Helicobacter pylori (Hp), one of the most common infectious diseases in humans. It is a risk factor for many diseases, such as gastric ulcer, chronic gastritis, gastric adenocarcinoma, and even mucosa-associated lymphoid tissue (MALT) lymphoma. Studies have shown that eradication of Hp can reduce the risk of gastric cancer, increase the cure rate of ulcers, and currently need to be combined with drugs can directly eradicate Hp. There are a variety of clinical eradication options available: first-line treatment for infection includes standard triple therapy, expectorant quadruple therapy, sequential therapy, and concomitant therapy. In 2007, the American College of Gastroenterology combined triple therapy with clarithromycin as a first-line therapy for the eradication of people who had not received clarithromycin and had no penicillin allergy. However, in recent decades, the eradication rate of standard triple therapy has been ≤80% in most countries. In Canada, the resistance rate of clarithromycin has increased from 1% in 1990 to 11% in 2003. Among the treated individuals, the drug resistance rate was even reported to exceed 60%. Clarithromycin resistance may be the main cause of eradication failure. Maastricht IV consensus report in areas with high resistance to clarithromycin (resistance rate over 15% to 20%), replacing standard triple therapy with quadruple or sequential therapy with expectorant and/or no sputum, while carat Quadruple therapy can also be used as a first-line therapy in areas with low resistance to mycin. In addition to the above methods, high doses of PPI plus amoxicillin or alternative antibiotics such as rifampicin, furazolidone, levofloxacin have also been suggested as an alternative first-line treatment.

Improvement of standard triple therapy

1.1 Quadruple therapy

As the eradication rate of standard triple therapy falls, as a remedy, quadruple therapy has a high eradication rate. Shaikh et al. treated 175 patients with Hp infection, using per protocol (PP) analysis and intention. The results of the intention to treat (ITT) analysis evaluated the eradication rate of the standard triple therapy: PP=66% (49/74, 95% CI: 55-76), ITT=62% (49/79, 95% CI: 51-72); quadruple therapy has a higher eradication rate: PP = 91% (102/112, 95% CI: 84-95), ITT = 84%: (102/121, 95% CI : 77 ~ 90). Although the success rate of Hp eradication was reduced after each failed treatment, the quadruple treatment of tincture proved to have a high eradication rate (95%) as a remedy after the failure of standard triple therapy. Another study also reached a similar conclusion: after the failure of standard triple therapy and levofloxacin triple therapy, the eradication rate of barium quadruple therapy was 67% and 65%, respectively, for those who were allergic to penicillin or had received large In patients with cyclic lactone antibiotics, expectorant quadruple therapy is also preferred. Of course, the use of tincture quadruple therapy has a higher probability of adverse events, such as nausea, diarrhea, abdominal pain, melena, dizziness, headache, metallic taste, etc., but because the expectorant is widely used in China, it is relatively easy to obtain, and has A higher eradication rate can be used as a remedial treatment. It is worth promoting in the clinic.

 1.2 SQT

SQT was treated with PPI + amoxicillin for 5 days, then treated with PPI + clarithromycin + metronidazole for 5 days. SQT is currently recommended as a first-line eradication therapy for Hp. A meta-analysis of six randomized controlled trials (RCTs) in Korea based on SQT is 79.4% (ITT) and 86.4% (PP), and HQ eradication of SQT The rate is higher than the standard triple therapy, 95% CI: 1.403 ~ 2.209), the mechanism may be that the first 5d (or 7d) use amoxicillin to destroy the clarithromycin efflux channel on the cell wall, making the effect of clarithromycin more effective. SQT is often used as a remedy for failure of standard triple therapy abroad. However, studies have shown that the triple therapy eradication rate (82.8%) over extended time (14d) is higher than that of classical sequential therapy (76.5%). One study also found that there was no significant difference in Hp eradication rates between SQT and standard triple therapy, which may be related to a higher rate of clarithromycin resistance. SQT has a longer course of treatment, which may reduce patient compliance and is not suitable for areas with high resistance to clarithromycin, so SQT may be considered when contraindications for tincture use.

1.3 Companion therapy

Accompanying therapy is PPI combined with amoxicillin, metronidazole and clarithromycin. A meta-analysis showed that the eradication rate was higher than the standard triple therapy. Another meta-analysis also found that the eradication rate (90%) was significantly higher than that of standard triple therapy (78%). The Maastricht IV Consensus suggests that SQT or concomitant therapy can be used in the absence of expectorants, and the eradication rates of the two therapies are similar. However, in areas where clarithromycin is resistant to metronidazole, it is more advantageous with concomitant therapy. However, because the accompanying therapy consists of three kinds of antibiotics, the choice of antibiotics will be reduced after the treatment failure, so it is not recommended as the first treatment plan except for areas where clarithromycin and metronidazole are resistant. Mostly used in areas with low resistance to clarithromycin and metronidazole.

1.4 high dose therapy

Studies have found that increasing the dose and/or frequency of administration of PPI and amoxicillin is greater than 90%. The bactericidal effect of amoxicillin on Hp is considered to be time-dependent, and therefore, it is more effective to increase the frequency of administration. Secondly, when the pH in the stomach is maintained between 3 and 6, the replication can be effectively inhibited. When the pH in the stomach exceeds 6, Hp will no longer replicate and is sensitive to amoxicillin. Ren et al conducted randomized controlled trials in 117 patients with Hp-positive patients. The high-dose group was given amoxicillin 1g, tid and rabeprazole 20mg, bid, and the control group was given amoxicillin 1g, tid and rabeprazole. 10mg, bid, after 2 weeks of treatment, the Hp eradication rate of high dose group was 89.8% (ITT), 93.0% (PP), significantly higher than the control group: 75.9% (ITT), 80.0% (PP), P <0.05. A study from the United States showed that using esomeprazole 40 mg, ld + amoxicillin 750 mg, 3 days, ITT = 72.2% after 14 days of treatment, PP = 74.2%. Franceschi et al. retrospectively analyzed three treatments: 1 standard triple therapy: lansoola 30mg, bid, clarithromycin 500mg, bid, amoxicillin 1000mg, bid, 7d; 2 high-dose therapy: Lansuo Carbazole 30mg, bid, clarithromycin 500mg, bid, amoxicillin 1000mg, tid, the course of treatment is 7d; 3SQT: lansoprazole 30mg, bid + amoxicillin 1000mg, bid treatment for 5d, lansoprazole 30mg bid, carat The 500mg bid and the tinidazole 500mg bid were treated for 5 days. The eradication rates of the three treatment regimens were: 55%, 75%, and 73%. The difference between high-dose therapy and standard triple therapy was statistically significant, and the difference was compared with SQT. Not statistically significant. Of course, studies have shown that high-dose omeprazole and amoxicillin therapy did not effectively improve eradication rates, probably due to the CYP2C19 genotype. Most PPIs are metabolized by the CYP2C19 enzyme, so the strength of the CYP2C19 gene metabolite may affect the metabolism of PPI. Esomeprazole is mainly metabolized by cytochrome P450 3 A4 enzyme, which can reduce the influence of CYP2C19 gene to some extent. In addition, in addition to PPI, amoxicillin, rifampicin, furazolidone, levofloxacin, is also recommended as a high-dose treatment alternative.

Combined microbial preparation

Adding microbial ecological agents (MEA) to standard therapy can reduce adverse reactions, but it is still controversial whether Hp eradication rate can be increased. A meta-analysis found that the triple therapy of B. sphaeroides combined with triple therapy alone increased Hp eradication rate (4 randomized controlled trials, n=915, RR=l.13, 95% CI: 1.05) ~1.21), also reduce adverse reactions including diarrhea. Zhao Baomin et al. also showed that the combination of probiotics can significantly improve the eradication rate, even after shortening the course of treatment, there is still a high eradication rate. A study of 85 patients with Hp-positive patients was randomized into 4 groups of Lactobacillus 20 mg bid, clarithromycin 500 mg bid, and tinidazole 500 mg bid. , B. cerevisiae, Lactobacillus combined with bifidobacteria, placebo for 1 week, fill out a questionnaire on symptom research every week for 4 weeks, 5 to 7 weeks later to check the infection, the study found: probiotics group and comfort There was no significant difference in the eradication rate between the groups, but all the probiotic groups were more advantageous in preventing adverse reactions than the control group, and there was no significant difference in the incidence of adverse reactions among the probiotic groups. The mechanism by which probiotics eradicate Hp is still unclear, and may inhibit or inactivate with competitive adhesion sites and various substances such as organic acids and bacteriopeptides. However, some studies have found that the combination of probiotics does not improve the eradication rate, which may be related to the extra effect of probiotics only when antibiotics are relatively ineffective. There is still a great research space in the joint probiotics, and further research is needed on the types, treatment courses, indications and timing of probiotic preparations.

Factors affecting Hp eradication rate

Several factors affecting Hp eradication include antibiotic resistance, geographic region, patient age, smoking status, compliance, treatment time, bacterial density, chronic atrophic gastritis, gastric acid concentration, individual response to PPI, and CYP2C19 gene polymorphism. The presence. Studies have reported that in univariate analysis, age, residential area, medication, gastrointestinal disease, comorbidity, eradication history, PPI, course of treatment, and treatment adherence are associated with eradication rates. In addition, some potential chronic diseases, such as diabetes, hypertension, chronic kidney disease, chronic liver disease, and chronic lung disease may also be related to the eradication rate of Hp. However, the results of the current study are not the same, and further large-scale studies are needed.