Disease trends after Helicobacter pylori eradication based on Japanese nationwide claims and the health check-up database

BACKGROUND Helicobacter pylori(H.pylori)infection is a risk factor for many diseases,including peptic ulcer disease and gastric cancer.While H.pylori eradication therapy can prevent these diseases,potentially unfavorable effects of eradication therapy have also been reported in some diseases,such as gastroesophageal reflux disease(GERD),Barrett’s esophagus(BE),inflammatory bowel disease(IBD),allergic diseases,and metabolic diseases.Consequently,both positive and negative impacts should be considered when assessing the effects of H.pylori eradication therapy.AIM To compare the incidence of these diseases before and after H.pylori eradication and to comprehensively assess its effects.METHODS This retrospective cohort study used a Japanese nationwide health claims database(April 2009-March 2020),developed by the Japanese Ministry of Health,Labour and Welfare.The database contained almost all health insurance claims data issued in Japan,and specific health check-up data for individuals who took the check-ups.Descriptive statistics were used for the analyses.Patients who received primary eradication therapy were defined as those prescribed medication for H.pylori eradication.New diagnoses,defined as incidence of upper gastrointestinal diseases and IBD,and prevalence of allergic diseases were compared before and after eradication.The incidence and prevalence of each disease were also compared between the 3-year period before eradication(from the 4th to the 2nd year prior to the year of eradication)and the 3-year period after eradication(from the 1st to the 3rd year after the year of eradication)based on the age category and calendar year and month.Changes in body mass index and proportion of patients with metabolic syndrome(MS)were examined before and after eradication.RESULTS We identified 5219731 patients who received primary eradication therapy.The 65-69 years age group had the greatest number of patients in both sexes.There was no significant increase in the incidence of GERD after eradication when considering the effects of aging and reporting period.However,the incidence of BE was higher in the 3-year period after eradication than in the 3-year period before eradication for all age categories(0.02%-0.10%vs<0.01%-0.05%).The incidence of IBD and prevalence of allergic disease were also higher after eradication.In contrast,the incidence of gastric and duodenal ulcers and gastritis was reduced after eradication.In patients with at least one entry of health check-up data(1701111 patients),the percentage of patients with MS showed a slight increase following eradication(11.0%in the year of eradication and 12.2%after 5 years).CONCLUSION The results suggest that H.pylori eradication therapy reduces peptic ulcers and gastritis;however,it is associated with increased incidence of several other chronic diseases.

Latest insights into the effects of Helicobacter pylori infection on gastric carcinogenesis

There appears to be the strong association between Helicobacter pylori （H pylori） and gastric cancer. We reviewed the latest evidences about the effects of H pylori infection on gastric carcinogenesis, classified into epidemiology, dynamics of gastric mucosal changes, DNA damages, virulence factors, host factors, and source of gastric malignancy. Through the considerable progress made in research into virulence factors resulting from differences between Hpylori strains, such as cagA positivity, as well as into host factors, such as gene polymorphisms, a diverse spectrum of H pyloriassociated diseases, including gastric cancer, is beginning to lend itself to elucidation. The impact of the novel hypothesis advanced by Houghton et al proposing bonemarrow derived stem cells （BMDC） as a potential source of gastric malignancy on evolving research remains to be seen with interest. Further progress in research into H pylori eradication as a viable prophylaxis of gastric cancer, as well as into the mechanisms of gastric carcinogenesis, is to be eagerly awaited for the current year and beyond.

Helicobacter pylori-infected animal models are extremely suitable for the investigation of gastric carcinogenesis

Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helocobacter pylori（H pylori）, several animal models with H pylori infection have been developed to confirm the association between Hpylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53 mutation after long-term infection of Hpylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methyl- N-nitrosourea and N-methyl-N-nitro-N＇-nitrosoguanidine. The histopathological changes of these animal models after H pylori inoculation are closely similar to those in human beings with Hpylori infection. Eradication therapy attenuated the development of gastric cancer in Hpylori- infected Mongolian gerbil. Although several features of animal models differ from those seen in human beings, these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of Hpylon infection and assist the planning of eradication therapy to prevent gastric carcinoma.

Expression of mutant type-p53 products in H pylori-associated chronic gastritis

AIM： To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and aEer H pylori eradication therapy. METHODS： 53 subjects （36 male, 17 female, mean age ± SEM, 57.1 ± 12.1） undergoing endoscopic examination were included in this study. 42 of 53 patients were H pylori-positive, and 11 were H pylorinegative. All H pylori-positive patients had successful eradication therapy. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system. Immunohistochemical studies were performed by using primary antibodies against p53 （DO-7 and PAb240）. RESULTS： p53 （DO-7 and PAb240） immunoreactivity was shown in the neck region of the gastric pits, however, quite a few cells were found to be immunopositive for p53 （PAb240）in the Hpylori-infected gastric mucosa. The proportion of patients immunopositive for p53 （PAb240） was significantly reduced 6 mo after eradication [28/42 （66.7%） to 6/42 （14.3%）] （P 〈 0.05）, while the biopsies taken from H pylori-negative patients showed no immunoreactivity for p53 （PAb240）. p53 （PAb240）-positive patients were divided into two groups by the number of positive cells detected： one with more than six positive cells per 10 gastric pits （group A, n = 12）, and the other with less than five positive cells per 10 gastric pits （group B, n = 30）. Atrophy scores in group A were significant higher than those in group B at the greater curvature of the antrum （group A： 2.00 ± 0.14 vs group B： 1.40 ± 0.15, P = 0.012）, the lesser curvature of the corpus （group A： 2.00 ± 0.21 vs group B： 1.07 ± 0.23, P = 0.017）, and the greater curvature of the corpus （group A： 1.20 ± 0.30 vs group B： 0.47 ±0.21, P = 0.031）. Group A showed significant higher intestinal metaplasia scores than group B only at the lesser curvature of the antrum （group A： 2.10 ± 0.41 vs group B： 1.12 ± 0.29, P = 0.035）. CONCLUSION： H pylori-associated chronic gastritis expressed the mutant-type p53, which was significantly associated with more severe atrophic and metaplastic changes. Hpylori eradication led to a significant reduction in the expression of the mutant-type p53. It is considered that H pylori-infected chronic gastritis is associated with a genetic instability that leads to gastric carcinogenesis, and H pylori eradication may prevent gastric cancer.

Influence of proton pump inhibitor treatment on Helicobacter pylori stool antigen test

AIM: To investigate the effects of proton pump inhibitor (PPI) treatment on stool antigen test using the TestMate pylori enzyme immunoassay. METHODS: This study assessed 28 patients [16 men and 12 women; mean age (63.1 ± 5.9) years; range, 25-84 years] who underwent stool antigen test and urea breath test (UBT) before and after PPI administration. RESULTS: Using the UBT as the standard, the sensitivity, specif icity and agreement of the stool antigen test in all 28 patients were 95.2%, 71.4%, and 89.3%, respectively, before PPI administration, and 88.9%, 90.9%, and 89.3%, respectively, after PPI treatment. Mean UBT values were 23.98% ± 5.33% before and 16.19% ± 4.75% after PPI treatment and, in 15 patients treated for ≥ 4 wk, were signif icantly lower after than before 4 wk of PPI treatment (12.58% ± 4.49% vs 24.53% ± 8.53%, P = 0.048). The mean optical density (A450/630) ratios on the stool antigen test were 1.16 ± 0.20 before and 1.17 ± 0.24 after PPI treatment (P = 0.989), and were 1.02 ± 0.26 and 0.69 ± 0.28, respectively, in the group treated for > 4 wk (P = 0.099).

Two cases of adenocarcinoma occurring in sporadic fundic gland polyps observed by magnifying endoscopy with narrow band imaging

Gastric fundic gland polyps(FGPs) are common nonadenomatous gastric polyps arising from normal fundic mucosa without Helicobacter pylori(H. pylori) infection. Although systemic FGPs associated with familial adenomatous polyposis(FAP) often have dysplasia, there are few reports of dysplasia occurring in sporadic F G P s, e s p e c i a l l y w h e n d e t e c t e d b y m a g n i f y i n g endoscopy with narrow band imaging(ME-NBI). We experienced two cases of adenocarcinoma occurring in sporadic FGPs, and their ME-NBI findings were very useful for differentiating FGP with cancer from nondysplastic FGP. A 68-year-old man and a 63-year-old woman were referred to our institution for medical checkup. H. pylori was negative in both patients. Endoscopic examination revealed a small reddishpolypoid lesion on the anterior wall of the upper gastric body and several FGPs. ME-NBI showed an irregular microvascular architecture composed of closed loop- or open loop-type vascular components, plus an irregular microsurface structure composed of oval-type surface components which was different from that of FGPs. FAP was denied because of the absence of colon polyps and no familial history of FAP. Pathological diagnosis was adenocarcinoma occurring in sporadic FGP.

Aspirin-induced small bowel injuries and the preventive effect of rebamipide

AIM:To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide.METHODS:This study was conducted as a single-center,randomized,double-blind,cross-over,placebo-controlled study.Eleven healthy male subjects were enrolled.Each subject underwent video capsule endos-copy after 1 and 4 wk of taking aspirin and omepra-zole,along with either rebamipide or placebo therapy.The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk.RESULTS:The number of subjects with mucosal breaks(defined as multiple erosions and/or ulcers)were 1 at 1 wk and 1 at 4 wk on the jejunum,and 6 at 1 wk(P = 0.0061)and 7 at 4 wk on the ileum(P =0.0019).Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group(P = 0.0173 at 1 wk and P = 0.0266 at 4 wk).CONCLUSION:Longer-term,low-dose aspirin adminis-tration induced damage in the small bowel.Rebamipide prevented this damage,and may be a candidate drug for treating aspirin-induced small bowel complications.

Benefits of nucleos(t)ide analog treatments for hepatitis B virus-related cirrhosis

Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs(NUCs) became established as a safe and effective treatment for hepatitis B,it was difficult to suppress the activity of the hepatitis B virus(HBV). Currently,many patients withhepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time,and the effects,benefits,and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis,its natural course and survival,histological improvement after NUC treatments,treatment effects for decompensated cirrhosis,the incidence of hepatocellular carcinoma(HCC) after NUC treatments,and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements,including regression of fibrosis,that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied,and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However,cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments,and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur,it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved.

Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as melena with long-term survival: A case report and review of literature

BACKGROUND Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is a rare primary intestinal T-cell lymphoma,previously known as enteropathy-associated T-cell lymphoma type II.MEITL is an aggressive T-cell lymphoma with a poor prognosis and high mortality rate.The known major complications of MEITL are intestinal perforation and obstruction.Here,we present a case of MEITL that was diagnosed following upper gastrointestinal bleeding from an ulcerative duodenal lesion,with recurrence-free survival for 5 years.CASE SUMMARY A 68-year-old female was admitted to our hospital with melena and mild anemia.An urgent esophagogastroduodenoscopy(EGD)revealed bleeding from an ulcerative lesion in the transverse part of the duodenum,for which hemostatic treatment was performed.MEITL was diagnosed following repeated biopsies of the lesion,and cyclophosphamide,doxorubicin,vincristine,and prednisone(CHOP)chemotherapy was administered.She achieved complete remission after eight full cycles of CHOP therapy.At the last follow-up examination,EGD revealed a scarred ulcer and 18Fluorodeoxyglucose(18FDG)positron emission tomography/computed tomography showed no abnormal FDG accumulation.The patient has been in complete remission for 68 mo after initial diagnosis.CONCLUSION To rule out MEITL,it is important to carefully perform histological examination when bleeding from a duodenal ulcer is observed.

Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

AIM:To identify factors that influence long-term liver function following radiofrequency ablation(RFA)in patients with viral hepatitis-related hepatocellular carcinoma.METHODS:A total of 123 patients with hepatitis B virus-or hepatitis C virus-related hepatocellular carcinoma(HCC)(n=12 and n=111,respectively)were enrolled.Cumulative rates of worsening Child-Pugh(CP)scores(defined as a 2-point increase)were examined.RESULTS:CP score worsening was confirmed in 22patients over a mean follow-up period of 43.8±26.3mo.Multivariate analysis identified CP class,platelet count,and aspartate aminotransferase levels as significant predictors of a worsening CP score(P=0.000,P=0.011 and P=0.024,respectively).In contrast,repeated RFA was not identified as a risk factor for liver function deterioration.CONCLUSION:Long-term liver function following RFA was dependent on liver functional reserve,the degreeof fibrosis present,and the activity of the hepatitis condition for this cohort.Therefore,in order to maintain liver function for an extended period following RFA,suppression of viral hepatitis activity is important even after the treatment of HCC.

COVID-19 vaccination and liver disease

Various vaccines against severe acute respiratory syndrome coronavirus 2 have been developed in response to the coronavirus disease 2019(COVID-19)global pandemic,several of which are highly effective in preventing COVID-19 in the general population.Patients with chronic liver diseases(CLDs),particularly those with liver cirrhosis,are considered to be at a high risk for severe COVID-19 and death.Given the increased rates of disease severity and mortality in patients with liver disease,there is an urgent need to understand the efficacy of vaccination in this population.However,the data regarding efficacy and safety of COVID-19 vaccination in patients with CLDs is limited.Indeed,several organ-specific or systemic immune-mediated side effects following COVID-19 vaccination,including liver injury similar to autoimmune hepatitis,have been recently reported.Although the number of cases of vaccine-related liver injury is increasing,its frequency,clinical course,and mechanism remain unclear.Here,we review the current findings on COVID-19 vaccination and liver disease,focusing on:(1)The impact of COVID-19 in patients with CLD;(2)The efficacy,safety,and risk-benefit profiles of COVID-19 vaccines in patients with CLD;and(3)Liver injury following COVID-19 vaccination.

Rupture of small cystic pancreatic neuroendocrine tumor with many microtumors

Pancreatic neuroendocrine tumors(p NETs) are particularly rare. The various forms of PNETs, such as cystic degeneration, make differentiation from other similar pancreatic lesions difficult. We can detect small lesions by endoscopic ultrasound(EUS) and obtain preoperative pathological diagnosis by EUS-guided fine needle aspiration(FNA). We describe, here, an interesting case of p NET in a 42-year-old woman with no family history. Computed tomography and magnetic resonance imaging revealed an 18 mm × 17 mm cystic lesion with a nodule in the pancreatic tail. Two microtumors about 7 mm in diameter in the pancreatic body detected only by EUS, cystic rim and nodules all showed similar enhancement on contrast-harmonic EUS. Preoperative EUS-FNA of the microtumor was performed, diagnosing multiple p NETs. Macroscopic examination of the resected pancreatic body and tail showed that the cystic lesion had morphologically changed to a 13-mm main nodule, and 11 new microtumors(diameter 1-3 mm). Microscopically, all microtumors represented p NETs. From the findings of a broken peripheral rim on the main lesion with fibrosis, rupture of the cystic p NET was suspected. Postoperatively, pituitary adenoma and parathyroid adenoma were detected. The final diagnosis was multiple grade 1 p NETs with multiple endocrine neoplasia type 1. To the best of our knowledge, no case of spontaneous rupture of a cystic p NET has previously been reported in the English literature. Therefore, this case of very rare p NET with various morphological changes is reported.