Esps manuscript no: 18744 Manuscript Type: topic highlight 2015 Advances in Helicobacter pylori

UPDATED H.PYLORI THERAPY

Successful eradication of H. pylori is a major component in treating these conditions^[95]. However, the rate of H. pylori eradication after triple therapy is decreasing, with standard amoxicillin plus clarithromycin-based triple therapy achieving eradication rates of only approximately 75% in many series^[96-97]. Apart from the conventional first-line regimen (triple therapy), other therapies have been proposed (sequential, concomitant, quadruple, and miscellaneous) to face the growing problem of antibiotic resistance. Although unsuccessful eradication can be caused by increasing antimicrobial resistance, an additional critical contributor is the treatment-related side effects and resultant incomplete therapy. New treatment regimens for H. pylori infections should be optimized to achieve an eradication rate of ≥ 95%^[98]. Patient allergies and the local availability of drugs should be considered when selecting a treatment. H. pylori eradication should be confirmed after treatment, and, if second-line therapy is required, clarithromycin or a fluoroquinolone should not be reused^[99].

Sequential therapy

First developed in Italy in the 1990s, sequential therapy (5-d PPI and amoxicillin, followed by 5-d PPI, clarithromycin, and metronidazole), is a regimen that has proven more effective in eradicating H. pylori than has triple therapy in many studies^[100-104]. Recent multicenter randomized trials conducted in Taiwan have shown the superiority of sequential therapy over standard triple therapy. These findings also support that the most effective eradication regimen should be chosen on the basis of the prevalence of antibiotic-resistant H. pylori in a region^[105]. The ability of sequential therapy to eradicate clarithromycin-resistant bacteria has been demonstrated, and sequential therapy has been included in a recent consensus report as a valid first-line option for eradicating H. pylori in geographic regions with high clarithromycin resistance^[106].

Hybrid and concomitant therapy

Two novel eradication regimens, namely concomitant and hybrid therapy, have proven more effective than triple and sequential therapy in the last few years, particularly in patients with dual- (clarithromycin- and metronidazole-) resistant H. pylori strains^[107-111]. Meta-analyses have shown that the outcome of concomitant therapy is duration-dependent^[112]. Molina-Infante et al^[113] proposed that optimized nonbismuth quadruple hybrid (consisting of omeprazole 40 mg twice daily and amoxicillin 1 g twice daily for 14 d, plus clarithromycin 500 mg twice daily and nitroimidazole 500 mg twice daily for the final 7 d as a quadruple therapy) and concomitant (consisting of omeprazole 40 mg twice daily, amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, and nitroimidazole 500 mg twice daily, all concurrently for 14 d) therapies cured more than 90% of patients with H. pylori infections in areas of high clarithromycin and metronidazole resistance. In concomitant therapy, all four drugs are administered for the entire therapy duration, indicating that this regimen is less complex than sequential therapy because it does not involve changing the number or type of drugs halfway through the therapy. A recently proposed hybrid therapy has proven as effective as a 14-d concomitant regimen in a pilot study^[106].

High-dose amoxicillin therapy

The efficacy of treatment for H. pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin. Therefore, Yang et al^[114] proposed that a combination of a high-dose PPI and amoxicillin (dual therapy), consisting of rabeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily) for 14 d, is superior to standard regimens as empirical first-line or rescue therapies for H. pylori infection and has similar safety profiles and tolerability.

Bismuth-based quadruple therapy

During the initial development of bismuth quadruple therapy, the dose and duration of bismuth therapy were shown to be crucial variables, particularly in regions where metronidazole resistance was common^[115]. However, many studies on these regimens have used suboptimal doses and durations of bismuth therapy, producing relatively poor results^[116]. Bismuth-containing quadruple therapy is an alternative to standard triple therapy in areas with low clarithromycin resistance and the main first-line therapeutic option in areas with high prevalence of clarithromycin resistance. Using this regimen at full doses for 14 d produces a 95% or greater treatment success rate, irrespective of the level of metronidazole resistance^[117].

Salvage therapy

Tailored antimicrobial therapy for an infectious disease is typically selected on the basis of susceptibility testing^[99,118]. The treatment of H. pylori infection differs from that of most common infectious diseases because culture and susceptibility testing is generally not offered for H. pylori infections by hospital laboratories. In addition, many H. pylori infections can be identified using noninvasive testing (such as UBT or stool antigen testing), indicating that endoscopies are neither necessary nor acceptable to patients, and clinicians must choose treatment empirically. Therefore, culture and susceptibility testing should be performed before third-line treatment^[106]. Salvage therapy (after multiple treatment failures) should be chosen on the basis of susceptibility testing whenever possible^[101].

Probiotic therapy

Song et al^[119] proposed that supplementation with Saccharomyces boulardii could be effective for improving H. pylori eradication rates by reducing side effects, thus facilitating completion of eradication therapy. Probiotics are mostly administered by modulating the balance of its microflora^[120]. Probiotic adjunct therapy is particularly useful in patients with a history of GI intolerance to antibiotic treatment^[121]. These effects have been demonstrated for several species of probiotics, including Lactobacillus acidophilus, Lactobacillus salivarius, Lactobacillus rhamnosus, and Bifidobacterium bifidum, among others^[122-124]. Proposed mechanisms include modulating the colonization of the gastric mucosa and the direct killing of H. pylori through secreted metabolites with antimicrobial properties^[95]. The lack of protocol standardization is problematic, and interpreting the various results is difficult.

CONCLUSION

Although other factors influence the onset of peptic ulcer and recurrent peptic ulcer in ESRD and cirrhotic patients, H. pylori eradication therapy is the primary method of treating ESRD and cirrhotic patients with peptic ulcers. Culture susceptibility testing before first- or second-line therapy is unadvisable. The known obstacles to culture susceptibility testing include the need for endoscopic examination and the fact that culture is time-consuming, costly, and not 100% sensitive. Using highly effective empiric first-line and rescue regimens can yield acceptable results^[100,97,125]. In the near future, in vivo and in vitro studies may possibly be grouped according to geographic area to identify the most effective therapy for eradicating H. pylori, which relates to the local habitat.

ACKNOWLEDGEMENTS

We wish to thank the Taiwan Ministry of Education for their support for this work through its “Aim for the Top University Plan.”

REFERENCES

1 Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med 2002; 347: 1175-1186 [PMID: 12374879 DOI: 10.1056/NEJMra020542]

2 Thiede C, Morgner A, Alpen B, Wündisch T, Herrmann J, Ritter M, Ehninger G, Stolte M, Bayerdörffer E, Neubauer A. What role does Helicobacter pylori eradication play in gastric MALT and gastric MALT lymphoma? Gastroenterology 1997; 113: S61-S64 [PMID: 9394762 DOI: 10.1016/S0016-5085(97)80014-5]

3 Van der Hulst RW, Rauws EA, Köycü B, Keller JJ, Bruno MJ, Tijssen JG, Tytgat GN. Prevention of ulcer recurrence after eradication of Helicobacter pylori: a prospective long-term follow-up study. Gastroenterology 1997; 113: 1082-1086 [PMID: 9322501 DOI: 10.1053/gast.1997.v113.pm9322501]

4 Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001; 345: 784-789 [PMID: 11556297 DOI: 10.1080/003655202760230793]

5 Hopkins RJ, Girardi LS, Turney EA. Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology 1996; 110: 1244-1252 [PMID: 8613015 DOI: 10.1053/gast.1996.v110.pm8613015]

6 Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology 2008; 134: 306-323 [PMID: 18166359 DOI: 10.1053/j.gastro.2007.11.009]

7 Wu MS, Chen CJ, Lin JT. Host-environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 1878-1882 [PMID: 16103430 DOI: 10.1158/1055-9965.EPI-04-0792]

8 Gisbert JP, Calvet X. Review article: Helicobacter pylori-negative duodenal ulcer disease. Aliment Pharmacol Ther 2009; 30: 791-815 [PMID: 19706147 DOI: 10.1111/j.1365-2036.2009.04105.x]

9 Xia HH, Phung N, Kalantar JS, Talley NJ. Demographic and endoscopic characteristics of patients with Helicobacter pylori positive and negative peptic ulcer disease. Med J Aust 2000; 173: 515-519 [PMID: 11194733 DOI: 10.1093/ageing/27.4.427]

10 Shahin WA, Abdel-Baset EZ, Nassar AK, Atta MM, Kabil SM, Murray JA. Low incidence of Helicobacter pylori infection in patients with duodenal ulcer and chronic liver disease. Scand J Gastroenterol 2001; 36: 479-484 [PMID: 11346200 DOI: 10.1080/003655201750153250]

11 Ierardi E, Giorgio F, Losurdo G, Di Leo A, Principi M. How antibiotic resistances could change Helicobacter pylori treatment: A matter of geography? World J Gastroenterol 2013; 19: 8168-8180 [PMID: 24363506 DOI: 10.3748/wjg.v19.i45.8168]

12 Tseng GY, Lin HJ, Fang CT, Yang HB, Tseng GC, Wang PC, Hung TL, Deng YC, Cheng YT, Huang CH. Recurrence of peptic ulcer in uraemic and non-uraemic patients after Helicobacter pylori eradication: a 2-year study. Aliment Pharmacol Ther 2007; 26: 925-933 [PMID: 17767477 DOI: 10.1111/j.1365-2036.2007.03438.x]

13 Kang JY, Ho KY, Yeoh KG, Guan R, Wee A, Lee E, Lye WC, Leong SO, Tan CC. Peptic ulcer and gastritis in uraemia, with particular reference to the effect of Helicobacter pylori infection. J Gastroenterol Hepatol 1999; 14: 771-778 [PMID: 10482427 DOI: 10.1046/j.1440-1746.1999.01947.x]

14 Sotoudehmanesh R, Ali Asgari A, Ansari R, Nouraie M. Endoscopic findings in end-stage renal disease. Endoscopy 2003; 35: 502-505 [PMID: 12783348 DOI: 10.1055/s-2003-39672]

15 Loffeld RJ, Peltenburg HG, vd Oever H, Stobberingh E. Prevalence of Helicobacter pylori antibodies in patients on chronic intermittent haemodialysis. Nephron 1991; 59: 250-253 [PMID: 1956486 DOI: 10.1159/000186560]

16 Davenport A, Shallcross TM, Crabtree JE, Davison AM, Will EJ, Heatley RV. Prevalence of Helicobacter pylori in patients with end-stage renal failure and renal transplant recipients. Nephron 1991; 59: 597-601 [PMID: 1766499 DOI: 10.1159/000186650]

17 Luzza F, Imeneo M, Maletta M, Mantelli I, Tancre D, Merando G, Biancone L, Pallone F. Helicobacter pylori-specific IgG in chronic haemodialysis patients: relationship of hypergastrinaemia to positive serology. Nephrol Dial Transplant 1996; 11: 120-124 [PMID: 8649619 DOI: 10.1093/oxfordjournals.ndt.a027026]

18 Jaspersen D, Fassbinder W, Heinkele P, Kronsbein H, Schorr W, Raschka C, Brennenstuhl M. Significantly lower prevalence of Helicobacter pylori in uremic patients than in patients with normal renal function. J Gastroenterol 1995; 30: 585-588 [PMID: 8574329 DOI: 10.1007/BF02367783]

19 Khedmat H, Ahmadzad-Asl M, Amini M, Lessan-Pezeshki M, Einollahi B, Pourfarziani V, Naseri MH, Davoudi F. Gastro-duodenal lesions and Helicobacter pylori infection in uremic patients and renal transplant recipients. Transplant Proc 2007; 39: 1003-1007 [PMID: 17524875 DOI: 10.1016/j.transproceed.2007.03.034]

20 Sugimoto M, Sakai K, Kita M, Imanishi J, Yamaoka Y. Prevalence of Helicobacter pylori infection in long-term hemodialysis patients. Kidney Int 2009; 75: 96-103 [PMID: 18843261 DOI: 10.1038/ki.2008.508]

21 Chang SS, Hu HY. Lower Helicobacter pylori infection rate in chronic kidney disease and end-stage renal disease patients with peptic ulcer disease. J Chin Med Assoc 2014; 77: 354-359 [PMID: 24907021 DOI: 10.1016/j.jcma.2014.04.004]

22 Gür G, Boyacioglu S, Gül C, Turan M, Gürsoy M, Baysal C, Ozdemir N. Impact of Helicobacter pylori infection on serum gastrin in haemodialysis patients. Nephrol Dial Transplant 1999; 14: 2688-2691 [PMID: 10534513 DOI: 10.1093/ndt/14.11.2688]

23 Tseng GY, Lin HJ. Aspirin prescription and outcomes in hemodialysis patients. Am J Kidney Dis 2008; 51: 1070-1071 [PMID: 18501791 DOI: 10.1053/j.ajkd.2008.01.035]

24 López T, Quesada M, Almirall J, Sanfeliu I, Segura F, Calvet X. Usefulness of non-invasive tests for diagnosing Helicobacter pylori infection in patients undergoing dialysis for chronic renal failure. Helicobacter 2004; 9: 674-680 [PMID: 15610083 DOI: 10.1111/j.1083-4389.2004.00282.x]

25 Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56: 772-781 [PMID: 17170018 DOI: 10.1136/gut.2006.101634]

26 Huang JJ, Huang CJ, Ruaan MK, Chen KW, Yen TS, Sheu BS. Diagnostic efficacy of (13)C-urea breath test for Helicobacter pylori infection in hemodialysis patients. Am J Kidney Dis 2000; 36: 124-129 [PMID: 10873881 DOI: 10.1053/ajkd.2000.8284]

27 Wang YL, Sheu BS, Huang JJ, Yang HB. Noninvasive stool antigen assay can effectively screen Helicobacter pylori Infection and assess success of eradication therapy in hemodialysis patients. Am J Kidney Dis 2001; 38: 98-103 [PMID: 11431188 DOI: 10.1053/ajkd.2001.25200]

28 Chang SS, Hu HY. Reply. J Chin Med Assoc 2014; 77: 657-658 [PMID: 25443803]

29 Ala-Kaila K, Kataja M, Keyriläinen O, Pasternack A. The gastric secretion profile of patients with chronic renal failure. Ann Clin Res 1981; 13: 65-70 [PMID: 7235612 DOI: 10.3109/00365528708991969]

30 Ala-Kaila K. Gastric secretion kinetics in chronic renal failure. Scand J Gastroenterol 1987; 22: 1185-1192 [PMID: 3324296]

31 Kim H, Park C, Jang WI, Lee KH, Kwon SO, Robey-Cafferty SS, Ro JY, Lee YB. The gastric juice urea and ammonia levels in patients with Campylobacter pylori. Am J Clin Pathol 1990; 94: 187-191 [PMID: 2371972 DOI: 10.1097/00004836-200205000-00020]

32 Working Party of the European Helicobacter pylori Study Group. Guidelines for clinical trials in Helicobacter pylori infection. Working Party of the European Helicobacter pylori Study Group. Gut 1997; 41 Suppl 2: S1-S9 [PMID: 9404236 DOI: 10.1136/gut.43.5.e728]

33 Calvet X, Quesada M, Roselló M, Salceda F, Sanfeliu I, Dalmau B, Gil M. Stool antigen for the diagnosis of Helicobacter pylori infection in cirrhosis: comparative usefulness of three different methods. Aliment Pharmacol Ther 2003; 17: 727-731 [PMID: 12641523 DOI: 10.1046/j.1365-2036.2003.01466.x]

34 Thijs JC, van Zwet AA, Thijs WJ, Oey HB, Karrenbeld A, Stellaard F, Luijt DS, Meyer BC, Kleibeuker JH. Diagnostic tests for Helicobacter pylori: a prospective evaluation of their accuracy, without selecting a single test as the gold standard. Am J Gastroenterol 1996; 91: 2125-2129 [PMID: 8855734 DOI: 10.1016/0016-5085(95)23623-6]

35 Mak SK, Loo CK, Wong AM, Wong PN, Lo KY, Tong GM, Lam EK, Wong AK. Efficacy of a 1-week course of proton-pump inhibitor-based triple therapy for eradicating Helicobacter pylori in patients with and without chronic renal failure. Am J Kidney Dis 2002; 40: 576-581 [PMID: 12200810 DOI: 10.1053/ajkd.2002.34916]

36 Tamura H, Tokushima H, Murakawa M, Matsumura O, Itoyama S, Sekine S, Hirose H, Mitarai T, Isoda K. Eradication of Helicobacter pylori in patients with end-stage renal disease under dialysis treatment. Am J Kidney Dis 1997; 29: 86-90 [PMID: 9002534 DOI: 10.1016/S0272-6386(97)90012-3]

37 Mak SK, Loo CK, Wong PN, Lo KY, Tong GM, Lam EK, Wong AK. A retrospective study on efficacy of proton-pump inhibitor-based triple therapy for eradication of Helicobacter pylori in patients with chronic renal failure. Singapore Med J 2003; 44: 74-78 [PMID: 14503780]

38 Tsukada K, Miyazaki T, Katoh H, Masuda N, Ojima H, Fukai Y, Nakajima M, Manda R, Fukuchi M, Kuwano H, Tsukada O. Seven-day triple therapy with omeprazole, amoxycillin and clarithromycin for Helicobacter pylori infection in haemodialysis patients. Scand J Gastroenterol 2002; 37: 1265-1268 [PMID: 12465723 DOI: 10.1080/003655202761020524]

39 Itatsu T, Miwa H, Nagahara A, Kubota M, Miyazaki A, Sato N, Hayashida Y. Eradication of Helicobacter pylori in hemodialysis patients. Ren Fail 2007; 29: 97-102 [PMID: 17365917 DOI: 10.1080/08860220601039122]

40 Chang WC, Jo YI, Park HS, Jegal J, Park JH, Lee JH, Jin CJ. Helicobacter pylori eradication with a 7-day low-dose triple therapy in hemodialysis patients. Clin Exp Nephrol 2010; 14: 469-473 [PMID: 20632062 DOI: 10.1007/s10157-010-0319-7]

41 Arancibia A, Drouguett MT, Fuentes G, González G, González C, Thambo S, Palombo G. Pharmacokinetics of amoxicillin in subjects with normal and impaired renal function. Int J Clin Pharmacol Ther Toxicol 1982; 20: 447-453 [PMID: 7141752 DOI: 10.1046/j.1365-2125.2000.00149.x]

42 Fraschini F, Scaglione F, Demartini G. Clarithromycin clinical pharmacokinetics. Clin Pharmacokinet 1993; 25: 189-204 [PMID: 8222460 DOI: 10.2165/00003088-199325030-00003]

43 Wermeille J, Cunningham M, Dederding JP, Girard L, Baumann R, Zelger G, Buri P, Metry JM, Sitavanc R, Gallaz L, Merki H, Godin N. Failure of Helicobacter pylori eradication: is poor compliance the main cause? Gastroenterol Clin Biol 2002; 26: 216-219 [PMID: 11981460]

44 Harris A, Misiewicz JJ. Treating Helicobacter pylori--the best is yet to come? Gut 1996; 39: 781-783 [PMID: 9038656 DOI: 10.1136/gut.39.6.781]

45 Aydemir S, Boyacioglu S, Gur G, Demirbilek M, Can FK, Korkmaz M, Yilmaz U. Helicobacter pylori infection in hemodialysis patients: susceptibility to amoxicillin and clarithromycin. World J Gastroenterol 2005; 11: 842-845 [PMID: 15682477 DOI: 10.3748/wjg.v11.i6.842]

46 McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med 2010; 362: 1597-1604 [PMID: 20427808 DOI: 10.1056/NEJMcp1001110]

47 Parasa S, Navaneethan U, Sridhar AR, Venkatesh PG, Olden K. End-stage renal disease is associated with worse outcomes in hospitalized patients with peptic ulcer bleeding. Gastrointest Endosc 2013; 77: 609-616 [PMID: 23357495 DOI: 10.1016/j.gie.2012.11.014]

48 Liang CC, Muo CH, Wang IK, Chang CT, Chou CY, Liu JH, Yen TH, Huang CC, Chung CJ. Peptic ulcer disease risk in chronic kidney disease: ten-year incidence, ulcer location, and ulcerogenic effect of medications. PLoS ONE 2014; 9: e87952 [PMID: 24498412 DOI: 10.1371/journal.pone.0087952]

49 Luo JC, Leu HB, Huang KW, Huang CC, Hou MC, Lin HC, Lee FY, Lee SD. Incidence of bleeding from gastroduodenal ulcers in patients with end-stage renal disease receiving hemodialysis. CMAJ 2011; 183: E1345-E1351 [PMID: 22083684 DOI: 10.1503/cmaj.110299]

50 Wu CY, Wu MS, Kuo KN, Wang CB, Chen YJ, Lin JT. Long-term peptic ulcer rebleeding risk estimation in patients undergoing haemodialysis: a 10-year nationwide cohort study. Gut 2011; 60: 1038-1042 [PMID: 22083684]

51 Sugimoto M, Yamaoka Y. Review of Helicobacter pylori infection and chronic renal failure. Ther Apher Dial 2011; 15: 1-9 [PMID: 21272246 DOI: 10.1111/j.1744-9987.2010.00851.x]

52 Chang SS, Hu HY. Association between early Helicobacter pylori eradication and a lower risk of recurrent complicated peptic ulcers in end-stage renal disease patients. Medicine (Baltimore) 2015; 94: e370 [PMID: 25569660 DOI: 10.1097/MD.0000000000000370]

53 Calvet X, Navarro M, Gil M, Lafont A, Sanfeliu I, Brullet E, Campo R, Dalmau B, Rivero E, Mas P. Epidemiology of peptic ulcer disease in cirrhotic patients: role of Helicobacter pylori infection. Am J Gastroenterol 1998; 93: 2501-2507 [PMID: 9860415 DOI: 10.1016/S0002-9270(98)00592-9]

54 Tsujii M, Kawano S, Tsuji S, Fusamoto H, Kamada T, Sato N. Mechanism of gastric mucosal damage induced by ammonia. Gastroenterology 1992; 102: 1881-1888 [PMID: 1587407 DOI: 10.1016/S0016-5085(00)85070-2]

55 Kim DJ, Kim HY, Kim SJ, Hahn TH, Jang MK, Baik GH, Kim JB, Park SH, Lee MS, Park CK. Helicobacter pylori infection and peptic ulcer disease in patients with liver cirrhosis. Korean J Intern Med 2008; 23: 16-21 [PMID: 18363275 DOI: 10.3904/kjim.2008.23.1.16]

56 Jung SW, Lee SW, Hyun JJ, Kim DI, Koo JS, Yim HJ, Park JJ, Lee HS, Chun HJ, Um SH, Choi JH, Kim CD, Ryu HS. Efficacy of Helicobacter pylori eradication therapy in chronic liver disease. Dig Liver Dis 2009; 41: 134-140 [PMID: 18436489 DOI: 10.1016/j.dld.2008.03.005]

57 Siringo S, Vaira D, Menegatti M, Piscaglia F, Sofia S, Gaetani M, Miglioli M, Corinaldesi R, Bolondi L. High prevalence of Helicobacter pylori in liver cirrhosis: relationship with clinical and endoscopic features and the risk of peptic ulcer. Dig Dis Sci 1997; 42: 2024-2030 [PMID: 9365129 DOI: 10.1136/gut.35.3.309]

58 Bhargava N, Venkateswaran S, Ramakrishna BS, Mathan M. Colonization by Helicobacter pylori and its relationship to histological changes in the gastric mucosa in portal hypertension. J Gastroenterol Hepatol 1994; 9: 507-511 [PMID: 7827303 DOI: 10.1111/j.1440-1746.1994.tb01282.x]

59 Chang SS, Hu HY. Helicobacter pylori is not the predominant etiology for liver cirrhosis patients with peptic ulcer disease. Eur J Gastroenterol Hepatol 2013; 25: 159-165 [PMID: 23044811 DOI: 10.1097/MEG.0b013e32835a1b26]

60 Lo GH, Yu HC, Chan YC, Chen WC, Hsu PI, Lin CK, Lai KH. The effects of eradication of Helicobacter pylori on the recurrence of duodenal ulcers in patients with cirrhosis. Gastrointest Endosc 2005; 62: 350-356 [PMID: 16111950 DOI: 10.1016/S0016-5107(05)01633-0]

61 Wang CH, Ma LR, Lin RC, Kuo JY, Chang KK. Helicobacter pylori infection and risk of peptic ulcer among cirrhotic patients. J Formos Med Assoc 1997; 96: 55-58 [PMID: 9033184]

62 Chen LS, Lin HC, Lee FY, Hou MC, Lee SD. Prevalence of duodenal ulcer in cirrhotic patients and its relation to Helicobacter pylori and portal hypertension. Zhonghua Yi Xue Za Zhi (Taipei) 1995; 56: 226-231 [PMID: 8548663 DOI: 10.1111/j.1440-1746.1996.tb00011.x]

63 Wu CS, Lin CY, Liaw YF. Helicobacter pylori in cirrhotic patients with peptic ulcer disease: a prospective, case controlled study. Gastrointest Endosc 1995; 42: 424-427 [PMID: 8566632 DOI: 10.1016/S0016-5107(95)70044-7]

64 Dore MP, Mura D, Deledda S, Maragkoudakis E, Pironti A, Realdi G. Active peptic ulcer disease in patients with hepatitis C virus-related cirrhosis: the role of Helicobacter pylori infection and portal hypertensive gastropathy. Can J Gastroenterol 2004; 18: 521-524 [PMID: 15372116 DOI: 10.1016/S1590-8658(01)80485-0]

65 Calvet X, Navarro M, Gil M, Mas P, Rivero E, Sanfeliu I, Brullet E, Campo R, Dalmau B, Lafont A. Seroprevalence and epidemiology of Helicobacter pylori infection in patients with cirrhosis. J Hepatol 1997; 26: 1249-1254 [PMID: 9210611 DOI: 10.1016/S0168-8278(97)80459-X]

66 Farinati F, De Bona M, Floreani A, Foschia F, Rugge M. Helicobacter pylori and the liver: any relationship? Ital J Gastroenterol Hepatol 1998; 30: 124-128 [PMID: 9615280 DOI: 10.1016/S0168-8278(98)80805-2]

67 van Nieuwkerk CM, Kuipers EJ. Liver cirrhosis and peptic ulcer disease; a correlation with Helicobacter pylori? Neth J Med 2000; 56: 203-205 [PMID: 10821974 DOI: 10.1016/S0300-2977(00)00013-9]

68 Saad RJ, Chey WD. Peptic ulcer disease in patients with chronic liver disease: looking beyond bugs and drugs. Gastrointest Endosc 2005; 62: 357-359 [PMID: 16111951 DOI: 10.1016/j.gie.2005.06.003]

69 Gisbert JP, Moreno-Otero R, Pajares JM. [Prevalence of Helicobacter pylori infection in chronic liver disease and relationship with its complications: systematic review and meta-analysis]. Med Clin (Barc) 2002; 119: 464-474 [PMID: 12385656 DOI: 10.1016/S1590-8658(02)90225-2]

70 Blaser MJ, Atherton JC. Helicobacter pylori persistence: biology and disease. J Clin Invest 2004; 113: 321-333 [PMID: 14755326 DOI: 10.1172/JCI20925]

71 Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest 2009; 119: 2475-2487 [PMID: 19729845 DOI: 10.1172/JCI38605]

72 Furuta T, Baba S, Takashima M, Futami H, Arai H, Kajimura M, Hanai H, Kaneko E. Effect of Helicobacter pylori infection on gastric juice pH. Scand J Gastroenterol 1998; 33: 357-363 [PMID: 9605256 DOI: 10.1080/00365529850170973]

73 Suzuki H, Ishii H. [Peptic ulcer disease complicated with liver cirrhosis]. Nihon Rinsho 2004; 62: 532-540 [PMID: 15038099 DOI: 10.1016/S1590-8658(10)60366-0]

74 Chen CT, Wang TF, Chan CC, Lee FY, Chang FY, Lin HC, Hou MC, Lu RH, Chu CJ, Wang SS, Lee SD. Role of chronic Helicobacter pylori infection in hyperdynamic circulation of cirrhotic patients. Hepatogastroenterology 2002; 49: 208-212 [PMID: 11941956]

75 Kitano S, Dolgor B. Does portal hypertension contribute to the pathogenesis of gastric ulcer associated with liver cirrhosis? J Gastroenterol 2000; 35: 79-86 [PMID: 10680661 DOI: 10.1007/s005350050018]

76 Luo JC, Leu HB, Hou MC, Huang CC, Lin HC, Lee FY, Chang FY, Chan WL, Lin SJ, Chen JW. Cirrhotic patients at increased risk of peptic ulcer bleeding: a nationwide population-based cohort study. Aliment Pharmacol Ther 2012; 36: 542-550 [PMID: 22817655 DOI: 10.1111/j.1365-2036.2012.05225.x]

77 Chang SS, Hu HY. H. pylori eradication lower ulcers in cirrhosis. [Corrected]. J Dig Dis 2014; 15: 451-458 [PMID: 24825443 DOI: 10.1111/1751-2980.12159]

78 Jiang HX, Qin SY, Min ZG, Xie MZ, Lin T, Hu BL, Guo XY. Association of Helicobacter pylori with elevated blood ammonia levels in cirrhotic patients: a meta-analysis. Yonsei Med J 2013; 54: 832-838 [PMID: 23709415 DOI: 10.3349/ymj.2013.54.4.832]

79 Dasani BM, Sigal SH, Lieber CS. Analysis of risk factors for chronic hepatic encephalopathy: the role of Helicobacter pylori infection. Am J Gastroenterol 1998; 93: 726-731 [PMID: 9625117 DOI: 10.1016/S0002-9270(98)00094-X]

80 Miyaji H, Ito S, Azuma T, Ito Y, Yamazaki Y, Ohtaki Y, Sato F, Hirai M, Kuriyama M, Kohli Y. Effects of Helicobacter pylori eradication therapy on hyperammonaemia in patients with liver cirrhosis. Gut 1997; 40: 726-730 [PMID: 9245925 DOI: 10.1136/gut.40.6.726]

81 Agrawal A, Gupta A, Chandra M, Koowar S. Role of Helicobacter pylori infection in the pathogenesis of minimal hepatic encephalopathy and effect of its eradication. Indian J Gastroenterol 2011; 30: 29-32 [PMID: 21416318 DOI: 10.1007/s12664-011-0087-7]

82 Miquel J, Barcena R, Boixeda D, Fernández J, SanRoman AL, Martín-de-Argila C, Ramosa F. Role of Helicobacter pylori infection and its eradication in patients with subclinical hepatic encephalopathy. Eur J Gastroenterol Hepatol 2001; 13: 1067-1072 [PMID: 11564957 DOI: 10.1097/00042737-200109000-00012]

83 Scotiniotis IA, Lucey MR, Metz DC. Helicobacter pylori infection is not associated with subclinical hepatic encephalopathy in stable cirrhotic patients. Dig Dis Sci 2001; 46: 2744-2751 [PMID: 11768268]

84 Quero JC, Hartmann IJ, de Rooij F, Wilson JH, Schalm SW. Hyperammonaemia and Helicobacter pylori. Lancet 1995; 346: 713-714 [PMID: 7658863 DOI: 10.1016/S0140-6736(95)92332-2]

85 Nilsson I, Lindgren S, Eriksson S, Wadström T. Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease. Gut 2000; 46: 410-414 [PMID: 10673306 DOI: 10.1136/gut.46.3.410]

86 Fox JG, Ge Z, Whary MT, Erdman SE, Horwitz BH. Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer. Mucosal Immunol 2011; 4: 22-30 [PMID: 20944559 DOI: 10.1038/mi.2010.61]

87 Fox JG, Yan LL, Dewhirst FE, Paster BJ, Shames B, Murphy JC, Hayward A, Belcher JC, Mendes EN. Helicobacter bilis sp. nov., a novel Helicobacter species isolated from bile, livers, and intestines of aged, inbred mice. J Clin Microbiol 1995; 33: 445-454 [PMID: 7536217 DOI: 10.1099/jmm.0.032144-0]

88 Ward JM, Fox JG, Anver MR, Haines DC, George CV, Collins MJ, Gorelick PL, Nagashima K, Gonda MA, Gilden RV. Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species. J Natl Cancer Inst 1994; 86: 1222-1227 [PMID: 8040890 DOI: 10.1093/jnci/86.16.1222]

89 Fox JG, Li X, Yan L, Cahill RJ, Hurley R, Lewis R, Murphy JC. Chronic proliferative hepatitis in A/JCr mice associated with persistent Helicobacter hepaticus infection: a model of helicobacter-induced carcinogenesis. Infect Immun 1996; 64: 1548-1558 [PMID: 8613359 DOI: 10.1128/IAI.73.12.8449-8452.2005]

90 Fox JG, Feng Y, Theve EJ, Raczynski AR, Fiala JL, Doernte AL, Williams M, McFaline JL, Essigmann JM, Schauer DB, Tannenbaum SR, Dedon PC, Weinman SA, Lemon SM, Fry RC, Rogers AB. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut 2010; 59: 88-97 [PMID: 19850960 DOI: 10.1136/gut.2009.183749]

91 Fukuda Y, Shimoyama T, Ohmura T, Sano Y, Nakabayashi N, Takahashi R, Fujioka T, Mitchell HM, Shimoyama T. Characterization and application of a new monoclonal antibody with high specificity for Helicobacter hepaticus. Helicobacter 2009; 14: 66-71 [PMID: 19191899 DOI: 10.1111/j.1523-5378.2009.00652.x]

92 Murakami K, Takahashi R, Ono M, Watanabe K, Okimoto T, Kodama M, Abe D, Kimura M, Fujioka T. Serodiagnosis of Helicobacter hepaticus infection in patients with liver and gastrointestinal diseases: western blot analysis and ELISA using a highly specific monoclonal antibody for H. hepaticus antigen. J Gastroenterol 2011; 46: 1120-1126 [PMID: 21656014 DOI: 10.1007/s00535-011-0414-x]

93 Pellicano R, Ménard A, Rizzetto M, Mégraud F. Helicobacter species and liver diseases: association or causation? Lancet Infect Dis 2008; 8: 254-260 [PMID: 18353266 DOI: 10.1016/S1473-3099(08)70066-5]

94 Kleine M, Worbs T, Schrem H, Vondran FW, Kaltenborn A, Klempnauer J, Förster R, Josenhans C, Suerbaum S, Bektas H. Helicobacter hepaticus induces an inflammatory response in primary human hepatocytes. PLoS One 2014; 9: e99713 [PMID: 24932686 DOI: 10.1371/journal.pone.0099713]

95 Medeiros JA, Pereira MI. The use of probiotics in Helicobacter pylori eradication therapy. J Clin Gastroenterol 2013; 47: 1-5 [PMID: 23222208 DOI: 10.1097/MCG.0b013e3182702dbc]

96 Scaccianoce G, Zullo A, Hassan C, Gentili F, Cristofari F, Cardinale V, Gigliotti F, Piglionica D, Morini S. Triple therapies plus different probiotics for Helicobacter pylori eradication. Eur Rev Med Pharmacol Sci 2008; 12: 251-256 [PMID: 18727457 DOI: 10.1016/j.ejim.2012.07.006]

97 de Bortoli N, Leonardi G, Ciancia E, Merlo A, Bellini M, Costa F, Mumolo MG, Ricchiuti A, Cristiani F, Santi S, Rossi M, Marchi S. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J Gastroenterol 2007; 102: 951-956 [PMID: 17313499 DOI: 10.1111/j.1572-0241.2007.01085.x]

98 O'Connor A, Gisbert JP, McNamara D, O'Morain C. Treatment of Helicobacter pylori infection 2011. Helicobacter 2011; 16 Suppl 1: 53-58 [PMID: 21896086]

99 Rimbara E, Fischbach LA, Graham DY. Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2011; 8: 79-88 [PMID: 21293508 DOI: 10.1038/nrgastro.2010.210]

100 Chuah SK, Tsay FW, Hsu PI, Wu DC. A new look at anti-Helicobacter pylori therapy. World J Gastroenterol 2011; 17: 3971-3975 [PMID: 22046084 DOI: 10.3748/wjg.v17.i35.3971]

101 Rinaldi V, Zullo A, Pugliano F, Valente C, Diana F, Attili AF. The management of failed dual or triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther 1997; 11: 929-933 [PMID: 9354202 DOI: 10.1046/j.1365-2036.1997.00228.x]

102 Gisbert JP, Calvet X, O'Connor A, Mégraud F, O'Morain CA. Sequential therapy for Helicobacter pylori eradication: a critical review. J Clin Gastroenterol 2010; 44: 313-325 [PMID: 20054285 DOI: 10.1016/S0016-5085(10)61541-7]

103 Gatta L, Vakil N, Vaira D, Scarpignato C. Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy. BMJ 2013; 347: f4587 [PMID: 23926315 DOI: 10.1136/bmj.f4587]

104 Kate V, Kalayarasan R, Ananthakrishnan N. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a systematic review of recent evidence. Drugs 2013; 73: 815-824 [PMID: 23625272 DOI: 10.1007/s40265-013-0053-z]

105 Liou JM, Chen CC, Chen MJ, Chen CC, Chang CY, Fang YJ, Lee JY, Hsu SJ, Luo JC, Chang WH, Hsu YC, Tseng CH, Tseng PH, Wang HP, Yang UC, Shun CT, Lin JT, Lee YC, Wu MS. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet 2013; 381: 205-213 [PMID: 23158886 DOI: 10.1016/S0140-6736(12)61579-7]

106 Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut 2012; 61: 646-664 [PMID: 22491499]

107 Georgopoulos SD, Papastergiou V, Karatapanis S. Current options for the treatment of Helicobacter pylori. Expert Opin Pharmacother 2013; 14: 211-223 [PMID: 23331077 DOI: 10.1097/00001574-199801000-00012]

108 Hsu PI, Wu DC, Wu JY, Graham DY. Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days. Helicobacter 2011; 16: 139-145 [PMID: 21435092 DOI: 10.1111/j.1523-5378.2011.00828.x]

109 Sardarian H, Fakheri H, Hosseini V, Taghvaei T, Maleki I, Mokhtare M. Comparison of hybrid and sequential therapies for Helicobacter pylori eradication in Iran: a prospective randomized trial. Helicobacter 2013; 18: 129-134 [PMID: 23121338 DOI: 10.1111/hel.12017]

110 Molina-Infante J, Pazos-Pacheco C, Vinagre-Rodriguez G, Perez-Gallardo B, Dueñas-Sadornil C, Hernandez-Alonso M, Gonzalez-Garcia G, Mateos-Rodriguez JM, Fernandez-Bermejo M, Gisbert JP. Nonbismuth quadruple (concomitant) therapy: empirical and tailored efficacy versus standard triple therapy for clarithromycin-susceptible Helicobacter pylori and versus sequential therapy for clarithromycin-resistant strains. Helicobacter 2012; 17: 269-276 [PMID: 22759326 DOI: 10.1111/j.1523-5378.2012.00947.x]

111 Georgopoulos SD, Xirouchakis E, Martinez-Gonzalez B, Sgouras DN, Spiliadi C, Mentis AF, Laoudi F. Clinical evaluation of a ten-day regimen with esomeprazole, metronidazole, amoxicillin, and clarithromycin for the eradication of Helicobacter pylori in a high clarithromycin resistance area. Helicobacter 2013; 18: 459-467 [PMID: 23714140 DOI: 10.1111/hel.12062]

112 Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing "concomitant therapy" versus triple therapy for Helicobacter pylori eradication. Helicobacter 2009; 14: 109-118 [PMID: 19298338 DOI: 10.1111/j.1523-5378.2009.00671.x]

113 Molina-Infante J, Romano M, Fernandez-Bermejo M, Federico A, Gravina AG, Pozzati L, Garcia-Abadia E, Vinagre-Rodriguez G, Martinez-Alcala C, Hernandez-Alonso M, Miranda A, Iovene MR, Pazos-Pacheco C, Gisbert JP. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology 2013; 145: 121-128.e1 [PMID: 23562754 DOI: 10.1053/j.gastro.2013.03.050]

114 Yang JC, Lin CJ, Wang HL, Chen JD, Kao JY, Shun CT, Lu CW, Lin BR, Shieh MJ, Chang MC, Chang YT, Wei SC, Lin LC, Yeh WC, Kuo JS, Tung CC, Leong YL, Wang TH, Wong JM. High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol 2015; 13: 895-905.e5 [PMID: 25460556 DOI: 10.1016/j.cgh.2014.10.036]

115 van der Wouden EJ, Thijs JC, van Zwet AA, Sluiter WJ, Kleibeuker JH. The influence of in vitro nitroimidazole resistance on the efficacy of nitroimidazole-containing anti-Helicobacter pylori regimens: a meta-analysis. Am J Gastroenterol 1999; 94: 1751-1759 [PMID: 10406231 DOI: 10.1016/S0002-9270(99)00258-0]

116 Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD. Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: Systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol 2010; 105: 65-73 [PMID: 19755966 DOI: 10.1038/ajg.2009.508]

117 Liang X, Xu X, Zheng Q, Zhang W, Sun Q, Liu W, Xiao S, Lu H. Efficacy of bismuth-containing quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone-resistant Helicobacter pylori infections in a prospective study. Clin Gastroenterol Hepatol 2013; 11: 802-7.e1 [PMID: 23376004 DOI: 10.1016/j.cgh.2013.01.008]

118 Graham DY. Helicobacter pylori eradication therapy research: Ethical issues and description of results. Clin Gastroenterol Hepatol 2010; 8: 1032-1036 [PMID: 20656062 DOI: 10.1016/j.cgh.2010.07.002]

119 Song MJ, Park DI, Park JH, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI. The effect of probiotics and mucoprotective agents on PPI-based triple therapy for eradication of Helicobacter pylori. Helicobacter 2010; 15: 206-213 [PMID: 20557362 DOI: 10.1111/j.1523-5378.2010.00751.x]

120 Fuller R. Probiotics in man and animals. J Appl Bacteriol 1989; 66: 365-378 [PMID: 2666378 DOI: 10.1111/j.1365-2672.1989.tb05105.x]

121 Wilhelm SM, Johnson JL, Kale-Pradhan PB. Treating bugs with bugs: the role of probiotics as adjunctive therapy for Helicobacter pylori. Ann Pharmacother 2011; 45: 960-966 [PMID: 21693698 DOI: 10.1345/aph.1Q104]

122 Zou J, Dong J, Yu X. Meta-analysis: Lactobacillus containing quadruple therapy versus standard triple first-line therapy for Helicobacter pylori eradication. Helicobacter 2009; 14: 97-107 [PMID: 19751434 DOI: 10.1111/j.1523-5378.2009.00716.x]

123 Canducci F, Cremonini F, Armuzzi A, Di Caro S, Gabrielli M, Santarelli L, Nista E, Lupascu A, De Martini D, Gasbarrini A. Probiotics and Helicobacter pylori eradication. Dig Liver Dis 2002; 34 Suppl 2: S81-S83 [PMID: 12408448 DOI: 10.1016/S1590-8658(02)80172-4]

124 Chenoll E, Casinos B, Bataller E, Astals P, Echevarría J, Iglesias JR, Balbarie P, Ramón D, Genovés S. Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori. Appl Environ Microbiol 2011; 77: 1335-1343 [PMID: 21169430 DOI: 10.1128/AEM.01820-10]

125 Gisbert JP. Is culture necessary before first-line treatment for Helicobacter pylori infection? Intern Med 2011; 50: 2717; author reply 2719-2720 [PMID: 22041399 DOI: 10.2169/internalmedicine.50.5135]

P-Reviewer: Pellicano R, Vorobjova T, Vermi W S-Editor: Yu J

L-Editor: E-Editor: