HBV-viremia animals, and this efficacy may improve with prolonged therapy. Although SCID mice lack adaptive immunity (functio- nal T and B cells), they retain innate immunity in C.B17/ icr species (e.g. functional granulocytes and NK cells). Thus, liver damage that might be caused by adaptive immunity in normal mice might not be observed in SCID mice (30). Apparent suppression of NK cell activity was observed after intraperitoneal administration of BNE. NK cells play a critical role in host innate defense against viruses and may be partly responsible for liver injury resulting from anti-viral responses. However, the exact role of NK cells in liver injury remains unclear (31). In this model, the observed increase in ALT level could not be conclusively attributed to the mouse liver cells or tumor cells. Nonetheless, histological examination of the liver of all mice revealed no apparent damage (data not shown), suggesting that the elevated serum ALT activity probably was a result of expression from the implanted tumor cells. Taken together, the data support the anti- HBV effects of BNE and the chemical composition of BNE is subject to for further investigation. Acknowledgment We thank Dr Chang DTM for polishing the English and giving us comments on this article. References 1. Nakamoto Y, Guidotti LG, Kuhlen CV, Fowler P, Chisari FV. Immune pathogenesis of hepatocellular carcinoma. J Exp Med 1998;188:341–50. 2. Ganem D, Varmus HE. The molecular biology of the hepatitis B viruses. Annu Rev Biochem 1987;56:651–93. 3. Ocama P, Opio CK, Lee WM. Hepatitis B virus infection: current status. Am J Med 2005;118:1413. 4. Mailliard ME, Gollan JL. Emerging therapeutics for chronic hepatitis B. Annu Rev Med 2006;57:155–66. 5. Tenney DJ, Levine SM, Rose RE, Walsh AW, Weinheimer SP, Discotto L, et al. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob Agents Chemother 2004;48:3498–507. 6. Lee SK, Wong CK, Poon PM, Ip PS, Che CT, Fung KP, et al. In vitro immunomodulatory activities of a newly concocted traditional Chinese medicine formula: VI-28. Phytother Res 2006;20:883–8. 7. Fischer KP, Gutfreund KS, Tyrrell DL. Lamivudine resistance in hepatitis B: mechanisms and clinical implications. Drug Resist Updat 2001;4:118–28. 8. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004;127:S35–50. 9. Liu J, Lin H, McIntosh H. Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review. J Viral Hepat 2001;8:358–66. 10. Kang EH, Kown TY, Oh GT, Park WF, Park SI, Park SK, et al. The flavonoid ellagic acid from a medicinal herb inhibits host immune tolerance induced by the hepatitis B virus-e antigen. Antiviral Res 2006;72:100–6. 11. Li H, Zhou C, Zhou L, Chen Z, Yang L, Bai H, et al. In vitro antiviral activity of three enantiomeric sesquiterpene lactones from eCAM 2010;7(2) 195 Senecio species against hepatitis B virus. Antivir Chem Chemother 2005;16:277–82. 12. Chang JS, Liu HW, Wang KC, Chen MC, Chiang LC, Hua YC, et al. Ethanol extract of Polygonum cuspidatum inhibits hepatitis B virus in a stable HBV-producing cell line. Antiviral Res 2005;66:29–34. 13. Huang KL, Lai YK, Lin CC, Chang JM. Inhibition of hepatitis B virus production by Boehmeria nivea root extract in HepG2 2.2.15 cells. World J Gastroenterol 2006;12:5721–5. 14. Locarnini S. Molecular virology and the development of resistant mutants: implications for therapy. Semin Liver Dis 2005;25 (Suppl 1): 9–19. 15. Guha C, Mohan S, Roy-Chowdhury N, Roy-Chowdhury J. Cell culture and animal models of viral hepatitis. Part I: hepatitis B. Lab Anim 2004;33:37–46. 16. Prince AM, Brotman B. Perspectives on hepatitis B studies with chimpanzees. Ilar J 2001;42:85–8. 17. Takahashi H, Fujimoto J, Hanada S, Isselbacher KJ. Acute hepatitis in rats expressing human hepatitis B virus transgenes. Proc Natl Acad Sci USA 1995;92:1470–4. 18. Zhai WR, Vajta G, Acs G, Paronetto F. A nude mouse model for the in vivo production of hepatitis B virus. Gastroenterology 1990;98:470–7. 19. Sato H, Goto W, Yamamura J, Kurokawa M, Kageyama S, Takahara T, et al. Therapeutic basis of glycyrrhizin on chronic hepatitis B. Antiviral Res 1996;30:171–7. 20. Dandri M, Volz TK, Lutgehetmann M, Petersen J. Animal models for the study of HBV replication and its variants. J Clin Virol 2005;34 (Suppl 1): S54–62. 21. Condreay LD, Jansen RW, Powdrill TF, Johnson LC, Selleseth DW, Paff MT, et al. Evaluation of the potent anti- hepatitis B virus agent (-) cis-5-fluoro-1-[2-(hydroxymethyl)- 1,3-oxathiolan-5-yl]cytosine in a novel in vivo model. Antimicrob Agents Chemother 1994;38:616–9. 22. Euhus DM, Hudd C, LaRegina MC, Johnson FE. Tumor measurement in the nude mouse. J Surg Oncol 1986;31:229–34. 23. Sitia G, Iannacone M, Muller S, Bianchi ME, Guidotti LG. Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice. J Leukoc Biol 2007;81:100–7. 24. Morrey JD, Bailey KW, Korba BE, Sidwell RW. Utilization of transgenic mice replicating high levels of hepatitis B virus for antiviral evaluation of lamivudine. Antiviral Res 1999;42:97–108. 25. Morrey JD, Korba BE, Sidwell RW. Transgenic mice as a chemotherapeutic model for hepatitis B virus infection. Antivir Ther 1998;3:59–68. 26. Jilbert AR, Botten JA, Miller DS, Bertram EM, Hall PM, Kotlarski J, et al. Characterization of age- and dose-related outcomes of duck hepatitis B virus infection. Virology 1998;244:273–82. 27. Liu N, Zhu B, Huang Z, Zhu Y, Chen Q, Guo X, et al. [The inhibitive effects of the ethanol extract from Radix et Rhizoma Rhei on the secretion of HBsAg and HBeAg]. Zhong Yao Cai 2004;27:419–21. 28. Ganem D, Prince AM. Hepatitis B virus infection–natural history and clinical consequences. N Engl J Med 2004;350:1118–29. 29. Mommeja-Marin H, Mondou E, Blum MR, Rousseau F. Serum HBV DNA as a marker of efficacy during therapy for chronic HBV infection: analysis and review of the literature. Hepatology 2003;37:1309–19. 30. Sun Y, Chen HY, Xin SJ. Effect of IL-18 on peripheral blood mononuclear cells of chronic hepatitis B and hepatitis B virus DNA released by HepG2.2.15 cell lines. Hepatobiliary Pancreat Dis Int 2004;3:230–4. 31. Sjolin H, Tomasello E, Mousavi-Jazi M, Bartolazzi A, Karre K, Vivier E, et al. Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection. J Exp Med 2002;195:825–34. Received April 30, 2007; accepted December 5, 2007