Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85–90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with Pmeta = 1.89×10−12 for rs3077 and Pmeta = 9.69×10−10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (Pmeta = 4.40×10−19 for rs3077 and Pmeta = 1.28×10−15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule

Epidemiology and Clinical Features of Pulmonary Nontuberculous Mycobacteriosis in Nagasaki, Japan

Background and Objectives: Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan. Methods: The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features. Results: A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m2, underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up. Conclusions: The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region

Dilutions of the WHO HCV RNA Standard that were assayed by CAP/CTM and ART.

<p>Positivity rates of the assays of replicate samples at each concentration are shown. N. S., not significant by the Fisher exact test.</p

Typical cases receiving TVR-based triple therapy with HCV RNA undetectable by CAP/CTM and detectable by ART.

<p>These 3 patients were receiving TVR-based triple therapy and achieved SVR24. (a) Case 1 received TVR-based triple therapy for 12 weeks, and then the patient was treated without TVR up to week 24. HCV RNA was detected by ART only at week 8. *The CAP/CTM result was obtained at week 3. (b) Case 2 received TVR-based triple therapy for 5 weeks, and then the patient was treated without TVR up to week 24. HCV RNA was detected by ART only at week 4. (c) Case 3 received TVR-based triple therapy for 10 weeks, and HCV RNA was detected by ART only at weeks 4 and 8. y.o., year old.—, HCV RNA was undetected. NT, not tested.</p

Typical results of <i>in vitro</i> cell transfection assay and detection of HCV RNA by CAP/CTM and ART.

<p>These experiments were performed twice, and the mean values of the 2 experiments are shown in Fig 5A and 5B. At day 13, ART detected HCV RNA below the reported lower limit of detection. (A) Results of cell cultures containing TVR 10 μM. (B) Results of cell cultures containing TVR 10 μM plus IFN 100 IU/mL. Bar graph, HCV Ag. Solid lines, CAP/CTM results. Dashed lines, ART results. n. d., not detected. Light-colored characters and lines show the lower limits of detection.</p