Professor Cheng Hong's interpretation: Why does the Maastricht VI consensus and the latest consensus in China recommend Hp eradication treatment options?

After 5 years, the "Management of Helicobacter pylori infection: Maastricht VI/Florence Consensus Report" 1 (hereinafter referred to as "Maastricht VI consensus") has been updated again! This time, we specially invited Professor Cheng Hong of Peking University First Hospital to interpret
the consensus eradication treatment part.

China is a country with high infection with Helicobacter pylori (Hp) infection and high incidence of gastric cancer, nearly half of the world's new gastric cancer is in China, and Hp infection has caused a heavy burden of disease
.
The Kyoto global consensus on Hp gastritis proposes that Hp infection is an infectious disease, and if there are no counterfactors, Hp positive patients should receive eradication therapy
.

At present, eradication treatment of Hp infection faces some challenges, the most important of which is that antibiotic resistance has reduced the eradication rate
.
In order to standardize the diagnosis and treatment of Hp infection and improve the eradication rate of Hp infection treatment, especially the primary treatment, a series of consensus
has been issued at home and abroad.
This paper interprets
the content of Hp infection eradication treatment in the "Equine VI Consensus" and China's "Sixth National Helicobacter Pylori Infection Treatment Consensus Report" 2 (hereinafter referred to as the "China VI Consensus").

No.
1 

Highlights of the update to the "Eradication treatment" section of the "Management of Helicobacter pylori infection – Maastricht VI/Florence Consensus Report"?

Compared with the MCV consensus, there are several aspects of the MA VI consensus that require clinicians' attention: First, the new version of the consensus focuses on recommending the antibiotic combination of "tetracycline + metronidazole", that is, the classic quadruple regimen (proton pump inhibitor, bismuth, tetracycline and metronidazole).

This update further recommends it as first-line therapy
in areas with low clarithromycin resistance (<15%) compared to the horse V.
consensus recommended for first-line treatment in areas with high clarithromycin resistance (>15%).
The reason behind this update is closely related
to the rising rate of antibiotic resistance to bacteria.
At present, the resistance rate of Hp to clarithromycin, levofloxacin, and metronidazole has increased significantly, but the drug resistance can be overcome and the eradication rate can be improved by increasing the dose of metronidazole, and the current drug resistance rate of tetracycline is low, and the clinical combination of "metronidazole + tetracycline" can not be tested for bacterial resistance, which has become the reason
for the consensus to recommend this program.

Second, the equine VI consensus recommends a dual regimen for first- and second-line therapy, particularly in settings where
bismuth or tetracycline is not available.

Third, in areas with low resistance rates of clarithromycin, where bismuth is not available, the consensus also recommends companion therapy, i.
e.
, three antibiotics combined with antacids (PPI, amoxicillin, clarithromycin, and a nitroimidazole) as first-line regimens
.

No.
2 

What are the similarities and differences of Hp eradication programs in the latest guideline consensus at home and abroad?

On the basis of the classic quadruple scheme recommended by the MAVI consensus, China's new version of the China VI Consensus still focuses on recommending the bismuth-containing quadruple scheme, and expands 5 antibiotic combination schemes: PPI + bismuth + two antibiotics (amoxicillin combined with clarithromycin, amoxicillin-levofloxacin, tetracycline combined with metronidazole, amoxicillin combined with metronidazole, amoxicillin combined with tetracycline).

In addition, like the MA VI consensus, the Chinese consensus also recommends high-dose dual regimens for primary and retreatment
.

For patients allergic to penicillin, China VI consensus has specially recommended treatment regimens, and bismuth quadruple regimens containing tetracycline plus metronidazole are preferred for empiric eradication therapy
.

No.
3 

Why do the new guidelines in China and the MAVI consensus recommend high-dose amoxicillin dual regimens for primary and re-eradication therapy?

The latest consensus at home and abroad has unanimously recommended the high-dose amoxicillin dual regimen for primary and retreatment
.
This recommendation is also based on the growing problem
of antibiotic resistance.
At present, Hp on clinical antibiotics such as clarithromycin, levofloxacin, metronidazole whether primary or secondary resistance problems are constantly prominent, especially clarithromycin and levofloxacin have a "full or nothing" effect on Hp, that is, once drug resistance occurs, then choose such antibiotics have almost no antibacterial effect, so the resistance of such antibiotics is an important factor
affecting the eradication effect.

Other antibiotics with relatively low resistance rates, such as amoxicillin, tetracycline, and rifabutin recommended in the equine VI consensus, and furazolidone, recommended only in China, face problems such as
drug accessibility or high incidence of adverse reactions in addition to amoxicillin.
For example, furazolidone regimens, which are banned in many countries due to their high risk of adverse reactions, are also only used in patients with refractory Hp infection in China
.

Although rifabutin is recommended in the equine VI consensus for patients who have failed multiple treatments, the consensus in China does not recommend the regimen of rifabutine, because it is considered that the tuberculosis infection rate in China is high, and this drug is used for anti-tuberculosis treatment
.
If we recommend rifabutin, it may lead to the emergence and spread of drug-resistant bacteria of tuberculosis, affecting the prevention and control
of tuberculosis.

No.
4 

The equine VI consensus recommends that the duration of all Hp eradication therapy should be extended to 14 days as much as possible unless the 10-day course is shown to be effective
.
How is the course of treatment recommended for Hp eradication based on clinical practice in China?

Starting from the consensus of China V, China has recommended a 14-day course of treatment
for both patients who have been treated for first or retreated.
The MA VI consensus also emphasized the 14-day course of treatment, while the 10-14 day course of treatment
was more recommended in the past.

Prolonging the course of Hp eradication to 14 days has been recommended by consensus at home and abroad, and one of the main reasons is the problem
of Hp resistance to antibiotics.
Studies have shown that prolonged eradication courses increase eradication rates, without a significant increase
in adverse drug effects.
Therefore, unless a 10-day course is proven, it is recommended that all courses of Hp eradication therapy be extended to 14 days as much as possible, regardless of treatment-naïve or retreated patients
.

Selection of sensitive antibiotics is critical
to successful eradication of Hp.
Although the equine VI consensus recommends different regimens for regions with >clarithromycin resistance rate of 15% and clarithromycin resistance rate <15%, the actual regimen is similar<b11>.
Moreover, the Ma VI consensus also specifically mentioned that it is becoming more and more difficult
to find people around the world who have a really low rate of bacterial resistance.

On the other hand, it has been nearly 40 years since the discovery of Hp, and the antibiotics that can be selected clinically are still limited, and we cannot increase the types of antibiotics without limit, so the long-term treatment program plays an important role
in overcoming bacterial resistance and improving the eradication rate.

Hp infection is an infectious disease, and domestic and foreign consensus emphasizes the importance of improving the success rate
of first eradication.
Selection of sensitive antibiotics is critical
to successful eradication of Hp.
At present, the resistance rate of Hp to clarithromycin, levofloxacin and metronidazole in most parts of the world is increasing
.
The situation of drug resistance in China is more serious, so the bismuth quadruple scheme is still the main scheme
recommended by the current guidelines.
Acid suppression and eradication course is also an important factor affecting the success of Hp eradication, the selection of better acid inhibitory drugs can help improve the eradication rate, and comprehensive domestic and foreign consensus, unless the 10 day course is proved to be effective, the eradication course should be extended to 14 days as much as possible to improve the eradication rate
.

References:

1.
Malfertheiner P, et al.
Gut.
2022 Aug 8: gutjnl-2022-327745.

2.
What does the new version of the Chinese Helicobacter pylori infection treatment guide say, this one is a sneak peek! https://mp.
weixin.
qq.
com/s/9dm7CzdPjJ2V-BHaq5nYBQ.

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