Neneng Ratnasari

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. J. Med. Virol. 84:44–51, 2011.

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.

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.

Ultrasound-Diagnosed Non-Alcoholic Fatty Liver Disease among Medical Check Up Patients

Background : Non-alcoholic fatty liver disease (NAFLD) is recognised as one of the most important causes of chronic liver disease and has become an important health issue in many countries. The aim of the study was to evaluate the prevalence and risk factors of NAFLD patients based on ultrasound diagnosed in medical check up setting. Method : In this study, of 2,105 patients undergoing medical check up in Charitas Hospital, Palembang between January 2011 to August 2013, 115 NAFLD patients and 113 non-NAFLD patients as controls were included. Diagnosis of NAFLD was based on ultrasound appearance, patients did not consume alcohol, with negative HBsAg and hepatitis C virus antibodies. Results : The prevalence of NAFLD in medical check up patients was 7.9% whereas 39% patients had normal body mass index (BMI) (< 25 kg/m2). Patients with NAFLD compared with non-NAFLD patients had higher values of BMI (p < 0.001), triglycerides (p = 0.001), aspartate aminostransferase (AST) (p < 0.001), alanine aminotransferase (ALT) (p < 0.001), fasting glucose (p = 0.002), and lower HDL cholesterol (p = 0.001). Obesity was the strongest associated factor for NAFLD (95% CI = 1.87-7.85; OR = 3.83; p < 0.001), followed by high glucose levels (95% CI = 1.38 - 8.31; OR = 3.83; p = 0.008) and hypertriglyceridemia (95% CI = 1.38 - 4.11; OR = 2.38; p = 0.002). Conclusion : About 7.9% patients suffered from NAFLD. Approximately 39% medical check up patients had NAFLD with normal BMI. Obesity, hypertriglyceridemia and high glucose levels were the risk factors for NAFLD. Keywords : non-alcoholic liver disease, body mass index, prevalence, metabolic syndrome

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.

Non-alcoholic Fatty Liver Disease Related to Metabolic Syndrome: a Case-control Study

Background : Non-alcoholic fatty liver disease (NAFLD) is a benign condition, but it can go for years and progress to liver cirrhosis or eventually to liver cancer. Metabolic syndrome (MS) is a condition associated with NAFLD. This study was aimed to know the risk factors of NAFLD related to metabolic syndrome. Method : A case-control study was performed in NAFLD patients with or without MS and healthy individuals. All subjects were recruited from population that underwent routine medical check-up at Sardjito Hospital, Jogjakarta, during March 2007–August 2008. Diagnosis of NAFLD is defined based on clinical and liver ultrasound findings. Diagnosis of MS is defined by International Diabetes Federation on criteria for the diagnosis of MS. Data were analyzed by using T-test, ANOVA and linear regression. Odds ratio (OR) (95% CI and p < 0.05) was calculated by cross-tab analysis. Results : There were 84 patients enrolled in the study (group I = 30 NAFLD + MS subjects; group II = 26 NAFLD patients; group III = 28 healthy). The data showed statistically significant Results in waist circumference, systole blood pressure, fasting glucose, triglyceride, high density lipoprotein (HDL) cholesterol level, homeostasis models assessment index ratio (HOMA-IR), free fatty acid (FFA), and adiponectin. The ANOVA and linear regression test among NAFLD groups showed significant difference only on HDL-cholesterol and FFA level. The lowest OR was 1.674 for HDL-cholesterol and highest OR was 13.571 for triglyceride. Conclusion : The independent factors of NAFLD related to metabolic syndrome are FFA and HDL- cholesterol level, even though a decreasing of HDL-cholesterol level has a lowest risk of NAFLD. Keywords: NAFLD, metabolic syndrome, FFA, adiponectin, HDL-cholesterol

Colorectal Cancer in Young Patient: A Distinguished Disease Entity?

Background : Some studies suggested that colorectal cancer at young age had a distinct biological characteristic: more advanced stage at time of diagnosis, poorer differentiated, and consisted of large proportion of mucin producing tumors. Aim of the study : To analyze clinical and histopathological differences between young aged colorectal cancer patients (< 40 years old) and the older patients Methods : A cross-sectional retrospective study was conducted among our colorectal cancer patients in a general hospital between 1999-2004, using C.18, C.19, C20 ICD X code in medical record searching. It was requested that the patients had surgical treatment in Dr. Sardjito General Hospital. An inconclusive clinical staging and/or histological data were among the exclusion criteria. Chi-square, Fisher’s exact test, T-test, and Mann Whitney U-test was performed to analyze the difference between patients < 40 years old and ³ 40 years old, in respect to diagnostic staging, histological type, histological grade (differentiation), CEA level, hemoglobin, albumin, tumor location, and chief complain. With p < 0.05 was considered as significant. Results : Sixteen young aged (< 40 years old) and 72 older patients had been identified. No differences in gender proportion and mean of symptoms to diagnosis period between two groups. No statistical differences between young aged and the older patients in diagnostic staging, histological grade and type, CEA level, and hemoglobin. Young aged patients had higher albumin value at presentation (p = 0.014), all had left sided tumors (p = 0.035), more complain of anal pain (p < 0.001), and less change of bowel habits complain (p = 0.009) Conclusion: The study results had failed to confirm the difference in respect to diagnostic staging, histological type and grade, CEA level, and hemoglobin. Most of our young aged patients had left sided tumors with chief complain of anal pain, and less complain of change of bowel habits Keywords : Young aged colorectal cancer patients, cross sectional analysis, clinical and histological difference

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.

Maximum Tolerated Volume in Nutrient Drinking Test for Diagnosis of Functional Dyspepsia

Background. Diabetes and hypertension are related to each other and have a strong pre-disposition on the incidence of atherosclerosis. The incidence of hypertension 2 times greater in patients with DM than non DM. Endothelial dysfunction underlies these events. Endothelial markers, endothelin-1 is known to affect blood pressure. Aim. The aim of this study is to determine the difference plasma levels of endothelin-1 in type 2 diabetes mellitus in women with and without hypertension. Methods. The cross sectional design was conducted on women with type 2 diabetes mellitus with and without hypertension at metabolic and endocrinology clinic, Dr. Sardjito General Hospital Yogyakarta from July 2010 until the sample met the criterias. Subjects were divided into two groups, type 2 DM woman with hypertension groups and without hypertension. ELISA sandwich’s method was used to measure plasma levels of endothelin-1. Characteristics of the study are presented in the form of mean Kurniaatmaja et al. Results. In this research, the plasma levels of endothelin-1 in in type 2 diabetes mellitus in women with hypertension (n=32) and without hypertension (n=32) respectively 19.17±7.53 ng/ml and 13.75±6.19 ng/dl, and this difference was stastistically signifi cant with p= 0.003 CI 95% -8.87 to -1.97. Conclusion. Plasma levels of endothelin-1 in type 2 diabetes woman with hypertension higher than without hypertension.ABSTRACT Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder that can be severe and life threatening. Mortality in SLE may due to lupus activity or long-term sequel. Systemic Lupus Activity Measurement (SLAM) score is a tool that can count lupus disease activity inpatients. Aims: To analyze the relationship between SLAM score and mortality in lupus inpatients. Methods: Retrospective cohort study used for reaching objective of the study. Lupus inpatients was used as research population. Medical record was used as study data collection over periods of 2006 until 2011. Independent variable was a SLAM score. The cut point of SLAM score was made based on the mean of SLAM score (16.7 point score). Dependent variable was mortality. Results: There were differences between number of ACR criteria fi ndings, pneumonia, heart rate with SLAM score (p value 0.001; 0.001; 0.002 respectively).There was a difference of median survival between less and more than 16.7 point score, 45 and 28 respectively (p 0.034). There was a relationship between SLAM score (more than 16.7 point score) and mortality HR 2.78 (96% CI 1.01-7.53). There was a difference of mortality incidence between more and less than 16.7 point score, 0.35 and 0.10 respectively. There was a relationship between SLAM score (more than 16.7 point score) and mortality RR 3.5 (95% CI). Mortality in lupus inpatients was 23%. Conclusion: There was a relationship between SLAM score and mortality on lupus inpatients. Keywords: SLE, SLAM, MortalityABSTRACT Background . The nutritional problem is a significant role factor in determine of health, mortality and quality of life of people with HIVA with the p value was statistically insignificant. Conclusion . There was no significant correlation between nutritional statuses which is measured by the anthropometric value with the quality of life in people with HIV&AIDS. Keywords: HIV, nutrition, anthropometric, QOLABSTRACT Background : Magnesium Serum in some previous studies had been related to asthma events and severity levels. Correlation between magnesium serum levels and severity of asthma was controversies. It might be influenced by race, genetic pattern, diet and demography factor. Objective : The objective of this study was to know relationship between magnesium serum levels and predictive PEF (Peak Expiratory Flow) in chronic asthma patients in Yogyakarta. Method : This was a cross-sectional study; subjects were asthma patients who visited Pulmonology Outpatient Department in Dr. Sardjito General Hospital Yogyakarta, from September 2004 - March 2005. We performed clinical evaluation, magnesium serum levels (normal 0.65 mmol/L-1.04 mmol/L), predictive PEF and medications. Correlation between magnesium serum levels and PEF were analyzed by Pearson correlation test. This study used analysis of variance (anova) to analyze mean difference among more than 2 groups and multiple regressions to know the variables which influenced serum magnesium levels. Result : There were 62 asthma patients in this study. There was no hypomagnesaemia. The mean of magnesium was 0.89 ± 0.08 mmol/L. Results showed that serum magnesium levels and predictive PEF had weak correlation (r= 0.281; p=0.027). There was no significant correlation between admission rate to Emergency Room due to asthma by magnesium levels ( r =0.029 p = 0.8). Conclusion : Results showed weak relationship serum magnesium levels and PEF in chronic asthma patients. Keywords : bronchial asthma; serum magnesium levels, Peak Expiratory Flow rateBackground. Methods to evaluate pathophysiology of functional dyspepsia (FD) such as barostat are invasive, expensive and not readily available. Nutrient drink test was developed as noninvasive, safe and low cost means to assess impaired gastric accommodation in FD patients. The aim of this study is to evaluate whether this test could be used for diagnostic tool for FD patients. Method. A cross sectional study was conducted from July 2014 to December 2014, at Sardjito General Hospital, Yogyakarta, Indonesia. Twenty FD patients (according Rome III criteria with normal gastroscopy) were matched by age, gender and body mass index with 20 healthy controls. All of FD patient and healthy controls ingested nutrient drink tests (UltraMilk contain 0.6 kcal /mL). Maximum tolerated volume (MTV) of each subject was recorded. Sensitivity, specifi city, positive predictive value (PPV) and negative predictive value (NPV) were analyzed.Results. Using ≤ 950 mL of maximum tolerated volume as cut off point, sensitivity, specificity, PPV and NPV were 95%, 100%, 100% and 95%. Conclusions. A nutrient drinking test can discriminate between FD patients and healthy controls with high sensitivity and specifi city. This test could be used as objective, safe and non-invasive diagnostic tool for FD patients.ABSTRACT Introduction . Hemodialysis patients experience major changes in lifestyle and suffer various physical and emotional symptoms, especially symptoms of depression and sexual dysfunction in more than half of patients. Sexual dysfunction in women is often not identified because of lack of attention, especially by the clinician. Symptoms of depression limit intimacy, and affect sexual arousal and orgasm. Aim : the aim of the study was to determine the correlation between depressive symptoms and female sexual function index (FSFI) in women hemodialysis patients in the Hemodialysis Unit of Dr. Sardjito General Hospital Yogyakarta. Methods . The method of this study was cross-sectional. Research was conducted at the Hemodialysis Unit by Dr. Sardjito General Hospital Yogyakarta from 10 April to 24 April 2012. Result . There were 42 female patients undergone routine hemodialysis who met the criteria. The median age was 49 years old and had undergone hemodialysis for a median duration of 40 months. Conclusion . There was a negative correlation of depression symptoms and female sexual dysfunction with a moderate strength (r = -0.421) and statistical significantly (P <0.05). Age and prolactin had a negative correlation with a moderate strength of FSFI score. HDL levels and menstrual status had a positive correlation with FSFI, with weak and strong correlation respectively. Key Words : Female sexual function index, depression, hemodialysisABSTRACT Background . Depression is more common in persons with chronic illnesses such as diabetes, epilepsy and infection of Human Immunodeficiency Virus (HIV). Depression can make HIV worse. Antidepressant may need, but there can be interaction and side effect when use Antiretroviral (ARV) and antidepressant in combination. Complementary and alternative medicine (CAM) include Latihan Pasrah Diri(LPD) may seem safe to treat depression in HIV patient. Methods. This is a quasi experimental study, participant include outpatient dan inpatient at RSUP Dr. Sardjito, Yogyakarta. They were aged >18 years. After scoring with Zung Self Rating Scale for depression, participants allocated into two groups, with dan without Latihan Pasrah Diri program. Zung Self Rating Scale for depression was evaluated after 1 cycle of program. Result. The means of Zung Self-Rating Depression Scale score before and after LPD were 42,21 ± 9,3 and 35 ± 10,73 (p 0,003). While in control group (without LPD / brief psychotherapy) the means of Zung Self-Rating Depression Scale score before and 3 weeks after brief psychotherapy were 42,93 ± 7.45 and 39,36 ± 7,69 (p 0,019). Statistically there was no significancy in the means of delta Zung Self-Rating Depression Scale in LPD group and control group. Conclusion. It was concluded from this study that there is an influence on the improvement of depressive symptoms post- Latihan Pasrah Diri program to people with HIV / AIDS. Key words: depression, HIV, Latihan Pasrah Diri, Zung Self-Rating ScaleINTRODUCTION The word sepsis is derived from the Greek term for rotten or “to make putrid”. Sepsis, defined as the systemic host response to microorganisms in previously sterile tissues, is a syndrome related to severe infections and is characterized by end-organ dysfunction away from the primary site of infection. To meet the definition of sepsis, patients need to satisfy at least two of the Systemic Inflammatory Response Syndrome (SIRS) criteria in association with having a suspected or confirmed infection. The severity and mortality increase when this condition is complicated by predefined organ dysfunction (severe sepsis) and cardiovascular collapse (septic shock). The normal host response to infection is complex, aiming to both identify and control pathogen invasion and start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to anti-inflammatory and proinflammatory responses. Exacerbating these mechanisms can cause a chain of events that leads to sepsis, promoting massive liberation of mediators and the progression of multiple organ dysfunction 1 . Sepsis remains a critical problem with significant morbidity and mortality even in the modern era of critical care management. Despite intense efforts, sepsis remains a serious clinical problem and still associated with a high mortality rate. Septic shock and sequential multiple organ failure/dysfunction syndrome (MOF/MODS) correlate with poor outcome, and septic shock is the most common cause of death in intensive care units. A recent review by Angus et al estimated the 1995 incidence of sepsis in the United States to be 751,000 cases, resulting in 215,000 deaths. The average cost per case of sepsis was

Gallstones and Choledocolithiasis with Severe Cholestatic Jaundice in beta-Thalasemia Intermedia Patient

22,100 with total costs of