3 antibiotics (amoxicillin, clarithromycin, and metronidazole). The results with the 3 common triple therapies (a proton pump inhibitor and amoxicillin plus clarithromycin, or amoxicillin plus metronidazole, or clarithromycin plus metronidazole) are each well known. In fact, the current recommendation is that triple therapy failures should receive another course switching clarithromycin for metronidazole or vice versa. One would not be surprised if the effects were additive such that sequential therapy may actually be “concomitant triple therapies.” There are data to support this hypothesis as this 3 antibiotic combination has previously been examined as a nonsequential therapy (concomitant therapy) given for 5 days with very good results (eg, per protocol cure rate of ranging from 89%–96% with a PPI 8 –10 or
GASTROENTEROLOGY Vol. 130, No. 6
ranitidine bismuth citrate).11,12 The unanswered question is whether the sequential part of sequential therapy actually provides the proposed theoretical advantage or whether it is makes concomitant triple therapies more complicated than necessary. The studies comparing sequential quadruple therapy and legacy triple therapy have used 7or 10-day duration triple therapies.1,3–5 It is unfortunate that the investigators did not extend the duration of triple therapy to 14 days as that has been shown to improve the success rate on average by about 12%, which would have increased the cure rates with triple therapy to approximately the same range. There have now been at least 4 randomized trials of sequential quadruple therapy and 7 or 10 day legacy triple therapy. No more are needed. Do the investigators now plan the important trial where sequential is randomized with concomitant therapy using the same combination of drugs. This would address whether the “sequential” in sequential quadruple therapy is actually helpful. As 5 days duration was arbitrary, do they plan to test longer durations with the hope to achieve the 95% eradication rates with susceptible organisms considered the standard for other serious infectious diseases. DAVID Y. GRAHAM Department of Medicine Michael E. DeBakey VAMC and Baylor College of Medicine Houston, Texas HONG LU Department of Gastroenterology Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai Institute of Digestive Disease Shanghai, China 1. Francavilla R, Lionetti E, Castellaneta SP, Magista AM, Boscarelli G, Piscitelli D, Amoruso A, Di LA, Miniello VL, Francavilla A, Cavallo L, Ierardi E. Improved efficacy of 10-day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology 2005;129:1414 –1419. 2. De Francesco V, Della VN, Stoppino V, Amoruso A, Muscatiello N, Panella C, Ierardi E. Effectiveness and pharmaceutical cost of sequential treatment for Helicobacter pylori in patients with nonulcer dyspepsia. Aliment Pharmacol Ther 2004;19:993–998. 3. Zullo A, Vaira D, Vakil N, Hassan C, Gatta L, Ricci C, De Francesco V, Menegatti M, Tampieri A, Perna F, Rinaldi V, Perri F, Papadia C, Fornari F, Pilati S, Mete LS, Merla A, Poti R, Marinone G, Savioli A, Campo SM, Faleo D, Ierardi E, Miglioli M, Morini S. High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther 2003;17:719 –726. 4. Zullo A, Gatta L, De Francesco V, Hassan C, Ricci C, Bernabucci V, Cavina M, Ierardi E, Morini S, Vaira D. High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study. Aliment Pharmacol Ther 2005;21:1419 –1424. 5. Scaccianoce G, Hassan C, Panarese A, Piglionica D, Morini S, Zullo A. Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol 2006;20:113–117. 6. Graham DY. Antibiotic resistance in Helicobacter pylori: implications for therapy. Gastroenterology 1998;115:1272–1277. 7. Nakayama Y, Graham DY. Helicobacter pylori infection: diagnosis and treatment. Expert Rev Anti-Infect Therapy 2004;2:599 – 616. 8. Nagahara A, Miwa H, Ogawa K, Kurosawa A, Ohkura R, Iida N, Sato N. Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an
May 2006
9.
10.
11.
12.
CORRESPONDENCE
excellent cure rate with five-day therapy. Helicobacter 2000;5:88 –93. Treiber G, Ammon S, Schneider E, Klotz U. Amoxicillin/metronidazole/omeprazole/clarithromycin: a new, short quadruple therapy for Helicobacter pylori eradication. Helicobacter 1998;3:54 – 58. Treiber G, Wittig J, Ammon S, Walker S, van Doorn LJ, Klotz U. Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med 2002;162: 153–160. Gisbert JP, Marcos S, Gisbert JL, Pajares JM. High efficacy of ranitidine bismuth citrate, amoxicillin, clarithromycin and metronidazole twice daily for only five days in Helicobacter pylori eradication. Helicobacter 2001;6:157–162. Hopkins RJ. In search of the Holy Grail of Helicobacter pylori remedies. Helicobacter 2001;6:81– 83. doi:10.1053/j.gastro.2006.03.037
Reply. We are afraid that our therapeutic regimen was misunderstood by Drs. Graham and Lu. We claim that the sequential regimen is represented by a 5-day dual therapy (Proton Pump Inhibitor – PPI plus amoxycillin) followed by a 5-day triple therapy (PPI, clarithromycin, and tinidazole). Therefore, it should be regarded neither as a quadruple therapy nor as 2 concomitant triple therapies. In the dual scheme, we administered amoxycillin, which is able to eradicate H pylori in some patients and to reduce the bacterial load in all the remaining cases, without inducing bacterial resistance. Indeed, it has been found that regimens containing amoxycillin may prevent the selection of secondary clarithromycin resistance1 and such a finding has not been reported yet for bismuth. For that reason, the “question whether the sequential part of sequential therapy actually provides the proposed theoretical advantage” has both a rational basis and a proven outcome with an intention-to-treat analysis eradication rate of 93.5% (95% CI, 92–95) observed in more than 1200 patients.2 Current European Guidelines suggest the use of a quadruple therapy in patients who fail standard triple therapy eradication, and do not recommend a second course of triple therapy, as reported in Dr. Graham’s letter. The letter, moreover, asserts that a 5-day quadruple therapy (PPI, clarithromycin, amoxycillin, metronidazole) has achieved very high eradication rates (intention to treat analysis: 86%–95%).3 However, side effects have been experienced by as much as 51% of patients,4 and the simultaneous administration of such a large number of tablets is troublesome for patients, and therefore the compliance is questionable. Data regarding such a 5-day quadruple were published between 1998 and 2002, and no further information has appeared thereafter.3 Instead quadruple therapy (PPI, bismuth, tetracycline, and metronidazole) for 14 days has been suggested.5 The assertion that a 14-day triple therapy is able to increase the eradication rate by 12% refers to a single study.6 On the contrary, a meta-analysis including 13 well-designed, “head-to-head” comparison studies found a small difference in the success rate between 7-day and 14-day triple therapy showing that bacterial infection was cured in only 339 of 470 (72%) and in 353 of 436 (81%) patients, respectively.7 Therefore, the success rate following the 14-day triple therapy is far from the desirable 95% eradication rate, and its cost is obviously twice as compared with the 7-day regimen. In conclusion, the 10-day sequential regimen is a sequential administration of an initial dual therapy immediately followed by triple therapy. Such a therapeutic regimen constantly achieved very high eradication rates with few side effects in children, adult, and elderly
1931
patients. Moreover, it has been shown to be significantly better than 7-day or 10-day standard regimen, even in those patients harbouring clarithromycin resistant strains.8 We do not think that a 14-day therapy with its unsatisfactory eradication rate,7 cost and side-effect profile is warranted in a population of children. Thus, we invite Dr. Graham to prove whether the 5-day quadruple therapy is effective in a large clinical trial such as ours. We would be delighted to have two weapons instead of one! RUGGIERO FRANCAVILLA Department of Biomedicina dell’Età Evolutiva Clinica Pediatrica “B. Trambusti” Università degli Studi di Bari Bari, Italy ENZO IERARDI Department of Scienze Mediche e del Lavoro Università degli Studi di Foggia Foggia, Italy 1. Murakami K, Fujioka T, Okimoto T, Sato R, Kodama M, Nasu M. Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy. Int J Antimicrob Agents 2002;19:67–70. 2. Scaccianoce G, Hassan C, Panarese A, Piglionica D, Morini S, Zullo A. Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol 2006;20:113–117. 3. Fischbach LA, Van Zanten SV, Dickason J. Meta-analysis: the efficacy, adverse events, and adherence related to first-line antiHelicobacter pylori quadruple therapies. Aliment Pharmacol Ther 2004;20:1071–1082. 4. Neville PM, Everett S, Langworthy H, Tompkins D, Mapstone P, Axon ATR, Moayyedi P. The optimal antibiotic combination in a 5-day Helicobacter pylori eradication regimen. Aliment Pharmacol Ther 1999;13:497–501. 5. Graham DY, Belson G, Abudayyeh S, Osato MS, Dore MP, ElZimaity HMT. Twice a day, mid-day, quadruple therapy for H. pylori infection in the United States. Dig Liver Dis 2004;36:384 –387. 6. Nakayama Y, Graham DY. Helicobacter pylori infection: diagnosis and treatment. Expert Rev Anti-Infect Therapy 2004;2:599 – 616. 7. Calvet X, Garcia N, Lopez T, Gisbert JP, Gene E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther 2000;14:603– 608. 8. De Francesco V, Margiotta M, Zullo A, Hassan C, Troiani L, Burattini O, Stella F, Di Leo A, Russo F, Marangi S, Monno R, Stoppino V, Morini S, Panella C, Ierardi E. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med 2006;144:94 –100. doi:10.1053/j.gastro.2006.03.038YGAST
Coffee and Tea Consumption and Chronic Liver Disease Dear Sir: We read with interest Ruhl and Everhart’s finding of an inverse association between coffee and tea consumption and the consequent development of chronic liver disease (CLD).1 Coffee, green tea, and black tea are important dietary sources of phytochemicals with disease-modifying properties,2 and the authors attribute the beneficial effect of drinking these beverages to their high content of caffeine, an alkaloid with antioxidant and insulin-sensitizing properties, given the
CORRESPONDENCE
1. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, Macintosh D, Panaccione R, Wolf D, Pollack P. Human anti-tumor necrosis factor monoclonal antibody (Adalimumab) in Crohn’s disease: the CLASSIC-I Trial. Gastroenterology 2006;130:323–333. 2. van Deventer SJH. Transmembrane TNF-alpha, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn’s disease. Gastroenterology 2001;121:1242–1246. 3. Schreiber S, Khaliq-Kareemi M, Lawrance I, Hanauer S, McColm J, Bloomfield R, Sandborn W. Certolizumab pegol, a humanized antiTNF pegylated Fab= fragment, is safe and effective in the maintenance of response and remission following induction in active Crohn’s disease: a phase III study (PRECiSE) (abstr). Gut 2005; 54:A82. 4. Will M, Nikolaus S, Freitag S, Arpe N, Krawczak M, Schreiber S. Placebo response in the therapy of Crohn’s disease: a comprehensive analysis of primary data from 733 patients from 13 randomized, controlled trials. (abstr) Gastroenterology 2005;128: A48. 5. Nesbitt AM, Henry AJ. High affinity and potency of the pegylated FAB= fragment CDP870 - a direct comparison with other anti-TNF agents. Am J Gastroenterol 2004;99:S253. 6. Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D, Wagner C. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 2002;301:418 – 426. doi:10.1053/j.gastro.2006.03.050
Is There a Role for Sequential in Sequential Anti–H. pylori Therapy? Dear Sir: Recently, Francavilla et al1 reported excellent results with sequential therapy for H pylori infection in children. Similar results have been reported in adults.2–5 Is there something special about sequential administration of the components of therapy? The mucosal surface area of the stomach is very large such that there are a tremendous number of bacteria present (in the range of 107 to 1011), which increases the likelihood that a few naturally resistant mutants are always present. The initial use of antibiotics associated with a low rate of spontaneous mutation to a resistant phenotype or to rapidly reduce the total number of bacteria with a drug with low or absent resistance potential (eg, bismuth) would have theoretical advantages over concomitant therapy.6 It has become clear that the success rates of 7 or 10 days of standard triple therapy (a proton pump inhibitor plus 2 antibiotics) are now typically below 80% and that the outcome can be improved on average about 12% by increasing the duration to 14 days.7 These low cure rates were confirmed in the comparative studies of sequential and triple therapy.2–5 However, sequential therapy is not sequential administration of triple therapy, rather it is a quadruple therapy containing 3 antibiotics (amoxicillin, clarithromycin, and metronidazole). The results with the 3 common triple therapies (a proton pump inhibitor and amoxicillin plus clarithromycin, or amoxicillin plus metronidazole, or clarithromycin plus metronidazole) are each well known. In fact, the current recommendation is that triple therapy failures should receive another course switching clarithromycin for metronidazole or vice versa. One would not be surprised if the effects were additive such that sequential therapy may actually be “concomitant triple therapies.” There are data to support this hypothesis as this 3 antibiotic combination has previously been examined as a nonsequential therapy (concomitant therapy) given for 5 days with very good results (eg, per protocol cure rate of ranging from 89%–96% with a PPI 8 –10 or
GASTROENTEROLOGY Vol. 130, No. 6
ranitidine bismuth citrate).11,12 The unanswered question is whether the sequential part of sequential therapy actually provides the proposed theoretical advantage or whether it is makes concomitant triple therapies more complicated than necessary. The studies comparing sequential quadruple therapy and legacy triple therapy have used 7or 10-day duration triple therapies.1,3–5 It is unfortunate that the investigators did not extend the duration of triple therapy to 14 days as that has been shown to improve the success rate on average by about 12%, which would have increased the cure rates with triple therapy to approximately the same range. There have now been at least 4 randomized trials of sequential quadruple therapy and 7 or 10 day legacy triple therapy. No more are needed. Do the investigators now plan the important trial where sequential is randomized with concomitant therapy using the same combination of drugs. This would address whether the “sequential” in sequential quadruple therapy is actually helpful. As 5 days duration was arbitrary, do they plan to test longer durations with the hope to achieve the 95% eradication rates with susceptible organisms considered the standard for other serious infectious diseases. DAVID Y. GRAHAM Department of Medicine Michael E. DeBakey VAMC and Baylor College of Medicine Houston, Texas HONG LU Department of Gastroenterology Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai Institute of Digestive Disease Shanghai, China 1. Francavilla R, Lionetti E, Castellaneta SP, Magista AM, Boscarelli G, Piscitelli D, Amoruso A, Di LA, Miniello VL, Francavilla A, Cavallo L, Ierardi E. Improved efficacy of 10-day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology 2005;129:1414 –1419. 2. De Francesco V, Della VN, Stoppino V, Amoruso A, Muscatiello N, Panella C, Ierardi E. Effectiveness and pharmaceutical cost of sequential treatment for Helicobacter pylori in patients with nonulcer dyspepsia. Aliment Pharmacol Ther 2004;19:993–998. 3. Zullo A, Vaira D, Vakil N, Hassan C, Gatta L, Ricci C, De Francesco V, Menegatti M, Tampieri A, Perna F, Rinaldi V, Perri F, Papadia C, Fornari F, Pilati S, Mete LS, Merla A, Poti R, Marinone G, Savioli A, Campo SM, Faleo D, Ierardi E, Miglioli M, Morini S. High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther 2003;17:719 –726. 4. Zullo A, Gatta L, De Francesco V, Hassan C, Ricci C, Bernabucci V, Cavina M, Ierardi E, Morini S, Vaira D. High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study. Aliment Pharmacol Ther 2005;21:1419 –1424. 5. Scaccianoce G, Hassan C, Panarese A, Piglionica D, Morini S, Zullo A. Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol 2006;20:113–117. 6. Graham DY. Antibiotic resistance in Helicobacter pylori: implications for therapy. Gastroenterology 1998;115:1272–1277. 7. Nakayama Y, Graham DY. Helicobacter pylori infection: diagnosis and treatment. Expert Rev Anti-Infect Therapy 2004;2:599 – 616. 8. Nagahara A, Miwa H, Ogawa K, Kurosawa A, Ohkura R, Iida N, Sato N. Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an
May 2006
9.
10.
11.
12.
CORRESPONDENCE
excellent cure rate with five-day therapy. Helicobacter 2000;5:88 –93. Treiber G, Ammon S, Schneider E, Klotz U. Amoxicillin/metronidazole/omeprazole/clarithromycin: a new, short quadruple therapy for Helicobacter pylori eradication. Helicobacter 1998;3:54 – 58. Treiber G, Wittig J, Ammon S, Walker S, van Doorn LJ, Klotz U. Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med 2002;162: 153–160. Gisbert JP, Marcos S, Gisbert JL, Pajares JM. High efficacy of ranitidine bismuth citrate, amoxicillin, clarithromycin and metronidazole twice daily for only five days in Helicobacter pylori eradication. Helicobacter 2001;6:157–162. Hopkins RJ. In search of the Holy Grail of Helicobacter pylori remedies. Helicobacter 2001;6:81– 83. doi:10.1053/j.gastro.2006.03.037
Reply. We are afraid that our therapeutic regimen was misunderstood by Drs. Graham and Lu. We claim that the sequential regimen is represented by a 5-day dual therapy (Proton Pump Inhibitor – PPI plus amoxycillin) followed by a 5-day triple therapy (PPI, clarithromycin, and tinidazole). Therefore, it should be regarded neither as a quadruple therapy nor as 2 concomitant triple therapies. In the dual scheme, we administered amoxycillin, which is able to eradicate H pylori in some patients and to reduce the bacterial load in all the remaining cases, without inducing bacterial resistance. Indeed, it has been found that regimens containing amoxycillin may prevent the selection of secondary clarithromycin resistance1 and such a finding has not been reported yet for bismuth. For that reason, the “question whether the sequential part of sequential therapy actually provides the proposed theoretical advantage” has both a rational basis and a proven outcome with an intention-to-treat analysis eradication rate of 93.5% (95% CI, 92–95) observed in more than 1200 patients.2 Current European Guidelines suggest the use of a quadruple therapy in patients who fail standard triple therapy eradication, and do not recommend a second course of triple therapy, as reported in Dr. Graham’s letter. The letter, moreover, asserts that a 5-day quadruple therapy (PPI, clarithromycin, amoxycillin, metronidazole) has achieved very high eradication rates (intention to treat analysis: 86%–95%).3 However, side effects have been experienced by as much as 51% of patients,4 and the simultaneous administration of such a large number of tablets is troublesome for patients, and therefore the compliance is questionable. Data regarding such a 5-day quadruple were published between 1998 and 2002, and no further information has appeared thereafter.3 Instead quadruple therapy (PPI, bismuth, tetracycline, and metronidazole) for 14 days has been suggested.5 The assertion that a 14-day triple therapy is able to increase the eradication rate by 12% refers to a single study.6 On the contrary, a meta-analysis including 13 well-designed, “head-to-head” comparison studies found a small difference in the success rate between 7-day and 14-day triple therapy showing that bacterial infection was cured in only 339 of 470 (72%) and in 353 of 436 (81%) patients, respectively.7 Therefore, the success rate following the 14-day triple therapy is far from the desirable 95% eradication rate, and its cost is obviously twice as compared with the 7-day regimen. In conclusion, the 10-day sequential regimen is a sequential administration of an initial dual therapy immediately followed by triple therapy. Such a therapeutic regimen constantly achieved very high eradication rates with few side effects in children, adult, and elderly
1931
patients. Moreover, it has been shown to be significantly better than 7-day or 10-day standard regimen, even in those patients harbouring clarithromycin resistant strains.8 We do not think that a 14-day therapy with its unsatisfactory eradication rate,7 cost and side-effect profile is warranted in a population of children. Thus, we invite Dr. Graham to prove whether the 5-day quadruple therapy is effective in a large clinical trial such as ours. We would be delighted to have two weapons instead of one! RUGGIERO FRANCAVILLA Department of Biomedicina dell’Età Evolutiva Clinica Pediatrica “B. Trambusti” Università degli Studi di Bari Bari, Italy ENZO IERARDI Department of Scienze Mediche e del Lavoro Università degli Studi di Foggia Foggia, Italy 1. Murakami K, Fujioka T, Okimoto T, Sato R, Kodama M, Nasu M. Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy. Int J Antimicrob Agents 2002;19:67–70. 2. Scaccianoce G, Hassan C, Panarese A, Piglionica D, Morini S, Zullo A. Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol 2006;20:113–117. 3. Fischbach LA, Van Zanten SV, Dickason J. Meta-analysis: the efficacy, adverse events, and adherence related to first-line antiHelicobacter pylori quadruple therapies. Aliment Pharmacol Ther 2004;20:1071–1082. 4. Neville PM, Everett S, Langworthy H, Tompkins D, Mapstone P, Axon ATR, Moayyedi P. The optimal antibiotic combination in a 5-day Helicobacter pylori eradication regimen. Aliment Pharmacol Ther 1999;13:497–501. 5. Graham DY, Belson G, Abudayyeh S, Osato MS, Dore MP, ElZimaity HMT. Twice a day, mid-day, quadruple therapy for H. pylori infection in the United States. Dig Liver Dis 2004;36:384 –387. 6. Nakayama Y, Graham DY. Helicobacter pylori infection: diagnosis and treatment. Expert Rev Anti-Infect Therapy 2004;2:599 – 616. 7. Calvet X, Garcia N, Lopez T, Gisbert JP, Gene E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther 2000;14:603– 608. 8. De Francesco V, Margiotta M, Zullo A, Hassan C, Troiani L, Burattini O, Stella F, Di Leo A, Russo F, Marangi S, Monno R, Stoppino V, Morini S, Panella C, Ierardi E. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med 2006;144:94 –100. doi:10.1053/j.gastro.2006.03.038YGAST
Coffee and Tea Consumption and Chronic Liver Disease Dear Sir: We read with interest Ruhl and Everhart’s finding of an inverse association between coffee and tea consumption and the consequent development of chronic liver disease (CLD).1 Coffee, green tea, and black tea are important dietary sources of phytochemicals with disease-modifying properties,2 and the authors attribute the beneficial effect of drinking these beverages to their high content of caffeine, an alkaloid with antioxidant and insulin-sensitizing properties, given the