Global research trends in non-alcoholic fatty liver disease.

OBJECTIVES: This study aimed to analyze the global profile of the literature in non-alcoholic fatty liver disease (NAFLD) research. BACKGROUND: Non-alcoholic fatty liver disease is a clinically heterogeneous condition characterized by fat accumulation in the liver and the absence of significant alcohol consumption or underlying genetic disorders. These manifestations are associated with inflammation, steatosis, and fibrosis that can develop into cirrhosis and even hepatocellular carcinoma. However, a study about the research trend in NAFLD has never been reported before. METHODS: The NAFLD bibliometric analysis was performed on articles indexed in the Scopus database from 1973 to 2022. RESULTS: The total number of articles published worldwide is 28,673 documents, with an annual average of 561 documents. The United States generated the most articles (n = 6548), followed by China (n = 6180), Italy (n = 2434), and Japan (n = 2032). Since 2013, the number of publications on NAFLD has increased dramatically worldwide. The popular topics in the field include medicine, biochemistry, genetics and molecular biology, pharmacology, toxicology and pharmaceutics, and nursing. CONCLUSIONS: This study provides a unique composite picture of NAFLD research worldwide and evaluates research productivity from 1973 to 2022. This finding suggests that the prospects for interventions in NAFLD remain promising (Tab. 5, Fig. 4, Ref. 57). Text in PDF www.elis.sk Keywords: bibliometric analysis, NAFLD, Scopus.

"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).

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.

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients.

Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection, allowing HBV to evade neutralizing antibodies. These escape variants may contribute to chronic infections. In this study, we looked for MHR variants in HBV quasispecies using ultradeep sequencing and evaluated the relationship between these variants and clinical manifestations in infected patients. We enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic hepatitis and 19 with advanced liver disease). The most common subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in patients with advanced liver disease than that in patients with chronic hepatitis. The MHR variants were grouped based on the percentage of the viral population affected: major, ≥20% of the total population; intermediate, 5% to <20%; and minor, 1% to <5%. The rates of MHR variation that were present in the major and intermediate viral population were significantly greater in patients with advanced liver disease than those in chronic patients. The most frequent MHR variants related to immune evasion in the major and intermediate populations were P120Q/T, T123A, P127T, Q129H/R, M133L/T, and G145R. The major population of MHR variants causing impaired of HBsAg secretion (e.g., G119R, Q129R, T140I, and G145R) was detected only in advanced liver disease patients. This is the first study to use ultradeep sequencing for the detection of MHR variants of HBV quasispecies in Indonesian patients. We found that a greater number of MHR variations was related to disease severity and reduced likelihood of HBsAg titer.

A deep-sequencing method detects drug-resistant mutations in the hepatitis B virus in Indonesians.

OBJECTIVE: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection. METHODS: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). RESULTS: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12-1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%. CONCLUSION: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients.

A longitudinal controlled signage intervention to increase stair use at university buildings: Process and impact evaluation using RE-AIM framework.

Introduction: Stair climbing intervention could be suggested to address low occupational physical activity amongst university students and employees. Strong evidence showed the effectiveness of signage intervention in increasing stair use in public areas. However, evidence in worksite settings, including university settings, was inconclusive. This study aimed to evaluate the process and impact of a signage intervention to increase stair use at a university building using the RE-AIM framework. Method: We conducted a non-randomised controlled pretest-posttest study to examine the effect of signage intervention placed in university buildings in Yogyakarta (Indonesia) between September 2019 and March 2020. The process of designing the signage involved the employees in the intervention building. The main outcome was the change in the proportion of stair use to elevator use measured by manual observations of video recordings from closed-circuit television. A linear mixed model examined the intervention effect by controlling the total visitor count as a confounder. RE-AIM framework was used in the process and impact evaluation. Results: The change in the proportion of stair climbing from baseline to the 6th-month phase at the intervention building (+0.067 (95% CI = 0.014-0.120)) was significantly higher than that of the control building. However, the signs did not change the proportion of the stair descending at the intervention building. The signs were potentially viewed 15,077-18,868 times/week by visitors. Conclusion: Signage intervention using portable posters could easily be adopted, implemented, and maintained in similar settings. A co-produced low-cost signage intervention was found to have a good reach, effectiveness, adoption, implementation, and maintenance dimension.

Increased serum activin A level in congenital heart disease-associated pulmonary artery hypertension: A comparative study from the COHARD-PH registry.

Activin A, a member of TGF-ß superfamily, has been implicated in the pathogenesis of pulmonary artery hypertension (PAH). PAH due to congenital heart disease (CHD-PAH) is a major problem in developing countries. Activin A may have a role in PAH development and progression among uncorrected CHD. In this comparative study, serum activin A level was significantly increased in subjects with uncorrected CHD without the presence of PH and were more significantly risen in CHD-PAH, as compared to control. The utilization of serum activin A measurement seems promising to identify uncorrected CHD patients with PAH development and progression.

Physical activity virtual intervention for improving mental health among university students during the COVID-19 pandemic: A Co-creation process and evaluation using the Behavior Change Wheel.

Background: During the COVID-19 pandemic, there were reductions in university students' physical activity, which further increased their mental distress, calling for technology-based physical activity interventions to address the challenges in delivering in-person interventions. This study aimed to develop a technology-based physical activity intervention and pilot test it. Methods: We developed a virtually-delivered team-based physical activity challenge using the Behavior Change Wheel and Co-creation Framework based on Self-determination Theory. A pilot study was conducted in the evaluation phase to measure the recruitment rate, dropout rate, change in physical activity, and mental distress while identifying problems and collecting participants' opinions regarding the challenge. Wilcoxon signed-rank tests were conducted to assess the change in physical activity and mental distress. Qualitative data were analyzed using thematic analysis. Results: A three-week physical activity challenge comprising five identified intervention functions was held with 480 participants. The recruitment rate was 84.8% resulting from 407 virtual challenge participants who were conveniently joined as research participants. The dropout rate for the pilot study was 10.96% resulting from the incompatibility problems with the application. Among sample participants who lacked physical activity, participation in this challenge improved their physical activity by 52.5 min of moderate-intensity physical activity per week and reduced their mental distress by three points of self-reporting questionnaire-20 score. Issues regarding the virtual application and the influence of participation in the challenge on basic psychological needs emerged. Participants' opinions identified lack of time as the main barrier to physical activity. Conclusion: A co-created physical activity intervention developed using the Behavioral Change Wheel Framework inspired high interest from university students and may increase their physical activity and improve their mental health. Several suggestions were discussed to address the identified problems and improve the internal and external validity of the evaluation phase. Trial registration: TCTR20220720004 (retrospectively registered on July 19, 2022).

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.

Significance of BMPR2 mutations in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a debilitating disease that results from progressive remodeling and inflammation of pulmonary arteries. PAH develops gradually, is difficult to diagnose, and has a high mortality rate. Although mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene has been identified as the main genetic cause of PAH, the underlying pathways involving the pathophysiology of PAH are complex and still not fully understood. Endothelial dysfunction has been observed in PAH development that results in a multitude of disturbances in the cellular processes in pulmonary vessels. Changes in the pulmonary vasculature caused by the disruption of BMPR2 signaling are observed in three main vascular components; endothelial cells, smooth muscle cells, and fibroblasts. BMPR2 also has a prominent role in maintenance of the immune system. The disruption of BMPR2 signaling pathway causes an increased degree of inflammation and decreases the ability of the immune system to resolve it. Inflammatory processes and changes in pulmonary vasculature interact with one another, resulting in the progression of chronic PAH. In this review, we highlight the various components of vascular remodeling and immune response that are caused by disruption of BMPR2 signaling, including the clinical evidence and the prospects of these components as a potential target for PAH therapy. Indeed, development of drugs to target the pathogenic pathways involved in PAH may complement existing treatment regimens and improve patient prognosis.

The neuroprotective effect of ethanolic extract Ocimum sanctum Linn. in the regulation of neuronal density in hippocampus areas as a central autobiography memory on the rat model of Alzheimer's disease.

The aim of this study was to identify the effects of Ocimum sanctum Linn. ethanolic extract (OSE) on the neurons of the CA1, CA3, and DG hippocampal areas with the use of in vivo and in vitro models of Alzheimer's diseases (AD). Twenty-one two-month-old male rats were divided into three groups: untreated (Group A, n = 3), AD rats model pretreated with OSE followed by induction for Trimethyltin (TMT) on day 7 (group B, n = 9), and AD rats model treated with OSE both as pre-TMT introduction for 7 days and post-TMT induction for 21 days (group C, n = 9). AD rats were sacrificed on days 7, 14, and 21, and brain samples were collected and analyzed for neuronal density and neuropeptide Y (NPY) immunoreactivity. To corroborate the in vivo observations, HEK-293 cells were treated with TMT and used as an in vitro model of AD. The results were then analyzed using FITC Annexin V and flow cytometry. Nuclear fragmentation was observed in cells stained with Hoechst 33342 by confocal microscopy. The results showed a significant increase in the number of neurons and NPY expression in the AD rats that were pre- and post-treated with OSE (p < 0.05). Indeed, OSE was able to retain and promote neuronal density in the rat model of AD. Further studies of an in vitro model of neurodegeneration with Ocimum sanctum Linn. ethanolic extract inhibited apoptosis in TMT-induced HEK-293 cells. Moreover, OSE prevented nuclear fragmentation, which was confirmed by staining the nuclei of HEK-293 cells. Taken together, there findings suggest that OSE has the potential as a neuroprotective agent (retaining the autobiographical memory),and the neuroproliferation of neurons in the CA1, CA3, and DG hippocampal areas in the rats¡ model of neurodegeneration was mediated by activation of NPY expression.

Effects of Yacon on Colonic IFN-γ and Goblet Cells of 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis Mouse Model.

Background: Inflammatory bowel disease is a chronic inflammatory condition associated with damage to the intestinal mucosal barrier. Supplementation of yacon tubers has been known to have positive effect on intestinal health. Therefore, we conducted the present study to investigate the effect of yacon tuber powder on Th1 activation pathway by evaluating IFN-γ levels and the number of goblet cells in the colon of colitis mouse models. Methods: Thirty BALB/c mice were divided into five groups: 1, control group (G1) and 2-5, TNBS-induced colitis groups (GII-GV). Yacon powder was given to three of the TNBS-induced colitis groups with the doses of 0.165 g/30 g BW (GIII), 0.331 g/30 g body weight (BW; GIV), and 0.662 g/30 g BW (GV) for 14 days. IFN-γ levels were assessed using ELISA, while number of goblet cells was calculated based on histological observation. Results: Significantly lower IFN-γ levels was observed in GV compared to colitis group (GII) (p = 0.007). GV also showed significantly higher number of goblet cells per 100 epithelial cells in 20 crypts (p = 0.000) than GII. Conclusion: The administration of yacon powder at a dose of 0.662 g/30 g BW could decrease IFN-γ levels and improve the healing of intestinal mucosa in colitis mouse models by increasing the number of goblet cells.

Mothers' knowledge of breastfeeding and infant feeding types affect acute respiratory infections.

INTRODUCTION: World Health Organization (WHO) recommends exclusive breastfeeding for new-borns until 6 months of age. However, exclusive breastfeeding in Indonesia only reached 52.3% in 2014 and 65.16% in 2018. It is known that administration of infant formula and non-formula supplements to infants aged less than 6 months increases the risk of Acute Respiratory Infections (ARIs). In addition, the high prevalence of ARIs in infants in Sleman Regency, Indonesia indicates the need of optimal early prevention. Therefore, we conducted this study to confirm that mothers' knowledge of breastfeeding and infant feeding types affect the prevalence of Acute Respiratory Infections (ARIs). METHODS: Data were collected through questionnaires from 50 mothers with infants aged 7-12 months who had experienced ARIs in the last 3 months (case group) and 50 mothers with healthy infants (control group). Collected data were then analysed using Chi-Square, Logistic Regression, Lambda, and Somers' D tests. RESULTS: The results showed that types of infant feeding are associated with the prevalence of ARIs. Non-breastfed infants were 14 times riskier to contract ARIs. Mothers' knowledge of exclusive breastfeeding influenced their preferences of feeding practice. However, their attitude towards breastfeeding did not appear to significantly affect their choices of feeding practice. CONCLUSIONS: Exclusive breastfeeding during the first 6 months of an infant's life can lower the prevalence of ARIs for when they are older. Mothers' good knowledge of breastfeeding is associated with its practice.

Effects of low and moderate treadmill exercise on liver of d-galactose-exposed aging rat model.

Aging increases liver susceptibility to diseases and it causes inflammation in liver tissue which can lead to fibrosis. Studies suggest that aging is caused by the accumulation of free radicals. Lack of physical activity can lower hormone levels and increase free radicals that can accelerate the aging process. Hence, physical activity is very important to maintain functions of organs. This research was aimed to study the effects of low and moderate treadmill exercise on d-Galactose-exposed aging rat model by evaluating the degree of hepatic fibrosis, number of M1 and M2, and M1/M2 ratio. Twenty-four 3-month-old male Wistar aging model rats were randomly divided into four groups, that is, three treatment groups with daily 300 mg kgBW-1 d-Galactose injection administrated intraperitoneally for 4 weeks and 1 control group with normal saline injection. Two of the d-Galactose treated groups were given low and moderate treadmill exercise for 4 weeks. It was concluded that low intensity treadmill exercise significantly lowered the degree of d-Galactose-exposed hepatic fibrosis, and moderate treadmill exercise was able to restore the injured liver tissue back to the non-aging state. Administration of d-Galactose causes inflammation marked by the elevated number of M1 and M2 macrophages. Moderate treadmill exercise drove M1/M2 ratio back to the control condition.

Association Between HBx Variations and Development of Severe Liver Disease Among Indonesian Patients.

Multi-site mutations in the hepatitis B virus (HBV) X gene are often found in patients with advanced liver diseases such as liver cirrhosis and hepatocellular carcinoma. It has been reported that modifications in the X protein play crucial roles in the development of HBV-related severe liver disease. However, the prevalence of genetic variations in Indonesian strains has not been systematically assessed. In this study, we sought to investigate the profile of nonsynonymous mutations in the X gene. Overall, 114 Indonesian HBV strains, including 12 in-house samples, were retrieved from GenBank. The mutation frequency in the X gene was compared among strains obtained from patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The mutation frequencies of the domain and basal core promoter regions were significantly greater in advanced liver diseases compared with chronic hepatitis. In addition, the double mutation K130M/V131I and the triple mutation N88V/K130M/V131I were associated with a 2.5 times higher risk of advanced liver disease. However, the roles of two novel X gene mutations (A12S/T and L16F/P) on hepatocarcinogenesis are unclear relative to wild-type X gene. In conclusion, the development of multi-site mutations in the X gene may represent a strategy by which HBV can escape immune surveillance and thus contribute to hepatocarcinogenesis, even though the biological roles of some variants remain unclear.

Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers.

Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome are an important factor in low therapeutic effectiveness. Nonetheless, the prevalence of these mutations in HBV strains isolated previously in Indonesia has not been systematically examined. Therefore, in this study, we investigated the profile of mutations in the RT region and the associations of these mutations with amino acid changes in the surface protein in the virus of treatment-naïve Indonesian HBV carriers. Overall, 96 sequences of the full-length Indonesian HBV genomes (genotype B, n = 54; genotype C, n = 42) were retrieved from the National Center for Biotechnology Information. Naturally occurring primary and/or compensatory drug resistance mutations were found in 6/54 (11.1%) genotype B strains and in 1/42 (2.4%) genotype C strains. The potential mutations underlying resistance to a nucleos(t)ide analog and/or pretreatment mutations were more frequent in both genotypes but more frequent in genotype C strains than in genotype B strains. The A-B interdomain region in the RT gene was more frequently mutated in genotype C than in genotype B (3.51 ± 2.53 vs. 1.08 ± 1.52, P ＜ 0.001). Knowledge about the mutational profiles of the RT gene and changes in the surface protein may help clinicians to select the most appropriate antiviral drug and vaccination or HBV immunoglobulin regimen for management of HBV infection in Indonesia.

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.

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.