Review of MR spectroscopy analysis and artificial intelligence applications for the detection of cerebral inflammation and neurotoxicity in Alzheimer's disease.

INTRODUCTION: Magnetic resonance spectroscopy (MRS) has an emerging role as a neuroimaging tool for the detection of biomarkers of Alzheimer's disease (AD). To date, MRS has been established as one of the diagnostic tools for various diseases such as breast cancer and fatty liver, as well as brain tumours. However, its utility in neurodegenerative diseases is still in the experimental stages. The potential role of the modality has not been fully explored, as there is diverse information regarding the aberrations in the brain metabolites caused by normal ageing versus neurodegenerative disorders. MATERIALS AND METHODS: A literature search was carried out to gather eligible studies from the following widely sourced electronic databases such as Scopus, PubMed and Google Scholar using the combination of the following keywords: AD, MRS, brain metabolites, deep learning (DL), machine learning (ML) and artificial intelligence (AI); having the aim of taking the readers through the advancements in the usage of MRS analysis and related AI applications for the detection of AD. RESULTS: We elaborate on the MRS data acquisition, processing, analysis, and interpretation techniques. Recommendation is made for MRS parameters that can obtain the best quality spectrum for fingerprinting the brain metabolomics composition in AD. Furthermore, we summarise ML and DL techniques that have been utilised to estimate the uncertainty in the machine-predicted metabolite content, as well as streamline the process of displaying results of metabolites derangement that occurs as part of ageing. CONCLUSION: MRS has a role as a non-invasive tool for the detection of brain metabolite biomarkers that indicate brain metabolic health, which can be integral in the management of AD.

Irisin promotes odontogenic differentiation and angiogenic potential in human dental pulp cells.

AIM: To determine whether irisin, a newly discovered myokine that links exercise-induced and metabolic homeostasis, is able to promote odontogenic differentiation and angiogenesis in human dental pulp cells (HDPCs). METHODOLOGY: Cell viability in the presence of irisin was measured. Real-time PCR and Western blot analysis were performed to evaluate the expression levels of irisin, odontogenic and angiogenic markers. The involvement of mitogen-activated protein kinase (MAPK) and the protein kinase B (Akt) signalling pathway was evaluated by Western blot. To evaluate mineralization nodule formation, alkaline phosphatase (ALP) staining and alizarin red S staining were performed. Scratch wound assays were performed to evaluate the effects of irisin on cell migration. The data were analysed using one-way analysis of variance (anova) followed by Tukey post hoc test and Student's t-test. Statistical significance was considered at P < 0.05. RESULTS: Irisin significantly promoted odontogenic differentiation as evidenced by formation of mineralized nodules, induction of ALP activity and upregulation of odontogenic and angiogenic markers (P < 0.05). Scratch wound assays revealed that irisin significantly increased migration of HDPCs (P < 0.05). Phosphorylation of both MAPK and Akt was increased by irisin. MAPK and Akt inhibitors inhibited mineralization, cell migration and the increased expression of odontogenic and angiogenic markers. CONCLUSIONS: Irisin promoted odontogenic differentiation and mineralization and has the potential for angiogenesis through activation of the MAPK and Akt signalling pathways in HDPCs.

Lysyl oxidase-mediated VEGF-induced differentiation and angiogenesis in human dental pulp cells.

AIM: To investigate the effects of recombinant human vascular endothelial growth factor (rhVEGF) on odontoblastic differentiation, in vitro angiogenesis, and expression and activity of lysyl oxidase (LOX) in human dental pulp cells (HDPCs), compared with rhFGF-2. To identify the underlying molecular mechanisms, the study focused on whether LOX was responsible for the actions of rhVEGF. METHODOLOGY: Recombinant human vascular endothelial growth factor (rhVEGF) was constructed using the pBAD-HisA plasmid in Escherichia coli. HDPCs were treated with 1-50 µg mL-1 rhVEGF for 14 days. Alkaline phosphatase (ALP) activity was measured, and the formation of calcified nodules was assessed using alizarin red staining after the induction of odontogenic differentiation of HDPCs. The expression level of the odontogenic differentiation markers was detected by reverse transcription polymerase chain reaction. Signal pathways were assessed by Western blot and immunocytochemistry. The data were analysed by anova with Bonferroni's test (α = 0.05). RESULTS: Recombinant human vascular endothelial growth factor significantly increased cell growth (P < 0.05), ALP activity (P < 0.05) and mineralization nodule formation and upregulated the mRNA expression levels of the osteogenic/odontogenic markers that were lower with rhFGF-2. rhVEGF significantly increased amine oxidase activity (P < 0.05) and upregulated LOX and LOXL mRNA expression in HDPCs. Additionally, rhVEGF dose-dependently upregulated angiogenic gene mRNAs and capillary tube formation to a greater degree than rhFGF-2. Inhibition of LOX using ß-aminopropionitrile (BAPN) and LOX or LOXL gene silencing by RNA interference attenuated rhVEGF-induced growth, ALP activity, mineralization, the expression of marker mRNAs and in vitro angiogenesis. Furthermore, treatment with rhVEGF resulted in phosphorylation of Akt, ERK, JNK and p38, and activation of NF-κB, which was inhibited by LOX or LOXL silencing and BAPN. CONCLUSION: Recombinant human vascular endothelial growth factor promoted cell growth, odontogenic potential and in vitro angiogenesis via modulation of LOX expression. These results support the concept that rhVEGF may offer therapeutic benefits in regenerative endodontics.

Anterolateral femoral bowing and loss of thigh muscle are associated with occurrence of atypical femoral fracture: Effect of failed tension band mechanism in mid-thigh.

BACKGROUND: The purpose of this study was to characterize anterolateral bowing of the femur using X-rays and muscular atrophy in the mid-thigh using computed tomography (CT) in patients with atypical femoral fractures (AFFs). We then compared the results with those of an intertrochanteric fracture to understand whether these measures act as causative factors of AFFs. METHODS: From January 2009 to December 2015, 37 patients with complete AFF and 12 patients with incomplete AFF were enrolled in this study. Lateral femoral bowing, anterior femoral bowing, cross-sectional area (CSA), and attenuation coefficient of thigh muscles in the AFF group are measured and compare with those in the intertrochanteric fracture group. RESULTS: Lateral and anterior femoral bowing in the AFF group were significantly higher than those in the intertrochanteric fracture group. The level of fracture was found to be significantly associated with lateral and anterior femoral bowing (r = 0.569, r2 = 0.324, p < 0.001; r = -0.530, r2 = 0.281, p < 0.001, respectively). Total CSA and CSA of anterior and medial compartments were significantly lower in the AFF group (p < 0.05). The attenuation coefficient of the total thigh muscle and all three compartments in the AFF group were significantly lower than those in the intertrochanteric fracture group (p < 0.05). CONCLUSIONS: This study demonstrated that anterolateral femoral bowing and loss of thigh muscle were highly associated with the occurrence of AFFs.

Artefacts at a glance: differentiating features of artefactual stenosis from true stenosis at the genu of the petrous internal carotid artery on TOF MRA.

AIM: To investigate the distinguishing features of artefactual stenosis from true stenosis at the genu of the petrous internal carotid artery (ICA) on time of flight (TOF) magnetic resonance angiography (MRA). MATERIALS AND METHODS: Both TOF MRA and digital subtraction angiography (DSA) were performed in 65 patients with 74 vessels who demonstrated artefactual stenosis in 43 patients with 50 vessels and true stenosis in 22 patients with 24 vessels. The following findings of the signal loss were compared between the two groups: (1) margin, (2) darkness, (3) the presence of bilaterality, (4) the presence of tandem arterial stenosis, (5) the location of the epicentre, and (6) length. RESULTS: In five out of the six evaluated items, statistically significant differences were present between the two groups (p<0.00 in all five items). Artefactual stenosis more frequently showed signal loss with ill-defined margins (47/50), less darkness compared to the background darkness (46/50), the absence of tandem arterial stenosis (35/50), epicentre at the genu (34/50), and shorter length (2.57 ± 0.68 mm). No significant difference was noted in the presence of bilaterality of signal loss between the two groups (p=0.706). CONCLUSION: Several MRA features can be useful for suggesting artefactual stenosis rather than true stenosis at the genu of the petrous ICA on TOF MRA.

Incidence of infection according to intravenous immunoglobulin use in autologous hematopoietic stem cell transplant recipients with multiple myeloma.

BACKGROUND: Although intravenous immunoglobulin (IVIG) is not routinely recommended, many centers still use IVIG during the post-hematopoietic stem cell transplant (HSCT) period. METHOD: A total of 162 multiple myeloma (MM) patients who underwent autologous (auto-) HSCT between January 2008 and June 2013 were retrospectively reviewed. Primary objective was determination of the impact of IVIG on post-transplant infection, and secondary objectives included identification of overall incidence of infection, type of infection, and risk factors for infection after auto-HSCT in MM patients. RESULTS: After auto-HSCT, 53 of 162 patients (32.7%) experienced 104 infectious events. Upper respiratory infection was most common (n = 31, 29.8%) and pneumonia (n = 27, 26.0%) and herpes zoster (n = 15, 14.4%) came next. Among the identifiable organisms causing respiratory infection, influenza virus (n = 10) and Pneumococcus (n = 9) were predominant. Incidence of infection was not statistically different according to IVIG use (34.8% in IVIG (-) vs. 31.3% in IVIG (+), P = 0.631). Incidence of infection requiring hospitalization and multiple episodes of infection showed no difference between the groups (P = 0.147, P = 0.156). In a Cox proportional hazard model, none of the factors including age, gender, type of disease, stage, tandem (vs. single) transplantation,and IVIG was prognostic for infectious event after auto-HSCT (P = 0.955, hazard ratio 0.980 with 95% confidence interval 0.481-1.997 for IVIG). CONCLUSION: In auto-HSCT recipients with MM, incidence of post-transplant infection was not different according to prophylactic IVIG use.

A new HLA-A*30 allele, A*30:81, identified by sequence-based typing.

The new allele, HLA-A*30:81, differs from A*30:01:01 by one nucleotide substitution at codon 272 (CTG→ATG).

Frequency of FMR1 premutation carriers and rate of expansion to full mutation in a retrospective diagnostic FMR1 Korean sample.

Detection of female premutation (PM) carriers of fragile X syndrome may be important in that a PM allele from the mother can expand to a full mutation (FM) when transmitted to the fetus. Although the PM carrier frequency might be different in varying populations, there is a little data on the Korean population. Furthermore, the risks of expansion to FM have not been studied in Korean PM carriers. In this retrospective study, we estimated the female PM carrier frequency and the risks of expansion to FM in Korean diagnostic samples collected for FMR1 gene testing. Of 10,241 pre-conceptional or pregnant women, 13 PM [1 in 788; 95% confidence interval (CI), 1/1,250-1/455] and 75 intermediate allele carriers (1 in 137; 95% CI, 1/172-1/110) were identified. In 26 prenatal diagnoses cases, the PM allele was transmitted to the fetus in 13 pregnancies (50%), and five of these expanded to FM. All of the maternal alleles exceeding 70 repeats expanded to FM. In conclusion, the PM frequency in Korean diagnostic samples was lower than that reported in Western populations, while the risk for FM expansion in alleles exceeding 70 repeats might be higher than expected based upon previous reports.

Incidence and risk factors of poor mobilization in adult autologous peripheral blood stem cell transplantation: a single-centre experience.

BACKGROUND AND OBJECTIVES: Collection of sufficient CD34+ cells for autologous peripheral blood stem cell (PBSC) transplantation is frequently failed in patients with lymphoma or multiple myeloma (MM). We investigated the incidence and the predictive factors for poor mobilization. MATERIALS AND METHODS: A total of 205 adult patients (101 lymphoma and 104 MM) were retrospectively included for identifying the incidence of mobilization failure and the predictive factors for poor mobilization in conventional G-CSF-based mobilization regimen. Another 17 patients who used plerixafor for mobilization were included. RESULTS: Overall, 14·1% of patients (21·8% of patients with lymphoma, 6·7% of patients with MM) were poor mobilizers. Univariate analysis and multivariate analysis revealed an interval from G-CSF administration to PBSC collection exceeding 10 days and peripheral blood mononuclear cells count on the first day of collection were predictive factors for poor mobilization in lymphoma, but not in MM. Among plerixafor-treated patient group, 9 of 11 poor mobilizers who received second-cycle plerixafor mobilization were able to collect higher number of CD34+ cells than that of CD34+ cells during the G-CSF-based first mobilization. All patients who had received initial plerixafor mobilization reached 2·0 × 10(6) CD34+ cells/kg during the four leukaphereses. CONCLUSION: In conventional G-CSF-based mobilization, early PBSC collection after G-CSF administration might enhance CD34+ cell yield. A combination of a new mobilizing agent, plerixafor, would be helpful to harvest sufficient number of CD34+ cells for successful transplantation outcome while reducing the effort of collection procedures in poor mobilizers.

Therapeutic drug monitoring of mirtazapine in a routine outpatient setting in Asian psychiatric patients.

INTRODUCTION: Mirtazapine is an antidepressant that acts by enhancing serotonergic and noradrenergic neurotransmission. This study aimed to evaluate mirtazapine pharmacokinetic data from Korean psychiatric patients and to identify the potential factors affecting its steady-state concentration. METHODS: A total of 337 samples of steady-state mirtazapine concentrations from 188 adult psychiatric outpatients were retrospectively evaluated. Serum mirtazapine concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Median mirtazapine concentration was 43.6 µg/L (164.37 nmol) at a daily dosage range of 7.5-60 mg. At the steady state, mirtazapine dose had a positive correlation with the drug concentration. Mean concentration-to-dose (C/D) ratio was 1.48 µg/L/mg/day (5.58 nmol/mg/day), which was higher than that in a previous study in Caucasian subjects. Age and paroxetine co-medication were positively associated with C/D ratio. Initial mirtazapine concentration and C/D ratio did not show an association with responsiveness in depressive patients. DISCUSSION: This study presented the therapeutic drug monitoring data for mirtazapine and pharmacokinetic variations of mirtazapine in an Asian population. A further study could be helpful for clinical decision making based on the characteristics of patients.

Acetylation changes at lysine 5 of histone H4 associated with lytic gene promoters during reactivation of Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a pathogenic agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease in humans. Similarly to other gammaherpesviruses such as Epstein-Barr virus (EBV) and herpesvirus saimiri (HVS), KSHV displays two alternative life cycles, latent and lytic one. The transactivation from latency to the lytic phase is the result of transcriptional changes in the KSHV genome caused by the replication and transcriptional activator (RTA). During KSHV reactivation, epigenetic modifications of histone protein on the viral genome occur, which regulate the transcriptional activation of a number of lytic genes. The reactivation of EBV from latency to lytic cycle, induced by an immediate-early Zta protein, was shown to be accompanied by acetylation of specific lysines in histone H4. Accordingly, we hypothesized that the RTA-induced transactivation of KSHV could also be accompanied by histone acetylation. To validate this hypothesis, we assayed alterations of acetyl-histone H4-lysine 5 (acH4K5) during the RTA-mediated KSHV reactivation. While the modified histone protein in a total cell lysate was not distinguished between control and RTA-expressed cells, upregulated acH4K5 was detected on several lytic gene promoter regions during KSHV reactivation. Our results clearly indicate that this epigenetic change is related to transcription of genes expressed in the lytic cycle of KSHV.

Outcomes after hepatic resection and subsequent multimodal treatment of recurrence for multifocal hepatocellular carcinoma.

BACKGROUND: The role of liver resection in patients with multifocal hepatocellular carcinoma (HCC) with well preserved liver function is controversial. This study was conducted to evaluate the outcomes of such patients. METHODS: This was a retrospective analysis of patients who underwent liver resection for multifocal HCC between 1992 and 2011. Postoperative outcomes, survival and predictors of outcomes were analysed. RESULTS: Of 46 patients who underwent hepatic resection for multifocal HCC, 38 had Barcelona Clinic Liver Cancer stage B disease. Major hepatectomy was performed in 27 patients, and major complications occurred in nine (20 per cent). The 90-day postoperative mortality rate was 7 per cent. Overall 1-, 2-, 3- and 5-year survival rates were 78, 64, 59 and 53 per cent respectively (median 70 months), whereas corresponding recurrence-free survival rates were 53, 32, 30 and 27 per cent (median 14 months). Recurrence developed in 28 (61 per cent) of the 46 patients, affecting the liver only in 22. Three-quarters of patients with recurrence underwent further therapy. Major hepatectomy (hazard ratio (HR) 0.37, 95 per cent confidence interval 0.14 to 0·95; P = 0·038), microvascular (HR 3·44, 1·35 to 8·74; P = 0·009) and macrovascular (HR 2·68, 1·11 to 6·43; P = 0·028) invasion, and cirrhosis (HR 3·15, 1·12 to 8·86; P = 0·029) were associated with overall survival. Microvascular invasion (HR 2·81, 1·06 to 7·40; P = 0·037), cirrhosis (HR 3·12, 1·41 to 6·88; P < 0·001) and bilobar disease (HR 2·93, 1·09 to 7·88; P = 0·033) were associated with recurrence-free survival. CONCLUSION: In selected patients with multifocal HCC and well preserved liver function, long-term survival is possible after liver resection and subsequent aggressive treatment of recurrence.

Characterization and optimization of vascular endothelial growth factor(165) (rhVEGF(165)) expression in Escherichia coli.

Vascular endothelial growth factors(165) (VEGF(165)) is the most potent and widely used pro-angiogenic factor. Here we determined optimal culture condition of recombinant human VEGF(165) (rhVEGF(165)) in Escherichia coli (E. coli). rhVEGF(165) expression was the highest in 0.25% of L-arabinose induction concentration, at 20 °C induction temperature, and for 5 h induction time under the control of araBAD promoter using pBADHisA vector. In biological activity test, rhVEGF(165) significantly increased the proliferative activity of CPAE cells (p<0.001) and upregulated the expressions of endothelial cell growth-related genes, such as platelet endothelial cell adhesion molecule (PECAM-1), endothelial-specific receptor tyrosine kinase (TEK), kinase insert domain protein receptor (KDR), and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) in calf pulmonary artery endothelial (CPAE) cells.

Elastin-like polypeptide matrices for enhancing adeno-associated virus-mediated gene delivery to human neural stem cells.

The successful development of efficient and safe gene delivery vectors continues to be a major obstacle to gene delivery in stem cells. In this study, we have developed an elastin-like polypeptide (ELP)-mediated adeno-associated virus (AAV) delivery system for transducing fibroblasts and human neural stem cells (hNSCs). AAVs have significant promise as therapeutic vectors because of their safety and potential for use in gene targeting in stem cell research. ELP has been recently employed as a biologically inspired 'smart' biomaterial that exhibits an inverse temperature phase transition, thereby demonstrating promise as a novel drug carrier. The ELP that was investigated in this study was composed of a repetitive penta-peptide with [Val-Pro-Gly-Val-Gly]. A novel AAV variant, AAV r3.45, which was previously engineered by directed evolution to enhance transduction in rat NSCs, was nonspecifically immobilized onto ELPs that were adsorbed beforehand on a tissue culture polystyrene surface (TCPS). The presence of different ELP quantities on the TCPS led to variations in surface morphology, roughness and wettability, which were ultimately key factors in the modulation of cellular transduction. Importantly, with substantially reduced viral quantities compared with bolus delivery, ELP-mediated AAV delivery significantly enhanced delivery efficiency in fibroblasts and hNSCs, which have great potential for use in tissue engineering applications and neurodegenerative disorder treatments, respectively. The enhancement of cellular transduction in stem cells, as well as the feasibility of ELPs for utilization in three-dimensional scaffolds, will contribute to the advancement of gene therapy for stem cell research and tissue regenerative medicine.

Live attenuated nephropathogenic infectious bronchitis virus vaccine provides broad cross protection against new variant strains.

Infectious bronchitis virus (IBV) infections cause great economic losses to the poultry industry worldwide, and the emergence of new variant strains complicates disease control. The present study investigated the genetic and protectotypic features of newly emerged Korean IBV strains. A phylogenetic analysis showed that several recent isolates formed 2 different clusters (new cluster 1 and 2), which were distinct from other preexisting clusters. New cluster 1 IBV strains represented recombinants between Korean nephropathogenic strain KM91 and the QXIBV strain. New cluster 2 IBV strains showed low amino acid homology (<58.7%) compared with previous isolates. We evaluated the protective efficacy of commercial IBV vaccines (H120 and K2 strain) against these new isolates. In cross-protection studies, the H120 strain did not provide sufficient protection against these variants. However, highly attenuated nephropathogenic IBV vaccine, K2 strain, provided significantly higher levels of protection against variants compared with chickens vaccinated with H120 (P < 0.05 or better). These results indicate that the K2 vaccine could be helpful for the reduction of economic losses caused by newly evolving IBV recombinants (new cluster 1) and variants (new cluster 2).

Outbreak of gizzard erosion associated with fowl adenovirus infection in Korea.

The pathogenicity of a fowl adenovirus serotype-1 (FAdV-1, K181 strain) isolated from a case of gizzard erosion in layer chickens was investigated in specific-pathogen-free (SPF) chicks. One-week-old SPF chicks were inoculated orally or intramuscularly with the isolate of FAdV-1 and euthanized for necropsy at 7, 14, and 21 d postinoculation. Although there were no clinical signs after inoculation, gizzard erosions were observed grossly and the virus was recovered from the gizzards in the inoculated chickens. Histologically, in the chickens that were infected orally, the lesions found in the gizzard consisted of severe degeneration and necrosis of glandular epitheliums and eosinophilic inclusion bodies. These results indicate that the Korean FAdV-1 isolate could induce gizzard lesions in chickens. Moreover, the present investigation reproduced an outbreak of gizzard erosion caused by FAdV-1 infection and, for the first time, described the isolation of FAdV-1 from chickens in Korea. These findings provide important information on the epidemiology and pathogenesis of FAdV-1 infection in chickens.

Prevalence and antimicrobial resistance of Salmonella species isolated from chicken meats produced by different integrated broiler operations in Korea.

Prevalence and antimicrobial resistance profiles of Salmonella serotypes isolated from 7 chicken meat brands produced by different integrated broiler operations in Korea were determined. In total, 210 samples were collected from retail supermarkets in Seoul, South Korea, and analyzed for the presence of Salmonella. Of 210 chicken meat samples, overall Salmonella prevalence was 22.4%. Salmonella Enteritidis was the dominant serovar, with an isolation rate of 57.4% from the Salmonella-positive chickens, followed by Salmonella Montevideo. Salmonella isolates frequently were resistant to various antibiotics, including 100% to erythromycin, 87% to cephalothin, 85% to nalidixic acid, and 70% to streptomycin. Of the 47 isolates, 41 (87.2%) isolates were resistant to 3 or more antibiotics. Moreover, the Salmonella profiles of each chicken meat brand were different by broiler operation. Brand A showed the highest prevalence of Salmonella (18 isolates, 60%), whereas brand G showed the lowest prevalence (one isolate, 3.3%). Eight among the 18 isolates of brand A were resistant to 11 antibiotics, whereas 5 of the 6 brand C isolates were resistant to only 2 antibiotics. This study demonstrates that a high proportion of chicken meat in Korea is contaminated with Salmonella and the prevalence and antimicrobial resistance patterns of Salmonella of chicken meat differ significantly according to the integrated broiler operation.

Clevudine for chronic hepatitis B: antiviral response, predictors of response, and development of myopathy.

Clevudine has been approved for the treatment of chronic hepatitis B (CHB) in South Korea. However, its long-term antiviral effect and safety awaits more study. The aim of this study was to evaluate antiviral efficacy, predictors of virologic response, and development of myopathy after clevudine therapy for CHB. The study included 102 nucleoside naïve CHB patients who had received clevudine for more than 6 months with good compliance. The median duration of clevudine treatment was 53 weeks (range, 25-90 weeks). A retrospective analysis of data retrieved from medical records was performed. The cumulative rate of virologic response [hepatitis B virus (HBV) DNA level <2000 copies/mL] at 48 weeks of clevudine therapy was 81%, and cumulative rate of clevudine resistance was 11% at 60 weeks of treatment. Independent predictors of virologic response to clevudine therapy were hepatitis B e antigen (HBeAg) negativity and rapid decrease of viral load during the early phase of treatment. The clevudine-related myopathy developed in 3.9% of patients, and was reversible after discontinuation of clevudine. Clevudine showed a potent antiviral response, and its effect was higher in HBeAg-negative patients, with rapid viral load reduction after therapy. However, long-term therapy for more than 1 year resulted in the development of considerable resistance and myopathy. Therefore, we should consider alternative antiviral agents if clevudine resistance or clevudine-induced myopathy is developed in patients on clevudine for the treatment of CHB.

Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea.

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution.