Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020

Helicobacter pylori infection is one of the most common infectious diseases worldwide. Although the prevalence of H. pylori is gradually decreasing, approximately half of the world''s population still becomes infected with this disease. H. pylori is responsible for substantial gastrointestinal morbidity worldwide, with a high disease burden. It is the most common cause of gastric and duodenal ulcers and gastric cancer. Since the revision of the H. pylori clinical practice guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin-based triple therapy for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance, especially from clarithromycin. The clinical practice guidelines for the treatment of H. pylori were updated according to evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after an expert consensus on three recommendations regarding the indication for treatment and eight recommendations for the treatment itself. These guidelines were designed to provide clinical evidence for the treatment (including primary care treatment) of H. pylori infection to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards and will be revised if more evidence emerges in the future.     

Population-based strategies for Helicobacter pylori-associated disease management: a Japanese perspective

The prevalence of Helicobacter pylori infection is decreasing gradually in Japan mainly owing to an improvement in sanitary conditions. The guidelines for H. pylori management by the Japanese Society for Helicobacter Research, initially established in 2000 and revised in 2003, were revised dramatically in January 2009. The new guidelines accepted the use of new drugs and recommended trying the second-line eradication regimen. Moreover, the revised guidelines reflected the recent knowledge in Japan that metachronous gastric cancer prevalance is decreased significantly by the eradication of H. pylori infection. The Japanese Society for Helicobacter Research proposed that the cure of H. pylori infection should be presupposed to prevent gastric cancer from active gastritis universally developed in the infected subjects. Overall, the most important and dramatic revision is that all infected people are recommended to receive eradication therapy irrespective of the clinical outcomes in the Japanese population.     

Management of Helicobacter pylori Infection: A Comparison between Korea and the United States

Helicobacter pylori has been well known to cause gastritis, peptic ulcers, mucosa-associated lymphoid tissue, and gastric cancer. The importance of H. pylori eradication has been emphasized; however, the management of H. pylori infection is difficult in clinical practice. In both Eastern and Western countries, there has been a constant interest in confirming individuals who should be tested and treated for H. pylori infection and developing methods to diagnose H. pylori infection. Many studies have been implemented to successfully eradicate H. pylori, and various combinations of eradication regimens for H. pylori infection have been suggested worldwide. Based on the findings of previous studies, a few countries have published their own guidelines that are appropriate for their country; however, these country-specific guidelines may differ depending on the circumstances in each country. Evidence-based guidelines and clinical practice updates for the treatment of H. pylori infection have been published in Korea and the United States in 2021. This review will summarize the similarities and differences in the management of H. pylori infection in Korea and the United States, focusing on indications, diagnosis, and treatments based on recent guidelines and recommendations in both countries.     

A Planned Prospective, Randomized, Placebo-Controlled Multicenter Trial Assessing the Effect of Helicobacter pylori Eradication on the Healing of Iatrogenic Ulcer after Endoscopic Resection of Gastric Neoplasm

Background/Aims

Helicobacter pylori eradication may facilitate the healing of iatrogenic ulcer after endoscopic resection of gastric neoplasm. This study involved designing a randomized, double-blinded, placebo-controlled, multicenter trial, performed by the Korean College of Helicobacter and Upper Gastrointestinal Research and the Medical Research Collaboration Center, Seoul National University Hospital.

Methods

We intend to enroll up to 232 patients H.-pylori-positive patients who have gastric adenoma or early gastric cancer after endoscopic resection. The enrolled patients are being randomly allocated to the H.-pylori-eradication-plus-proton-pump-inhibitor group or the placebo-plus-proton-pump-inhibitor group based on their histology results and the size of the resected specimen. After random allocation, the iatrogenic ulcer size and stage are evaluated at 4- and 8-week follow-ups (with a window of ±7 days). The primary end point is the healing rate of the ulcer by stage, and the secondary end point is the rate of ulcer size reduction, relief rate from ulcer-related symptoms, and adverse-event rates.

Results

More than 90% of the target subjects have already been enrolled into the study and are receiving ongoing periodic monitoring by the Medical Research Collaboration Center.

Conclusions

Completion of the study should reveal whether H. pylori eradication can facilitate the healing of ulcer after endoscopic resection in Korea.     

Asia-Pacific consensus guidelines on gastric cancer prevention

Background and Aim: Gastric cancer is a major health burden in the Asia–Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. Methods: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Results: Helicobacter pylori infection is a necessary but not sufficient causal factor for non‐cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host–bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high‐risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high‐risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First‐line treatment of H. pylori infection should be in accordance with national treatment guidelines. Conclusion: A strategy of H. pylori screening and eradication in high‐risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.     

Detection of Helicobacter species in liver and stomach tissues of patients with chronic liver diseases using polymerase chain reaction-denaturing gradient gel electrophoresis and immunohistochemistry

Objective.Helicobacter DNA has been detected in the hepatobiliary tree of patients with chronic liver diseases (CLD). The presence of H. pylori in the stomach compared with in the liver of the same patients with CLD has not been studied, therefore to the aim of this study was to investigate the presence of Helicobacter DNA and antigens in the liver and stomach of Polish patients with chronic liver diseases using molecular and immunological methods. Material and methods. Gastric mucosa and liver tissue samples and sera were collected from 97 Polish patients with CLD. Anti-H. pylori antibodies were detected by enzyme immunoassay (EIA), and H. pylori-like antigens detected by immunohistochemistry. Helicobacter DNA was detected in stomach and liver samples using a semi-nested Helicobacter genus-specific polymerase chain reaction (PCR) assay, and Helicobacter species identified by denaturing gradient gel electrophoresis (DGGE) and sequencing analysis of amplified PCR products. Results.H. pylori was identified by DGGE and sequence analysis in 60/62 (97%) and 25/25 (100%) of the gastric and liver Helicobacter genus-positive samples, respectively, whereas DNA of H. heilmannii was detected in 2/62 (3%) of the Helicobacter genus-positive gastric samples. H. pyloricagA gene was detected in 23/62 (36%) and 3/25 (12%) gastric and liver tissue samples, respectively. H. pylori-like antigens were detected in 61/97 (63%) gastric mucosa and in 40/97 (41%) liver tissue samples. Conclusions.H. pylori-like organisms appeared to dominate the gastric mucosa and liver tissue of Polish patients with CLD. The prevalence of the cagA gene was higher in stomach compared with liver samples, which suggests a possible role of cagA negative H. pylori-like organisms in CLD. On the other hand, no significant correlation was found between the presence of H. pylori-like DNA and antigens in the liver and liver function tests.     

Helicobacter pylori infection and the risk of gastric cancer among the Korean population

Helicobacter pylori infection has been associated with chronic atrophic gastritis, a precursor of gastric cancer. We conducted a prospective, case-controlled study to investigate whether H. pylori infection increases the risk of gastric cancer in Korean people with a high risk of gastric cancer. We enrolled 160 gastric cancer patients who were confirmed by endoscopic biopsy during 1994 and 160 age-matched control subjects with non-ulcer dyspepsia were compared to document the relationship between H. pylori infection and gastric cancer. The presence of H. pylori infection was determined by the rapid urease test and/or histology by Wright-Giemsa staining. The overall presence of H. pylori infection was 60% in gastric cancer patients and 51.9% in age-matched control subjects (odds ratio 1.39; 95% confidence interval 0.894–2.17; P= 0.143). Carcinomas of cardia, body and antrum were not associated with H. pylori infection (odds ratio 1.43, 1.69 and 1.29, respectively; 95% confidence interval, 0.271–7.52, 0.787–3.62 and 0.689–2.43, respectively; P= 0.178, 0.177 and 0.642, respectively) nor was the intestinal or diffuse type of cancer (odds ratio 1.39 and 1.40, respectively; 95% confidence interval 0.791–2.45 and 0.681–2.87, respectively; P= 0.250 and 0.835, respectively). Gender was not a risk for gastric cancer. In contrast to previous studies, these results do not provide evidence of H. pylori infection for gastric carcinogenesis in Korea.     

Helicobacter infection in patients with HCV-related chronic hepatitis,cirrhosis, and hepatocellular carcinoma

Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). HCC represents one of the most common human cancers. Incidence rates for this tumor vary widely on a worldwide, suggesting that environmental factors such as infectious microorganisms, carcinogens, or nutrition play a role in its pathogenesis. Several Helicobacter spp. colonize the liver of animals and induce hepatitis. The aim of this study was to determine whether Helicobacter infection was associated with HCV-related liver diseases in humans. Liver tissue samples, including biopsy and surgically excised tissues, were collected from patients positive for hepatitis C viruses (HCV) RNA in the serum. Genomic DNA was extracted from sections of formalin-fixed paraffin-embedded tissues by using the QIAamp Tissue Kit and subjected to polymerase chain reaction (PCR) analysis using two sets of Helicobacter-specific 16S ribosomal RNA primers. To identify positive samples for H. pylori, a set of primers specific for a conserved region in the H. pylori vacA gene were also used. The patients' H. pylori status was determined by ELISA. Forty-one patients (mean age 54.9, range 19–78 years; 24 men) were studied. Thirty patients had chronic viral hepatitis (CH) without (N = 18) or with (N = 12) cirrhosis (CIR), and 11 patients had HCC. Anti-H. pylori IgG was detected in 54%. The expected 422- and 210-bp fragments of Helicobacter 16S rRNA were amplified from 27% of liver samples, including 17% of CH-CIR and 55% of HCC (P = 0.004). The vacA sequence was amplified in 10 of 41(24%) samples (27% of those with HCC).: These data confirm the presence of H. pylori DNA sequences in human liver and suggest an association of Helicobacter spp. with HCV-related chronic liver diseases. Further studies are needed to ascertain whether Helicobacter spp. infection plays a role in the development of HCC.     

Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study

Background. Gastric cancer is still the most common malignant tumor in Koreans. Although many reports have supported the association of Helicobacter pylori infection and the development of gastric cancer, few studies have been adjusted by variable factors such as age, sex, education, and economic status. Furthermore, most results from areas with a high incidence of gastric cancer, such as China and Korea, have failed to document any relationship between H. pylori infection and gastric cancer. We conducted a prospective case-controlled study, with controls matched for and adjusted by age, sex, education, and economic status, to evaluate the causal relationship between H. pylori infection and gastric cancer in Korean people. Methods. From March 1997 to October 1998, 136 consecutive patients with gastric cancer, diagnosed by endoscopic histology, and 136 age- and sex-matched control subjects, confirmed to be free of gastric cancer by endoscopy during the same period, were enrolled in the study. The presence of H. pylori infection was determined by enzyme immunoassay (EIA) serology test. Results. Seventy-two of the 136 gastric cancer patients (53%) were positive for H. pylori infection and 54 of the 136 control subjects (40%) were positive for H. pylori infection. The odds ratio (OR), adjusted by variable risk factors, such as age, sex, education, and economic status, for gastric cancer in H. pylori-infected patients was 1.82 (95% confidence internal [CI], 1.10–3.00; P = 0.019). The age- and sex-matched OR by conditional logistic regression was 1.6 (95% CI, 1.01–2.53; P = 0.043). Conclusions. H. pylori infection may be one of the important risk factors for the development of gastric cancer in Korea, an area of high prevalence of H. pylori infection and a high incidence of gastric cancer. Received: September 27, 2000 / Accepted: May 25, 2001     

Helicobacter pylori infection is associated with greater impairment of cytochrome P-450 liver metabolic activity in anti-HCV positive cirrhotic patients

Helicobacter pylori gastric infection has been associated with various digestive and extradigestive diseases. In liver disease bacterial infections have been associated with impairment of cytochrome P-450 liver metabolic activity. Moreover, infection by Helicobacter spp. seems to be linked with the development of hepatocellular carcinoma (HCC) in mice. Our aims were to evaluate the influence of H. pylori infection on cytochrome P-450 liver metabolic activity as assessed by means of monoethylglycinexylidide (MEGX) test and to assess the prevalence of H. pylori infection in patients with HCC. Ninety-six hepatitis C virus (HCV) -positive cirrhotic patients, 36 of whom had HCC, were tested for H. pylori infection by means of anti-H. pylori IgG. Patients underwent the MEGX test. Characteristics of the patients were then analyzed on the basis of the presence of H. pylori infection. Seroprevalence of H. pylori infection was similar between cirrhotic patients without (68%) or with (63.8%) HCC. Mean MEGX values were significantly (P < 0.0001) lower in H. pylori infected patients (18.2±13.9 ng/ml) as compared to the noninfected ones (46.9±17.1 ng/ml), independently of Child-Pugh's classification. These differences persisted even after subdividing patients according to the presence of HCC. In conclusion, in anti-HCV positive cirrhotic patients H. pylori infection is associated to an impairment of cytochrome P-450 liver metabolic activity. Seroprevalence of H. pylori infection in HCC patients is similar to that observed in tumor-free cirrhotics.     

<Emphasis Type="Italic">Helicobacter</Emphasis> Genus DNA Fragments Are Commonly Detectable in Bile from Patients with Extrahepatic Biliary Diseases and Associated with Their Pathogenesis

Several Helicobacter species are known to colonize the biliary tract in animals and have been identified in the gallbladder bile of a high proportion of Chilean patients with gallbladder cancer. In this study, we tried to examine the presence of Helicobacter species in the bile to know their participation in the development of extrahepatic biliary diseases. DNA was extracted from 57 bile samples from 30 patients with benign biliary diseases (cholecystolithiasis and choledochocystolithiasis), 6 malignant biliary diseases (gallbladder cancer and common bile duct cancer), and 21 nonbiliary diseases. The presence of Helicobacter genus-, H. pylori-, H. hepaticus-, and H. bilis-specific 16S rRNA genes, the H. pylori urease A gene, and the H. pylori 26K protein gene in the bile was determined by PCR and sequencing analysis. Helicobacter genus DNA (shorter amplicons, 400 bp) was statistically frequently detected in biles from 53% (16/30) and 86% (5/6) of benign and malignant biliary diseases, compared with 9% (2/21) of nonbiliary diseases, but longer amplicons (1200 bp) were not detectable in any samples. The H. pylori urease A gene (nested amplicon) was also frequently found in bile, whether benign, malignant, or control, though neither H. pylori 16S rRNA nor the 26K protein gene was detectable in any bile samples. H. bilis-16S rRNA genes were detectable in only two cases. H. hepaticus was not detectable in any samples. DNA fragments of Helicobacter species other than H. pylori, H. hepaticus, and H. bilis are commonly detectable in the bile of patients with extrahepatic biliary diseases, whether benign or malignant, implying that the Helicobacter genus may be directly or indirectly involved in the pathogenesis of these diseases.     

Helicobacter pylori management in ASEAN: The Bangkok consensus report

Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa‐associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow‐up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.     

Increased Helicobacter felis colonization in male 129/Sv mice fails to suppress gastritis

Development of the pathologies associated with Helicobacter pylori infection, most seriously gastric adenocarcinoma, are a consequence of chronic inflammation, which both host and pathogen go to some lengths to minimize. Recently, we presented evidence that H. pylori can suppress the development of inflammation in its immediate microenvironment in the gastric mucosa of 129/Sv mice.

We have now extended this study by showing that H. felis, a gastric colonizing Helicobacter closely related to H. pylori, does not possess the same ability to suppress Helicobacter-induced gastritis in mice. Differences between these bacterial species may provide clues as to the mechanism behind the inflammation-regulating ability of H. pylori. Moreover, our demonstration that H. pylori but not H. felis can locally suppress inflammation in vivo may explain why H. felis infection induces superior levels of gastritis as compared with H. pylori infection of mice.     

A Nationwide Cohort Study Shows a Sex-Dependent Change in the Trend of Peptic Ulcer Bleeding Incidence in Korea between 2006 and 2015

Background/AimsThe incidence of peptic ulcer disease has decreased in past decades; however, the trends in peptic ulcer bleeding (PUB) are inconsistent among regions. This study aimed to investigate the trends in PUB incidence and the effect of risk factors on PUB in Korea.MethodsThe records of patients hospitalized with PUB from 2006 to 2015 were retrieved from the Korean National Health Insurance Service Database. Standardized incidences of PUB were calculated, and the clinical characteristics such as age, sex, Helicobacter pylori infection, drug exposure, comorbidities, and mortality were obtained.ResultsIn total, 151,507 hospitalizations with PUB were identified. The overall annual hospitalization rate was 34.98 per 100,000 person-years. The incidence of PUB showed no significant change from 2006 to 2008 and decreased from 2008 to 2015, with an annual change of –2.7% (p<0.05); however, this change was only significant in men. The incidence of PUB was higher in men than in women between 40 and 70 years old and higher in women than in men older than 80 years. From 2006 to 2015, the H. pylori infection rate increased significantly in patients with PUB; however, there was no significant change in exposure to nonsteroidal anti-inflammatory drugs or other drugs that increase the risk of PUB.ConclusionsOver the past decade, the incidence of PUB has decreased in a sex-specific manner. There has been a decreasing trend in the H. pylori infection rate and no change in exposure to drugs that increase the risk of PUB in Korea.     

Current progress toward eradicating Helicobacter pylori in East Asian countries: Differences in the 2013 revised guidelines between China,Japan, and South Korea

New 2013 guidelines on Helicobacter pylori(H. pylori) infection have been published in China, Japan, and South Korea. Like the previous ones, these new guidelines differ between the three countries with regard to the indications for H. pylori eradication, diagnostic methods, and treatment regimens. The most profound change among all of the guidelines is that the Japanese national health insurance system now covers the expenses for all infected subjects up to second-line treatment. This makes the Japanese indications for eradication much wider than those in China and South Korea. With regard to the diagnosis, a serum H. pylori antibody test is not recommended in China, whereas it is considered to be the most reliable method in Japan. A decrease relative to the initial antibody titer of more than 50% after 6-12 mo is considered to be the most accurate method for determining successful eradication in Japan. In contrast, only the urea breath test is recommended after eradication in China, while either noninvasive or invasive methods(except the bacterial culture) are recommended in South Korea. Due to the increased rate of antibiotics resistance, first-line treatment is omitted in China and South Korea in cases of clarithromycin resistance. Notably, the Japanese regimen consists of a lower dose of antibiotics for a shorter duration(7 d) than in the other countries. There is neither 14 d nor bismuth-based regimen in the first-line and second-line treatment in Japan. Such differences among countries might be due to differences in the approvals granted by the governments and national health insurance system in each country. Further studies are required to achieve the best results in the diagnosis and treatment of H. pylori infection based on cost-effectiveness in East Asian countries.     

Has Peptic Ulcer Disease Changed During the Past Ten Years in Korea? A Prospective Multi-center Study

Background The incidence of H. pylori-negative, idiopathic peptic ulcer disease (IPUD) seems to be increasing with the changing trends of PUD and H. pylori infection in some developed countries. Aim To investigate the changing trend of PUD and the prevalence of H. pylori infection during the last decade and the prevalence of IPUD in Korea. Methods We prospectively evaluated H. pylori infection and the characteristics of PUD in 895 patients with newly diagnosed PUD from September 2004 to February 2005. Results The H. pylori infection rate in PUD was 72.0% and the proportion of IPUD was 22.2%. The proportion of gastric ulcer (GU) has significantly increased (47.8% vs. 44.3%) and the proportion of duodenal ulcer (DU) has significantly decreased (38.9% vs. 44.9%) compared with ten years ago. The changing trend in the prevalence of H. pylori infection in GU and DU showed an increase in GU (66.1% vs. 73.1%, P = 0.014) and a decrease in DU (79.3% vs. 68.1%, P = 0.001). Conclusion Compared with our results of ten years ago, there has been a significant change in the distribution of PUD and in the prevalence of H. pylori infection in GU and DU. Patients with IPUD are not uncommon in Korea.     

Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: a prospective, randomized study

Background and Aims: The eradication rate of proton pump inhibitor (PPI)‐based triple therapy for Helicobacter pylori (H. pylori) infection has decreased, mainly due to increasing antibiotic resistance, especially against clarithromycin. It has been reported that a 10‐day sequential strategy can produce good outcomes. The aim of this prospective study was to assess the efficacy of sequential therapy as the first‐line treatment for the eradication of H. pylori in Korea. Methods: A total of 116 patients with proven H. pylori infection received 10‐day sequential therapy (20 mg rabeprazole and 1 g amoxicillin, twice daily for the first 5 days, followed by 20 mg rabeprazole, 500 mg clarithromycin, and 500 mg metronidazole, twice daily for the remaining 5 days); 130 patients received 7‐day triple therapy (20 mg rabeprazole, 500 mg clarithromycin, and 1 g amoxicillin, twice daily for 7 days). Eradication was evaluated by the ¹³C‐urea breath test, 4 weeks after the completion of treatment. Compliance and adverse events were assessed. Results: The eradication rates of 10‐day sequential therapy and PPI‐based triple therapy were 79.3% (92/116) and 63% (82/130) by intention‐to‐treat analysis, respectively (P = 0.005), and 81.9% (91/111) and 64.5% (82/127) by per protocol analysis, respectively (P = 0.003). Mild adverse events occurred in both therapy groups (27.5% vs 23.8%), but both treatments were well tolerated. Conclusion: The eradication rate of the 10‐day sequential therapy regimen was significantly higher than that of PPI‐based triple therapy in the Korean population. Ten‐day sequential therapy might be effective as a first‐line treatment for H. pylori infection in Korea.     

Diagnosis and treatment of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Opinion statement Helicobacter pylori infection remains a ubiquitous infection, especially in populations with poor socioeconomic conditions. Severe clinical outcomes of chronic infection include peptic ulcer disease and gastric cancer. Consensus meetings have developed guidelines for diagnosis, treatment, and management of H. pylori infection and related disorders in various populations. Clear benefits are obtained for H. pylori eradication in peptic ulcer disease and gastric mucosa-associated lymphoid tissue lymphoma. Most authorities agree that first-degree relatives of gastric cancer patients should undergo testing for H. pylori infection. H. pylori eradication in dyspepsia remains controversial. Global investigations continue to identify specific host and bacterial factors that are responsible for H. pylori-related inflammatory processes and development of clinical disease. Effective eradication regimens have been identified. The proton pump inhibitor (PPI)-based triple therapies are considered first-line therapy because of high patient compliance and good eradication rates. “Quadruple therapy” with bismuth-metronidazoletetracycline plus a PPI is another first-line therapy with a similar eradication rate. This therapy is preferred in patients with penicillin allergy or prior exposure to clarithromycin. Rescue regimens are being developed because of rising antimicrobial resistance to metronidazole and clarithromycin in H. pylori strains. Emerging rescue combination therapies include furazolidone, rifabutin, and quinolones. These combination regimens are still preliminary and should be reserved for patients who have failed first-line therapies. Vaccine development remains elusive.     

Non-Helicobacter Bacterial Flora Rarely Develops in the Gastric Mucosal Layer of Children

Non-Helicobacter bacteria can be cultured from the gastric mucosa in adults but in children, there are no studies about such microflora. The purpose of this study, therefore, was to clarify whether gastric biota develops in children. In 10 children and 10 adults or elderly (5 H. pylori-infected and 5 uninfected in each group), biopsy specimens of the gastric antrum and corpus and gastric juice were studied for bacterial examinations and the data were compared between both age groups in relation to H. pylori status and luminal pH. Bacterial genera and species were analyzed using both culture and real-time polymerase chain reaction (PCR) with the 52 genus- and species-specific primer sets. Non-Helicobacterbacteria in the mucosa were cultured from all adult patients, whereas microorganisms were cultured in only one child (p < .001). Gastric pH was lower in children (median, 1.4) than in adults (median, 2.6) (p < .005). The grade of endoscopic gastric atrophy was moderate or severe in 8 adults, but absent or mild in all 10 children. Among adults, there was a significant positive correlation between gastric pH and total bacterial counts of both the mucosa and juice. These data indicate that impaired gastric acid secretion associated with long-term H. pylori infection enables non-Helicobacter bacteria to colonize in the human stomach. Such microorganisms rarely colonize in the gastric mucosa in children regardless of H. pylori status.     

Helicobacter pylori–can the mechanisms of pathogenesis guide us towards novel strategies for treatment and prevention?

Falk P (Gastrointestinal Research Laboratory, Department of Medicine, the Karolinska Institute, Stockholm, Sweden and the Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, USA). Helicobacter pylori—Can the mechanism of pathogenesis guide us towards novel strategies for treatment and prevention? (Review). J Intern Med 1996; 240: 319–32. Helicobacter pylori establishes a chronic infection in the stomach of humans. The infection is associated with a low grade inflammatory response in the epithelium that can develop into chronic active gastritis, peptic ulcer disease or neoplasia. Antibiotics have dramatically decreased the rate of recurrence of peptic ulcers. However, antibiotic resistance is already evident, casting doubts on the future efficacy of these strategies. The link between childhood infection and severe health problems, including increased risk for gastric tumours motivate efforts to develop vaccines. Characterization of the molecular mechanisms of pathogenesis will pave the way for novel strategies for treatment and prevention of H. pylori infection.