De Novo Superinfection of Hepatitis B Virus in an Anti-HBs Positive Patient with Recurrent Hepatitis C Following Liver Transplantation

A 60-year-old woman with end stage liver cirrhosis caused by genotype 2 hepatitis C virus (HCV) infection received an orthotopic liver transplantation (OLT). The patient was negative for the hepatitis B surface antigen (HBsAg) and positive for the anti-hepatitis B surface antibody (anti-HBs) prior to and one and a half months following the OLT. Due to reactivation of hepatitis C, treatment with interferon-alpha and Ribavirin started two months following the OLT and resulted in a sustained virological response. We performed a liver biopsy because a biochemical response was not achieved. Surprisingly, liver pathology showed HBsAg-positive hepatocytes with a lobular hepatitis feature, which had been negative in the liver biopsy specimen obtained one and a half months post-OLT. High titers of both HBsAg and HBeAg were detected, while anti-HBs antibodies were not found. Tests for IgM anti-hepatitis B core antibody and anti-delta virus antibodies were negative. The serum HBV DNA titer was over 1x10(7) copies/mL. A sequencing analysis showed no mutation in the "a" determinant region, but revealed a mixture of wild and mutant strains at an overlapping region of the S and P genes (S codon 213 (Leu/Ile); P codons 221 (Phe/Tyr) and 222 (Ala/Thr)). These findings suggest that de novo hepatitis B can develop in patients with HCV infection during the post-OLT period despite the presence of protective anti-HBs.

A YIDD Mutation in a Case of Recurrent Hepatitis B after Liver Transplantation Induced by an S-escape Mutant

A 47-year-old woman underwent orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related end-stage liver cirrhosis. The patient received hepatitis B immunoglobulin prophylaxis after OLT. Despite the protective level of the serum anti-hepatitis-B surface antibody, HBV recurred at 22 months post-OLT and induced subacute hepatic failure. The pre-OLT HBV genome contained a complex mutation pattern in overlapping frame regions of the surface (S) and polymerase (P) genes, which is the same mutation pattern as seen in post-OLT HBV DNA. G145R and K141R mutations in the "a" determinant were detected only in the post-OLT sample. Clevudine (30 mg once daily) was administered for recurrent hepatitis B. Hepatitis B was reactivated with a flare-up, and a M204I mutation (YIDD mutant type) appeared with a higher viral load at 9 months after clevudine treatment. We report here a case of a YIDD mutation that developed in recurrent hepatitis B after OLT induced by an S-escape mutant.

Clinical Effectiveness of Restriction Fragment Mass Polymorphism Assay for Human Papillomavirus Genotyping / 임상검사와정도관리

BACKGROUND: Human papillomavirus (HPV) infection is the main cause of cervical cancer and with the advent of genotype specific vaccines, there is increased need for accurate, broad-spectrum and high-throughput methods for HPV genotyping. A MALDI-TOF mass spectrometry (MS)-based restriction fragment mass polymorphism (RFMP) assay has proven to accurately and reliably genotype a wide variety of HPV. METHODS: We evaluated the clinical utility of the RFMP assay in HPV genotyping by testing a total of 2,689 specimens taken from liquid-based cytology, which was composed of normal cytology, atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and invasive squamous cervical cancer (SCC). RESULTS: Overall HPV positive rate of total specimens was 32.5% and the high-risk positivity was 16.4%. The HPV positive rates were increased as increasing severity level of cervical lesion. Predominant high-risk HPV genotypes were found as following order; 52 (18.6%), 16 (13.7%), 18 (3.8%), 58 (3.4%), 56 (2.6%) and 31 (2.5%). The high-risk HPV positivities according to cytologic diagnosis were 10.7% (238/2229), 31.7% (76/240), 50.0% (88/176), 86.0% (37/43), 100% (1/1) in normal, ASCUS, LSIL, HSIL and SCC subgroups, respectively. The concordance rate and Kappa value between sequencing and RFMP assays were 96.6% and 0.932 (95%CI: 0.908-0.956). CONCLUSIONS: The RFMP HPV genotyping assays showed high concordance with sequencing. The assay is simple, and can accurately detect and identify HPV genotypes in samples with various levels of cytological lesions. The results demonstrated that RFMP assay should be clinically suitable for HPV genotyping in laboratories.

The Associtation between Methylenetetrahydrofolate Reductase Gene Polymorphisms and a Risk of Spontaneously Aborted Embryos / 대한불임학회지

OBJECTIVE: This study was performed to understand the influence of the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) genotypes on the spontaneously aborted embryos. METHODS: DNA was extracted from tissue samples of 95 spontaneously aborted embryos and 100 samples of normal children randomly and 449 samples of normal adults were selected as the controls. MTHFR genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The aborted embryo group had higher frequency of MTHFR 677CC type (p=0.014) and lower 677CT type (p=0.063) than the controlled child group. The frequency of MTHFR 677CT type was drastically lower than that of controlled adult group (p=0.032). In the MTHFR C677T/A1298C combination, 677CC/1298AC genotype of the aborted embryo was significantly higher (p=0.034) than that of controlled child group, but it was not statistically significant in controlled adult group (p=0.063). CONCLUSION: MTHFR 677CC and MTHFR 677CC/1298AC genotypes may represent genetic markers for the risk of spontaneously aborted embryos at least in Koreans.