Management of dyspepsia and Helicobacter pylori infection: the 2022 Indonesian Consensus Report.

Dyspepsia still becomes a major challenge in upper gastrointestinal disease in Indonesia. This disease often correlated with Helicobacter pylori infection. However, the prevalence of this bacterium is generally low in Indonesia. Therefore, several considerations should be taken into consideration during the management of dyspepsia and H. pylori infection. "Management of dyspepsia and H. pylori infection in Indonesia: The Indonesian consensus report" comprises information gathered from 22 gastroenterology centers across Indonesia. The experts gathered to evolve a consensus, that consists of the statements, grades of recommendations, evidence levels, and rationales for the dyspepsia and H. pylori infection management for daily clinical practice. The report explains several aspects from the updated epidemiology information to comprehensive management therapy. After the experts worked together on all statements in the recommendations, the results are presented with the final agreement as a consensus to help clinicians in understanding, diagnosing, and treating dyspepsia and H. pylori infection patients in daily clinical practice in Indonesia.

Comparison enteral superoxide dismutase 1 IU and 5 IU from Cucumis melo L.C extract combined with gliadin as an antioxidant and anti-inflammatory in LPS-Induced sepsis model rats.

Sepsis is a major cause of death in intensive care units whose development is supported by an imbalance of oxidative stress and antioxidant. Superoxide dismutase (SOD) is a primer endogen antioxidant that prevents reactive oxygen species (ROS). Extensive studies on animals and humans have examined Cucumis melo L.C, a cantaloupe rich in SOD, and its combination with gliadin. The studies aimed to determine the effect of enteral administration of Cucumis melo L.C. gliadin (CME-gliadin) 28 days before inducing sepsis in rats. This experimental study aimed to compare four groups of male Wistar rats, including negative and positive control rats and those supplemented with SOD CME-gliadin 1 IU/day and SOD CME-gliadin 5 IU/day. All rats were given the same standard, except the supplementation for 28 days. Sepsis was induced by intraperitoneal injection of LPS 10 mg/kg. Enteral administration of SOD - gliadin extract of CME-gliadin for 28 days was used as antioxidant prophylaxis against oxidative stress due to sepsis. The results showed that enteral administration of CME-gliadin of 1 IU/day and 5 IU/day significantly increased SOD levels based on examination after 14 and 28 days. Also, it significantly decreased MDA (p < 0.001), TNF-α (p < 0.001), and lactate levels in rats induced by sepsis. However, the increase in lactate levels was above >1.64 mmol/l, indicating a high mortality rate. There was no significant difference in SOD, MDA, TNF-α, and Lactate levels between SOD 1 IU and SOD 5 IU. This descriptive data show that SOD 5 IU has a better result in MDA, TNF-α, and Lactate levels than SOD 1 IU.

Urease Levels and Gastritis Stage in Dyspeptic Patients.

BACKGROUND: Dyspepsia is a frequent main symptom of inpatients and outpatients scenario in Indonesia. However, the number of endoscopy facilities are still low, thus the use of non-invasive method to detect gastritis is necessary. We measured the relationship between urease levels and the stage of gastritis in dyspeptic adult patients. METHODS: A cross-sectional study included outpatient dyspepsia patient from November 2018 to February 2019. We examined 14C-Urea Breath Test (UBT) and determined the stage of gastritis based on the Updated Sydney System classification. RESULTS: The urease level of acute and chronic gastritis positive patients were higher than negative patients (p = 0.001, r = 0.353; p <0.0001, r = 0.433, respectively). The AUC value of 14C-UBT to detect acute, chronic, and atrophic gastritis are 0.889, 0.632 and 0.544, respectively. The best cut-off points of 14C-UBT to predict acute gastritis was ≥26.50δ‰ with sensitivity and specificity being 88.89% and 63.95%, respectively. Whereas the best cut-off points for chronic gastritis was ≥34.50δ‰ with 82.89% sensitivity, 63.16% specificity. As for atrophic gastritis, it showed very low AUC value, hence it is not a sufficient test modality to predict atrophic gastritis cases. CONCLUSION: 14C-UBT is sufficient for predicting acute or chronic gastritis but not for atrophic gastritis.

Effectiveness and Efficacy of Vaccine on Mutated SARS-CoV-2 Virus and Post Vaccination Surveillance: A Narrative Review.

The ongoing COVID-19 pandemic, as a result of the SARS-CoV-2 virus, since December 2019, is a major health problem and concern worldwide. The pandemic has impacted various fields, from the social to the development of health science and technology. The virus has been mutating and thus producing several new variants, rushing research in the field of molecular biology to develop rapidly to overcome the problems that occur. Vaccine clinical studies are developing promptly with the aim of obtaining vaccines that are effective in suppressing the spread of the virus; however, the development of viral mutations raises concerns about the decreasing effectiveness of the resulting vaccine, which also results in the need for more in-depth studies. There have been 330 vaccines developed, including 136 clinical developments and 194 pre-clinical developments. The SARS-CoV-2 variant continues to evolve today, and it poses a challenge in testing the effectiveness of existing vaccines. This is a narrative review describing the emergence of the COVID-19 pandemic, development of vaccine platforms, identification of concerning mutations and virus variants in various countries of the world, and real-world monitoring of post-vaccination effectiveness and surveillance.

Serum pepsinogen level as a biomarker for atrophy, reflux esophagitis, and gastric cancer screening in Indonesia.

Background: Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. Materials and Methods: We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Results: Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Conclusion: Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.

Current Status, Distribution, and Future Directions of Natural Products against Colorectal Cancer in Indonesia: A Systematic Review.

In 2020, an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths have occurred worldwide, with colorectal cancer ranking as the third most frequently diagnosed (10.0%). Several attempts have been conducted against cancer, including surgery, radiation, monoclonal antibodies, and chemotherapy. Many people choose natural products as alternatives against cancer. These products will not only help in human life preservation but also work as a source of up-to-date information, leading people away from incorrect information. We discuss the current status, distribution, and future implications of protecting populations with natural products as an alternative against colorectal cancer in Indonesia. Thirty-eight studies were included in this review for data extraction. The distribution of natural products in Indonesia that have potential activity against colorectal cancer cells was predominated by terpenoids, followed by phytosterols, phenolics, alkaloids, and polyisoprenoids. The type of cell line utilized in the cytotoxic activity analysis of natural products was the WiDr cell line, followed by HT-29 cells and HCT-116 cells. This review showed that MTT in vitro assay is a general method used to analyze the cytotoxic activity of a natural product against colorectal cancer cells, followed by other in vitro and in vivo methods. The systematic review provided predictions for several secondary metabolites to be utilized as an alternative treatment against colorectal cancer in Indonesia. It also might be a candidate for a future co-chemotherapy agent in safety, quality, and standardization. In addition, computational methods are being developed to predict the drug-likeness of compounds, thus, drug discovery is already on the road towards electronic research and development.

Vascular Endothelial Growth Factor (VEGF) and Neopterin Levels in Children with Steroid-sensitive and Steroid-resistant Nephrotic Syndrome.

BACKGROUND: The most common glomerular disease in children is nephrotic syndrome. Steroid-resistant nephrotic syndrome tends to have a worse disease course, which bears a significant risk of chronic kidney disease in children. OBJECTIVE: To compare VEGF and neopterin levels between children with steroid-sensitive nephrotic syndrome (SSNS), steroid-resistant nephrotic syndrome (SRNS), and also healthy (control) children. METHODS: This cross-sectional study was conducted at H. Adam Malik General Hospital, Indonesia from January to December 2018. There were 160 children aged 1 to 8 years with confirmed nephrotic syndrome and without end-stage renal disease and systemic diseases, divided into SSNS, SRNS, and control groups. Data regarding age, gender, urine albumin creatinine ratio (UACR), serum albumin, total cholesterol, urea, creatinine, VEGF, and neopterin levels were collected. A p-value of less than 0.05 is considered statistically significant. RESULTS: There were no differences between groups in gender (p = 0.269) and age (p = 0.375), but there was significant difference of UACR, albumin level, total cholesterol level, and VEGF level between groups, (all p< 0.001). There was a moderate positive correlation between VEGF level and UACR (r(158) = 0.439, p< 0.001) and a moderate negative correlation between neopterin level and albumin level (r(158)= -0.312, p = 0.005). CONCLUSION: There were no differences in serum VEGF and neopterin levels between steroid-sensitive and steroid-resistant nephrotic syndrome groups. Serum VEGF level was positively correlated with UACR while serum neopterin level was negatively correlated with serum albumin level.

Diagnostic Value of 14C Urea Breath Test for Helicobacter pylori Detection Compared by Histopathology in Indonesian Dyspeptic Patients.

PURPOSE: Histopathology method is often used as a gold standard diagnostic for Helicobacter pylori infection in Indonesia. However, it requires an endoscopic procedure which is limited in Indonesia. A non-invasive method, such as 14C Urea Breath Test (UBT), is more favorable; however, this particular method has not been validated yet. PATIENTS AND METHODS: A total of 55 dyspeptic patients underwent gastroscopy and 14C-UBT test. We used Heliprobe® UBT for UBT test. As for the histology, May-Giemsa staining of two gastric biopsies (from the antrum and corpus) were evaluated following the Updated Sydney System. RESULTS: The Receiver Operating Characteristics analysis showed that the optimum cut-off value was 57 with excellence Area under Curve = 0.955 (95% CI = 0.861-1.000). By applying the optimum cut-off value, Heliprobe® UBT showed 92.31% for sensitivity, 97.62% for specificity, 92.31% for positive predictive value, 97.62% for negative predictive value, 38.77 for positive likelihood ratio, 0.0788 for negative likelihood ratio, and 96.36% for the accuracy. CONCLUSION: The 14C-UBT is an accurate test for H. pylori diagnosis with excellent sensitivity, specificity, and accuracy. The different optimum cut-off points suggested that a validation is absolutely necessary for new test prior application to the new population.

Helicobacter pylori in the Indonesian Malay's descendants might be imported from other ethnicities.

BACKGROUND: Even though the incidence of H. pylori infection among Malays in the Malay Peninsula is low, we observed a high H. pylori prevalence in Sumatra, which is the main residence of Indonesian Malays. H. pylori prevalence among Indonesian Malay descendants was investigated. RESULTS: Using a combination of five tests, 232 recruited participants were tested for H- pylori and participants were considered positive if at least one test positive. The results showed that the overall H. pylori prevalence was 17.2%. Participants were then categorized into Malay (Aceh, Malay, and Minang), Java (Javanese and Sundanese), Nias, and Bataknese groups. The prevalence of H. pylori was very low among the Malay group (2.8%) and no H. pylori was observed among the Aceh. Similarly, no H. pylori was observed among the Java group. However, the prevalence of H. pylori was high among the Bataknese (52.2%) and moderate among the Nias (6.1%). Multilocus sequence typing showed that H. pylori in Indonesian Malays classified as hpEastAsia with a subpopulation of hspMaori, suggesting that the isolated H. pylori were not a specific Malays H. pylori. CONCLUSIONS: Even though the ethnic groups live together as a community, we observed an extremely low H. pylori infection rate among Indonesian Malay descendants with no specific Indonesian Malay H. pylori. The results suggest that H. pylori was not originally among these groups and H. pylori was imported from other ethnic groups.

CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.

Oxidative stress markers in initial therapy and remission of nephrotic syndrome and serum malondialdehyde level predictor from routine laboratory test.

Aim To compare oxidative stress state of children with nephrotic syndrome at the first week of treatment and in remission, and to predict malondialdehyde (MDA) level from routine laboratory tests. Methods This cross-sectional study involved 80 1-18 years old children with nephrotic syndrome, who were divided into two groups: initial group (40 children in the first week of therapy) and remission group (40 children in remission). Demographic characteristics of the patients were taken by a questionnaire. Laboratory tests were measured in the initial group; in the remission group negative or trace proteinuria was measured for three consecutive days. Serum urea, creatinine, albumin, total cholesterol, MDA, superoxide dismutase, glutathione peroxidase, and urine albuminto-creatinine ratio (UACR) were measured and compared between the groups. Albumin, total cholesterol, and UACR were subjected to predict high serum MDA using a mean of all patients' MDA level as a cutoff. Results There were higher albumin levels and lower UACR, total cholesterol, and MDA in the remission group compared to the initial group. Albumin and UACR showed good accuracy, and total cholesterol showed very good accuracy to predict serum MDA level more than 1.35 µmol/L. Conclusion Children with nephrotic syndrome in the first week of therapy showed a higher oxidative stress state than the children in remission. Serum albumin, serum total cholesterol, and UACR can predict serum MDA level with good accuracy.

The effect of bay leaf extract (Syzygium polyanthum) on vascular endothelial growth factor (VEGF) and CD31 (PECAM-1) expression in acute coronary syndrome.

Aim To investigate effect of bay leaf extract in endothelial integrity, observed by vascular endothelial growth factor (VEGF) level, VEGF and CD31 expression. Methods Thirty-two acute coronary syndrome surgery-induced Wistar Rats (Rattus novergicus) were divided into 16 bay leaf extract (treatment) groups and 16 control groups, sacrificed on day 1, 4, 7, and 14 after the induction. Serum VEGF level was determined by ELISA and expression of VEGFR-2 and CD31 were detected on immunohistochemistry. Results This study showed increased expression of serum VEGF level, and VEGFR-2 expression was found significantly on day 7 and 14 in the treatment group compared to the control group. CD31 expression was significantly different compared to the control groups on day 4, 7, and 14 of administration. Conclusion The potential effect of bay leaf extract on angiogenesis in acute coronary syndrome (ACS) as adjuvant for the treatment. Bay leaf extract has been shown to support angiogenesis and maintain endothelial integrity that leads to better prognosis for reperfusion on ischemic tissue.

The effect of roselle flower petals extract (Hibiscus sabdariffa Linn.) on reducing inflammation in dextran sodium sulfateinduced colitis.

Aim To determine the effect of roselle (Hibiscus sabdariffa) petals in dextran sodium sulfate (DSS)-induced colitis model by measuring pro-inflammatory cytokines expressions (IL-6, and TNF-α), anti-inflammatory cytokine expression (IL-10) and histological colitis inflammation score (HCIS). Methods This study was conducted in two phases. For the first phase, five DSS-induced colitis mice were sacrificed (group 1) and compared with six healthy mice (group 2) after five-cycle induction (70 days). For the second phase, roselle-treated DSS-induced colitis mice were sacrificed on day 7, 14, 21, and 28 after induction and compared with mesalazine-treated DSS-induced colitis mice. Expressions of IL-6, TNF-α, and IL-10 were determined by immunohistochemistry and HCIS were assessed by two experienced pathologists. Results The expressions of IL-6, TNF-α, and IL-10, and HCIS in DSS-induced colitis mice were increased compared with control. The expressions of IL-6, TNF-α were significantly higher in roselle-treated group on day 7 and 14, but not on day 21 and 28, whereas, the expression of IL-10 was significantly lower only on day 7 compared with mesalazine-treated group. The inflammation was higher in roselle-treated group assessed by using HCIS. Compared to day 0, the reduction of HCIS was significant in roselle-treated and mesalazine-treated groups. Conclusion Roselle flower petal can attenuate the inflammation in DSS-induced colitis in mice. The extract of roselle can be given as an adjuvant therapy to the first-line therapy to enhance anti-inflammatory effect by increasing expression of anti-inflammatory cytokines and decreasing pro-inflammatory cytokines.

Interleukin-8 heterozygous polymorphism (-251 T/A and +781 C/T) increases the risk of Helicobacter pylori-infection gastritis in children: a case control study.

Aim To investigate the effects of interleukin-8 (IL-8) -251 T/A and +781 C/T polymorphism on the risk of Helicobacter pyloriinfection gastritis in children, and the IL-8 level of children with or without gastritis H. pylori infection according to polymorphism. Methods This prospective, case control clinical study included 64 children 2-18 years old. A disease group (32 gastritis patients with H. pylori-infection) was compared with a control group (32 gastritis patients without H. pylori infection). Demographic characteristics of patients were taken by a questionnaire; gastritis was confirmed by gastroscopy, H. pylori infection was confirmed with rapid urease test. Serum IL-8 level was measured by ELISA, and IL-8 -251 T/A and +781 C/T polymorphisms were analysed by RT-PCR. Demographic characteristics, IL-8 level, polymorphism of patients, and IL-8 level according to polymorphisms were compared between the groups. Results Children with tobacco exposure were associated with an increased risk of H. pylori-infection gastritis by 3.4-fold. There was a higher IL-8 level in the disease group compared to the control group. The disease group with IL-8 -251 AT polymorphism had a higher risk compared to TT polymorphism by 8.7-fold, and with IL-8 +781 CT polymorphism had a higher risk compared to CC polymorphism by 10.7-fold. Children in the disease group with IL-8 -251 AT and TT, and +781 CT and CC polymorphisms produced a higher IL-8 level than the control group in respective polymorphisms. Conclusion Children with H. pylori-infection gastritis have higher IL-8 production. There was an increased risk of developing H. pylori-infection in heterozygous -251 AT and +781 CT.

Serum pepsinogens as a gastric cancer and gastritis biomarker in South and Southeast Asian populations.

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker.

Syzygium Polyanthum Reduced TNF-α and ADAM17 Protein Expression in Myocardial Infarction Rat Model.

BACKGROUND: In myocardial infarction (MI), inflammatory cytokine including tumor necrosis factor-α (TNF-α) plays pivotal role throughout worsening processes and recovery, whereas its cleavage is controlled by a disintegrin and metalloproteinases-17 (ADAM-17). Syzygium polyanthum (Wight) is widely used plant in Indonesia and Southeast Asian countries to treat various illnesses. OBJECTIVE: This study aimed to analyze the effect of S. polyanthum extract towards TNF-α and ADAM17 expressions in MI rat model. METHODS: Myocardial infarction were surgically induced in wistar rats by ligating left anterior descending coronary artery in both treatment and control group. Around 3.6 mg of S. polyanthum extract (SPE) was administered via nasogastric tube to treatment groups, while control group received only saline. Serum TNF-α level and expression of TNF-α and ADAM17 in blanching heart muscle was examined in both groups on day 1, day 4, day 7, and day 14 after treatment with SPE. RESULTS: Reduction of serum TNF-α levels was markedly seen from day 4 in treatment group and was lower than in control group since day 4. Expression of ADAM17 was reduced and expression of TNF-α was only seen in myocardial membrane in group with SPE treatment. CONCLUSION: Syzygium polyanthum exerts its anti-inflammatory effect by decreasing ADAM17 expression subsequently lowering TNF-α regulation in MI rat model.

The effect of bay leaf extract Syzygium polyanthum (Wight) Walp. on C-reactive protein (CRP) and myeloperoxidase (MPO) level in the heart of rat model of myocardial infarction.

Aim To study the anti-inflammatory effect of bay leaf on C-reactive protein (CRP) and myeloperoxidase (MPO) level in the heart of rat model with myocardial infarction. Methods In the first phase, results of pathological examination and biochemical assay were compared between rats with and without induction of myocardial infarction. In the second phase, the effect of bay leaf extract on CRP and MPO of rats with myocardial infarction was studied. Results C-reactive protein and MPO were higher in rats which had myocardial infarction. Administration of bay leaf extract reduced levels of CRP and MPO in the rats started from day 4 after the induction of myocardial infarction. Conclusion Anti-inflammatory effect of bay leaf is confirmed, reflected by decreasing of CRP and MPO levels of rat model with myocardial infarction.

The Difference of Serum Gastrin-17 Level Based on Gastritis Severity and Helicobacter Pylori Infection.

BACKGROUND: Gastritis was defined as the histological presence of gastric mucosal inflammation. One of the most common aetiology was H. pylori. Gastrin-17 was a hormone that was secreted by G cells. H. pylori infection induced increased in gastrin-17 in gastritis. Therefore, this study was to investigate the relationship of gastrin-17 with gastritis severity and H. pylori infection. AIM: To determine the difference in serum Gastrin-17 level based on gastritis severity and H. pylori infection. METHODS: A cross-sectional study enrolling 45 patients with gastritis was conducted in Haji Adam Malik General Hospital between April and July 2018. Endoscopy and biopsy examinations were performed to confirm the diagnosis of gastritis. Gastritis severity was assessed using the Updated Sydney System. The presence of H. pylori infection was detected by a Campylobacter-like organism (CLO) examination. Gastrin-17 level and demographic data were also gathered. The analysis was done using Mann Whitney and Kruskal-Wallis test. P-value of < 0.05 was considered statistically significant. RESULTS: Serum Gastrin-17 level was significantly different based on gastritis severity (P = 0.001 according to neutrophils infiltration and P = 0.023 according to degree of atrophy), H. pylori infection (P = 0.038), and combined gastritis severity and H. pylori infection (P < 0.001). Serum Gastrin-17 level was higher in subjects with severe neutrophils infiltration, without atrophy, and with H. pylori infection. CONCLUSION: There was a significant difference in serum Gastrin-17 level based on gastritis severity and H. pylori infection.

Analysis of risks of gastric cancer by gastric mucosa among Indonesian ethnic groups.

Indonesia is a big country with multiethnic populations whose gastric cancer risks have not been elucidated. We performed a nationwide survey and obtained histological specimens from 1053 individuals in 19 cities across the country. We examined the gastric mucosa, the topography, the atrophic gastritis risk factors, and the gastric cancer risk scores. Almost half (46.1%) of the patients with dyspeptic symptoms had histological abnormalities; chronic (36.3%) and atrophic gastritis (28.9%) being the most frequent. Individuals of the Timor ethnicity had the highest prevalence of acute (52.6%) and chronic gastritis (68.4%), even those negative for H. pylori. Our topographic analysis showed the majority of patients had predominantly antral acute and chronic gastritis. A multivariate logistic regression model showed age (Odds ratio [OR], 1.107), Timor ethnicity (OR, 8.531), and H. pylori infection (OR, 22.643) as independent risk factors for presence of atrophic gastritis. In addition, the gastric cancer risk score was highest in those from Timor, Papuan, and Bugis ethnic populations. Overall, Indonesia is a low-risk gastric cancer country. However, several ethnic groups displayed severe gastric mucosa symptoms suggesting policy makers should focus on those ethnic groups to perform gastric cancer screenings and to eradicate H. pylori.

Alternative eradication regimens for Helicobacter pylori infection in Indonesian regions with high metronidazole and levofloxacin resistance.

BACKGROUND: The prevalence of Helicobacter pylori resistance to metronidazole and clarithromycin is high in Indonesia. Moreover, the increasing levofloxacin resistance rates in the absence of bismuth treatment in Indonesia has led to the use of other antibiotics as alternative regimens. METHODS: We determined the minimum inhibitory concentrations (MICs) of five alternative antibiotics for H. pylori (rifaximin, rifabutin, furazolidone, garenoxacin, and sitafloxacin) using the agar dilution method and assessed mutations associated with antibiotic resistance using next-generation sequencing. RESULT: Analysis of 106 strains isolated from 1039 adult dyspeptic patients revealed that none of the strains were furazolidone-resistant. All strains were also sensitive to rifabutin and sitafloxacin. In contrast, the rates of resistance to rifaximin and garenoxacin were high (38.9% and 6.7%, respectively). The strains isolated from patients on Java Island had the highest resistance rates to garenoxacin and rifaximin. In addition, the resistance was distributed evenly among the ethnic groups, ranging between 25.0% and 69.2%. Except for rifaximin, for which the resistance rate was 38.9%, the other four antibiotics could be successfully employed to eradicate levofloxacin- and metronidazole-resistant H. pylori infections in vitro. Interestingly, garenoxacin-sensitive strains were found in regions with high clarithromycin resistance rates such as Bali and Papua Islands. In contrast, rifaximin might not be considered as an alternative antibiotic in regions with high clarithromycin resistance. There was an inconsistent association between gyrA and gyrB mutations and garenoxacin resistance. We confirmed that the I837V (replacement of isoleucine at position 837 with valine), A2414T/V, Q2079K and K2068R were the predominant rpoB point mutations. There was an association between vacA genotypes of H. pylori and rifaximin resistance (P = 0.048). CONCLUSION: furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as alternative regimens to eradicate H. pylori in Indonesia, including regions with high metronidazole and clarithromycin resistance rates. Moreover, sitafloxacin but not garenoxacin should be considered for eradication of levofloxacin-resistant strains.