Detection of Mutations in Chronic Hepatitis B Virus under Lamivudine Treatment: Direct Sequencing and CLIP Sequencing / 임상검사와정도관리

BACKGROUND: Hepatitis B Virus (HBV) is a major risk factor for hepatocellular carcinoma, and about five to six percents of people are infected with HBV in Korea. Lamivudine is a first-line drug having good control against HBV replication, but long-term treatment by lamivudine induces drug resistance. We analyzed the rate of HBV resistance mutation for lamivudine by direct sequencing and CLIP sequencing. METHODS: HBV DNA was isolated from 371 patients who were in treatment, or were planning to be treated with lamivudine. The direct sequencing for lamivudine resistance mutation was performed in 371 patients and CLIP sequencing in 138 patients. We analyzed the mutation rate and the type of mutations for lamivudine resistance. RESULTS: The mutation was detected in 203 patients (54.7%) and (CTG) L180M (ATG) was most common (36.1%) followed by (ATG) M204I (ATT) (29.9%) and (ATG) M204V (GTG) (18.6%). According to the duration of treatment, mutation rates were as follows: 45.3% for less than one year, 71.7% for one to two years, 66.7% for two to three years, and 87.9% for more than three years. The results of the direct sequencing and CLIP sequencing agreed in 134 out of 138 patients, in whom both tests were performed. CONCLUSIONS: We confirmed that HBV mutation rates for lamivudine resistance increased as the lamivudine treatment period increased. The lamivudine resistance mutations detected were similar to the previous studies. CLIP sequencing showed good correlation with the direct sequencing and gave additional mutation information. CLIP sequencing is a promising tool for the detection of lamivudine resistance mutation in HBV that can assist treatment plans.

A Case of ABO*Ael02/O04 Genotype with Typical Phenotype O / 대한진단검사의학회지

Ael is a rare blood type which has the least amount of A antigen among A subgroups. It can be detected by special tests performed to resolve the discrepancy between red cell and serum typing in routine serological typing. The presence of A antigen on Ael red cell is demonstrable only by adsorption and elution tests. An Ael individual does not secret A substance in the saliva and may have anti-A antibody in the serum which is usually less reactive with the reagent red cells than anti-B antibody. In Korea, Ael02 has been reported more frequently than other Ael alleles. We report a case of Ael02/O04 who presented as typical phenotype O with strong anti-A and anti-B antibodies and no A antigen detected even by adsorption and elution tests. The case has been proved to be Ael02/O04 by direct sequencing analysis. In individuals with history of discrepancies in the results of ABO phenotyping, ABO genotyping is needed for an accurate evaluation of their blood type.