H. Pylori infektsioon

H. Pylori infektsioon on

* Kokkuvõte
* Mälupalee

## Diagnoos

### Kaebused

In the authors' opinion, there are no significant differences in the presence and frequency of symptoms, such as nausea, vomiting, pain, heartburn, or diarrhea, in patients who are infected with H pylori and those who are not. No definite evidence demonstrates a clear relationship between the symptoms of the H pylori-associated gastritis and abdominal pain or dyspeptic symptoms from other conditions, although H pylori gastritis is the cause of dyspepsia in a subset of patients (as when successful H pylori eradication results in sustained symptomatic remission) and is considered a distinct entity. [1] In infected patients, 30%-35% have no symptoms.

Adults and children differ in the immune response to H pylori infection. This is probably due to a physiologic lower density of neutrophils and T lymphocytes during childhood, especially in children younger than 8 years.

Although H pylori infection is not significantly related to recurrent abdominal pain, weekly pain is reported more often in children who are infected with H pylori compared with children who are not infected.

### Objektiivne leid

No specific clinical signs have been described in patients with H pylori infection. Patients may feel dyspepsia or abdominal discomfort, such as during gastritis or with epigastric pain (eg, duodenal ulcers). In some cases, patients may feel hungry in the morning and may have halitosis.

### Analüüsid

Noninvasive diagnostic studies include the carbon 13 urea breath test (UBT), fecal antigen test, and serologic parameters (pepsinogen I and II, H pylori antibody) as surrogate markers of H pylori gastritis and as indicators of gastritis severity. [1, 9]

Patients with new peptic ulcer disease should have a carbon 13 UBT, they should be tested for antibody titers, or they may require an investigation for stool antigens.
H pylori fecal antigen test

This novel rapid test is based on monoclonal antibody immunochromatography of stool samples. The test has been reported to be very specific (98%) and sensitive (94%).The results are positive in the initial stages of infection and can be used to detect eradication after treatment.

Although the H pylori fecal antigen test is an interesting tool, information about the cost of the test is pending.
Carbon 13 urea breath test

The carbon 13 UBT is based on the detection of the products created when urea is split by the organism.

Patients are asked to drink urea (usually with a beverage) labeled with a carbon isotope (carbon 13 or carbon 14). After a certain duration, the concentration of the labeled carbon is measured in the breath. The concentration is high only when urease is present in the stomach. Because the human stomach does not produce urease, such a reaction is possible only with H pylori infection.

The breath test is expensive but is becoming increasingly more available. Other problems include false-negative results due to infection with coccoid forms of H pylori that do not produce as much urease or the use of antibiotics, bismuth, histamine 2 (H2) blockers, or proton pump inhibitors.
H pylori serology

The serology test has a high (>90%) specificity and sensitivity. It is currently based on the quantitation of immunoglobulin G antibodies against H pylori by the means of an enzyme-linked immunosorbent assay.

It is useful for detecting a newly infected patient, but it is not a good test for follow-up of treated patients because the results do not indicate present infection with H pylori. The antibody titer may remain elevated for a long time after H pylori eradication. The number of false-positive results is age related and increases with age.
Antibiogram

In geographic areas with a high resistance rate against metronidazole and clarithromycin, culture for antibiotic susceptibility testing (antibiogram) seems to be useful. [3, 4] Alternatively, metronidazole and clarithromycin should not be recommended as first-line drugs in such areas.

### Uuringud

Esophagogastroduodenoscopy

In patients with prior peptic ulcer disease, an esophagogastroduodenoscopy (EGD) with biopsy and histological studies may be performed. Also, a carbon 13 urea breath test (UBT) is helpful in these patients.

An EGD is often necessary in patients with symptoms of peptic ulcer disease in order to view the condition of the mucosal lining of the stomach and duodenum and to obtain biopsy specimens from the gastric antrum and corpus.

An echography associated with an EGD is mandatory in patients with biopsy results that are positive for gastric MALTomas in order to allow a more precise staging of the disease.

H pylori is a gram-negative bacterium. It produces urease, has a spiral-like conformation, and is microaerophilic and motile because of the flagella. Flagella and urease are very important for its colonization of the gastric mucosa. Urease neutralizes gastric acidity, converting the gastric urea to ammonium ions, and flagella help the bacterium pass from the acidic gastric lumen into the mucus lining of the stomach. Two of the most important genes of H pylori are VACA and CAGA. The VACA gene codes the Vac-A cytotoxin, a vacuolating toxin, and the CAGA gene codes for Cag-A protein, which seems to stimulate the production of chemotactic factors for the neutrophils by the gastric epithelium of the host.

Biopsy specimens from esophagogastroduodenoscopy (EGD), stained with Giemsa stain, usually demonstrate a variable number of H pylori organisms adhering to the gastric epithelium, both coating the gastric wall and lining the gastric glands. The mucous film appears to be decreased. A large inflammatory infiltrate is present, with lymphocytes, neutrophils, and a variable number of mast cells that seem to play an important role in the pathogenesis of the gastric injury in persons infected with H pylori. [12, 13] Other stains are Genta, Warthin-Starry silver, and the classic hematoxylin and eosin. A rapid urease test may demonstrate the presence of H pylori in the gastric mucosa via histochemistry results. Bacterial culture is very difficult. It is not used for diagnosis; it is used in patients with resistant infection and for experimental purposes.

Staging

Although a staging system for the H pylori infection does not exist, some steps in the disease process are well described. The first step is chronic gastritis, followed after a time by the second step, atrophic gastritis. The third step is intestinal metaplasia, which may evolve into dysplasia. The last step is gastric adenocarcinoma. This process is very slow and may stop at any step because gastric cancers undoubtedly require several other factors to develop, not only an H pylori infection. As reported above, ultrasonography and esophagogastroduodenoscopy should be considered in patients with gastric MALTomas in order to allow a more precise staging of the disease.

The risk of gastric cancer is correlated with the severity and extent of atrophic gastritis; histologic staging systems can aid in risk stratification (eg, the operative link for gastritis assessment [OLGA] and operative link for gastric intestinal metaplasia assessment [OLGIM] staging systems). [1]

### Diferentsiaaldiagnoosid

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   Acute Gastritis

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   Atrophic Gastritis

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   Chronic Gastritis

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   Gastric Cancer

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   Gastrinoma

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   Gastroesophageal Reflux Disease

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   Non-Hodgkin Lymphoma

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   Peptic Ulcer Disease

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   Stress-Induced Gastritis

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## Ravi

### Farmakoloogiline

Only treat patients who have a positive test result for H pylori infection. The optimal timing of H pylori eradication in asymptomatic persons is during the period when the mucosal damage remains nonatrophic. [1]

Carefully educate patients regarding the importance of completing the prescription and about the potential adverse effects of the medications. [1] Importantly, consider possible antibiotic resistance when selecting the treatment regimen. Note that surgery is not required for patients with H pylori infection, but it may be considered in patients with severe complications, such as cancer.

The US Food and Drug Administration has approved several regimens, which are now accepted internationally, for the treatment of H pylori infection in patients with peptic ulcer disease, both gastric and duodenal. These regimens are also known as triple therapies and have reported cure rates from 85%-90%. Unfortunately, with the increasing rise in antimicrobial resistance there has been an associated increase in the failure rate of standard triple therapy for H pylori infection. [14] Thus eradication regimens should be based on the best locally effective regimen, optimally with the use of individual susceptibility testing or community antibiotic susceptibility, or data regarding antibiotic use and clinical outcomes. [1, 15]

Administer triple therapies for 10-14 days. The treatment regimens are omeprazole, amoxicillin, and clarithromycin (OAC) for 10 days; bismuth subsalicylate, metronidazole, and tetracycline (BMT) for 14 days; and lansoprazole, amoxicillin, and clarithromycin (LAC), which has been approved for either 10 days or 14 days of treatment.

It is recommended that the outcome of eradication therapy (test for cure) always be evaluated, with noninvasive means preferred. [1]

A trial of empiric therapy for H pylori infection in 7 Latin American sites found higher eradication rates with 14 days of standard triple therapy (LAC) than with shorter 4-drug therapies. Neither 5 days of concomitant lansoprazole, amoxicillin, clarithromycin, and metronidazole nor 10-day sequential treatment (5 days of LA, then 5 days of LCM) was significantly better than the standard therapy at any site. [16]

H pylori eradication rates were higher for a 7-day antibiotic regimen containing lansoprazole, amoxicillin, and clarithromycin (LAC), when used as first-line therapy compared with levofloxacin, amoxicillin, and lansoprazole (LAL). [17] Additionally, LAC did not achieve a higher rate of eradication than LAL as second-line therapy; thus, consideration of the sequence of administering antibiotic regimens for H pylori is important.

Hsu et al reported that the 7-day concomitant therapy is superior to the 7-day standard triple therapy for H pylori eradication, and it is also simpler to administer than the 10-day sequential therapy, because the drugs are not changed halfway through the treatment course. [14] Similarly, Apostolopoulos et al reported that the 10-day concomitant quadruple therapy resulted in statistically significant higher eradication of H pylori than 10-day sequential quadruple therapy in an area of Greece with a greater than 20% local resistance to clarithromycin. [18]

A study by Yoon et al investigated the efficacy of a moxifloxacin-containing triple therapy as second-line therapy for H pylori infection as well as the effect of treatment duration and antibiotic resistance on the eradication rate. [19] In 2004, 41 patients who had persistent H pylori infection were given a 7-day course of 400 mg qd moxifloxacin, 1000 mg bid amoxicillin, and 20 mg bid esomeprazole; the intention-to-treat (ITT) rate was 75.6% with a per-protocol (PP) eradication rate of 83.8% and a moxifloxacin resistance rate of 5.6%. During 2005-2006, 139 patients were treated to a 10-day course of this regimen, with an ITT rate of 71.9%, PP eradication rate of 82.6%, and moxifloxacin resistance rate of 12%. One-hundred eight-one patients treated in 2007-2008 received a 14-day triple-therapy regimen: ITT rate, 68%; PP eradication rate, 79.9%; moxifloxacin resistance rate: 28.2%. [19]

Despite the increased duration of treatment in each successive group of patients, there was no statistical difference in efficacy among the 3 treatment groups. [19] The investigators attributed the low eradication rate despite increased duration of therapy to a coincident, marked increase in moxifloxacin resistance and concluded that when rapid antibiotic resistance occurs, tailored treatment based on antibiotic susceptibility testing may achieve higher eradication rates. [19]

Macrolide resistance in patients with H pylori infection is an important problem. Although the molecular mechanisms of nitroimidazole resistance are very complex and still unclear, resistance has been shown to be due to a single point mutation (usually in the RDXA gene, although other genes may also be involved, eg, FRDXA) in 1 of 4 positions of the bacterial 23S rDNA. Such mutations also determine cross-resistance to other macrolides.

An emerging and increasing problem in many Western countries is the fact that some H pylori strains in children are resistant to the antibiotic clarithromycin. [20] The causes are not known.

All the eradication treatments have a high incidence of certain adverse effects (eg, nausea, metallic taste). If skin rash, vomiting, or diarrhea occurs, discontinue the treatment.

The links between H pylori and nonulcer dyspepsia are debated; however, some patients with nonulcer dyspepsia benefit from eradication. Indeed, H pylori eradication is the first-line and preferred treatment for H pylori -infected dyspeptic individuals. [1] Patients with symptoms have a higher eradication rate than patients with nonulcer dyspepsia disease. Eradication of H pylori in patients without peptic ulcer disease has resolved the dyspepsia in a few cases. If successful H pylori eradication does not resolve dyspeptic symptoms, patients should be considered to have "functional dyspepsia." [1]

### Muu ravi

Diet and activity

No dietary restrictions are usually needed, and no limitations of physical activity are needed if patients do not have complications.
Posttreatment monitoring

Consider performing a urea breath test (UBT) 4-12 weeks after the end of treatment. An esophagogastroduodenoscopy (EGD) with biopsy and a urease test also may be useful, but, importantly, remember that this test does have a significant rate of false-negative results.

Prevention

Searching and screening for H pylori gastritis depends on the epidemiologic setting and is appropriate at an age before the onset of atrophic gastritis and intestinal metaplasia. [1]

Note that the risk of gastric cancer is increased in patients who have an H pylori infection and whose first-degree relatives have a history of gastric cancer, even if they are asymptomatic. Thus, eradicating H pylori reduces the risk of gastric cancer; the risk reduction relies on the presence, severity, and extent of atrophic damage at the time of eradication. [1]

Persons emigrating from geographic areas with a high incidence of gastric cancer have an increased risk.

Consider any patient with precancerous lesions of the stomach (ie, intestinal metaplasia) for treatment of H pylori infection.