Iswan A Nusi

Risk Factors and Prevalence of Helicobacter pylori in Five Largest Islands of Indonesia: A Preliminary Study

The prevalence of Helicobacter pylori infection in Indonesia is still controversial and mainly investigated in the largest ethnic group, Javanese. We examined the prevalence of H. pylori infection using four different tests including culture, histology confirmed by immunohistochemistry and rapid urease test. We also analyzed risk factors associated with H. pylori infection in five largest islands in Indonesia. From January 2014–February 2015 we consecutively recruited a total of 267 patients with dyspeptic symptoms in Java, Papua, Sulawesi, Borneo and Sumatera Island. Overall, the prevalence of H. pylori infection was 22.1% (59/267). Papuan, Batak and Buginese ethnics had higher risk for H. pylori infection than Javanese, Dayak and Chinese ethnics (OR = 30.57, 6.31, 4.95; OR = 28.39, 5.81, 4.61 and OR = 23.23, 4.76, 3.77, respectively, P <0.05). The sensitivity and specificity for RUT and culture were 90.2%, 92.9% and 80.5%, 98.2%, respectively. The patients aged 50–59 years group had significantly higher H. pylori infection than 30–39 years group (OR 2.98, P = 0.05). Protestant had significantly higher H. pylori infection rate than that among Catholic (OR 4.42, P = 0.008). It was also significantly lower among peoples who used tap water as source of drinking water than from Wells/river (OR 9.67, P = 0.03). However only ethnics as become independent risk factors for H. pylori infection. Although we confirmed low prevalence of H. pylori in Javanese; predominant ethnic in Indonesia, several ethnic groups had higher risk of H. pylori infection. The age, religion and water source may implicate as a risk factor for H. pylori infection in Indonesia.

Helicobacter, Hygiene, Atopy, and Asthma

The hygiene hypothesis links environmental and microbial exposures in early life to the prevalence of atopy, allergy, and asthma. Helicobacter pylori infection is typically acquired in childhood and acquisition of the infection is associated with poor household hygiene. Some population surveys have shown an inverse association between H. pylori infection and atopy, allergy, and asthma leading to the suggestion that H. pylori infection may be protective against disease; others consider it simply a biomarker for poor household hygiene. We review the relevant surveys, cohort studies, meta-analyses, and studies testing the protective hypothesis. Overall, the results of surveys and cohort studies are inconsistent, whereas meta-analyses show a significant but weak inverse correlation. In contrast, studies directly testing the protection hypothesis in relation to asthma in populations with poor hygiene and low H. pylori prevalence failed to confirm a protective effect. H. pylori is a major cause of human disease including chronic gastritis, peptic ulcer, and gastric malignancies. H. pylori infections most likely serve as a biomarker for poor hygienic conditions in childhood. We conclude that while synergistic interactions between environmental factors in childhood are important determinants of the pathogenesis of atopy, allergy, and asthma; H. pylori is inversely related to good hygiene and thus its presence serves as a biomarker rather than for a specific prevention role for H. pylori or H. pylori antigens.

Surveillance of Helicobacter pylori Antibiotic Susceptibility in Indonesia: Different Resistance Types among Regions and with Novel Genetic Mutations.

Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.

Gastric mucosal status in populations with a low prevalence of Helicobacter pylori in Indonesia

In Indonesia, endoscopy services are limited and studies about gastric mucosal status by using pepsinogens (PGs) are rare. We measured PG levels, and calculated the best cutoff and predictive values for discriminating gastric mucosal status among ethnic groups in Indonesia. We collected gastric biopsy specimens and sera from 233 patients with dyspepsia living in three Indonesian islands. When ≥5.5 U/mL was used as the best cutoff value of Helicobacter pylori antibody titer, 8.6% (20 of 233) were positive for H. pylori infection. PG I and II levels were higher among smokers, and PG I was higher in alcohol drinkers than in their counterparts. PG II level was significantly higher, whereas PG I/II ratios were lower in H. pylori-positive than in H. pylori-negative patients. PG I/II ratios showed a significant inverse correlation with the inflammation and atrophy scores of the antrum. The best cutoff values of PG I/II were 4.05 and 3.55 for discriminating chronic and atrophic gastritis, respectively. PG I, PG II, and PG I/II ratios were significantly lower in subjects from Bangli than in those from Makassar and Surabaya, and concordant with the ABC group distribution; however, group D (H. pylori negative/PG positive) was the lowest in subjects from Bangli. In conclusion, validation of indirect methods is necessary before their application. We confirmed that serum PG level is a useful biomarker determining chronic gastritis, but a modest sensitivity for atrophic gastritis in Indonesia. The ABC method should be used with caution in areas with a low prevalence of H. pylori.

Response Evaluation of Patients Undergoing Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma with Respect to Tumour Size, Number of Lesion, and Alpha-Fetoprotein (AFP) Level

Background : Transarterial chemoembolization (TACE) is widely used as a palliative treatment for unresectable hepatocellular carcinoma (HCC). TACE is also used as bridging therapy before liver transplantation to avoid tumour progression and considered for downstaging to fulfill tumour resection or liver transplantation criterias. This study aimed to evaluate response of TACE in unresectable HCC according to changing of tumour size, number of lesion, and AFP level. Method : Retrospectively, we evaluate 69 HCC patients who underwent TACE in Dr. Soetomo General Hospital in January 2012-June 2015, including their age, sex, aetiologies, and Barcelona Clinic Liver Cancer/BCLC staging. Laboratory examinations such as complete blood count (hemoglobin/Hb, leucocyte, thrombocyte), liver function test (aspartate aminotransferase/AST, alanine aminotransferase/ALT, bilirubin, albumin, international normalized ratio/INR), alpha-fetoprotein/AFP level, and abdominal CT-scan were performed before and 1 month post-TACE. Data was analysed using paired t-test. Results : 69 patients with mean age of 51.81 ± 12.8 years old, predominantly 76.8% males, the most common aetiology was hepatitis B 68.1%, 92.8% BCLC B, 64.3% with stable disease, none achieved complete response, 97.1% had tumour size > 5 cm, 69.6% had single tumour, and 55.7% had AFP level >1000 ng/mL. There was a significant increase in tumour size and number of lesions in 1 month post-TACE that were approximately 1.76 cm and 2.33, respectively, and there was no significant difference between AFP level before and 1 month post TACE. Conclusion : In 1 month post TACE evaluation, there was a significant increase of tumour size and number of lesion, but there was no significant alteration in AFP level. TACE might be performed repeatedly with shorter evaluation interval than 1 month to achieve better response.

Su1926 Prevalence and Virulence Factors Characteristics of Helicobacter pylori Infection in Five Largest Islands in Indonesia

Background: Although the prevalence of Helicobacter pylori infection in Indonesia has been investigated, it is controversial and primarily investigated Javanese populations.We examined the prevalence of H. pylori infection using four different tests in five largest islands in Indonesia. We also analyzed virulence factors and population genetics. We hypothesized that the low prevalence ofH. pylori infection, characterized of virulence factors and population genetics contributes to the low incidence of gastric cancer in Indonesia. Methods: A total 245 subjects with dyspeptic symptoms from Jakarta and Surabaya (Java island), Medan (Sumatera Island), Pontianak (Borneo Island), Makassar (Celebes island) and Yowari (Papua Island) were included in this study. The status of H. pylori infection was based on culture, histology, immunohistochemistry and rapid urease test. Histological scores were evaluated according to the Update Sydney System and the Operative Link for Gastritis Assessment (OLGA) system. The genotypes of virulence factors and multilocus sequence typing (MLST) using seven housekeeping genes were examined by polymerase chain reaction (PCR) and DNA sequencing. In some isolated strains, whole-genome sequencing was also performed using the next generation sequencer. Results:We confirmed that low prevalence of H. pylori infection in Indonesia (15.9%). Papua and Makassar ethnics have higher risk for H. pylori infection than Javanese and Dayak ethnics (OR = 7.1 OR = 6.2 and OR = 7.40, OR = 6.49, respectively; P <0.05). Alcohol consumption had relation with the prevalence of H. pylori infection (OR = 6.8, P <0.05). H. pylori infection and ethnogeographic were associated with the severity outcome of histology. A total of 30 strains could be isolated and only one was cagA negative. East-Asian type cagA (46.6%), pre-EPIYA 18-bp deletion type (60.0%), vacA s1a (50.0%) and m1b (56.7%), dupA negative (93.3%), oipA off (53.3%), iceA1 positive/ iceA2 negative (56.7%) and double positive of jhp0562/β-(1,3)galT (50.0%) were predominant genotype in Indonesia. We also found high proportion of vacA m2 genotype (26.7%). Interestingly, Papua strains showed ABB type cagA and novel type of 0.7 kb middle region of vacA (m1d). MLST analysis using seven house keeping gene and whole genome revealed that Indonesian population were divided in to three spesific population type which have related with ethnogeographic region. Conclusions: The low incidence of gastric cancer in Indonesia could be attributed to the low prevalence of H. pylori infection, characteristic of virulence factors (high proportion of non East-Asia type cagA, vacA m2, dupA negative and oipA off) and population genetics.

The Knowledge Level of Primary Care Physicians in Surabaya Primary Health Care Center Concering Hepatitis B

Background: One of physician’s functions at primary health care center (PHC) is the ability to diagnose some diseases especially that contribute to high morbidity and mortality. Until now, hepatitis B virus infection has become a major health problem worldwide. The aim of this study was to identify the knowledge level of primary care physicians concerning hepatitis B in Surabaya. Method: The present study was a cross-sectional study that performed by investigators through interviews with primary care physicians in Surabaya to fill questionnaires for measuring their knowledge level. The questionnaires were modified from questionnaire survey in Tur Key performed by Peksen et al. It reflected the level of knowledge of the physicians including their comprehension, application and analysis. Validity and reliability test were performed on the Result of those questionnaires. The knowledge level was categorized as follows: > 75 (excellent), 70.0–74.9 (very high), 65.0–69.9 (high), 60.0–64.9 (medium), 55.0–59.9 (moderate), 47.5–54.9 (nearly moderate), 40.0-47.4 (less moderate), < 40 (low). Results: Based on validity test, we obtained 14 items of 17 question items with correlation coefficient 0.287–0.561 and alpha reliability index 0.639; therefore, the instrument can be used to measure the knowledge level. The results of mean score conversion included comprehension, which was 84.878 ± 16.499 (excellent category); application, which was 47.556 ± 31.870 (nearly moderate category) and analysis, which was 14.634 ± 35.562 (low category). Statistically, the mean value of the knowledge level scale, which was the combination of comprehension, application and analysis, was obtained at 49.023 ± 19.085 including the nearly moderate category. Conclusion: By using a valid and reliable instrument, the knowledge level of primary care physician in Surabaya concerning hepatitis B can be categorized as nearly moderate. Keywords : hepatitis B, liver cirrhosis, hepatoma

The Profile of Colonoscopy Examination Results in Surabaya Hajj General Hospital

Background : Colonoscopy is the most accurate examination to diagnose abnormalities in ileum terminalis, caecum, colon (ascendent, tranversum and descendent), sigmoid and rectum at present time. The aim of this study was to obtain the profile of colonoscopy examination in Surabaya Hajj General hospital. Method: One hundred and fifty patients who have undergone colonoscopy at Endoscopy Unit of Internal Medicine Department of Surabaya Hajj General Hospital were observed from July 1st, 2008 until October 30th, 2009. Result: There were 87 (58.0%) male and female patients 63 (42.0%) female subjects. Most subjects were at 51-70 years age group of 69 patients (46.0%). The results of colonoscopy examination were as follows: hemorrhoid in 38 subjects (25.3%), colorectal cancer in 32 subject (21.3%), colitis 25 subjects (16.7%), inflammatory bowel disease (IBD) in 15 subjects (10.0%), polyp in 8 subjects (5.3%), diverticulum in 5 subject (3.3%), redundant in 5 subject (3.3%), reduced peristaltic in 3 subject (2.0%), the mass pressure from external colon in 2 subject (1.3%), scybala in 2 subject (1.33%), adhesion in 3 subject (2.0 %), poor/dirty preparation in 6 subject (4.0%) and normal in 6 subject (4.0%). Conclusion: There were four major groups of disease found by colonoscopy in our sunjects including hemorrhoid, colorectal cancer, colitis and IBD. Our study found that colorectal cancer has the greatest number, paticularly the rectosigmoid cancer. Keywords: colonoscopy, colitis, rectosigmoid, IBD,colorectal cancer

Validation of 13C-urea Breath Test for the Diagnosis of Helicobacter pylori Infection Among Dyspeptic Patients at Dr Soetomo Hospital Surabaya

Background: The urea breath test (UBT) has been published as the most sensitive and specific non-invasive test to detect Helicobacter pylori (H. pylori) infection. The limitation of UBT is the need of expensive equipment that is not always widely available. Recently, UBT has already been available in Surabaya. In the other hand, our experience using rapid urease test which detected urease enzyme produced by H. pylori as UBT showed low sensitivity. Objective: To investigate the validation of UBT for the diagnosis of H. pylori infection in patient with dyspepsia. Design: Cross-sectional study. Method: Sixty patients who complained symptoms of dyspepsia were examined for H. pylori infection using UBT. Gastroscopy and biopsy was were performed and the biopsy specimens were examined by Pathologist. Results: Sixty patients consist of 28 male and 32 female were enrolled of this study. Eight patients had H. pylori positive by both UBT and histologic examination. One patient was H. pylori positive by UBT but negative by histologic examination. One patient was H. pylori negative by UBT but positive by histologic examination. The sensitivity of UBT was 88.9% and the specificity was 98 %. The negative predictive value was 98%. Conclusion: In this study, UBT has lower sensitivity (88.9%) and comparable specificity (98%) for diagnosing H. pylori infection. Comprehensive studies to determine the doses of 13C-urea, test meal and appropriate collection time, which is more suitable for local population was suggested. Keywords: 13C-Urea Breath Test, Helicobacter pylori, dyspepsia, diagnosis