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infection in Egyptian chronic hepatitis C patients. J Gastroenterol 2009;44:359-364. 13. Yuen MF, Lee CK, Wong DK, Fung J, Hung I, Hsu A, et al. Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood fonor population. Gut 2010;59:1389-1393. 14. Michalak TI, Pardoe IU, Coffin CS, Churchill ND, Freake DS, Smith P, et al. Occult life long persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acuteviral hepatitis. Hepatology1999;29:928-938. 15. Simonetti J, Bulkow L

review and meta-analysis of a diagnostic test.” Hepatol Int. 2015; 9: 558-66 6. Gheorghița V. et al.“Quantitative serum HBsAg in chronic hepatitis B.” Therapeutics, Pharmacology and Clinical Toxicology. 2012; 16 (3): 155-162. 7. LiawYF. “Clinical Utility of Hepatitis B surface Antigen Quantitation in Patients with Chronic Hepatitis B: A Review.” Hepatology. 2011; 53: 2121-2129. 8. Chevaliez S: “Is HBsAg quantification ready for prime time?” Clin Res Hepatolo Gastroenterol. 2013; 37: 559-63. 9. Loggi E, Vitale G., Conti F., Bernardi M. “Chronic hepatitis B: Are we close

:1544-1550. 9. Zhang GL, Xie DY, Lin BL, Xie C, Ye YN, Peng L, et al. Imbalance of interleukin-17-producing CD4T cells /requlatory T cells axis occurs in remission stage of patients with hepatitis B virus-related acute-on-chronic liver failure. J Gastroenterol Hepatol 2013; 28: 513-521. 10. Xue-Song L, Cheng-Zhong L, Ying Z, Mo-Bin W. Changes of Treg and Th17 cells balance in the development of acute and chronic hepatitis B virus infection. BMC Gastroenterol 2012; 12: 43. 11. Pan C, Gu Y, Zhang W, Zheng Y, Peng L, Deng H, et al. Dynamic changes of lipopolysaccharide levels in

Globally, hepatitis B virus (HBV) infection is a major health problem with variable geographical distribution. The rates of chronic hepatitis B virus (CHB) infection vary from 0.1%–20% in different areas of the world; and are 0.1%–2% in areas of low prevalence. In areas of intermediate prevalence, e.g., Mediterranean countries, Eastern Europe, the Indian subcontinent, and Singapore the prevalence is 3%–5%. Pakistan falls into the intermediate zone [ 1 , 2 , 3 ]. The reported prevalence of HBV surface antigen (HBsAg) in the general population of Pakistan is 2

References 1. Mao QG, Luo KX, Fu QF, Feng XR, Guo YB, Zhu YF, et al. Efficacy of interferon-alpha therapy for HBeAg-negative chronic hepatitis B and its influencing factors. Zhonghua Gan Zang Bing Za Zhi (Chin) 2004; 12:582-584. 2. Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B. Zhonghua Gan Zang Bing Za Zhi (Chin) 2005; 13:881-891. 3. Chinese Society of Hepatology, Chinese Medical Association and Chinese Society of Infectious Diseases

1 Introduction Chronic infection with the hepatitis B virus (HBV) is prevalent worldwide. According to the World Health Organization (WHO), approximately 2 billion people in the world have been infected with HBV, and 240 million of these patients have chronic HBV infection [ 1 ]. A total of 650,000 deaths occur annually from the complications caused by chronic HBV infection; these complications include liver failure, cirrhosis, and hepatocellular carcinoma [ 2 ]. HBV is the pathogen of chronic hepatitis B (CHB) and affects the development of the disease by

References 1 Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med 2004;350:1118-1129. 2 Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis 2006; 26:153-161. 3 Wong VW, Wong GL, Chim AM, Choi PC, Chan AW, Tsang SW, et al. Surrogate end points and long-term outcome in patients with chronic hepatitis B. Clin Gastroenterol Hepatol 2009;7:1113-1120. 4 Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma

References 1. Pramoolsinsap C, Pukrittayakamee S, Desakorn V. Hepatitis B problem in Thailand. Southeast Asian J Trop Med Public Health. 1986; 17:219-28. 2. Merican I, Guan R, Amarapuka D, Alexander MJ, Chutaputti A, Chien RN, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol. 2000; 15:1356-61. 3. Poovorawan Y, Sanpavat S, Pongpunglert W, Chumdermpadetsuk S, Sentrakul P, Vandepapeliere P, et al. Long term efficacy of hepatitis B vaccine in infants born to hepatitis B e antigen-positive mothers. Pediatr Infect Dis J. 1992; 11

References 1 Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11:97-107. 2 Ray MB, Desmet VJ, Bradburne AF, Desmyter J, Fevery J, DeGroote J. Differential distribution of hepatitis B surface and core antigen in liver of hepatitis B patients. Gastroenterology 1976;71:462-469. 3 Montano L, Miescher GC, Goodall AH, Wiedmann KH, Janossy G, Thomas HC. Hepatitis B virus and HLA antigen display in the liver during chronic hepatitis B virus infection. Hepatology 1982

activated monocytes from the site of inflammation in humans specifically promote Th17 responses. Proc Nati Acad Sci USA 2009;106:6232-6237. 4 O’Quinn DB, Palmer MT, Lee YK, Weaver CT. Emergence of the Th17 pathway and its role in host defense. Adv Immunol 2008;99:115-163. 5 Nan XP, Zhang Y, Yu HT, Li Y, Sun RL, Wang JP, et al. Circulating CD4+CD25high regulatory T cells and expression of PD-1 and BTLA on CD4+ T cells in patients with chronic hepatitis B virus infection. Viral Immunol 2010;23:63-70. 6 Perez-Andres M, Paiva B, Nieto WG, Caraux A, Schmitz A, Almeida J, et al