I. H. pylori eradication treatment indications
1, peptic ulcer is the most important indications for Hp eradication
Hp eradication can promote ulcer healing and significantly reduce the recurrence rate and complication rate of ulcers. The eradication of Hp makes most peptic ulcers no longer a chronic, recurrent disease, but completely curable.
2. Gastric MALT lymphoma is a rare malignant tumor of the stomach
Approximately 80% of Hp-positive gastric MALT lymphoma is completely responsive to Hp eradication in early stage (lesions limited to the mucosal or submucosal layer), but the efficacy is reduced in lesions deeper than the submucosal layer. Hp eradication has become the first-line treatment for Hp-positive early gastric MALT lymphoma. (2012 expert guidelines strongly recommend the above two conditions: Hp eradication)
3. Hp-positive chronic gastritis with dyspepsia
Hp eradication provides long-term symptom relief in 8-20% of Hp-positive FD patients, which is better than any other treatment.
4. Chronic gastritis with gastric mucosal atrophy or erosion
Intestinal gastric cancer eventually occurs in <1% of Hp-infected patients, and atrophy and intestinalization are important lesion stages in the evolution from non-atrophic gastritis to gastric cancer. Atrophy and intestinal chemosis can occur after recurrent erosions. Although the best time to eradicate Hp to prevent gastric cancer is before the occurrence of atrophy and intestinal chemosis, eradication of Hp at this stage can still eliminate the inflammatory response, slow down or stop the development of atrophy, and possibly reverse part of the atrophy, but intestinal chemosis is difficult to reverse.
5.Early gastric tumor has been resected endoscopically or surgically by subtotal gastrectomy.
6.People who need to take proton pump inhibitor for a long time (PPI)
The long-term use of PPI in Hp-infected patients can change the type of gastritis from sinus-based gastritis to gastric body-based gastritis. This is because the rise in gastric pH after PPI administration facilitates the displacement of Hp from the gastric sinus to the gastric body, and gastric body inflammation and atrophy further reduce gastric acid secretion. The risk of gastric cancer is significantly higher in gastric body atrophy-based gastritis with low or no acidity.
7. Family history of gastric cancer
Except for a small number (about 1%-3%) of hereditary diffuse gastric cancer, most gastric cancers occur as a result of the combination of Hp infection, environmental factors and genetic factors. Although it is difficult to change the genetic susceptibility, eradication of Hp can eliminate the important factors for the development of gastric cancer and thus improve the prevention effect.
8.Plan to take long-term non-steroidal anti-inflammatory drugs (NSAIDs) (including low-dose aspirin)
Hp infection and taking NSAIDs, including aspirin, are two independent risk factors for the development of peptic ulcer.
9. Hp infection is associated with iron deficiency anemia of unknown origin
Hp eradication increases hemoglobin levels, and Hp eradication increases platelet counts in more than 50% of patients with idiopathic thrombocytopenic purpura .
10. Individual request for treatment
Conditions and benefits vary and should be critically evaluated by a physician prior to treatment. The eradication of Hp is supported for those aged <45 years without alarm symptoms, but those aged >45 years or with alarm symptoms need to be evaluated first.
However, those aged >45 years or with alarming symptoms need to be examined by endoscopy first. The potential risks of this treatment strategy, including missed upper gastrointestinal cancers, masking and adverse drug reactions, should be clearly explained to the patient prior to treatment.
Detection methods of H. pylori
1.RUT (gastric mucosal tissue urease test).
The test results are affected by the pH value of the reagent, the site of sampling, the size of the tissue, the amount of bacteria, the observation time, the ambient temperature and other factors. Two pieces of tissue are taken at the same time for testing (one each for the gastric sinus and body).
2.Histological detection.
The detection of Hp can be accompanied by the diagnosis of gastric mucosal lesions (HE staining). There are some differences in the results of different staining methods. Immunohistochemical staining has high specificity, but the cost is also higher; HE staining can be used for pathological diagnosis at the same time.
3.Bacterial culture.
Complex, time-consuming, requires certain laboratory conditions, and the specimen needs special transfer fluid and low temperature for transfer culture. High specificity of culture detection, drug sensitivity testing and bacteriological studies can be performed.
4.UBT (urea whistle test).
The test is accurate and easy to operate; it can reflect the status of Hp infection in the whole stomach and overcome the false negative RUT caused by the “focal” distribution of bacteria. But the UBT test value is near the threshold, the results are unreliable, can be tested again after a period of time or with other methods.
5, fecal antigen detection.
The validated monoclonal antibody method has good sensitivity and specificity; can be used for pre-treatment diagnosis of Hp and post-treatment review; safe and easy to operate. International consensus that the accuracy of the method is comparable to the whistle test, but there are no corresponding reagents in China.
6.Serum antibody test.
Detection of antibodies is IgG, positive reflect a period of time hp infection, only applied to the population census, can not reflect whether the current infection and treatment after the review of eradication.
Issues that need attention.
1. Avoid the effect of certain drugs on the test.
The application of antibacterial drugs, bismuth and some antibacterial effect of Chinese medicine, should be tested at least 4 weeks after the cessation of the drug; application of acid suppressants should be tested at least 2 weeks after the cessation of the drug.
2. Different disease states will have an impact on the test results.
Active bleeding of peptic ulcer, severe atrophic gastritis, and gastric malignancy may lead to false-negative urease dependent tests. More reliable results can be obtained by testing at different times, using multiple methods or using non-urease dependent tests.
3. Low detection rate of Hp in gastric mucosal intestinal biogenesis tissue.
Pathology suggesting the presence of active inflammation is highly suggestive of Hp infection; in patients with active peptic ulcer excluding NSAID, the likelihood of Hp infection is >95%. Therefore, in the above-mentioned cases, false negatives should be highly suspected if Hp tests are negative.
III: H. pylori eradication therapy
1. Epidemiological and drug resistance rate survey :.
Epidemiological surveys have shown that the overall rate of Hp infection in China remains high, reaching 40-60% among adults. Among the six antimicrobial drugs recommended for eradication treatment, the resistance rate of metronidazole reaches 60%-70%, clarithromycin reaches 20%-38%”, and levofloxacin reaches 30%-38%, which significantly affects the eradication rate; the resistance rate of amoxicillin, vincristine and tetracycline is still very low (1%-5%).
The eradication rate of standard triple therapy recommended by Lushan Consensus in 2007: (PPI + clarithromycin + amoxicillin) and (PPI + clamoxol + metronidazole) eradication rate has been lower or far lower than 80%.
2. New internationally recommended eradication programs.
Sequential therapy: (first 5 days PPI + amoxicillin, after 5 days PPI + cladribine + metronidazole, a total of 10d) Accompanying therapy: (while taking PPI + cladribine + amoxicillin + metronidazole) hp eradication rate of the new therapy applied in China.
Sequential therapy did not show an advantage over standard triple therapy in our multicenter randomized controlled study. The efficacy of bismuth quadruple therapy is comparable to that of concomitant therapy, which requires 3 antimicrobial drugs and may not only increase the adverse effects of antimicrobial drugs, but also reduce the choice of antimicrobial drugs after treatment failure. Therefore, unless the use of bismuth is contraindicated, concomitant therapy is not recommended.
3. In the context of high Hp resistance rate, bismuth quadruple regimen is again emphasized.
The efficacy of the classical bismuth quadruple regimen (bismuth + PPI + tetracycline + metronidazole) has been reconfirmed. In the latest international consensus, the first-line regimen is recommended first in areas with high clathrin resistance rate, and if bismuth is not available, sequential therapy or concomitant therapy is recommended; in areas with low clathrin resistance rate, in addition to standard triple therapy, secret agent quadruple therapy is also recommended as the first-line regimen. In conclusion, facing the challenge of rising antimicrobial drug resistance rate, bismuth quadruple therapy is again emphasized. Bismuth is still commonly available in China, and we should make full use of this advantage.
4, the safety of bismuth.
At present, many countries and regions in the world can no longer obtain bismuth alone (due to the dosage form, dose, treatment course, etc., in the early years there is a high rate of adverse reactions and withdrawn from the market), but the new bismuth-containing mixed preparations (bismuth potassium citrate, tetracycline and metronidazole in the same capsule) are being tested and promoted again. The meta-analysis of bismuth safety showed that in Hp eradication therapy, there is a difference in adverse reactions of bismuth-containing regimen compared with non-bismuth-containing regimen, metered fecal black (bismuth color), suggesting that short-term (1-2 weeks) administration of bismuth has a relatively high safety profile.
5. Among the six antimicrobial drugs used in Hp eradication therapy.
Amoxicillin, furazolidone and tetracycline have a low resistance rate and are not prone to resistance after treatment failure (can be repeatedly applied); while clamoxyl, metronidazole and levofloxacin drugs have a high resistance rate and are prone to resistance after treatment failure (in principle, they cannot be repeatedly applied).
(i) eradication program composition recommended bismuth + PPI + 2 antibacterial drugs composed of quadruple therapy.
Four composition schemes.
(1) amoxicillin + clarithromycin.
(2) Amoxicillin + levofloxacin.
(3) Amoxicillin + furazolidone.
(4) Tetracycline + metronidazole or furazolidone.
The recommended antimicrobial drug regimen for penicillin allergy is.
(1) clarithromycin + levofloxacin.
(2) clarithromycin + furazolidone.
(3) Tetracycline + metronidazole or furazolidone.
(4) Clarithromycin + metronidazole.
After failure of initial treatment in penicillin-allergic patients, the choice of antimicrobial drugs is small and the eradication rate of initial treatment should be improved as much as possible
(ii) First- and second-line therapy issues.
The above four recommended regimens for non-penicillin-allergic patients all have high eradication rates, and each has advantages and disadvantages in other aspects, making it difficult to classify first- and second-line regimens. The specific operation can be based on the availability of drugs, cost, potential adverse reactions and other factors to consider, choose one of the options as the initial treatment If the initial treatment fails, you can choose another option among the remaining options for remedial treatment .
(iii) The course of eradication treatment in view of the secret agent quadruple therapy.
The recommended duration of treatment is 10d or 14d, and the 7d regimen is abandoned, since a longer duration of treatment can improve the efficacy to some extent.
(iv) Treatment after two treatment failures.
If after treatment with 2 of the above quadruple regimens, both of which are 10d or 14d in duration, failure is highly likely when treated again after failure.
In this case, the risk-benefit ratio of eradication therapy needs to be evaluated. The benefit of Hp eradication is greater in patients with gastric MALT lymphoma, peptic ulcer with a history of complications, gastritis with a risk of gastric cancer (severe total gastritis, gastric body-dominant gastritis, or severe atrophic gastritis), and a family history of gastric cancer.
The selection of the regimen needs to be carefully designed by an experienced physician based on a thorough evaluation of the drugs used and analysis of the possible causes of failure.
If available, drug sensitivity test can be performed, but the effect may be limited.
1. Emphasis on individualized treatment.
The selection of protocol, course and drugs needs to take into account the history of previous antimicrobial drug applications (clarithromycin, levofloxacin, metronidazole susceptible to resistance), smoking (reduces efficacy), history of drug (amoxicillin, etc.) allergy and potential adverse reactions, indications for eradication (peptic ulcer eradication rate is higher than non-ulcer dyspepsia; concomitant diseases (affect drug metabolism, excretion, increase adverse reactions) and age (elderly patients) The incidence of adverse drug reactions increases and the benefit rate decreases), etc.
2. Remedial therapy, with a recommended interval of 2-3 months.
3.The importance of potential adverse reactions and compliance with the eradication program should be informed.
4. PPIs play an important role in eradication regimens: choosing PPIs with stable effects, high efficacy and less affected by genetic polymorphisms, such as esomeprazole and rabeprazole, can improve eradication rates.
IV. Other measures that are still being explored
1. Combined application of microecological agents: some microecological agents can reduce or eliminate the imbalance of intestinal microecology caused by Hp eradication treatment, whether it can improve the eradication rate needs further study.
2, Chinese medicine: the results of a study suggest that a certain Chinese medicine has the effect of improving the eradication rate of Hp, but the exact efficacy and how to combine the eradication program, there is still more research to verify.
3, gastric mucosal protective agents: individual gastric mucosal protective agents have been proven to have anti-Hp effects, and can be used in place of bismuth for quadruple therapy to obtain the same efficacy.