The PDK1-FoxO1 signaling in adipocytes controls systemic insulin sensitivity through the 5-lipoxygenase-leukotriene B4 axis.

Although adipocytes are major targets of insulin, the influence of impaired insulin action in adipocytes on metabolic homeostasis remains unclear. We here show that adipocyte-specific PDK1 (3'-phosphoinositide-dependent kinase 1)-deficient (A-PDK1KO) mice manifest impaired metabolic actions of insulin in adipose tissue and reduction of adipose tissue mass. A-PDK1KO mice developed insulin resistance, glucose intolerance, and hepatic steatosis, and this phenotype was suppressed by additional ablation of FoxO1 specifically in adipocytes (A-PDK1/FoxO1KO mice) without an effect on adipose tissue mass. Neither circulating levels of adiponectin and leptin nor inflammatory markers in adipose tissue differed between A-PDK1KO and A-PDK1/FoxO1KO mice. Lipidomics and microarray analyses revealed that leukotriene B4 (LTB4) levels in plasma and in adipose tissue as well as the expression of 5-lipoxygenase (5-LO) in adipose tissue were increased and restored in A-PDK1KO mice and A-PDK1/FoxO1KO mice, respectively. Genetic deletion of the LTB4 receptor BLT1 as well as pharmacological intervention to 5-LO or BLT1 ameliorated insulin resistance in A-PDK1KO mice. Furthermore, insulin was found to inhibit LTB4 production through down-regulation of 5-LO expression via the PDK1-FoxO1 pathway in isolated adipocytes. Our results indicate that insulin signaling in adipocytes negatively regulates the production of LTB4 via the PDK1-FoxO1 pathway and thereby maintains systemic insulin sensitivity.

piRNA-Guided CRISPR-like Immunity in Eukaryotes.

Eukaryotic genomes contain virus-derived sequences called endogenous virus elements (EVEs). The majority of EVEs are related to retroviruses, which integrate into the host genome in order to replicate. Some retroviral EVEs encode a function; for example, some produce proteins that block infection by related viruses. EVEs derived from nonretroviral viruses - also recently found in many eukaryotic genomes - are more enigmatic. Here, we summarize the evidence that EVEs can act as templates to generate Piwi-interacting RNAs (piRNAs), whose canonical function is sequence-specific silencing of transposable elements (TEs) to maintain genomic integrity. We argue that EVEs may thus enable heritable, sequence-specific antiviral immune memory in eukaryotes - analogous to CRISPR-Cas immunity in prokaryotes.

Correction to: Suicidal ideation, psychopathology and associated factors among HIV-infected adults in Indonesia.

An amendment to this paper has been published and can be accessed via the original article.

Suicidal ideation, psychopathology and associated factors among HIV-infected adults in Indonesia.

BACKGROUND: Suicidal behavior is a prevalent psychiatric emergency in HIV-infected adults. Detection of suicidal ideation is important in planning early psychiatric intervention and optimizing HIV/AIDS management. Characterization of suicidal ideation among HIV-infected adults is crucial; however, practically there is no data in Indonesia, the country with the second largest burden of HIV/AIDS epidemic in Asia. This study aims to identify suicidal ideation and analyze the associated psychopathology and determining factors among HIV-infected adults in Indonesia. METHODS: An observational cross-sectional study was conducted among HIV-infected adults aged 18-65 years old receiving antiretroviral therapy (ART). Measurement using Symptom Checklist-90 (SCL-90) was performed to assess the existing psychopathology. Firth's penalized logistic regression analysis was performed to identify factors associated with suicidal ideation. RESULTS: A total of 86 subjects were recruited. Most subjects were male (65.1%), median age was 35 years, and median latest CD4 count was 463 cells/µl. Lifetime suicidal ideation was identified in 20 subjects (23.3%). Mean SCL-90 T-score for depressive and anxiety symptoms were both significantly higher among subjects with suicidal ideation (M = 60.75, SD = 12.0, p = 0.000 and M = 57.9, SD = 2.8, p = 0.001, respectively) compared to those without. Bivariate analyses showed that lifetime suicidal ideation was associated with depressive and anxiety symptoms, non-marital status, CD4 count < 500 cells/µl, and efavirenz use. Multivariate analysis identified that a single-point increase in SCL-90 depression symptoms score (AOR 1.16, 95% CI 4.5-123.6, p = 0.000) and efavirenz use (AOR 5.00, 95% CI 1.02-24.6, p = 0.048) were significant independent factors related to suicidal ideation. CONCLUSION: Suicidal ideation is commonly found among Indonesian HIV-infected adults on ART. Depressive symptoms and efavirenz use are independent factors related to the presence of suicidal ideation. Thus, early screening of psychopathology as well as substitution of efavirenz with other ART regiment are recommended to prevent suicide and improve HIV/AIDS management outcome.

"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).

MYC Amplification in the Form of Ring Chromosomes 8 in Acute Myeloid Leukemia with t(11;16)(q13;p11.2).

Oncogene amplification is uncommon in acute myeloid leukemia (AML). Cytogenetically, it is primarily found as double minute chromosomes (dmin) or homogeneously staining regions (hsr). A 62-year-old woman was admitted to our hospital because of anemia and thrombocytopenia. Her bone marrow was hypercellular with 78.6% myeloperoxidase- positive blasts. Some had micronuclei. The patient was diagnosed with AML M2 and remains in complete remission (CR) after induction therapy. G-banding at diagnosis showed 51,XX,t(11;16)(q13;p11.2),+r1,+mar1×4. Spectral karyotyping confirmed t(11;16) and revealed that the ring and the marker chromosomes were derived from multiple copies of ring chromosome 8. Fluorescence in situ hybridization (FISH) with a MYC probe at 8q24 detected amplified MYC signals on 1 large and 4 small ring chromosomes 8. One MYC signal was deleted from one of the 2 chromosomes 8. FISH with a FUS probe at 16p11.2 showed monoallelic deletion of FUS. Immunohistochemistry demonstrated MYC protein overexpression at diagnosis and almost negative expression in CR. These results indicate that MYC amplification could occur in ring chromosomes without dmin. A cryptic MYC deletion suggests that an episome model could be applicable to MYC amplification in ring chromosomes as observed for dmin and hsr. Furthermore, considering 2 further reported cases, t(11;16)(q13;p11) may be a very rare but recurrent translocation in AML.

Characterization of genome sequences and clinical features of coxsackievirus A6 strains collected in Hyogo, Japan in 1999-2013.

Coxsackievirus A6 (CV-A6) is an enterovirus, which is known to cause herpangina. However, since 2009 it has frequently been isolated from children with hand, foot, and mouth disease (HFMD). In Japan, CV-A6 has been linked to HFMD outbreaks in 2011 and 2013. In this study, the full-length genome sequencing of CV-A6 strains were analyzed to identify the association with clinical manifestations. Five thousand six hundred and twelve children with suspected enterovirus infection (0-17 years old) between 1999 and 2013 in Hyogo Prefecture, Japan, were enrolled. Enterovirus infection was confirmed with reverse transcriptase-PCR in 753 children (791 samples), 127 of whom (133 samples) were positive for CV-A6 based on the direct sequencing of the VP4 region. The complete genomes of CV-A6 from 22 positive patients with different clinical manifestations were investigated. A phylogenetic analysis divided these 22 strains into two clusters based on the VP1 region; cluster I contained strains collected in 1999-2009 and mostly related to herpangina, and cluster II contained strains collected in 2011-2013 and related to HFMD outbreak. Based on the full-length polyprotein analysis, the amino acid differences between the strains in cluster I and II were 97.7 ± 0.28%. Amino acid differences were detected in 17 positions within the polyprotein. Strains collected in 1999-2009 and those in 2011-2013 were separately clustered by phylogenetic analysis based on 5'UTR and 3Dpol region, as well as VP1 region. In conclusion, HFMD outbreaks by CV-A6 were recently frequent in Japan and the accumulation of genomic change might be associated with the clinical course.

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.

Comparison of Sofosbuvir Plus Ribavirin Treatment with Pegylated Interferon Plus Ribavirin Treatment for Chronic Hepatitis C Genotype 2.

BACKGROUND: Sofosbuvir plus ribavirin (RBV) therapy showed higher sustained virological response at 12 weeks after treatment (SVR12) than pegylated interferon (peg-IFN) plus RBV; however, liver function, fibrosis, and hepatocellular carcinoma markers have not been assessed so far. SUMMARY: Patients (n = 21) receiving Sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus RBV were enrolled in this study. Changes in alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels, platelet (PLT) counts, FIB-4, and aspartate aminotransferase-to-platelet ratio index (APRI) in both groups were assessed in patients achieving SVR12. Also, fibrosis regression was assessed using pathophysiological biomarkers, such as hyaluronic acid, bone morphogenetic protein 7 (BMP-7), and connective tissue growth factor (CTGF) in the Sofosbuvir plus RBV group. In both groups, while the reduction in ALT levels was significant that of AFP was not. Compared with the baseline, although serum PLT count at the end of treatment (EOT) was significantly higher in the Sofosbuvir plus RBV group, it was significantly lower in the peg-IFN plus RBV group. Although a significant decline in fibrosis markers such as FIB-4 and APRI was observed between the baseline and at EOT in the Sofosbuvir plus RBV group, no significant change of these markers was observed in the peg-IFN plus RBV group. Moreover, BMP-7 and CTGF were significantly lower at EOT than the baseline in the Sofosbuvir plus RBV group. Key Message: The treatment with Sofosbuvir plus RBV results in not only a higher SVR, but also improves the liver function and the degree of fibrosis.

Mixed Phenotype Acute Leukemia with t(12;17)(p13;q21)/TAF15-ZNF384 and Other Chromosome Abnormalities.

The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality. A 74-year-old woman was diagnosed with MPAL, B/myeloid, because bone marrow blasts were positive for myeloperoxidase, CD19, and CD22. Chromosome analysis showed 46,XX, +1,der(1;18)(q10;q10),t(2;16)(q13;q13),t(12;17)(p13;q21). Expression of the TAF15-ZNF384 fusion transcript was confirmed: TAF15 exon 6 was fused in-frame to ZNF384 exon 3. This type of fusion gene has been reported in 1 acute myeloid leukemia case and 3 ALL cases. Thus, at present, it is difficult to find a specific association between the structure of the TAF15-ZNF384 fusion gene and the leukemia phenotype. The TAF15-ZNF384 fusion may occur in early common progenitor cells that could differentiate into both the myeloid and lymphoid lineages. Furthermore, der(1;18)(q10;q10) might play some role in the appearance of an additional myeloid phenotype.

Efficacy and Safety of Sofosbuvir Plus Ribavirin Treatment for Patients with Chronic Hepatitis C Genotype 2.

OBJECTIVES: The efficacy of sofosbuvir plus ribavirin (RBV) treatment for hepatitis C virus (HCV) genotype 2 focusing on virological response was compared with that of pegylated interferon (peg-IFN) plus RBV treatment. Safety of the former focusing on the decline in hemoglobin levels was compared with that of the latter and assessed in terms of age and inosine triphosphatase (ITPA). METHODS: Patients (n = 17) receiving sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus RBV diagnosed with chronic HCV genotype 2 were enrolled in this study, and the efficacy and safety of both treatments were assessed. RESULTS: Rapid virological response was attained with sofosbuvir plus RBV treatment compared with peg-IFN plus RBV treatment. All patients under sofosbuvir plus RBV treatment achieved end-of-treatment response compared with 70% who sustained viral response under the peg-IFN plus RBV treatment, with the former demonstrating greater virological response. The decline in hemoglobin levels under the former treatment was greater than that under the latter and in patients over 65 years of age with ITPA gene major. CONCLUSION: Efficacy and safety of sofosbuvir plus RBV treatment were clearly demonstrated compared with those of peg-IFN plus RBV treatment. The decline in hemoglobin levels was not related to the discontinuation of the former treatment, irrespective of age or the effect of the ITPA gene.

Coffee Intake and Liver Enzyme Association in Korean Immigrants and Japanese: A Comprehensive Cross-Sectional Study.

OBJECTIVES: Significant inverse association between coffee intake and the levels of liver enzymes has been reported. We demonstrated higher prevalence of metabolic syndrome in Korean immigrants (KIs) than in indigenous Japanese (IJs). The aim of this study was to investigate whether the association between coffee intake and liver enzyme levels was different between the 2 ethnic groups. METHODS: This study is a cross-sectional study including a total of 966 subjects comprising KIs and IJs. The association between the quintiles of coffee intake and dichotomous values of liver enzymes was evaluated by logistic regression analysis in KIs, IJs, a high-risk group (current smokers or alcohol drinkers ≥45 g/day), and a low-risk group (non-smokers and alcohol drinkers <45 g/day). RESULTS: In KIs, a significant inverse association between coffee intake and serum aspartate aminotransferase (AST) levels was observed. In the IJs, a significant inverse association between coffee intake and serum alanine aminotransferase levels was observed. In the high-risk group, a significant inverse association between coffee intake and serum AST and gamma-glutamyltransferase levels was observed. CONCLUSION: No difference was observed between KIs and IJs regarding the association between coffee and liver enzymes. Coffee might inhibit hepatic damage by alcohol drinking and smoking.

PREVALENCE AND RISK FACTORS OF HEPATITIS B AND C VIRUS INFECTIONS AMONG HEMODIALYSIS PATIENTS FROM PRIVATE HEMODIALYSIS UNITS IN SURABAYA, INDONESIA.

The aims of the present study were to profile seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and possible risk factors among hemodialysis (HD) patients in private hemodialysis units (HDU) in Surabaya, Indonesia. Sera were obtained from 180 HD patients in 4 different private HDUs and tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Patients without HBsAg and anti-HCV at first sampling were followed serologically every 3 months for 9 months, while those with HBsAg or anti-HCV positive sera were subjected continually to PCR to detect HBV DNA and HCV RNA. The prevalence of hepatitis infections varied widely between the HDUs, from 0% to 8.1% of patients positive for HBsAg and 0% to 60.6% of those positive for anti-HCV, respectively. These values were markedly higher than those among the general population, but not as high as in governmental HDUs in Indonesia. New incidence of HBV was not detected in any HDU, whereas that of HCV was found in two HDUs, HCV-1b in one HDU and HCV-1a in the other. Inappropriate practices were observed, such as shortage of medical staff and malfunctions in infection-control committees. Prevalence of HBV and HCV infection among HD patients in private HDUs were high and varied among the HDUs. Isolation of both HBV- and HCV-infected patients and staff education should help to reduce the prevalence of hepatitis infections in HDUs.

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.

Comparison of Daclatasvir and Asunaprevir for Chronic HCV 1b Infection with Telaprevir and Simeprevir plus Peginterferon and Ribavirin, with a Focus on the Prevention of Occurrence and Recurrence of Hepatocellular Carcinoma.

OBJECTIVES: The efficacy of the all-oral administration of daclatasvir and asunaprevir for 24 weeks was compared with that of telaprevir for 12 weeks plus pegylated interferon and ribavirin (PEG-IFN/RBV) for 24 weeks, and that of simeprevir for 12 weeks plus PEG-IFN/RBV for 24 weeks, with a focus on the prevention of occurrence and recurrence of hepatocellular carcinoma (HCC). The levels of alanine aminotransferase (ALT) and α-fetoprotein (AFP) as suppressive markers of HCC were also measured. METHODS: Patients received daclatasvir and asunaprevir (n = 17), simeprevir plus PEG-IFN/RBV (n = 15) and telaprevir plus PEG-IFN/RBV (n = 25). Sustained virological response (SVR) and the mean change in the level of serum ALT, AFP and platelet (PLT) count were compared among the three groups. RESULTS: No difference in SVR was observed in patients given daclatasvir with asunaprevir (SVR4), telaprevir plus PEG-IFN/RBV or simeprevir plus PEG-IFN/RBV (SVR24). Also, no significant difference was observed in the mean change of serum ALT, AFP or PLT count among the three groups. CONCLUSION: The preventive effect of the IFN-free, all-oral regimen of daclatasvir and asunaprevir was observed with a focus on the occurrence and recurrence of HCC, as was IFN-based treatment with telaprevir or simeprevir plus PEG-IFN/RBV.

Full genome characterization and phylogenetic analysis of hepatitis B virus in gibbons and a caretaker in Central Kalimantan, Indonesia.

Hepatitis B virus (HBV) from gibbons was characterized, and the possibility of horizontal transmission between gibbons and humans was examined in a gibbon rehabilitation center in Central Kalimantan, Indonesia. Ten gibbons that were positive for the hepatitis B surface antigen (HBsAg) on arrival and 13 caretakers for those gibbons were included in this study. The duration of stay at the rehabilitation center ranged from 1 to 10 years. Serological and molecular analyses were performed. Six gibbons were positive for HBsAg, whereas HBV DNA was detected in all ten of the gibbons sampled. On the other hand, HBsAg was detected in only 1 of the 13 caretakers. HBV samples from seven gibbons and from the one infected human were chosen for complete genome sequencing. A phylogenetic analysis revealed that the cluster of gibbon strains in this study was distinct from strains previously reported from other countries. In the pre-S1 region, we found a unique amino acid residue substitution (P89K), three insertions between T87 and L88 in the genomes of three gibbons, and a 33-nucleotide deletion at the start of pre-S1 that is common in non-human primates. The caretaker sample was identified as HBV subgenotype B3, the most common type in Indonesia. For the complete HBV sequences, the similarity between gibbons in this study and other non-human primate and human HBV isolates was 90-91.9 % and 85.5-89.6 %, respectively. In conclusion, the gibbon HBV genotype was influenced by geographic location and species. To the best of our knowledge, this is the first report characterizing the HBV genes and genomes of indigenous gibbons in Indonesia.

Characteristics of Hypovascular versus Hypervascular Well-Differentiated Hepatocellular Carcinoma Smaller Than 2 cm - Focus on Tumor Size, Markers and Imaging Detectability.

OBJECTIVES: The characteristics of hypovascular and hypervascular well-differentiated hepatocellular carcinomas (HCCs) were compared in terms of tumor size, tumor markers and detectability by imaging modalities. METHODS: Well-differentiated HCC nodules that are smaller than 2 cm (n = 27) were evaluated in 27 patients using histopathology and divided into 2 groups: hypovascular (n = 10) and hypervascular (n = 17). The diagnostic sensitivity of imaging modalities was then evaluated for efficiency in disclosing tumor size and tumor markers in the 2 types. RESULTS: No difference was observed in tumor size and tumor markers between the 2 types; however, the sensitivity of contrast-enhanced CT, contrast-enhanced ultrasonography and arterioportal angiography was significantly different between the 2 types, whereas that by Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) demonstrated no difference. CONCLUSION: Hypovascular HCC could be diagnosed by Gd-EOB-DTPA MRI in the hepatobiliary phase.

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.

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.