Rapid Malignant Transformation of Tubulovillous Adenoma, Initially Presenting as McKittrick-Wheelock Syndrome: A Case Report.

Most cases of colorectal cancer develop from adenomatous polyps, slowly progressing within an average period of 8-10 years. McKittrick-Wheelock syndrome (MKWS) is a rare manifestation of tubulovillous adenoma. It generally presents as hypersecretory diarrhea with severe electrolyte and fluid depletion. Roughly, 5% of the published cases have reported malignant histopathology associated with MKWS, with little to no data regarding the malignant transformation process of those patients. Our patient was a 53-year-old Asian woman suffering from chronic secretory diarrhea, resulting in severe volume, electrolyte depletion, and prerenal azotemia, consistent for MKWS. Her symptoms initially improved with sulfasalazine but eventually worsened. She demonstrated signs of systemic (elevated leukocyte, CRP, and LDH) and local inflammation (dense lymphocyte infiltration in colorectal tissue) throughout the course of her disease. Serial pathological results showed rapid neoplastic progression of adenomatous polyp to adenocarcinoma within 1 year period. Surgical resection resulted in complete symptom resolution. Molecular examination showed a favorable profile of exon 4 Kirsten rat sarcoma viral oncogene homolog mutation, normal NRAS, BRAF, CDX2, and CK20 expressions. Her molecular pattern did not reflect the profile of an aggressive disease, suggesting the possibility of oncogenic processes outside the major pathways of adenoma to carcinoma progression. Chronic inflammation is a well-established risk factor for colorectal cancer, and prostaglandin E2 (PGE2) has been observed as one of the key regulators of tumor initiation and growth. PGE2 is also responsible for hypersecretory diarrhea associated with MKWS.

Abdominal Pain Due to Eosinophilic Gastroenteritis Diagnosed in 25-Year-Old and 27-Year-Old Sisters with a Family History of Asthma.

BACKGROUND Eosinophilic gastroenteritis (EG) can be associated with parasitic infections, atopic drug reactions, or atopic diseases, such as asthma. This report describes 25-year-old and 27-year-old sisters with a family history of asthma who presented with abdominal pain due to EG. CASE REPORT Case 1: A 25-year-old woman presented with a 4-month history of chronic left upper quadrant abdominal pain that did not improve with proton pump inhibitor and sucralfate therapy. She has a history of asthma and allergic rhinitis. Endoscopic pathology revealed pangastritis, with eosinophilic infiltration >25 per 1 high power field. Case 2: Her 27-year-old sister was admitted with chronic abdominal discomfort in the form of vomiting and recurrent abdominal pain for the past 2 years. Treatment with proton pump inhibitors and sucralfate did not lead to improvement. She also had intermittent asthma. Pathological findings on her endoscopy showed chronic inflammation of the fundus and antrum, with eosinophilic infiltration >40 per 1 high power field. Association of eosinophilic gastrointestinal diseases in siblings has not been reported previously. CONCLUSIONS This report has highlighted that atopic disease, such as asthma, is often familial, and can be associated with generalized eosinophilia, including EG. In these 2 sisters, the clinical history and histological findings on colonic biopsy were important to confirm the diagnosis.

Update on Non-Alcoholic Fatty Liver Disease-Associated Single Nucleotide Polymorphisms and Their Involvement in Liver Steatosis, Inflammation, and Fibrosis: A Narrative Review

Genetic factors are involved in the development, progression, and severity of non-alcoholic fatty liver disease (NAFLD). Polymorphisms in genes regulating liver functions may increase liver susceptibility to NAFLD. Therefore, we conducted this literature study to present recent findings on NAFLD-associated polymorphisms from published articles in PubMed from 2016 to 2021. From 69 selected research articles, 20 genes and 34 SNPs were reported to be associated with NAFLD. These mutated genes affect NAFLD by promoting liver steatosis (PNPLA3, MBOAT7, TM2SF6, PTPRD, FNDC5, IL-1B, PPARGC1A, UCP2, TCF7L2, SAMM50, IL-6, AGTR1, and NNMT), inflammation (PNPLA3, TNF-α, AGTR1, IL-17A, IL-1B, PTPRD, and GATAD2A), and fibrosis (IL-1B, PNPLA3, MBOAT7, TCF7L2, GATAD2A, IL-6, NNMT, UCP, AGTR1, and TM2SF6). The identification of these genetic factors helps to better understand the pathogenesis pathways of NAFLD.

Potential plasma biomarkers: miRNA-29c, miRNA-21, and miRNA-155 in clinical progression of Hepatocellular Carcinoma patients.

This study evaluated differences in the clinical appearance of patients with hepatocellular carcinoma (HCC) based on plasma level and regulation of microRNAs (miRNA-29c, miRNA-21, and miRNA-155). The observational-analytical study with a cross-sectional design was conducted on 36 HCC patients and 36 healthy controls. The blood samples were collected from 2 Province Hospitals (Dr. Sardjito Hospital and Prof. Dr. Margono Soekarjo Hospital) for HCC and the Blood Bank Donor of the Indonesian Red Cross for 36 healthy controls. These blood samples were treated as follows: plasma isolation, RNA isolation, cDNA synthesis, quantification by qRT-PCR using a sequence-specific forward primer, and normalization of miRNA using housekeeping-stably miRNA-16. There were only 27 HCC patients with complete clinical variables (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet count, albumin, C-reactive protein (CRP), and cholinesterase (ChE)) that were able to analyses for regulation miRNAs based on its fold change expression miRNA target. All 27 HCC subjects were follow-up until 3-years of monitoring for their overall survival. The miRNA plasma expression was analyzed by Bio-Rad CFX 96 Manager software to determine the cycle of quantification, followed by the calculation of expression levels using Livak's methods. Data were analyzed using STATA 11.0, with a significant value of p<0.05. The miRNAs expression of HCC subjects were lower than that healthy control subjects in miRNA-29c (down-regulation 1.83-fold), higher than that healthy control subjects in miRNA 21 and miRNA-155 (up-regulation, 1.74-fold; 1.55-fold) respectively. NLR, CRP, ChE, and platelet count showed a significant difference in miRNA-29c regulation, though neutrophil count showed a significant difference in miRNA-21 and miRNA-155 regulation (p<0.05). Conclusion: Plasma biomarkers: miRNA-21 and miRNA-155 might be potential biomarkers as onco-miR in HCC subjects, while miRNA-29c might act as a tumor suppressor. Significant evidence was identified with clinical progression based on the regulation of miRNAs, which was consistent with miRNA -29c.

Potential relative quantities of miR-122 and miR-150 to differentiate hepatocellular carcinoma from liver cirrhosis.

Cirrhosis and hepatocellular carcinoma (HCC) are related to chronic liver diseases. Diagnostic algorithms are needed to discriminate HCC from cirrhosis for better patient management. This study aimed to determine the potential of miR-122 and miR-150 to differentiate HCC from liver cirrhosis. This study used a cross-sectional method involving 66 patients with liver cirrhosis, 27 subjects with HCC, and 29 healthy controls. Examination of miR-122 and miR-150 levels from blood plasma used real-time quantitative polymerase chain reaction and their relative expressions were calculated. Clinical and laboratory data were collected and graphed for the Area Under the Curve (AUC) and also for comparison using unpaired T-tests, Kruskal-Wallis, Mann-Whitney, and Chi-square tests with significance set as p < 0.05. The relative expressions of miR-122 and miR-150 could differentiate HCC from cirrhosis, with cut-off 9.11, AUC 53.84%, p = 0.2120, and cut-off 1.47, AUC 67.65%, p = 0.0001, respectively. Meanwhile, the combined relative expressions of miR-122 and miR-150 can distinguish HCC from cirrhosis, with AUC 71.94%, p = 0.0006. The combination of miR-122 and miR-150 has the potential as a biomarker to differentiate HCC from liver cirrhosis.

Overview of Helicobacter pylori Infection in Indonesia: What Distinguishes It from Countries with High Gastric Cancer Incidence?

Helicobacter pylori infects more than half the human population. However, the prevalence in Indonesia is low, as is the prevalence of gastric cancer. Hence, it could be instructive to compare these prevalence rates and their determining factors with those of countries that have high gastric cancer incidence. Ethnicity and genetic characteristics of H. pylori are important determinants of the H. pylori infection rate in Indonesia. The infection rate is higher in Bataknese, Papuans and Buginese than in Javanese, the predominant ethnic group. Ethnicity is also an important determinant of the genetic characteristics of H. pylori. Analysis of CagA in the EPIYA segment showed that the predominant genotypes in Papuans, Bataknese and Buginese are ABB-, ABDand ABC-type CagA, respectively. Meanwhile, in the countries with high gastric cancer incidence, almost all strains had East Asian type CagA. An antibiotic susceptibility evaluation showed that the standard triple therapy can still be used with caution in several cities. There is a very high rate of resistance to second-line regimens such as levofloxacin and metronidazole. Recent studies have shown that furazolidone, rifabutin and sitafloxacin are potential alternative treatments for antibiotic-resistant H. pylori infection in Indonesia. Rather than focusing on early detection and eradication as in countries with high gastric cancer prevalence, countries with low gastric cancer prevalence should focus on screening the several groups that have a high risk of gastric cancer.

The Effectiveness of Right- vs Left-lateral Starting Position in Unsedated Diagnostic Colonoscopy with Modified-water Immersion Method: A Randomized Controlled Trial Study.

OBJECTIVE: A colonoscopy study in sedated patients with air insufflation showed that right-lateral starting position (RLP) improved abdominal discomfort and reduced cecal intubation time. The aim of this study was to determine if RLP vs left-lateral starting position (LLP) may produce similar results in unsedated patients examined with a modified-water immersion (m-WI) method. METHODS: Consecutive patients for diagnostic colonoscopy meeting the inclusion criteria were randomized. Patients and colonoscopist were unblinded. The m-WI method entailed suction during insertion not only for fecal debris evacuation but also to facilitate passage through difficult or angulated colonic flexures. Water was infused as needed when any difficulty was encountered during insertion. A bowel visualization scale (BVS) (0=totally blurred visualization; 1=blurred lumen visualization; 2=small fecal debris with clear mucosa visualization; 3= clear visualization) was used to evaluate the interference of fecal debris with cecal intubation rate and time. RESULTS: A total of 142 patients (72 in RLP and 70 in LLP) were enrolled. The respective pain score, visual analog scale, (VAS) and cecal intubation rate were not significantly different. The cecal intubation time was nearly significantly different (13.4±4.5 min vs 11.7±5.4 min; p=0.054) and was significantly different in the constipation subgroup (16.0±3.5 min vs 8.6±3.8 min; p=0.001). The cecal intubation time based on BVS showed significant difference between RLP and LLP in Scale 2 (13.9±4.6 min vs 10.3±4.2 min; p=0.003) and Scale 2 and 3 combined (13.2±4.3 min vs 10.6±4.8 min; p=0.01), respectively. CONCLUSION: RLP did not improve the pain score, and LLP showed better performance in unsedated m-WI colonoscopy patients (ClinicalTrial.gov, NCT03489824).

E-test versus agar dilution for antibiotic susceptibility testing of Helicobacter pylori: a comparison study.

OBJECTIVE: For evaluating the antibiotic resistance of Helicobacter pylori, the agar dilution method is the gold standard; however, using this method in daily practice is laborious. E-test has been proposed to be an uncomplicated method. This study was aimed at validating the E-test and detecting the presence of any bias between the agar dilution method and E-test. RESULTS: The agar dilution method and E-test were performed using five antibiotics for 72 strains of H. pylori obtained from clinical patients in Indonesia. The E-test's results showed a higher prevalence of resistance to all the antibiotics tested but the difference was not significant. Results showed high essential agreement (> 90.0%) for all the antibiotics, but only 84.7% for metronidazole. The agreement for MIC value was acceptable for levofloxacin, clarithromycin, and metronidazole. For amoxicillin, it showed only fair agreement (0.25) by the Kappa analysis and significant difference by Passing-Bablok regression. Even though some discrepancies were found, the E-test has an acceptable agreement for levofloxacin, metronidazole, tetracycline, and clarithromycin but further confirmation may be necessary for amoxicillin.

"Sarcopenia and intramuscular fat deposition are associated with poor survival in Indonesian patients with hepatocellular carcinoma: a retrospective study".

BACKGROUND: A large-scale Japanese study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients. METHODS: SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan-Meier method and Cox regression model to investigate which factors are associated with prognosis. RESULTS: Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm2/m2 for men and ≤ 29.6 cm2/m2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤ 39.3 HU for women). These groups had shorter median survival than the reference groups (both P < 0.0001). In multivariable analysis, sarcopenia (hazard ratio [HR], 1.921; P = 0.016), IMF deposition (HR, 3.580; P < 0.001), Barcelona Clinic Liver Cancer (BCLC) stages C and D (HR: 2.396, P < 0.01 and HR: 6.131, P < 0.01, respectively), Japan Integrated Staging (JIS) score 4 (HR: 2.067, P = 0.020), and male gender (HR: 3.211, P < 0.001) were independently associated with mortality. CONCLUSION: Sarcopenia and IMF deposition showed superior value in combination with BCLC stage and JIS score for predicting the survival of Indonesian HCC patients. Increased awareness and strategies to prevent or reverse these factors might improve patient outcomes. (Electric word counts: 249).

Endoscope-connected water pump with high flow rates improves the unsedated colonoscopy performance by water immersion method.

OBJECTIVES: The aim of this study was to determine if different water pump flow rates influence the insertion time of water immersion method in unsedated patients. We tested the hypothesis that high flow rate (HFR) is more effective than low flow rate (LFR) in facilitating insertion. Clinical registration number: NCT01869296. METHODS: Consecutive symptomatic patients without prior abdominal surgery were consented and enrolled. They were randomized to an HFR (10.4 mL/s) or LFR (1.7 mL/s) group. The patients were not informed about the flow rate of the water pump (single blinded). Patients underwent unsedated colonoscopy examination with standard colonoscope. Demographic and procedural parameters were recorded. Data were analyzed with Student's t-test or Chi-square test as appropriate. RESULTS: A total of 132 patients (66 in HFR and 66 in LFR group) were recruited. The HFR group showed significantly shorter cecal intubation time (12.5±6.2 min in HFR vs 16.3±7.3 min in LFR, p=0.004), shorter time to pass rectosigmoid (3.6±2.2 min in HFR vs 6.2±4.6 min in LFR, p<0.001), and lower pain score (4.2±2.8 in HFR vs 5.3±2.6 in LFR, p=0.024). The cecal intubation rate was not significantly different (87.9% in HFR vs 80.3% in LFR, p=0.34), and 29 (14 in HFR and 15 in LFR) patients with signs of colon redundancy were successfully intubated to the cecum after repeated loop reduction and position changes. CONCLUSION: Compared to LFR, HFR of the water infusion pump significantly reduced colonoscopy insertion time and pain score in unsedated patients. Significantly shorter time to pass the rectosigmoid appeared to play a contributory role.

Genetic polymorphisms of HLA-DP and isolated anti-HBc are important subsets of occult hepatitis B infection in Indonesian blood donors: a case-control study.

BACKGROUND: Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the serum and/or liver in HBsAg-negative individuals. OBI is associated with the risk of viral transmission, especially in developing countries, and with progressive liver disease and reactivation in immunosuppressive patients. The objective of this study was to evaluate the relation of OBI to HLA-DP single nucleotide polymorphisms (SNPs) encoding antigen-binding sites for the immune response to HBV infection. As HLA-DP variants affect the mRNA expression of HLA-DPA1 and HLA-DPB1 in the liver, we hypothesised that high levels of HLA-DPA1 and HLA-DPB1 expression favour OBI development. METHODS: The study enrolled 456 Indonesian healthy blood donors (HBsAg negative). OBI was defined as the presence of HBV-DNA in at least two of four open reading frames (ORFs) of the HBV genome detected by nested PCR. SNPs in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs2281388) were genotyped using real-time Taqman® genotyping assays. RESULTS: Of 122 samples positive for anti-HBs and/or anti-HBc, 17 were determined as OBI. The minor allele in rs3077 was significantly correlated with OBI [odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.58-9.49, p = 0.0015]. The prevalence of the minor allele (T) was significantly higher in subjects with OBI than in those without (59% and 33%, respectively). The combination of haplotype markers (TGA for rs3077-rs3135021-rs9277535) was associated with increased risk of OBI (OR = 4.90, 95%CI = 1.12-21.52 p = 0.038). The prevalence of OBI was highest in the isolated anti-HBc group among the three seropositive categories: anti-HBs <500 mIU/ml, anti-HBs ≥500 mIU/ml, and isolated anti-HBc (29.41%, p = 0.014). CONCLUSION: Genetic variants of HLA-DP and the presence of anti-HBc are important predictors of OBI in Indonesian blood donors. TRIAL REGISTRATION: Ref: KE/FK/194/EC; registered 01 March 2013. Continuing approval Ref: KE/FK/536/EC; registered 12 May 2014.

Difference of polymorphism VEGF-gene rs699947 in Indonesian chronic liver disease population.

BACKGROUND: The VEGF gene polymorphism rs699947 related to clinical pathology, mortality, and recurrence of HCC. Few studies mentioned an association between VEGF gene polymorphisms with illness progression in chronic liver disease. We aimed to explore differences of VEGF gene polymorphism rs699947 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma patients in Indonesian population. METHODS: A cross-sectional study with consecutive sampling and without matching was performed during a 3 years period (2011-2014) at Dr. Sardjito General Hospital Yogyakarta, Indonesia. Blood DNA was sequenced from 123 subjects with chronic liver diseases [39 chronic hepatitis (CH), 39 liver cirrhosis (LC), and 45 hepatocellular carcinoma (HCC)]. 59 healthy subjects also participated. Using isolated VEGF genes for specific primers for rs699947, blood samples were examined by targeting DNA sequences with Applied Bio systems. All data were analyzed using STATA version 11.0 with significance level at P<0.05. RESULTS: The mean of age in HCC and LC subjects were older than in CH and healthy (P value <0.05); there were more males in LC, HCC and the healthy groups but not in CH (P>0.05). HBV was the dominant etiology in HCC, LC, and CH besides HCV and non HBV-HCV (P<0.05). There were significant differences in the SNP -2578 distributions of allele C compared to allele A in all subjects (healthy vs. LC, and HCC; LC vs. CH (P<0.05), but no significant difference A>C vs. C>C, and genotypes distribution. Proportion of SNP -2578 A>C vs. C>C CH 1.8:1; HCC 1.4:1; healthy 1.7:1; but its proportion in LC was inversed (1:1.2). Genotype A was low in all subjects (5%-11%). Significant difference of allele distribution was found in healthy vs. LC, and HCC; CH vs. LC. Based on HWE analyses, distribution of allele C was dominant. There were not significant differences in deletion, insertion-deletion at -2547 until -2526, and haplotype (Ht) CCGACCCC (P>0.05). The OR analyses of allele and SNP showed that allele A can be a predictor of disease progression in LC to HCC (OR 2.26) and healthy to LC (OR 1.65); and SNP A>C also can be a predictor in healthy to HCC (OR 1.41) and CH (OR 1.14). CONCLUSION: The occurrence of allele A and SNP A>C VEGF gene (-2578) might predict illness progression from healthy to CH, LC or HCC and LC to HCC.

Different Variants in Reverse Transcriptase Domain Determined by Ultra-deep Sequencing in Treatment-naïve and Treated Indonesian Patients Infected with Hepatitis B Virus.

A nucleos(t)ide analog (NA) is the common antiviral drug available for directly treating hepatitis B virus (HBV) infection. However, its application has led to the emergence of NA-resistant mutations mostly in a conserved region of the reverse transcriptase domain of HBV polymerase. Harboring NA-resistant mutations decreases drug effectiveness and increases the frequency of end-stage liver disease. The invention of next-generation sequencing that can generate thousands of sequences from viral complex mixtures provides opportunities to detect minor changes and early viral evolution under drug stress. The present study used ultra-deep sequencing to evaluate discrepant quasispecies in the reverse transcriptase domain of HBV including NA-resistant hotspots between seven treatment-naïve Indonesian patients infected with HBV and five at the early phase of treatment. The most common sub-genotype was HBV B3 (83.34%). The substitution rate of variants determined among amino acids with a ratio of ≥ 1% changes was higher among the population in conserved regions (23.19% vs. 4.59%, P = 0.001) and in the inter-reverse transcriptase domain (23.95% vs. 2.94%, P = 0.002) in treatment naïve, than in treated patients. Nine hotspots of antiviral resistance were identified in both groups, and the mean frequency of changes in all patients was < 1%. The known rtM204I mutation was the most frequent in both groups. The lower rate of variants in HBV quasispecies in patients undergoing treatment could be associated with virus elimination and the extinction of sensitive species by NA therapy. The present findings imply that HBV quasispecies dynamically change during treatment.

The role of vascular endothelial growth factor -634 G/C and its soluble receptor on chronic liver disease and hepatocellular carcinoma.

BACKGROUND AND STUDY AIMS: The single nucleotide polymorphism (SNP) of the vascular endothelial growth factor (VEGF) gene -634 G/C (rs2010963) influences the progression of hepatocellular carcinoma (HCC). There have been no studies on the role of VEGF SNP -634 G/C in chronic liver disease (CLD). The aim of the present study was to analyse the correlation between VEGF SNP -634 and the clinical severity of CLD and HCC. PATIENTS AND METHODS: A cross sectional study was conducted on 182 subjects (46 HCC, 39 liver cirrhotic/LC, 38 chronic hepatitis/CH; and 57 healthy subjects). The study was conducted from 2010 to 2014 at the Dr. Sardjito Hospital Yogyakarta, Indonesia. All subjects submitted blood serum for DNA sequencing examination using primer. The clinical data of CLD and HCC were assessed, and sVEGFR-2 was examined in 149 subjects. All data were analysed using STATA programme 11.0. RESULTS: Significant differences were observed in genotypic frequency (GG/GC/CC) between HCC, LC, CH and healthy subjects (p=0.004), but though no significant differences were observed between the G>G and C>G genotypic frequencies (p=0.337). The frequency of genotype GG was significantly higher than genotype GC or CC in HCC and was associated with declining of clinical conditions (p<0.05). No significant difference in the distribution genotypes was observed with respect to the level of sVEGFR-2 in the serum. However, we observed a significant correlation between sVEGFR-2 and clinical characteristics in LC and CH (p<0.05). CONCLUSION: Genotype GG of the VEGF SNP -634 is the dominant genotype in severe CLD and HCC. sVEGFR-2 correlates with the disease severity but is not directly associated with the SNP -634 genotype.

Are Mucosa CD4+/CD8+ T-Cells Expressions Correlated with the Endoscopic Appearance of Chronic Gastritis Related with Helicobacter pylori Infection?

Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h)1 cytokine-producing CD4+ and CD8+T-cells Objective. To investigate the correlation between CD4+/CD8+ T-cells in gastric mucosa with endoscopic appearance in chronic gastritis with or without H.pylori infection. Prospective, cross sectional study is performed in a chronic dyspepsia population in July-November 2009 at Dr. Sardjito General Hospital Yogyakarta, Indonesia. The update Sydney system was used to analyze the gastroscopy appearance. Biopsy specimens were stained with HE-stain and IHC-stain. Data were analyzed by t-test, Mann-Whitney and Spearman correlation test. Number of 88 consecutive subjects are enrolled the study (50% male; 50% female), age 46±15 years; 25% H.pylori positive. The expression of CD4+ and CD8+ were higher in H.pylori negative subjects, but only the CD4+ was significant (P=0.011). A significant correlation was found between CD4+ and CD8+ in both subjects (r(Hp+)=0.62 and r(Hp-)=0.68; P<0.05). The expression of CD4+ and CD8+ in H.pylori positive showed a significant correlation with gastric lesions (r(CD4+)=-0.60; r(CD8+)=-0.42 ; P<0.05), only erosion showed a significant difference in both subjects. A positive correlation was found between CD4+ and CD8+ infiltration in both subjects with or without H.pylori infection, and a negative correlation was only found between gastric lesion with CD4+ and CD8+ infiltration in H.pylori subject.

Protective effects of HLA-DPA1/DPB1 variants against Hepatitis B virus infection in an Indonesian population.

Human leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen presentation to CD4(+) helper T cells and influences the outcome of HBV infection. To investigate the influence of HLA-DP variants on the outcome of HBV infection in an Indonesian population where it has the third-highest prevalence of HBV infection worldwide, we performed a case-control study of 686 participants, including patients with HBV-related advanced or nonadvanced liver disease, patients with spontaneously resolved HBV, and healthy controls. Single-nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs228388) were genotyped using real-time TaqMan® genotyping assays. Because rs2281388 deviated from Hardy-Weinberg equilibrium, it was excluded from subsequent analyses. The results of logistic regression analyses showed that the HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52-0.96, P=0.026, additive genetic model; OR 0.60, 95% CI 0.38-0.96, P=0.033, dominant genetic model). The HLA-DPA1 rs3077 variant was associated with a protective effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41-0.98, P=0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021 variant was not associated with the outcome of HBV infection, including susceptibility, spontaneously resolved, or disease progression. Combinations of haplotype markers were also associated with HBV susceptibility (CA for rs3077-rs9277535, OR 0.57, 95% CI 0.36-0.92, P=0.021; GA for rs3135021-rs9277535, OR 0.56, 95% CI 0.36-0.86, P=0.0087). In conclusion, these findings confirm that HLA-DPA1/DPB1 variants were associated with the outcomes of HBV infection in an Indonesian population.

Soluble Vascular Endothelial Growth Factor Receptor-2 as a Predictive Factor for Progression of Illness in Chronic Liver Diseases and Hepatocellular Carcinoma.

Angiogenesis is generally induced in the process of necro-inflammation and regeneration in chronic liver diseases (CLD). Whereas VEGF is a major humoral factor in relation to neo-vascularization, the receptor, VEGFR-2, is located in hepatocytes and sinusoid endothelial cells. The aim in this study is to investigate the significance of soluble form of VEGFR-2 (sVEGFR-2) in various CLDs. A cross sectional study was conducted from 2010 to 2013 at Dr. Sardjito Hospital Yogyakarta, Indonesia. 149 patients with chronic hepatitis (CH), liver cirrhosis (LC) or hepatocellular carcinoma (HCC) were enrolled in this study. sVEGFR-2 serum was examined using Quantikine®HS kit human immunoassay. Data were analyses by STATA (P value <0.05). The median of sVEGFR-2 was decreased according to the disease progression (LC: 7014.95 pg/mL; CH: 8805.15 pg/mL; healthy subject: 9785.2 pg/mL). However, sVEGFR-2 in HCC (8043.73 pg/mL) was significantly higher than that in LC (P= 0.0059). Based on AUROC analyses, the clinical cut-off point of sVEGFR-2 with >80% sensitivity was used (CH-LC ≤7236.7, LC-HCC ≥7215). The odds ratio (OR) LC to HCC was 5.87 and CH to LC was 4.63. The significant correlations were showed significantly between sVEGFR-2 with MELD and ALT in LC, and with APRI and FIB-4 in CH. In conclusion, the serum sVEGFR-2 could be used as a predictive factor progressing CH to LC, but not HCC.

Mutations within enhancer II and BCP regions of hepatitis B virus in relation to advanced liver diseases in patients infected with subgenotype B3 in Indonesia.

Studies on the characteristics of mutations within the hepatitis B virus (HBV) genome, their roles in the pathogenesis of advanced liver diseases, and the involvement of host properties of HBV-infected individuals have not been conducted in subgenotype B3-infected populations. For addressing this issue, 40 cases with HBV surface antigen (HBsAg)-positive advanced liver diseases, including advanced liver cancer and cirrhosis (male 31, female 9, age 54.4 ± 11.6-year-old), were collected and compared with 109 cases with chronic hepatitis B (male 71, female 38, age 38.0 ± 13.4-year-old). Mutations in enhancer II (Enh II) and basal core promoter (BCP)/precore regions were analyzed by PCR-direct sequencing method. HBV viral load was examined by real-time PCR. For all examined regions, the prevalence of mutation was significantly higher in cases with advanced liver diseases. Multivariate analysis showed that, in patients older than 45 years, C1638T and T1753V mutations constituted independent risk factors for the advancement of liver diseases. The presence of C1638T and T1753V mutations may serve as predictive markers for the progression of liver diseases in Indonesia and other countries, where subgenotype B3 infection is prevalent.

Abdominal malignant fibrous histiocytoma infiltrating stomach with Chilaiditi's sign manifestation (a rare case report).

The incidence and mortality rate of gastric cancer are decreasing within last 60 years. Approximately 85% of gastric cancer is carcinoma where as the rest 15% is lymphoma and sarcoma. Leiomyosarcoma is the most frequently encountered sarcoma in stomach and represents 1-3% gastric cancer. This tumor is frequently located in the anterior and posterior wall of gastric fundus accompanied by ulceration and bleeding. Malignant fibrous histiocytoma (MFH) is a soft tissue tumor with poor prognosis, rarely found in stomach. This tumor is most frequently originated from inner fascia or skeletal muscle (58-75%) and most frequently happen in the peritoneal cavity and abdomen (9-16 %). We reported a 45-year-old woman with abdominal MFH which infiltrated to the lesser curvature of stomach with Chilaiditi sign. Chilaiditi sign is a condition of intestine disposition (usually at the hepatic flexure of colon) which lies between liver and diagfragma, found in 0.1 ? 0.25% cases which is diagnosed by chest X Ray. This case is a very rare case.