Rate and durability of the clearance of HBsAg in Alaska Native persons with long-term HBV infection: 1982-2019.

BACKGROUND AND AIMS: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population. APPROACH AND RESULTS: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019. The original group in this cohort was identified during a 1982 to 1987 population-based screening for 3 HBV serologic markers in 53,000 Alaska Native persons. With close to 32,000 years of follow-up, we assessed the frequency and duration of HBsAg seroclearance (HBsAg-negative for > 6 mo). We examined factors associated with HBsAg clearance and followed persons for a median of 13.1 years afterward to assess the durability of HBsAg clearance. Among 1079 persons with an average length of follow-up of 33 years, 260 (24%) cleared HBsAg at a constant rate of 0.82% per person/per year. Of the 260 persons who cleared, 249 (96%) remained HBsAg-negative, while 11 persons had ≥ 2 transient HBsAg-positive results in subsequent follow-up. CONCLUSIONS: Of the patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and nontreated patients and lasted, on average, over 13 years without seroreversion.

Impact of HEART Score Decision Aid on Coronary Computed Tomography Angiography Utilization and Diagnostic Yield in the Emergency Department.

OBJECTIVE: Emergency physicians are challenged to efficiently and reliably risk stratify patients presenting with chest pain (CP) to optimize diagnostic testing and avoid unnecessary hospital admissions. The objective of our study was to evaluate the impact of a HEART score-based decision aid (HSDA) integrated in the electronic health record on coronary computed tomography angiography (CCTA) utilization and diagnostic yield in adult emergency department (ED) CP patients with suspected acute coronary syndrome. METHODS: We conducted a before and after study to determine whether implementation of a mandatory computerized HSDA would reduce CCTA utilization in ED CP patients and improve the diagnostic yield of obstructive coronary artery disease (CAD) (≥50%). We included all adult ED CP patients with suspected acute coronary syndrome during the first 6 months of 2018 (before) and 2020 (after) at a large academic center. CCTA utilization and obstructive CAD yield were compared in patients before and after implementing the HSDA using χ2 tests. Secondarily, we assessed the association of HEART scores and CCTA results. RESULTS: Of the 3095 CP patients during the before study period, 733 underwent CCTA. Of the 2692 CP patients during the after study period, 339 underwent CCTA. CCTA utilization before and after HSDA was 23.4% [95% confidence interval (95% CI), 22.2-25.2] and 12.6% (95% CI, 11.4-13.0), respectively; mean difference was 11.1% (95% CI, 0.9-13.0). Among 1072 patients undergoing CCTA, mean (SD) age and percent females before versus after HSDA were 54 (11) versus 56 (11) years and 50% versus 49%, respectively. We included 1014 patients (686 before and 328 after) for the yield analysis. Obstructive CAD was present in 15% (95% CI, 12.7-17.9) and 20.1% (95% CI, 16.1-24.7) before and after HSDA, respectively; mean difference was 4.9% (95% CI, 0.1-10.1). CONCLUSIONS: Implementation of a mandatory electronic health record HSDA aid reduced ED CCTA utilization by half and improved the diagnostic yield.

An Evidence-based Practical Guide to Vaccination for Hepatitis B Virus.

The hepatitis B virus (HBV) is highly infectious, with over 292 million chronically infected people worldwide and up to 2.4 million in the United States. Following infection, clinically silent liver damage can ensue, but symptoms or signs of advanced disease, including cirrhosis and hepatocellular carcinoma, can take decades to emerge. HBV has the heaviest public health burden of all hepatitis viruses and has now surpassed other major communicable diseases (eg, HIV, diarrheal disease, malaria, tuberculosis) as a leading cause of death globally. Preventing transmission is essential, and efforts are in place to reinforce screening, vaccination, and routine follow-up. Three safe and effective vaccines are available in the United States and other countries for HBV prevention, and the benefits of vaccination in preventing infection and its sequelae have been substantiated. For the first time in over 25 years, a new Food and Drug Administration-approved vaccine is available that offers a high degree of immunogenicity after 2, rather than 3, injections. Persistent challenges include the underutilization of vaccination, choice of vaccine, incomplete vaccinations, varying needs in different populations, management of nonresponders or those with undocumented or incompletely documented vaccination courses, and questions about whether and when booster injections may be needed. A panel of US academic hepatologists with expertise and experience in preventing and managing HBV infection have collaborated to write this practical clinical paper intended to guide clinicians in vaccinating for HBV and address questions that regularly arise in the clinic.

Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster dose.

BACKGROUND AND AIMS: The duration of protection from hepatitis B vaccination in children and adults is not known. In 1981, we used three doses of plasma-derived hepatitis B vaccine to immunize a cohort of 1578 Alaska Native adults and children from 15 Alaska communities who were ≥6 months old. APPROACH AND RESULTS: We tested persons for antibody to hepatitis B surface antigen (anti-HBs) levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received one booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days postbooster. Among the 320 recruited, 112 persons had not participated in the 22- or 30-year follow-up study (group 1), and 208 persons had participated but were not given an HBV booster dose (group 2). Among the 112 persons in group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml. Among group 1, 73.7% (28 of 38) of persons available for a booster dose responded to it with an anti-HBs level ≥10 mIU/ml at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 35 years. Among 8 persons who tested positive for antibody to hepatitis B core antigen, none tested positive for HBsAg or HBV DNA. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate that 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time.

Racial/ethnic disparities in hepatocellular carcinoma incidence and mortality rates in the United States, 1992-2018.

BACKGROUND AND AIMS: HCC is characterized by racial/ethnic disparities in rates. Recent USA reports suggest that incidence has begun to decline, but it is not clear whether the declines have occurred among all groups, nor whether mortality has declined. Thus, the current study examined USA incidence and mortality between 1992 and 2018. APPROACH & RESULTS: HCC incidence and incidence-based mortality data from the Surveillance, Epidemiology, and End Results program were used to calculate age-standardized rates by race/ethnicity, sex, and age. Trends were analyzed using joinpoint regression to estimate annual percent change (APC). Age-period-cohort models assessed the effects on trends of age, calendar period, and birth cohort. Overall, HCC incidence significantly declined between 2015 and 2018 (APC, -5.6%). Whereas most groups experienced incidence declines, the trends were most evident among Asians/Pacific Islanders, women, and persons <50 years old. Exceptions were the rates among non-Hispanic Black persons, which did not significantly decline (APC, -0.7), and among American Indians/Alaska Natives, which significantly increased (APC, +4.3%). Age-period-cohort modeling found that birth cohort had a greater effect on rates than calendar period. Among the baby boom cohorts, the 1950-1954 cohort had the highest rates. Similar to the overall incidence decline, HCC mortality rates declined between 2013 and 2018 (APC, -2.2%). CONCLUSIONS: HCC incidence and mortality rates began to decline for most groups in 2015, but persistent differences in rates continued to exist. Rates among non-Hispanic Black persons did not decline significantly, and rates among American Indians/Alaska Natives significantly increased, suggesting that greater effort is needed to reduce the HCC burden among these vulnerable groups.

Mortality among Alaska Native Adults with Confirmed Hepatitis C Virus Infection Compared with the General Population in Alaska, 1995-2016.

BACKGROUND: Hepatitis C virus (HCV) infection incidence rates in the United States have increased since 2010 as a byproduct of the opioid crisis despite the introduction of direct-acting antiviral agents in 2013. HCV infection is associated with higher rates of liver-related and nonhepatic causes of death. METHODS: This study compared demographic characteristics and age-adjusted death rates from 1995 to 2016 among Alaska Native (AN) adults infected with HCV (AK-HepC) to rates among the AN and non-AN adult populations living in Alaska. Liver-related disease (LRD) and other disease-specific age-adjusted death rates were compared between the populations. RESULTS: The all-cause death rate among the AK-HepC cohort was 2.2- and 3.4-fold higher than AN and non-AN adults, respectively, and remained stable over time in all populations. The LRD death rate among the AK-HepC cohort was 18- and 11-fold higher than the non-AN and AN, respectively. The liver cancer rate among the AK-HepC cohort was 26-fold higher compared to the Alaska statewide population. The AK-HepC cohort had elevated rates of death associated with nonhepatic diseases with circulatory disease having the highest rate in all populations. Among liver cancer deaths in the AK-HepC cohort, 32% had HCV listed as a contributing cause of death on the death certificate. CONCLUSIONS: Death rates in the AK-HepC cohort remained stable since 1995 and higher compared to the general population. People with HCV infection had an elevated risk for all-cause, liver-related, and nonhepatic causes of death. Hepatitis C infection may be underrepresented as a cause of mortality in the United States.

The Alaska Native/American Indian experience of hepatitis C treatment with sofosbuvir-based direct-acting antivirals.

BACKGROUND: Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir- based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people. METHODS: AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir. RESULTS: We included 501 patients with a mean age of 54.3 (range 21.3-78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria. CONCLUSIONS: In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status.

HBV Genotype: A Significant Risk Factor in Determining Which Patients With Chronic HBV Infection Should Undergo Surveillance for HCC: The Hepatitis B Alaska Study.

BACKGROUND AND AIMS: Information is limited regarding HBV genotype and the outcome of chronic HBV (CHB) infection. We examined the effect of HBV genotype on HCC occurrence in Alaska Native (AN) persons with CHB, where five HBV genotypes are found: A2, B6, C2, D, and F1. APPROACH AND RESULTS: We calculated HCC incidence per 1,000 person-years of follow-up to determine which groups by age, sex, and genotype met current American Association for the Study of Liver Diseases (AASLD) HCC surveillance criteria. We used Poisson regression to compare HCC risk by genotype, age, sex, and Alaska region. Incidence of HCC was calculated using the sex-specific AASLD cutoff recommended for the Asian population of 50 years for women and 40 years for men. HCC screening was conducted semiannually using alpha-fetoprotein levels and abdominal ultrasound. Among 1,185 AN persons, median follow-up was 35.1 years; 667 (63%) were male. The HBV genotype distribution was 49% D, 18% F, 13% A, 6% C, 3% B, 0.1% H, and 12% undetermined. Sixty-three cases of HCC occurred. HCC incidence for genotype F was 5.73 per 1,000 person-years of follow-up, followed by 4.77 for C, 1.28 for A, 0.47 for D, and 0.00 for B. The HCC risk was higher for genotypes F (relative rate [RR], 12.7; 95% CI, 6.1-26.4), C (RR, 10.6; 95% CI, 4.3-26.0), and A (RR, 2.9; 95% CI, 1.0-8.0) compared to genotypes B and D. Among men < 40 years of age and women < 50 years of age, genotype F had the highest incidence (4.79/1,000 person-years). CONCLUSIONS: HBV genotype was strongly associated with HCC. HBV genotype should be considered in risk factor stratification.

Hepatitis A vaccine immunogenicity 25 years after vaccination in Alaska.

The hepatitis A vaccine is recommended for all children greater than or equal to 1 year of age, however, the duration of vaccine protection is unknown and protection through adulthood is crucial to prevent symptomatic hepatitis later in life. We report on 25 years of follow-up of a cohort of Alaska Native individuals who were vaccinated in early childhood. We assessed the duration of vaccine protection by calculating the geometric mean concentration and proportion of participants with protective levels of IgG antibody to hepatitis A virus (anti-HAV) (≥20 mIU/mL) every 2 to 3 years. We estimated the amount of time until the anti-HAV dropped below protective levels using survival analyses. At 25 years, 43 of the original 144 participants were available, mean anti-HAV levels were 91.5 mIU/mL, and 35 (81.4%) had protective levels of anti-HAV. Using data from all persons and all time points, a survival analysis estimated 78.7% of participants had protective levels of anti-HAV at 25 years. The high level of protective antibodies in this cohort indicate that supplemental doses of hepatitis A vaccine are not needed 25 years after completion of the vaccine series.

Vaccination Status of Alaska Native Persons With Hepatitis A Virus Infection-Alaska, 1996-2018.

Following increases in reported cases of hepatitis A, we assessed the impact of hepatitis A vaccine in Alaska Native persons. During 1996-2018, only 6 cases of hepatitis A were identified, all in unvaccinated adults. Populations can be protected against hepatitis A by achieving sufficient vaccination coverage over time.

Presence of cagPAI genes and characterization of vacA s, i and m regions in Helicobacter pylori isolated from Alaskans and their association with clinical pathologies.

Introduction. Gastric cancer is a health disparity in the Alaska Native people. The incidence of Helicobacter pylori infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain.Aim. To genotype the vacA s, m and i and cag pathogenicity island (cagPAI) genes in H. pylori from Alaskans and investigate associations with gastropathy.Methodology. We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998-2005 and patients with gastric cancer in 2011-2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the cagPAI, the cagA, cagE, cagT and virD4 genes and to genotype the vacA s, m and i regions.Results. We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. H. pylori isolates from 150 (57%) people had an intact cagPAI; those were associated with a more severe gastropathy (P≤0.02 for all comparisons). H. pylori isolates from 77 % of people had either the vacA s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. vacA s1/i1/m1 was associated with a more severe gastropathy (P≤0.03 for all comparisons).Conclusions. In this population with high rates of gastric cancer, we found that just over half of the H. pylori contained an intact cagPAI and 40 % had the vacA s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy.

Cascade of Care for Alaska Native People With Chronic Hepatitis C Virus Infection: Statewide Program With High Linkage to Care.

Most persons with chronic hepatitis C virus (HCV) infection in the United States are undiagnosed or linked to care. We describe a program for the management of Alaska Native patients infection utilizing a computerized registry and statewide liver clinics resulting in higher linkage to care (86%) than national estimates (~25%).

Observed Changes in Natural Killer and T cell Phenotypes with Evaluation of Immune Outcome in a Longitudinal Cohort Following Sofosbuvir-Based Therapy for Chronic Hepatitis C Infection.

BACKGROUND: Chronic hepatitis C virus (HCV) infection diminishes immune function through cell exhaustion and repertoire alteration. Direct acting antiviral (DAA)-based therapy can restore immune cell subset function and reduce exhaustion states. However, the extent of immune modulation following DAA-based therapy and the role that clinical and demographic factors play remain unknown. METHODS: We examined natural killer (NK) cell, CD4+, and CD8+ T cell subsets along with activation and exhaustion phenotypes across an observational study of sofosbuvir-based treatment for chronic HCV infection. Additionally, we examined the ability of clinical variables and duration of infection to predict 12 weeks of sustained virologic response (SVR12) immune marker outcomes. RESULTS: We show that sofosbuvir-based therapy restores NK cell subset distributions and reduces chronic activation by SVR12. Likewise, T cell subsets, including HCV-specific CD8+ T cells, show reductions in chronic exhaustion markers by SVR12. Immunosuppressive CD4+ regulatory T cells decrease at 4-weeks treatment and SVR12. We observe the magnitude and direction of change in immune marker values from pretreatment to SVR12 varies greatly among participants. Although we observed associations between the estimated date of infection, HCV diagnosis date, and extent of immune marker outcome at SVR12, our regression analyses did not indicate any factors as strong SVR12 outcome predictors. CONCLUSION: Our study lends further evidence of immune changes following sofosbuvir-based therapy. Further investigation beyond SVR12 and into factors that may predict posttreatment outcome is warranted.

Hepatitis C in pregnant American Indian and Alaska native women; 2003-2015.

Recent reports have found a rise in Hepatitis C virus (HCV) infection in reproductive age women in the USA. Surveillance data suggests one group that is at increased risk of HCV infection is the American Indian and Alaska Native population (AI/AN). Using the National Center for Health Statistics (NCHS) birth certificate and the Indian Health Services, Tribal, and Urban Indian (IHS) databases, we evaluated reported cases of HCV infection in pregnant women between 2003 and 2015. In the NCHS database, 38 regions consistently reported HCV infection. The percentage of mothers who were known to have HCV infection increased between 2011 and 2015 in both the AI/AN population (0.57% to 1.19%, p < 0.001) and the non-AI/AN population (0.21% to 0.36%, p < 0.001). The IHS database confirmed these results. Individuals with hepatitis B infection or intravenous drug use (IDU) had significantly higher odds of HCV infection (OR 16.4 and 17.6, respectively). In total, 62% of HCV-positive women did not have IDU recorded. This study demonstrates a significant increase in the proportion of pregnant women infected with HCV between 2003 and 2015. This increase was greater in AI/AN women than non-AI/AN women. This highlights the need for HCV screening and prevention in pregnant AI/AN women.

Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission.

Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.

An Association Between Core Mutations in Hepatitis B Virus Genotype F1b and Hepatocellular Carcinoma in Alaskan Native People.

Hepatitis B virus (HBV) genotype F1b infection is strongly associated with hepatocellular carcinoma (HCC) in young Alaskan Native (AN) people. However, the mechanisms by which genotype F1b causes HCC are unclear. Here, we analyzed the clinical and virological significance of genotype F1b in long-term serial samples from 20 HCC patients with HBV infection. Complete sequence analyses revealed that all isolates were genotype F1b. In the HCC patients, T1938C and A2051C mutations in the core region had accumulated significantly with A1762T/G1764A mutations in the basal core promoter (BCP) region and G1896A mutation in the precore (PC) region. Several HBV clones containing the core mutations were examined for their replication efficiency and core stability in vitro. Clones containing the A2051C mutation replicated more efficiently than the wild type in association with enhanced stability of core protein dimerization. In chimeric mice with human hepatocytes carrying BCP/PC/2051 mutant but not with wild-type virus, liver fibrosis was induced in association with high levels of serum HBV DNA and hepatitis B surface antigen. Interestingly, microarray analysis and validation study showed that five genes associated with cell proliferation or carcinogenesis, v-myc avian myelocytomatosis viral oncogene homolog, Grb2-associated binding protein 2, bradykinin receptor B2, follistatin, and mitogen-activated protein kinase kinase kinase 8, were significantly up-regulated in human hepatocytes infected with genotype F1b, particularly the BCP/PC/2051 mutant, compared with other genotypes. Conclusion: We have identified an association between Alaska-specific core mutations and HCC development in AN people infected with genotype F1b; accumulation of these core mutations during the course of chronic infection with genotype F1b would contribute to HCC development in AN people earlier in life.

Summary of available surveillance data on hepatitis C virus infection from eight Arctic countries, 2012 to 2014.

We summarised available hepatitis C virus (HCV) surveillance data for 2012-14 from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template by email to public health authorities in all jurisdictions. Population statistics obtained from census sources for each country were used to estimate rates of reported acute and chronic/undifferentiated HCV cases. Seven countries with Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the United States, represented by the state of Alaska), including three Canadian territories and one province, as well as 11 Russian subnational Arctic regions, completed the data collection template. Data on acute HCV infection during 2014 was available from three Arctic countries and all Russian Arctic regions (rate range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian Republic of Komi). The rate of people with chronic/undifferentiated HCV infection in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most countries/regions, the majority of HCV-infected people were male and aged 19-64 years. Differences in surveillance methods preclude direct comparisons of HCV surveillance data between Arctic countries/regions. Our data can inform future efforts to develop standardised approaches to HCV surveillance in the Arctic countries/regions by identifying similarities/differences between the surveillance data collected.

H. pylori-associated pathologic findings among Alaska native patients.

Helicobacter pylori infection is common among Alaska native (AN) people, however scant gastric histopathologic data is available for this population. This study aimed to characterise gastric histopathology and H. pylori infection among AN people. We enrolled AN adults undergoing upper endoscopy. Gastric biopsy samples were evaluated for pathologic changes, the presence of H. pylori, and the presence of cag pathogenicity island-positive bacteria. Of 432 persons; two persons were diagnosed with gastric adenocarcinoma, two with MALT lymphoma, 40 (10%) with ulcers, and 51 (12%) with intestinal metaplasia. Fifty-five per cent of H. pylori-positive persons had cag pathogenicity island positive bacteria. The gastric antrum had the highest prevalence of acute and chronic moderate-severe gastritis. H. pylori-positive persons were 16 and four times more likely to have moderate-severe acute gastritis and chronic gastritis (p < 0.01), respectively. An intact cag pathogenicity island positive was correlated with moderate-severe acute antral gastritis (53% vs. 31%, p = 0.0003). H. pylori-positive persons were more likely to have moderate-severe acute and chronic gastritis compared to H. pylori-negative persons. Gastritis and intestinal metaplasia were most frequently found in the gastric antrum. Intact cag pathogenicity island positive was correlated with acute antral gastritis and intestinal metaplasia.