A preliminary report on the influence of baseline cellular immunity to the therapeutic responses of peg-interferon

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1 Journal of Microbes and Infection, September 2009, Vol. 4, No. 3 e 2a 1, 2, 1, 1, 1, 1, 1, 1 1., ; 2., : ( CHB) ( IFN), IFN IFN, e ( HBeAg) CHB 19, 14, IFN- 2a 180 g, 1, 48, 24 CD3 + CD4 + CD8 + CD4 + /CD8 + ( NK) CD3 + /CD25 + CD8 + /CD28 + ( LTT) ( TNF) IFN- ; e ( EOT) ( EOF), EOT 15, 4, 2 ( ALT) , ( = ) ; CD8 + / CD28 + ( = ) EOF 7, 12, LTT , ( = ) CD4 + CD3 + / CD25 + HBeAg, , EOF ( = ), CHB IFN, : ; ; A preliminary report on the influence of baseline cellular immunity to the therapeutic responses of peg-interferon 2a in HBeAg positive chronic hepatitis B patients GONG Qi-Ming 1, JIANG Wei-Jie 2, JIN Gen-Di 1, KONG Xiao-Fei 1, YU De-Min 1, LING Yun 1, LU Zhi-Meng 1, ZHANG Xin-Xin 1 1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai , China; 2. Clinical Laboratory Center, Longhua Hospital, Shanghai , China Abstract: The antiviral efficacy of interferon in the treatment of patients with chronic hepatitis B ( CHB) is influenced by the virus itself and the host factors. The host cellular immunity status is undoubtedly one of the most important factors of the interferon response. We analyzed baseline cellular immune factors before interferon treatment in order to understand the impact of immune status on virological response. Nineteen patients, including 14 males and 5 females with hepatitis B virus e antigen ( HBeAg) positive CHB, received peg-interferon 2a 180 g per week for 48 weeks and follow-up for 24 weeks. All had liver biopsies at baseline and at the end of follow-up( EOF). Hepatitis B virus ( HBV) viral load, liver functions were detected before and every two months after antiviral therapy. Cellular immunity was evaluated by detecting CD3 +, CD4 +, CD8 +, CD4 + / CD8 +, natural killer ( NK) cell, CD3 + / CD25 +, CD8 + / CD28 +, lymphocyte transformation test ( LTT), tumor necrosis factor ( TNF) and IFN-, using flow : ( 2005DFA30150), ( 863) ( 2006AA02A411), ( 2008 ZX ) :, gongqm@ hotmail. com Corresponding author: GONG Qi-Ming, gongqm@ hotmail. com

2 Journal of Microbes and Infection, September 2009, Vol. 4, No cytometry. The virological response was defined as a HBV viral load below copies/ ml at end of treatment ( EOT) and EOF. The results showed that 15 patients had an EOT virological response, while 7 patients had an EOF virological response. CD8 + /CD28 + was significantly higher in patients with an EOT virological response than that in non-responders ( = ), while LTT was significantly higher in patients with an EOF virological response ( = ). CD4 + and CD3 + / CD25 + were significantly higher in patients with HBeAg serum conversion ( = and ). Six patients had an EOF histological response( = ). Our data suggest that the cellular immune status of the host may be a good predictive indicator for the response of IFN therapy in CHB patients. Key words: Hepatitis B; Cellular immunity; eg-interferon ( hepatitis B virus, HBV), 2a ( interferon 2a, IFN- 2a) HBV, IFN, ( chronic hepatitis B, CHB) , 14, 5, 19 59, [ 1 ] , ( hepatitis B virus surface antigen, HBsAg ) e ( hepatitis B virus e antigen, HBeAg) ( hepatitis B virus core antibody, HBcAb) IFN- 2a 180 g, 1, 48, 24, ( ) HBV DNA < / ml, ( alanine aminotransferase, ALT) 48 ( end of treatment, EOT) 24 ( end of follow-up, EOF), ( ) HBV HBsAg ( hepatitis B virus surface antibody, HBsAb) HBeAg e ( hepatitis B virus e antibody, HBeAb ) HBcAb Abbott AXSYM, 1 Tab 1. Characteristics of patients at baseline Number of cases ALT: 1-2 ULN ULN 5 > 5 ULN 3 HBV DNA ( copies /ml) Genotype B 6 C 13 athology: Inflammation G3 2 G4 10 G5 2 G6 1 G7 3 G13 1 athology: Fibrosis S1 5 S2 8 S3 4 S4 1 S HBV DNA Roche Cobas Amplicor, HBV DNA < 300 / ml , ( Becton Dickinson FACScan)

3 Journal of Microbes and Infection, September 2009, Vol. 4, No. 3 CD3 + CD4 + CD8 + T, CD4 + / CD8 +, ( natural killer, NK), CD3 + /CD T, CD8 + /CD T, ( lymphocyte transformation test, LTT) ( ) ( tumor necrosis factor, TNF) IFN- ( pg/ ml) mean SD, t < 0. 05, < EOT EOT 15, 4 2, , ; 2 HBV DNA ( =0. 322) ; 2 ALT ( =0. 035) ( 2) ALT, EOT 2 EOT Tab 2. Data comparison between response and non-response groups at EOT ( n = 15) group ( n = 4) Age , ( = ), CD3 + CD4 + CD8 + CD4 + / CD8 + NK CD3 + ( 4) 3 / CD25 + LTT TNF IFN- EOF Tab 3. Data comparison between response and non-response groups at EOF ( n = 7) group( n = 12) Age Sex ( male /female) ALT HBV DNA ( log) EOT Tab 4. Comparison of baseline cellular immune factors between response and non-response groups at EOT ( n = 15) group ( n = 4) CD CD CD CD4 + /CD NK cell CD3 + /CD CD8 + /CD LTT TNF IFN Sex ( male /female) ALT HBV DNA ( log) EOT 15, 8 EOF HBV DNA, ALT 7, 12 2, ALT HBV DNA ( 3) 2. 3 EOT, EOT CD8 + / CD , 2. 4 EOF, LTT , , ( = ) CD3 + CD4 + CD8 + CD4 + CD25 + CD8 + ( 5) /CD8 + NK CD3 + / /CD28 + TNF IFN HBeAg 19 HBeAg EOT 3, EOF 2 HBeAg, % EOF HBeAg, CD4 + CD3 + /CD25 +

4 Journal of Microbes and Infection, September 2009, Vol. 4, No ( 6) 5 EOF Tab 5. Comparison of baseline cellular immune factors between response and non-response groups at EOF ( n = 7 ) group ( n = 12) CD CD CD CD4 + /CD NK cell CD3 + /CD CD8 + /CD LTT TNF IFN EOF HBeAg Tab 6. Comparison of baseline cellular immune factors between HBeAg serum conversion and non-conversion groups at EOF HBeAg serum conversion group ( n = 5 ) HBeAg serum non-conversion group ( n = 14) CD CD CD CD4 + /CD NK cell CD3 + /CD CD8 + /CD LTT TNF IFN EOF,,,, ( = ), 2 ( = ) ( 1) 1 EOF Fig 1. Comparison of liver histological changes between response and non-response groups at EOF 2. 7 IFN- 2a

5 Journal of Microbes and Infection, September 2009, Vol. 4, No. 3,,, ( ), 1, ;, 48 3 IFN- HBV,, HBV HBV, [ 2], HBV IFN-,, HBV C C IFN-, HBeAg CHB IFN-, [ 3, 4 ] 3 IFN- 2a CHB 1 [ 5 ], ALT,,, ALT, IFN, ALT IFN- 2a HBeAg CHB, IFN,, IFN, IFN CHB CD8 + / CD28 + T ( cytotoxic T lymphocyte, CTL), CD28 B B7-1 ( CD80) B7-2,, CTL, [ 6 ], EOT CD8 + / CD28 +, ,, TNF HBV [ 7], TNF ( histological activity index, HAI) [ 8 ] NK NK IFN- [ 9], HBV, T, HBcAg IFN- [ 10], IFN- Th1 + DNA [ 11 ] TNF IFN-, LTT T, [ ( phytohemagglutinin, HA ) A ( concanamycin A, ConA) ],,,, LTT, HBV [ 12] LTT [ 13], [ 14] CHB [ 15 ] LTT CHB IFN,, LTT IFN, HBV IFN 30% 40%, IFN, IFN, IFN,, ALT IFN- 2a EOT, LTT CD4 + CD3 + /CD25 +, IFN,,, [ 1]. [ J]., 2001, 19( 1) : [ 2],,,. [ J]., 2002, 20( 2) : [ 3],,. C [ J]., 2001, 19( 5) : [ 4] Ayoub WS, Keeffe EB. Current antiviral therapy of chronic hepatitis B[ J]. Aliment harmacol Ther, 2008, 28( 2) :

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