Gender-specific accuracy of lipid accumulation product index for the screening of metabolic syndrome in general adults: a meta-analysis and comparative analysis with other adiposity indicators.

BACKGROUND: Lipid accumulation product (LAP) is a novel predictor index of central lipid accumulation associated with metabolic and cardiovascular diseases. This study aims to investigate the accuracy of LAP for the screening of metabolic syndrome (MetS) in general adult males and females and its comparison with other lipid-related indicators. METHODS: A systematic literature search was conducted in PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ProQuest for eligible studies up to May 8, 2024. Outcomes were pooled mean difference (MD), odds ratio (OR), and diagnostic accuracy parameters (sensitivity, specificity, and area under the summary receiver operating characteristic [AUSROC] curve). Comparative analysis was conducted using Z-test. RESULTS: Forty-three studies involving 202,313 participants (98,164 males and 104,149 females) were included. Pooled MD analysis showed that LAP was 45.92 (P < 0.001) and 41.70 units (P < 0.001) higher in men and women with MetS, respectively. LAP was also significantly associated with MetS, with pooled ORs of 1.07 (P < 0.001) in men and 1.08 (P < 0.001) in women. In men, LAP could detect MetS with a pooled sensitivity of 85% (95% CI: 82%-87%), specificity of 81% (95% CI: 80%-83%), and AUSROC curve of 0.88 (95% CI: 0.85-0.90), while in women, LAP had a sensitivity of 83% (95% CI: 80%-86%), specificity of 80% (95% CI: 78%-82%), and AUSROC curve of 0.88 (95% CI: 0.85-0.91). LAP had a significantly higher AUSROC curve (P < 0.05) for detecting MetS compared to body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), body roundness index (BRI), a body shape index (ABSI), body adiposity index (BAI), conicity index (CI) in both genders, and waist circumference (WC) and abdominal volume index (AVI) in females. CONCLUSION: LAP may serve as a simple, cost-effective, and more accurate screening tool for MetS in general adult male and female populations.

Perioperative management of constrictive pericarditis with cardiac cirrhosis: A case report.

INTRODUCTION: The interactions between the heart and liver have been known for a long time, pericarditis constrictive could cause congestive hepatopathy via right-sided heart failure. Liver cirrhosis correlates with a high risk of mortality so perioperative management greatly influences outcomes. CASE PRESENTATION: An Indonesian man, 50 years old, complained of breath shortness. The patient had a history of pulmonary tuberculosis and was declared cured 30 years ago. The patient began experiencing fatigue 14 years ago, and the patient was diagnosed with constrictive pericarditis 5 years ago. Currently, the patient has an increased jugular venous pressure of 9 cmH2O and abnormal laboratory indicators, including a platelet count of 121,000/µL, albumin count of 3.41 g/L, direct bilirubin count of 0.7 mg/dL, total bilirubin count of 1.4 mg/dL, and INR of 1.4. Echocardiography revealed left ventricle hypertrophy, diastolic dysfunction, and right ventricle failure. Cardiac CT scan showed pericardial calcification. Abdominal ultrasound showed liver congestive and splenomegaly. Transient elastography showed severe fibrosis in liver and stiffness in spleen. The patient underwent pericardiectomy with CTP score of 6 and MELD of 12. The surgery was successful, and the complaint was reduced. The patient experienced an improvement in his condition and able to carry out activities well after 2 years post-surgery. DISCUSSION: The patient has no contraindications to pericardiectomy, CTP class A (5-6) and MELD score <13.5 has a low risk of mortality. CONCLUSION: CTP and MELD scores predict life expectancy in post-surgery cardiac cirrhosis patients.

Diagnosis and Management of Hepatic Hydrothorax.

Hepatic hydrothorax is a pleural effusion (typically ≥500 mL) that develops in patients with cirrhosis and/or portal hypertension in the absence of other causes. In most cases, hepatic hydrothorax is seen in patients with ascites. However, ascites is not always found at diagnosis and is not clinically detected in 20% of patients with hepatic hydrothorax. Some patients have no symptoms and incidental findings on radiologic examination lead to the diagnosis of the condition. In the majority of cases, the patients present with symptoms such as dyspnea at rest, cough, nausea, and pleuritic chest pain. The diagnosis of hepatic hydrothorax is based on clinical manifestations, radiological features, and thoracocentesis to exclude other etiologies such as infection (parapneumonic effusion, tuberculosis), malignancy (lymphoma, adenocarcinoma) and chylothorax. The management strategy involves a stepwise approach of one or more of the following: Reducing ascitic fluid production, preventing fluid transfer to the pleural space, fluid drainage from the pleural cavity, pleurodesis (obliteration of the pleural cavity), and liver transplantation. The complications of hepatic hydrothorax are associated with significant morbidity and mortality. The complication that causes the highest morbidity and mortality is spontaneous bacterial empyema (also called spontaneous bacterial pleuritis).

A Very Young Adult Female Patient with Hepatitis B Flare: A Case Report.

Hepatitis B virus (HBV) infection is a major global health problem. It can cause chronic infection and put people at high risk of death from cirrhosis and liver cancer. This study aims to present a case of chronic hepatitis B flare in a very young adult patient. An 18-year-old previously healthy female presented with jaundice developing in one week, following the previous complaints of nausea, vomiting, abdominal pain, loss of appetite, and tiredness for about three months. The patient had no risk factors for getting HBV infection, but her HBsAg-positive mother was probably an inactive HBV carrier. The hepatitis B serological testing revealed HBsAg positivity, anti-HBs seronegativity, HBeAg positivity, anti-HBe seronegativity, anti-HBc IgM seronegativity, and high levels of HBV DNA detected > 1.70 × 108 IU/mL. There was a sharp increase in serum ALT to ≥ 5-fold ULN. The abdominal ultrasonography revealed a hepatitis feature, unremarkable portal venous flow, and an extrahepatic biliary system. The liver transient elastography revealed 15.6 kPa of liver stiffness, which was in accordance with the F3-F4 fibrosis stage. These features were typical of a hepatitis B flare, the HBeAg-positive chronic hepatitis B, previously known as the immune reactive phase. A long-term nucleos(t)ide analog therapy was programmed with Tenofovir alafenamide 25 mg daily.

High levels of fecal calprotectin and C-reactive protein in patients with colitis.

Inflammatory bowel disease (IBD) with a poor prognosis may be due to persistent colitis. According to the latest guidelines, monitoring has become a part of the treatment process for colitis. Adequate monitoring of the patient's condition is necessary to determine the course of the disease to prevent the worsening of the condition and suppress the subclinical inflammatory process. This analytical study with a cross-sectional design was conducted to evaluate the activity of colitis using the results of C-reactive protein (CRP) and fecal calprotectin (FC) assays. FC levels were analyzed by ELISA, while CRP levels were analyzed using Siemens Flex particle-enhanced turbidimetric immunoassay. In 30 subjects with endoscopy and biopsy of colitis, 16 men and 14 women had a median age of 52.5 (18-70) years. The median FC value increased by 67 (7.3-722 g/g) and was positive (≥50 g/g) in 20 subjects (66.7%), and the mean CRP value was 13.64 mg/L, positive (10-15 mg/L) in 13 subjects (43.33%), and negative (<10 mg/L) in 17 subjects (56.67%). This study demonstrated that FC had a significant relationship with CRP (r=0.57; p<0.001) in patients with colitis. Assessing the levels of FC and CRP among patients with colitis can be useful to assess the worsening of symptoms early and reduce mortality and morbidity.

Correlation between interleukin-6 expression in post-mortem core liver biopsy and degree of liver injury in patients with fatal COVID-19.

Excessive release of interleukin-6 (IL-6) during the progression of coronavirus disease 2019 (COVID-19) induces cytokine storms, resulting in multi-organ damages including liver injury, similar in nature with mechanism of viral hepatitis. Systemic IL-6 has been associated with the incidence of liver injury among COVID-19 patients; however, studies on IL-6 expression in the liver tissue are completely lacking. The aim of this study was to measure the IL-6 expression in the liver tissues and to determine its correlation with the degree of liver injury in fatal COVID-19 patients. Through this first cross-sectional study, IL-6 expression was measured through immunohistochemical staining and the degree of liver injury was identified based on level of serum alanine aminotransferase (ALT). The Spearman correlation test was used to identify the correlation between IL-6 expression and the degree of liver injury. A total of 47 deceased COVID-19 patients were included and IL-6 expression was observed in all post-mortem liver specimens, ranging from mild to strong expression. Liver injury at various degrees (mild to severe) was found in more than half (59.5%) of the cases. The Spearman correlation analysis suggested a statistically insignificant correlation between liver IL-6 expression and the degree of liver injury (r=0.152; p=0.309). In conclusion, even IL-6 expression was observed in all post-mortem liver specimens, there was an insignificant correlation between IL-6 expression in the liver tissue with the degree of liver injury among fatal COVID-19 patients, suggesting that IL-6 was not the only main factor contributing to liver damage in COVID-19 patients.

Antiviral use in liver function abnormalities and Covid-19 patients: Serial cases.

Introduction: Some SARS-CoV-2 patients have liver function abnormalities due to anti-viral drug effects. Methods: The design of this study was a case series reported using retrospectives. Data collection was carried out from December 2020 to February 2021. All participants were diagnosed with SAR-CoV-2 and received an anti-viral drug which identified liver function abnormalities. Results: The patients' average age was 54.56 ± 14.46 years old. Most patients experienced shortness of breath and cough, with hypertension as the accompanying comorbid. Increased AST and ALT were found in one patient who used Lopinavir-Ritonavir. The increase was 1.0 times to 2.0 times the expected value. Increased CRP, D-dimer and procalcitonin were also found, with a mean of 12.27 ± 15,34, 1861.29 ± 1828.85 and 1.54 ± 2.84, respectively. One of the patients in the Lopinavir-Ritonavir group died while receiving treatment. Conclusion: SAR-CoV-2 is one of the risk factors that cause liver function abnormalities supported by anti-viral drugs that cause liver work to increase.

Baseline serum Mac-2 binding protein glycosylation isomer as a predictor of hepatocellular carcinoma in chronic hepatitis B patients: a systematic review and meta-analysis.

Background: A minimally invasive tool to promptly predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is currently needed. In this study, we aimed via a meta-analysis to identify the serum Mac-2 binding protein glycosylation isomer (M2BPGi) as a novel glycoprotein-based liver fibrosis marker for predicting HCC in CHB patients. Methods: We conducted a systematic search on PubMed, Scopus, ProQuest, Wiley Online Library, and CINAHL Plus (via EBSCOhost). The articles were screened based on several eligibility criteria and were further assessed for study qualities using the Newcastle-Ottawa Scale. The outcomes were presented as standard mean difference (SMD), hazard ratio (HR), and predictive accuracy parameters of a baseline cutoff index (COI) for serum M2BPGi. Results: Fourteen studies involving 5918 CHB patients were included in this systematic review and meta-analysis. Baseline COI serum M2BPGi was significantly higher in CHB patients who developed HCC than in those who did not (SMD 1.32, 95% confidence interval [CI] 0.91-1.72). A significant HCC risk prediction was also observed (multivariate HR 1.18, 95%CI 1.05-1.32). Baseline COI serum M2BPGi could predict HCC with a pooled sensitivity of 74% (95%CI 50-89%), specificity of 80% (95%CI 65-90%), and area under the summary receiver operating characteristic curve of 0.84 (95%CI 0.81-0.87). Conclusion: High baseline COI serum M2BPGi may predict the development of HCC in CHB patients with moderate-to-high accuracy.

Interleukin-6 (IL-6) expression of lung tissue in COVID-19 patient severity through core biopsy post mortem.

Introduction: In COVID-19 patients, Interleukin-6 (IL-6) will increase, and the production of antigens will be excessive, which will cause excessive inflammation of the tissues, especially the respiratory tract, which causes fibrosis in the lungs and can lead to death. Objective: To analyze IL-6 expression of lung tissue in COVID-19 patient severity. Methods: The study is an observational analytic design from July to December 2020. COVID-19 patient severity who died was examined for IL-6 expression on lung tissue. The lung tissue sampling uses the core biopsy method. Results: The total number of samples obtained was 38 samples. Characteristics of patients with a mean age of patients were 48 years, male, the most common chief complaint was shortness of breath, mean symptom onset was 5 days, patient length of stay was 10 days, the most common cause of death was a combination of septic shock and ARDS and the most common comorbid diabetes mellitus. There is an increased WBC, neutrophils, platelets, procalcitonin, CRP, BUN, creatinine serum, AST, ALT, and D-dimer. In this study, the average tissue IL-6 expression was 72.63, with the highest frequency of strong positive 47.4%. Conclusion: An increase in IL-6 expression on lung tissue showed the severity of COVID-19 infection.

Role of fecal calprotectin as a hypoxic intestinal damage biomarker in COVID-19 patients.

BACKGROUND: Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) appear to be substantial. Fecal calprotectin is a promising biomarker in COVID-19 associated gastrointestinal inflammation; however, its role in the severity of COVID-19 remains limited. We conducted a study to analyze the relationship between the severity of COVID-19 and hypoxic intestinal damage. METHODS: We assessed the severity of 44 hospitalized COVID-19 pneumonia patients based on the PaO2/FiO2 (P/F) ratio. Inflammatory markers were measured from blood samples, and fecal calprotectin was obtained from stool samples. RESULTS: Median levels of fecal calprotectin in COVID-19 patients involved in this study (n = 44) were found to be markedly elevated along with the severity of hypoxemia, as seen in the non-acute respiratory distress syndrome (ARDS) group 21.4 µg/g (5.2-120.9), mild ARDS 54.30 µg/g (5.2-1393.7), moderate ARDS 169.6 µg/g (43.4-640.5), and severe ARDS 451.6 µg/g (364.5-538.6). We also found significant differences in fecal calprotectin levels based on the severity of ARDS (P < 0.001), and although the patients were divided into ARDS and non-ARDS groups (P < 0.001). Furthermore, we found a strong negative correlation between the P/F ratio and fecal calprotectin levels (r = - 0.697, P < 0.001). CONCLUSION: Our findings support the potential role of fecal calprotectin as a biomarker of intestinal inflammation in COVID-19 as a consequence of hypoxic intestinal damage and as suggested by the reduced P/F ratio.

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.

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.

Lower Number and Percentage of Activated Natural Killer Cells in Colorectal Cancer Patients.

BACKGROUND: Colorectal cancer is a type of cancer that begins in the colon and/or rectum tissue. Natural killer (NK) cells play a critical role in the first line of defense against infection and tumors, as well as in autoimmunity and hypersensitivity reactions. NK cells also play a role in regulating tumor cell growth and metastasis. The number and percentage of activated natural killer cells have been determined in patients with colorectal cancer and benign lesion. METHODS: This was a cross-sectional observational analytic study. The number and percentage of activated NK cells in peripheral blood were determined using the flow cytometry method in 50 samples from patients who underwent colonoscopy and obtained a mass as evidenced by histopathological examination. RESULTS: Among the 50 samples, 24 samples included in the colorectal cancer group and 26 samples from benign lesion group. The mean number of NK cells in colorectal cancer was 161.71 ± 62.666 cells/µL, benign lesion was 553.92 ± 269.173 cells/µL. The mean percentage of activated NK cells in colorectal cancer was 2.82 ± 1.19%, benign lesion was 5.10 ± 2.48%. There was a significant difference in the number of NK cells and the percentage of activated NK cells between colorectal cancer and benign lesion patients (p = 0.000). CONCLUSION: The number and activity of NK cells decreases in patients with colorectal cancer.

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.

Gastric microbiota and Helicobacter pylori in Indonesian population.

BACKGROUND: The profile of gastric mucosal microbiota has not yet been described in the Indonesian population where the prevalence of Helicobacter pylori is low. METHODS: This is a cross-sectional study analyzing 16S rRNA of 137 gastric biopsy specimens. We analyzed the association between gastric microbiota, H. pylori infection, and gastric mucosal damage. RESULT: Among 137 analyzed samples, 27 were H. pylori-positive and 110 were H. pylori -negative based on culture, histology, and 16S rRNA gene analysis. Significantly lower α-diversity parameters, including Pielou's index, was observed in H. pylori-infected individuals compared with noninfected individuals (all P < .001). Among H. pylori-negative individuals, the permutational analysis of variance of Bray-Curtis dissimilarity distances showed a significant association with different ethnicities, suggesting some ethnic groups had specific microbiota profiles based on the presence of different operational taxonomic units. The linear discriminant analysis effect size (LEfSe) of the H. pylori-negative group showed significant associations between the presence of Micrococcus luteus and Sphingomonas yabuuchiae with Timor and Papuan ethnicities, respectively. The presence of Bulledia sp and Atopobium sp was associated with the Javanese ethnicity. We observed lower α-diversity scores in individuals with gastric mucosal damage and profiles with high abundances of Paludibacter sp and Dialister sp based on LEfSe analysis. CONCLUSION: Our findings suggest the presence of H. pylori is more correlated with a distinct microbiome profile than ethnic precedence.

Association between host TNF-α, TGF-ß1, p53 polymorphisms, HBV X gene mutation, HBV viral load and the progression of HBV-associated chronic liver disease in Indonesian patients.

In developing countries, including Indonesia, there is a high mortality rate associated with the progression of hepatitis B virus (HBV)-associated chronic liver disease (CLD). The pathogenesis of HBV infection is influenced by viral and host factors. To determine potential associations between these factors, host single nucleotide polymorphisms (SNPs) on TNF-α, TGF-ß1 and p53, HBV X gene mutation and HBV viral load were investigated in patients with HBV-associated CLD in Surabaya, Indonesia. Sera were collected from 87 CLD patients with HBV infection. TNF-α, TGF-ß1 and p53 SNPs were genotyped by PCR restriction fragment length polymorphism. The HBV X gene was sequenced and compared with reference strains to determine mutations and the viral load was measured using reverse transcription-quantitative PCR. In Indonesian patients, no association between TNF-α, TGF-ß1 and p53 SNPs and CLD or X gene mutation were identified. A total of 23% (20/87) of samples had HBV X gene mutations, including ten substitution types, one deletion and one insertion. Multinomial regression analysis revealed that the K130M/V131I mutations were correlated with CLD progression (OR, 7.629; 95% CI, 1.578-36.884). Significant differences in viral load were found in HBV-infected patients who had X gene mutations, such as R87W/G, I127L/T/N/S and K130M/V131I mutations (P<0.05). The presence of K130M and V131I mutations may be predictive for the progression of HBV-associated CLD in Indonesia.

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.

Gastroesophageal reflux disease in an area with low Helicobacter pylori infection prevalence.

The association between gastroesophageal reflux disease (GERD) prevalence and its risk factors in an area with low Helicobacter pylori prevalence is important to clarify. We analyzed the prevalence of GERD and risk factors in an area of Indonesia with low prevalence of H. pylori infection. We recruited 104 dyspeptic patients who underwent endoscopy in Surabaya. Patients were diagnosed with GERD based on the Los Angeles classification. We evaluated gastric biopsy specimens and measured serum pepsinogen levels. Interleukin polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism. Of 104 patients, 56 (53.8%) were endoscopically found to have GERD, with most categorized as grade A; 48 (46.2%) were classified as non-GERD. Higher economic status, smoking, and a history of proton-pump inhibitor use significantly increased the risk of GERD. GERD Questionnaire scores showed a positive correlation with GERD (P < 0.001). An association was found between antral atrophic gastritis and GERD (P = 0.030), and patients with GERD more frequently had severe antral atrophy than nonerosive reflux disease (P = 0.018). We found an association between pepsinogen I/II levels and GERD (P = 0.047), but with low accuracy. IL-1ß -511 TT and CT were predominant among the IL-1ß -511 genotypes, and IL-8-251 AT and TT were predominant among the IL-8-251 genotypes. In conclusion, we found a high prevalence of GERD in an area with low prevalence of H. pylori infection, which could be associated with acid reflux. Smoking, history of proton-pump inhibitor use, and higher economic group significantly increased the risk of GERD.

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.

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.