Factors Associated with Hepatitis B and Hepatitis C among Infected Patients in Indonesia and Their Knowledge and Attitude: A Multicenter Observational Study.

BACKGROUND: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections are global health problems, including in Indonesia. The purpose of this study was to assess the knowledge and attitudes about HBV and HCV infection among infected patients in Indonesia. METHODS: This cross-sectional study used a questionnaire survey. The questionnaire was adapted and translated into Indonesian language, and trialed with 27 HBV and 27 HCV patients. The final validated questionnaire was later used in the target population. Patients diagnosed with Hepatitis B or Hepatitis C were included. The patients were enrolled from November 2019 until February 2020 in sixteen multicenter locations. Multivariate analysis with logistic regression was conducted to determine the factors that are associated with the knowledge and attitude among HBV and HCV patients toward their illness. RESULTS: A total of 931 HBV patients and 254 HCV patients were included in this survey. The proportion of infected patients with adequate knowledge of Hepatitis B and Hepatitis C was 72.1% and 53.9%, respectively. Positive attitudes about Hepatitis B and Hepatitis C were 28.5% and 41.3%, respectively. Multivariate analysis revealed that higher education level, higher income level, diagnosis duration of more than 5 years, and receiving of antiviral therapy were independent factors associated with adequate knowledge about Hepatitis B among HBV patients. Among HCV patients, independent factors associated with adequate knowledge about Hepatitis C were being married, higher education level, higher income level, and receiving antiviral therapy. Moreover, older age and receiving of antiviral therapy were independent factors associated with positive attitudes towards Hepatitis B among HBV patients. However, only higher education level was found to be an independent factor associated with positive attitudes towards Hepatitis C among HCV patients. CONCLUSION: The knowledge and attitude of patients regarding HBV and HCV were quite low among infected patients in Indonesia.

Rare Case: Unilateral Acute Primary Angle-closure Glaucoma After Colonoscopy in Malang, East Java, Indonesia.

Glaucoma is a heterogeneous group of optic neuropathies characterized by a progressive loss of retinal ganglion cells (RGCs) with corresponding visual field defects, and one of the main risk factors is elevated intraocular pressure (IOP). Furthermore, colonoscopy procedures require insufflation of the colon lumen with gases which can increase intraabdominal pressure (IAP) and ends with an elevation of IOP. Glaucoma is an infrequent complication due to colonoscopy; in this case, a 63 years-old woman was diagnosed with glaucoma after a colonoscopy procedure. A few hours after the colonoscopy, the patient suffered blurred vision in the left eye, and the physical examination revealed mixed conjunctival and ciliary injection with visual acuity of 1/300. There was an increase in IOP with a value of 40,2 mmHg on Schiotz tonometry. This case presented the pitfalls of the procedure and the importance of taking glaucoma awareness before a colonoscopy.

Liver Cirrhosis in Woman with Ciliopathy Syndrome.

Ciliopathy syndrome is a congenital abnormality of structure and/or function of cilia, which causes pleiotropic disorder, including liver cirrhosis. This study aimed to describe a unique case of liver cirrhosis with possible aetiology of ciliopathy syndrome. A 44 year-old woman with chief complain of hematemesis had diabetes mellitus, obesity, dyslipidaemia, amenorrhoea and often became unconscious. We found short stature, brachydactyly, hyperpigmented maculae in trunk and four limbs, and hepatosplenomegaly. The laboratory results showed: haemoglobin 7.4 g/dl; albumin 2.42 g/dl; urea 84.8 mg/dl; creatinine 2.4 mg/dl; prolactin 138.8 ng/ml, while HBsAg was negative and anti-HCV was non-reactive. Abdominal ultrasonography showed liver cirrhosis; endoscopy showed grade 3 oesophageal varicose; FibroScan showed 75 kPa; liver biopsy showed hydropic degeneration and cirrhosis; and head CT scan showed chronic lacunar infarction of corona radiata and mega cisterna magna occipital. We reported female with oesophageal varicose rupture, short stature, brachydactyly, obesity, diabetes mellitus, dyslipidaemia, hyperpigmented maculae, liver cirrhosis and mega cisterna magna, which was likely to suffer from ciliopathy syndrome.

An 18-Year-Old Man with Idiopathic Non-cirrhotic Portal Hypertension.

Non-Cirrhotic Portal Hypertension (NCPH) is a rare cause of hematemesis and melena. Like in cirrhotic patient, hematemesis in NCPH patient was caused by rupture of esophageal varices. But unlike in cirrhotic patient, in NCPH there are no sign of liver failure, because liver physiology is still normal. We reported case of male patient with NCPH that had hematemesis because of rupture of esophageal varices.

The Expressions of CD44, CD90 and Alpha Fetoprotein Biomarkers in Indonesian Patients with Advanced Liver Disease: an Observational Study.

BACKGROUND: increased serum alpha fetoprotein (AFP) levels are often found in patients with advanced hepatocellular carcinoma (HCC). Cluster Differentiation 44 (CD44) and CD90 are stem cell biomarkers that have been assumed as the early HCC markers and associated with onset and progressivity of HCC. The study related to HCC stem cell has not been available in Indonesia. The present study aimed to evaluate the expression of cancer stem cell markers (CD44, CD90) and AFP levels in patients with advanced liver disease. METHODS: an observational study was conducted in 41 patients with chronic hepatitis B and/or C infection, liver cirrhosis, and HCC at dr. Saiful Anwar General Hospital. CD44 and CD90 expressions were measured with flow cytometry, and AFP serum levels with ELISA. Data on patient characteristics were evaluated using bivariate and multivariate statistical analysis (One-way ANOVA, Mann-Whitney, Chi-Square, Kruskal-Wallis). Data of CD44, CD90 and AFP were analyzed using Kruskal Wallis test with a significance value of p<0.05, and diagnostic power was analyzed using receiver operating characteristic (ROC). RESULTS: the subjects of our study were 16 patients with chronic hepatitis, 15 patients with liver cirrhosis, and 10 patients with HCC. There was a significant difference regarding CD44+CD90+ and AFP among those three groups (p=0.001; p=0.000) specifically in chronic hepatitis compared to liver cirrhosis (p=0.002; p=0.000) and HCC (p=0.002; p=0.000) respectively. ROC analysis showed the best diagnostic power for the combination of CD44+CD90+ and AFP (AUC=0.981; p=0.000). CONCLUSION: there are higher expressions of CD44+CD90+ and serum AFP levels in patients with HCC compared to the other two groups (those with chronic hepatitis and liver cirrhosis). The combination of both parameters has the best diagnostic power of HCC.

Interleukin-28B polymorphisms and response of chronic hepatitis C patients from Indonesia to pegylated interferon/ribavirin treatment.

This study demonstrated that Indonesian patients with chronic hepatitis C (mostly ethnic Java people) mostly were infected with hepatitis C virus (HCV) genotype 1; however, they carried mainly the major genotypes of interleukin 28B (IL-28B) single nucleotide polymorphisms (SNPs) (rs12979860 CC, rs11881222 TT, rs8103142 AA, and rs8099917 TT), and they mostly achieved sustained virological responses to pegylated interferon/ribavirin treatment.

Comparative analysis of short-chain fatty acid levels in non-alcoholic steatohepatitis rat model: Impact of high-fat high-fructose (HFHF), high fat, and Western diets.

The evidence on the role of diets in the production of short-chain fatty acids (SCFAs) was limited. The aim of this study was to assess the potential effects of high-fat high-fructose (HFHF), high-fat, and Western diets on the levels of SCFA. A research experiment employing a post-test-only control group design was carried out from January to April 2022. A total of 27 rats were randomly allocated to each study group. SCFA was measured two weeks after diet administration. Analysis of variance (ANOVA) test was used to analyze the differences among groups, and the effect estimate of each group was analyzed using post hoc Tukey. The concentrations of SCFAs post HFHF diets were recorded as follows: acetic acid at 54.60±10.58 mmol/g, propionic acid at 28.03±8.81 mmol/g, and butyric acid at 4.23±1.68 mmol/g. Following the high-fat diet, acetic acid measured 61.85±14.25 mmol/gr, propionic acid measured 25.19±5.55 mmol/gr, and butyric acid measured 6.10±2.93 mmol/gr. After the administration of Western diet, the levels of SCFA were 68.18±25.73, 29.69±12.76, and 7.48±5.51 mmol/g for acetic acid, propionic acid, and butyric acid, respectively. The level of butyric acid was significantly lower in HFHF diet group compared to the normal diet (mean difference (MD) 6.34; 95%CI: 0.61, 12.04; p=0.026). The levels of acetic acid (p=0.419) and propionic acid (p=0.316) were not statistically different among diet types (HFHF, high-fat, and Western diet). In conclusion, HFHF diet is associated with a lower level of butyric acid than the normal diet in a rat model.

Correlation Between Quantitative Hepatitis B Surface Antigen and Hepatitis B Virus Deoxyribonucleic Acid Levels in Hepatitis B e Antigen-Positive and Hepatitis B e AntigenNegative Chronic Hepatitis B Patients.

BACKGROUND: This study aimed to analyze the relationship between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in hepatitis B e antigen-positive and hepatitis B e antigen-negative chronic hepatitis B patients and to determine the best cut-off value for quantitative hepatitis B surface antigen to predict high hepatitis B virus deoxyribonucleic acid levels (≥2000 IU/mL). METHODS: Ninety-seven sera from chronic hepatitis B patients were collected in this study. Hepatitis B virus deoxyribonucleic acid levels were quantified by real-time polymerase chain reaction. Quantitative hepatitis B surface antigen and hepatitis B e antigen levels were determined by two-site sandwich chemiluminescence immunoassay. Alanine transaminase levels were measured by the International Federation of Clinical Chemistry-approved methods. RESULTS: A significant correlation between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid levels was observed in hepatitis B e antigen-positive group (r = 0.453, P = .002), but not in hepatitis B e antigen-negative group (r = 0.117, P = .454). No significant correlation between quantitative hepatitis B surface antigen and alanine transaminase was found in the hepatitis B e antigen-positive group (r = 0.521, P = .241). However, a significant correlation was shown between quantitative hepatitis B surface antigen and alanine transaminase levels in the hepatitis B e antigen-negative group (r = 0.455, P = .001). The best cut-off value of quantitative hepatitis B surface antigen for predicting high hepatitis B virus deoxyribonucleic acid levels was 3.422 × 103 IU/mL. CONCLUSION: Correlation between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid levels is significant in the hepatitis B e antigen-positive group. Quantitative hepatitis B surface antigen can be used to predict high hepatitis B virus deoxyribonucleic acid levels in the hepatitis B e antigen-positive group.

Antimicrobial Resistance Profile by Metagenomic and Metatranscriptomic Approach in Clinical Practice: Opportunity and Challenge.

The burden of bacterial resistance to antibiotics affects several key sectors in the world, including healthcare, the government, and the economic sector. Resistant bacterial infection is associated with prolonged hospital stays, direct costs, and costs due to loss of productivity, which will cause policy makers to adjust their policies. Current widely performed procedures for the identification of antibiotic-resistant bacteria rely on culture-based methodology. However, some resistance determinants, such as free-floating DNA of resistance genes, are outside the bacterial genome, which could be potentially transferred under antibiotic exposure. Metagenomic and metatranscriptomic approaches to profiling antibiotic resistance offer several advantages to overcome the limitations of the culture-based approach. These methodologies enhance the probability of detecting resistance determinant genes inside and outside the bacterial genome and novel resistance genes yet pose inherent challenges in availability, validity, expert usability, and cost. Despite these challenges, such molecular-based and bioinformatics technologies offer an exquisite advantage in improving clinicians' diagnoses and the management of resistant infectious diseases in humans. This review provides a comprehensive overview of next-generation sequencing technologies, metagenomics, and metatranscriptomics in assessing antimicrobial resistance profiles.

The role of non-Helicobacter pylori bacteria in the pathogenesis of gastroduodenal diseases.

Over the past decade, the development of next-generation sequencing for human microbiota has led to remarkable discoveries. The characterization of gastric microbiota has enabled the examination of genera associated with several diseases, including gastritis, precancerous lesions, and gastric cancer. Helicobacter pylori (H. pylori) is well known to cause gastric dysbiosis by reducing diversity, because this bacterium is the predominant bacterium. However, as the diseases developed into more severe stages, such as atrophic gastritis, premalignant lesion, and gastric adenocarcinoma, the dominance of H. pylori began to be displaced by other bacteria, including Streptococcus, Prevotella, Achromobacter, Citrobacter, Clostridium, Rhodococcus, Lactobacillus, and Phyllobacterium. Moreover, a massive reduction in H. pylori in cancer sites was observed as compared with noncancer tissue in the same individual. In addition, several cases of H. pylori-negative gastritis were found. Among these individuals, there was an enrichment of Paludibacter, Dialister, Streptococcus, Haemophilus parainfluenzae, and Treponema. These remarkable findings suggest the major role of gastric microbiota in the development of gastroduodenal diseases and led us to the hypothesis that H. pylori might not be the only gastric pathogen. The gastric microbiota point of view of disease development should lead to a more comprehensive consideration of this relationship.

Diagnostic Challenge in a Patient Presenting with Ascites and Hypergammaglobulinemia.

Ascites is defined as the accumulation of intra-peritoneal fluid that can be caused by several diseases. We described a 47-year-old female presenting with low serum-ascites albumin gradient (SAAG) and a markedly high level of serum globulin. Serum protein electrophoresis revealed an M spike in the gamma region. Other laboratory results showed a marked increase in aspartate aminotransferase and alanine aminotransferase and predominantly conjugated hyperbilirubinemia without a sign of dilatation of bile ducts from abdominal ultrasonography examination. Furthermore, the follow-up showed a positive result for the anti-nuclear antibody test. The patient was assessed with autoimmune hepatitis, and the cause of ascites was suggested from portal hypertension although the level of SAAG was low. The ascites condition got improved after salt restriction, diuretics treatment, and abdominal paracentesis. However, the patient passed away because of the intracranial hemorrhage as a result of prolonged INR and APTT due to liver failure.

Cut-off of anthropometry measurement and nutritional status among elderly outpatient in Indonesia: multi-centre study.

AIM: To obtain the cut-off value of anthropometric measurements and nutritional status of elderly in Indonesia. METHODS: A multicentre-cross sectional study was performed at 9 hospitals in Indonesia. The data collected comprises of samples characteristics, anthropometric measurements (weight, height, trisep, bisep, subscapular, suprailiac, and circumference of the hip, waist, arm, calf, and thigh), albumin value, MNA score and ADL Index of Barthel. RESULTS: A total of 702 subjects were collected. The average value of serum albumin is 4.28 g/dl, with 98% subjects had normal serum albumin (> 3.5 g/dl). The mean MNA score and BMI was 23.07 and 22.54 respectively. Most of subjects (56.70%) had risk of malnutrition based on MNA score, and 45.01% had normal nutritional status based on body mass index. Average value of several anthropometric measures (weight, stature, and body mass index; sub-scapular and supra-iliac skinfolds; thigh, calf, mid-arm, and waist circumferences) in various age groups in both groups of women and men were obtained. Cut-off values of various anthropometric indicators were also analyzed in this study with MNA as a gold standard. CONCLUSION: This study showed age related anthropometric measurement differences in both men and women aged 60 years and older.

Tenofovir-associated nephrotoxicity in patients with chronic hepatitis B: two cases.

Tenofovir disoproxil fumarate (TDF) is effective against chronic hepatitis B (CHB) infection and its use is increasing rapidly worldwide. However, it has been established that TDF is associated with renal toxicity in human immunodeficiency virus-infected patients, while severe or symptomatic TDF-associated nephrotoxicity has rarely been reported in patients with CHB. Here we present two patients with TDF-associated nephrotoxicity who were being treated for CHB infection. The first patient was found to have clinical manifestations of proximal renal tubular dysfunction and histopathologic evidence of acute tubular necrosis at 5 months after starting TDF treatment. The second patient developed acute kidney injury at 17 days after commencing TDF, and he was found to have membranoproliferative glomerulonephritis with acute tubular injury. The renal function improved in both patients after discontinuing TDF. We discuss the risk factors for TDF-associated renal toxicity and present recommendations for monitoring renal function during TDF therapy.

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.