Journal of Clinical Virology 31 (2004) 76–77 Letter to the Editor A novel pattern (sW195a) in surface gene of HBV DNA due to YSDD (L180M plus M204S) mutation selected during lamivudine therapy and successful treatment with adefovir dipivoxil A. Mithat Bozdayi a,b,* , Can Polat Eyigun c , Ahmet R. Turkyilmaz a , Ismail Yasar Avci c , Alaaddin Pahsa c , Cihan Yurdaydin a,b a Ankara University, Hepatology Institute, Ankara, Turkey b Ankara University, School of Medicine, Department of Gastroenterology, Ankara, Turkey c Department of Infectious Diseases and Clinical Microbiology, Gülhane Military Medical Academy, Ankara, Turkey Received 10 May 2004; accepted 11 May 2004 Dear Editor, We previously reported a mutation from methionine to serine (M204S) in YMDD motif of HBV polymerase gene in an HBeAg-negative patient having breakthrough under lamivudine treatment (Bozdayi et al., 2003). This mutation was associated with leucine to methionine (L180M) change in B subdomain of reverse transcriptase region of HBV poly- merase gene. M204S change was a result of ATG to AGT change, which also resulted in an amino acid change in cor- responding 195th codon of the surface gene from tryptophan to valine (sW195V). The same pattern in HBV pol and sur- face gene was also reported by Niesters et al. (2002). One important feature of this novel mutation may be its persis- tence and dominance over the wild-type strain even 9 months after stopping lamivudine, which is in contrast to the con- ventional mutations, where a reversal to wild-type strain is observed after stopping lamivudine (1). In our study, we also showed that this mutation pattern (L180M + M204S) con- ferred resistance to lamivudine in vitro (1). We recently identified a new L180M + M204S pattern in a patient. The patient was a 43-year-old Caucasian male with known HBV infection since 1997. A liver biopsy in 1998 revealed chronic active hepatitis with a histological activity index of 11/18 according to Knodell et al. (1981). He was HBeAg negative, anti-HBe positive, as well as pos- itive for HBV DNA by PCR (sensitivity: 1000copy/mL) * Corresponding author. Tel.: +90 312 362 05 66; fax: +90 312 363 62 13. E-mail address: bozdayi@medicine.ankara.edu.tr (A.M. Bozdayi). and had high ALT levels (84IU/mL). Interferon (IFN) al- pha (5 MU/daily) plus lamivudine therapy (300 mg/day) was initiated in October 1998, and IFN was stopped after 9 months due to ALT normalization and HBV DNA negativity by PCR. At 26th month of lamivudine treatment, a clinical breakthrough occurred, characterized by an ALT elevation and detection of HBV DNA by a commercial hybridization assay. Lamivudine was continued after the development of clinical breakthrough. However, HBV DNA and ALT lev- els remained high during this period. The rtM204S mutation was detected along with the rtL180M mutation by direct se- quencing of PCR products as described previously (Ogata et al., 1999) in all samples obtained since the development of lamivudine resistance. M204S change was a result of ATG to AGC alteration, which also resulted in an amino acid change in 195th codon of surface gene from tryptophan to alanine (sW195A) as a novel pattern in surface gene. This novel pattern does not alter any epitopes in surface proteins. The patient started to receive adefovir dipivoxil (10 mg/day) in addition to lamivudine (100 mg/day) treatment 22 months after occurrence of clinical breakthrough. HBV DNA be- came negative by PCR at month 4 and ALT normalization was maintained at month 6. Patient completed 13 months under adefovir dipivoxil plus lamivudine treatment and responded to the therapy well. Here, we report a novel pattern in surface gene as a con- sequence of a new nucleotide change, resulting in M204S alteration in HBV polymerase gene for the first time. It is also reported for the first time that patient with rtL180M plus rtM204S has been successfully treated by adefovir dipivoxil. 1386-6532/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2004.05.002