hepatitis b surface antigen

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hepatitis b surface antigen
Review Article
Hepatitis B Surface Antigen
°‘μ쑬» ¿Ÿà«√«√√≥
ªî¬–«—≤πå ‚°¡≈¡‘»√å
Àπ૬‚√§∑“߇¥‘πÕ“À“√·≈–μ—∫ ‚√ß欓∫“≈®ÿÓ≈ß°√≥å
○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○
‰«√— μ—∫Õ—°‡ ∫∫’‡ªìπªí≠À“∑’Ë ”§—≠¢Õߪ√–‡∑»‰∑¬ ·≈–‡ªì𠓇Àμÿ¢Õß
¿“«–μ—∫Õ—°‡ ∫‡©’¬∫æ≈—π μ—∫Õ—°‡ ∫‡√◊ÈÕ√—ß μ≈Õ¥®πμ—∫·¢Áß·≈–¡–‡√Áßμ—∫ °“√
«‘π‘®©—¬°“√μ‘¥‡™◊ÈÕ‰«√— μ—∫Õ—°‡ ∫∫’ §◊Õ°“√μ√«®À“ Hepatitis B surface antigen (HBsAg) ‚¥¬∑’˺à“π¡“°“√μ√«® HBsAg ®–·ª≈º≈„π‡™‘ß§ÿ≥¿“æ§◊Õ‡ªìπ
∫«°À√◊Õ≈∫ ªí®®ÿ∫—π¡’°“√μ√«®«—¥ HBsAg „π‡™‘ßª√‘¡“≥∑’ˇªìπ¡“μ√∞“π‚¥¬¡’
Àπ૬‡ªìπ IU/mL √«¡∑—Èß¡’°“√»÷°…“¡“°¢÷Èπ‡°’Ë¬«°—∫√–¥—∫ HBsAg ‡æ◊ËÕπ”¡“„™â
∑“ߧ≈‘π‘°„πÕπ“§μ
§«“¡‡ªìπ¡“¢Õß HBsAg
„πªï §.».1965 ‰¥â¡’°“√μ√«®æ∫ HBsAg §√—Èß·√°‚¥¬ Blumberg
·≈–§≥–1 ´÷Ëßμ√«®æ∫ Australian (Au) antigen ∑’ˇ°’ˬ«¢âÕß°—∫°“√‡°‘¥μ—∫
Õ—°‡ ∫‡©’¬∫æ≈—π „π¿“¬À≈—ß ‘Ëß∑’Ëμ√«®æ∫π—Èπ°Á§◊Õ HBsAg π—Ëπ‡Õß Dr. Baruch
Blumberg ‰¥â√—∫√“ß«—≈ Nobel “¢“«‘∑¬“»“ μ√å°“√·æ∑¬å„πªï §.».1976
HBsAg μ√«®æ∫‰¥â∑’ˇª≈◊Õ°πÕ°¢Õ߉«√— ∑’Ë ¡∫Ÿ√≥å (Dane particle)
·≈– à«πª√–°Õ∫∑’ˉ¡à ¡∫Ÿ√≥å¢Õ߉«√— ´÷Ëß¡’ 2 √Ÿª·∫∫ ‰¥â·°à√Ÿª·∫∫·∑àß (filamentous particle) ·≈–√Ÿª·∫∫°≈¡ (spherical particle) ‚¥¬ HBsAg ∑’Ëμ√«®æ∫
∫√‘‡«≥º‘«¢ÕßÕπÿ¿“§‡À≈à“π’È¡’ 3 ¢π“¥‰¥â·°à ¢π“¥‡≈Á° ¢π“¥°≈“ß ·≈–¢π“¥„À≠à
‚¥¬‡ªìπ‚ª√μ’π∑’Ë √â“ß®“° preS1, preS2 ·≈– S gene2 (¿“æ∑’Ë 1) °“√∑’ˉ«√— ¡’
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®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, ¡°√“§¡-‡¡…“¬π 2555
¿“æ∑’Ë 1 HBsAg ¢π“¥‡≈Á° ¢π“¥°≈“ß ·≈–¢π“¥„À≠à (SHBs proteins, MHBs protein,
LHBsprotein) ∑’Ëμ√«®æ∫‰¥â∑’ˇª≈◊Õ°πÕ°¢Õ߉«√— ∑’Ë ¡∫Ÿ√≥å (Dane particle) ·≈–
à«πª√–°Õ∫∑’ˉ¡à ¡∫Ÿ√≥å¢Õ߉«√— ∑—Èß Õß·∫∫‰¥â·°à filamentous particle ·≈– spherical
particle2
Õπÿ¿“§ à«π‡°‘ππ—Èπ‡™◊ËÕ«à“¡’º≈∑”„Àâ°“√°”®—¥‡™◊ÈÕ‚¥¬¿Ÿ¡‘§ÿâ¡°—π¢Õß√à“ß°“¬‡ªìπ‰ª
‰¥â¬“°¡“°¢÷Èπ
°≈‰°°“√ √â“ß HBsAg
‰«√— μ—∫Õ—°‡ ∫∫’®¥— Õ¬Ÿ„à πμ√–°Ÿ≈ Hepadnaviridae ‡ªìπ partially doublestranded DNA ª√–°Õ∫¥â«¬π‘«§≈’‚Õ‰∑¥åª√–¡“≥ 3,200 𑫧≈’‚Õ‰∑¥å ‚¥¬
‚§√ß √â“ßÀ≈—°¢Õ߉«√— ®–ª√–°Õ∫¥â«¬‡ª≈◊Õ°πÕ° (envelope) ·°π¢Õ߉«√— (core)
“√æ—π∏ÿ°√√¡ (DNA genome) ·≈– viral polymerase HBsAg ‡ªìπ à«π
ª√–°Õ∫¢Õ߇ª≈◊Õ°πÕ°¢Õ߉«√— ´÷ËßÀàÕÀÿâ¡ à«πª√–°Õ∫Õ◊ËπÊ ¢Õ߉«√— ·≈–¬—ß¡’
∫∑∫“∑„π°“√·æ√à°√–®“¬¢Õ߉«√— ‚¥¬°“√¬÷¥μ‘¥°—∫‡´≈≈åμ—∫ HBs protein ¡’
≈—°…≥–´÷Ëß¡’º≈μàÕ°“√ √â“ß¿Ÿ¡‘§ÿâ¡°—π¢ÕߺŸâμ‘¥‡™◊ÈÕ∑’ˇÀ¡◊Õπ°—π‡√’¬°«à“ a determinant ‚¥¬¡’À≈—°Ê 4 °≈ÿࡉ¥â·°à adw, ayw, adr ·≈– ayr3
HBsAg ∂Ÿ° √â“ߢ÷Èπ¿“¬„π‡´≈≈åμ—∫∑’Ëμ‘¥‡™◊ÈÕ ‡¡◊ËÕ “√æ—π∏ÿ°√√¡¢Õ߉«√— ‡¢â“‰ª„π𑫇§≈’¬ ¢Õ߇´≈≈åμ∫— ·≈–‡ª≈’¬Ë π√Ÿª√à“߇ªìπ cccDNA ‚¥¬¡’°≈‰°°“√ √â“ß
3 °≈‰° §◊Õ 1) HBsAg pathway 2) replication pathway ·≈– 3) integration
Hepatitis B Surface Antigen
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pathway (¿“æ∑’Ë 2)4 Õπÿ¿“§¢Õß HBsAg ∂Ÿ° √â“ߢ÷Èπ¿“¬„π‡´≈≈åμ—∫·≈–Õ¬Ÿà∑’Ë
endoplasmic reticulum ·≈– golgi complex °àÕπ∑’Ë®–∂Ÿ°„™âª√–°Õ∫‡ªìπº‘«
πÕ°¢Õßμ—«‰«√— HBsAg à«π∑’ˇÀ≈◊Õ®–∂Ÿ°ª≈àÕ¬ÕÕ°πÕ°‡´≈≈åμ—∫ ·μà¡’∫“ß à«π
¬—ߧßμ°§â“ßÕ¬Ÿ∑à Ë’ endoplasmic reticulum ´÷ßË ∑”„À⇰‘¥≈—°…≥–∑’‡Ë √’¬°«à“ groundglass appearance ¢Õ߇´≈≈åμ—∫‡¡◊ËÕμ√«®∑“ß欓∏‘«‘∑¬“
°“√μ√«®√–¥—∫ HBsAg
°“√μ√«® HBsAg π—Èπ “¡“√∂∑”‰¥âÀ≈“¬«‘∏’ ‚¥¬«‘∏’°“√μ√«®À≈—°‰¥â·°à
radioimmunoassay (RIA) ·≈– enzyme immunoassay (EIA) ‚¥¬°“√μ√«®
„πÕ¥’μ∑’ºË “à π¡“π—πÈ ‚¥¬¡“°¡’°“√·ª≈º≈„π‡™‘ß§ÿ≥¿“æ ªí®®ÿ∫π— ¡’°“√μ√«®«—¥√–¥—∫
HBsAg titer ∑’ˇªìπ¡“μ√∞“π‡ª√’¬∫‡∑’¬∫°—π‰¥â√–À«à“ßÀâÕߪؑ∫—μ‘°“√ ‚¥¬‡§√◊ËÕß
∑’Ë„™âμ√«®„πªí®®ÿ∫—π ‰¥â·°à The Architect HBsAg QT ¢Õß Abbott Diagnostic
´÷Ëß “¡“√∂μ√«® HBsAg ‰¥âμ—Èß·μà√–¥—∫ 0.2 ng/mL ‚¥¬°“√μ√«®«—¥ª√–‡¡‘π®“°
¿“æ∑’Ë 2 °≈‰°°“√ √â“ß HBsAg ®“°‡´≈≈åμ—∫∑’Ëμ‘¥‡™◊ÈÕ‰¥â·°à 1) HBsAg pathway 2) Replication
pathway ·≈– 3) Integration pathway4
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®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, ¡°√“§¡-‡¡…“¬π 2555
§à“°“√‡√◊Õß· ß∑“߇§¡’ ·≈–·ª≈ßÀπ૬‡ªìπ IU/mL ‚¥¬§à“∑’μË √«®®–Õ¬Ÿ„à π™à«ß 0.05250.0 IU/mL À“°ª√‘¡“≥¡“°°«à“ 250 IU/mL ®–μâÕß∑”°“√‡®◊Õ®“߇æ◊ËÕ„Àâ°“√
ª√–‡¡‘π§à“∂Ÿ°μâÕß ‡§√◊ËÕßμ√«® HBsAg ¢ÕßÕ’°∫√‘…—∑Àπ÷Ëߧ◊Õ Elecsys HBsAg II
¢Õß Roche Diagnostics ´÷Ëß„Àâº≈°“√μ√«® Õ¥§≈âÕß°—π·≈–‰¡à¡’§«“¡·μ°μà“ß
°—π‡¡◊ËÕ„™â ”À√—∫‰«√— μ—∫Õ—°‡ ∫∫’„π·μà≈– “¬æ—π∏ÿ5å
√–¥—∫ HBsAg „πºŸâªÉ«¬‰«√— μ—∫Õ—°‡ ∫∫’√–¬–μà“ßÊ
ªí®®ÿ∫—π‡√“·∫àß√–¬–¢Õß‚√§‰«√— μ—∫Õ—°‡ ∫∫’‡√◊ÈÕ√—ß‚¥¬Õ“»—¬°“√ª√–‡¡‘π
√–¥—∫°“√Õ—°‡ ∫¢Õßμ—∫ °“√μ√«® HBeAg ·≈–°“√μ√«®ª√‘¡“≥‰«√— ‚¥¬·∫àß
°≈ÿࡺŸâªÉ«¬ÕÕ°‡ªìπ√–¬–μà“ßÊ ‰¥â·°à immune-tolerance phase (IT), immuneclearance phase (IC), non/low-replicative phase (LR) ·≈– hepatitis B e
antigen negative hepatitis (ENH) ´÷Ëß°“√·∫àß√–¬–¢Õß‚√§π’ȇæ◊ËÕª√–‚¬™πå„π
°“√«“ß·ºπ°“√√—°…“ºŸâªÉ«¬6
ªí®®ÿ∫—π°“√ª√–‡¡‘π°“√‡æ‘Ë¡®”π«π¢Õ߉«√— ∑’Ëπ‘¬¡„™âÕ¬Ÿà‡ªìπÀ≈—° §◊Õ °“√
«—¥ª√‘¡“≥‰«√— ´÷Ëߙ૬„π°“√ª√–‡¡‘π√–¬–¢Õß‚√§°àÕπ°“√√—°…“·≈–‡ªìπ ‘Ëß∑’Ë
”§—≠„π°“√„™â쥑 μ“¡À≈—ß®“°‡√‘¡Ë °“√√—°…“·≈–«‘π®‘ ©—¬°“√‡°‘¥¿“«–¥◊ÕÈ ¬“¢Õ߉«√— ·μà°“√≈¥≈ߢÕ߉«√— ‡æ’¬ßÕ¬à“߇¥’¬«¬—߉¡à “¡“√∂∑’Ë®–∑”π“¬‚Õ°“ À“¬À≈—ß®“°
‡√‘Ë¡°“√√—°…“‰¥â °“√μ√«®√–¥—∫·Õπ쑇®π‡™àπ HBsAg Õ“®∫Õ°∂÷ß activity ¢Õß
‰«√— „π·ßà¡ÿ¡Õ◊ËππÕ°‡Àπ◊Õ‰ª®“°ª√‘¡“≥‰«√— ∑’Ëμ√«®°—π„πªí®®ÿ∫—π √–¥—∫¢Õß
HBsAg ∑’Ë«—¥‰¥â‡ªìπº≈∑’ˇ°‘¥®“°§«“¡ ¡¥ÿ≈¬å¢Õ߇™◊ÈÕ‰«√— ·≈–¿Ÿ¡‘μâ“π∑“π¢Õß
√à“ß°“¬„πºŸâªÉ«¬·μà≈–√“¬ ‚¥¬∫àß∂÷ß°“√ √â“ß®“° mRNA ¡“°°«à“∑’Ë®–‡ªìπ°“√
‡æ‘Ë¡®”π«π (replication) ¢Õ߉«√— °“√»÷°…“‡°’¬Ë «°—∫√–¥—∫ HBsAg „πºŸªâ «É ¬‰«√— μ—∫Õ—°‡ ∫∫’√–¬–μà“ßÊ æ∫«à“
√–¥—∫ HBsAg „π°≈ÿࡺŸâªÉ«¬∑’Ë¡’ HBeAg positive ®– Ÿß°«à“ „π°≈ÿࡺŸâªÉ«¬∑’Ë¡’
HBeAg negative πÕ°®“°π’Ȭ—ßæ∫«à“√–¥—∫ HBsAg „π√–¬– IT Ÿß°«à“„π√–¬–
IC ·≈–„π√–¬– ENH °Á Ÿß°«à“„π√–¬– LR · ¥ß„Àâ‡ÀÁπ«à“„π·μà≈–√–¬–¢Õß‚√§¡’
√–¥—∫ HBsAg ∑’Ë·μ°μà“ß°—π7
Hepatitis B Surface Antigen
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§«“¡ —¡æ—π∏å°—∫ viral markers Õ◊ËπÊ
Covalently closed circular DNA (cccDNA) ∑’Ëæ∫„π‡´≈≈åμ—∫∑’Ëμ‘¥‡™◊ÈÕ
· ¥ß∂÷ߪ√‘¡“≥°“√μ‘¥‡™◊ÈÕ„π‡π◊ÈÕμ—∫·≈–¡’º≈μàÕ°“√ √â“߉«√— ·≈– HBsAg ®“°
¢âÕ¡Ÿ≈°“√»÷°…“æ∫«à“ „πºŸâªÉ«¬‰«√— μ—∫Õ—°‡ ∫∫’‡√◊ÈÕ√—ß √–¥—∫ HBsAg ¡’§«“¡
—¡æ—π∏å°—∫ª√‘¡“≥¢Õ߉«√— „π‡≈◊Õ¥ (serum HBV DNA level) ª√‘¡“≥¢Õß
cccDNA „πμ—∫ ·≈–ª√‘¡“≥¢Õ߉«√— (HBV DNA) „π‡π◊ÈÕμ—∫ ‚¥¬æ∫§«“¡
—¡æ—π∏å‡À≈à“π’„È π°≈ÿ¡à ºŸªâ «É ¬∑’¡Ë ’ HBeAg positive8 ·μà ”À√—∫°≈ÿ¡à ºŸªâ «É ¬∑’¡Ë ’ HBeAg
negative π—Èπ °≈—∫æ∫«à“√–¥—∫¢Õß HBsAg „π‡≈◊Õ¥∫àß∂÷ߪ√‘¡“≥ HBsAg „π
‡π◊ÈÕμ—∫·μà‰¡à —¡æ—π∏å°—∫ª√‘¡“≥ cccDNA ·≈– HBV DNA „π‡π◊ÈÕμ—∫9 πÕ°®“°
π’Ȭ—ß¡’°“√»÷°…“æ∫°“√‡ª≈’ˬπ·ª≈ߢÕß√–¥—∫ HBsAg ´÷Ëß¡’§«“¡ —¡æ—π∏å°—∫
cccDNA „π√–À«à“ß∑’ˉ¥â√—∫°“√√—°…“‰«√— μ—∫Õ—°‡ ∫∫’ ‰¡à«à“®–¥â«¬¬“μâ“π‰«√— À√◊Õ¬“Õ‘π‡μÕ√å‡øÕ√Õπ10
ªí®®—¬∑’ËÕ“® àߺ≈μàÕ§«“¡ —¡æ—π∏å∑’Ë·μ°μà“ß°—ππ’ÈÕ“®‡°‘¥®“°ªí®®—¬∑“ß
¿Ÿ¡‘§ÿâ¡°—π¢ÕߺŸâªÉ«¬∑’Ë¡’§«“¡·μ°μà“ß°—π„π·μà≈–√–¬–¢Õß‚√§
ª√–‚¬™πå∑“ߧ≈‘π‘°
°“√μ√«® HBV DNA ‡ªìπ°“√μ√«®∑’ˇªìπ¡“μ√∞“πÀ≈—°„π°“√ª√–‡¡‘π
ª√‘¡“≥‰«√— ·μà¢âÕ®”°—¥¢Õß°“√μ√«®π’ȧ◊Õμâπ∑ÿπ„π°“√μ√«®∑’˧àÕπ¢â“ß Ÿß·≈–
Õ“®¡’§«“¡·μ°μà“ß°—π„π·μà≈–ÀâÕߪƑ∫—μ‘°“√ ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫°“√μ√«®√–¥—∫
HBsAg ·≈⫇ªìπ°“√μ√«®∑’Ë∑”‰¥âßà“¬°«à“ ·≈–¡’μâπ∑ÿπ„π°“√μ√«®∑’ËμË”°«à“
‡ªÑ“À¡“¬„π°“√√—°…“ºŸâªÉ«¬‰«√— μ—∫Õ—°‡ ∫∫’‡√◊ÈÕ√—ߧ◊Õ°“√ “¡“√∂§«∫§ÿ¡
‰«√— „ÀâÕ¬Ÿà„π√–¬– ß∫ ‡ΩÑ“μ‘¥μ“¡º≈·∑√°´âÕπ∑’ËÕ“®‡°‘¥¢÷Èπ ·≈–‡ªÑ“À¡“¬ Ÿß ÿ¥
§◊Õ°“√À“¬¢“¥®“°‰«√— ∫’ π—πË §◊Õ°“√∑’ Ë “¡“√∂‡°‘¥ HBsAg clearance ·≈– HBsAg
seroconversion °“√ª√–‡¡‘π√–¥—∫ HBsAg °àÕπ·≈–√–À«à“ß°“√√—°…“®÷ßπà“®–¡’
ª√–‚¬™πå„π°“√欓°√≥åº≈°“√√—°…“·≈–«“ß·ºπ°“√√—°…“„πºŸâªÉ«¬·μà≈–√“¬
®“°º≈°“√»÷°…“„πºŸâªÉ«¬‰«√— μ—∫Õ—°‡ ∫∫’‡√◊ÈÕ√—ß∑’ˉ¥â√—∫°“√√—°…“¥â«¬¬“
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®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, ¡°√“§¡-‡¡…“¬π 2555
Õ‘π‡μÕ√å‡øÕ√Õπ·≈–≈“¡‘«¥Ÿ ’π ‡¡◊ËÕ·¬°°≈ÿࡺŸâªÉ«¬μ“¡√–¥—∫ HBsAg °àÕπ°“√√—°…“
æ∫«à“À≈—ß®“°À¬ÿ¥¬“ 1 ªï „π°≈ÿࡺŸâªÉ«¬∑’Ë¡’ HBsAg °àÕπ°“√√—°…“„π√–¥—∫∑’ËμË”
°«à“ 10,000 IU/mL ¡’√âÕ¬≈– 43 ¢ÕߺŸâªÉ«¬∑’Ë¡’√–¥—∫‰«√— μË”°«à“ 10,000 copies/
mL à«π°≈ÿà¡∑’Ë¡’ HBsAg °àÕπ°“√√—°…“„π√–¥—∫∑’Ë Ÿß°«à“ 10,000 IU/mL ¡’‡æ’¬ß
√âÕ¬≈– 8 ¢ÕߺŸâªÉ«¬‡∑à“π—Èπ∑’Ë¡’√–¥—∫‰«√— μË”°«à“ 10,000 copies/mL11
„π°≈ÿࡺŸâªÉ«¬∑’Ë¡’ HBeAg negative °“√μ√«®μ‘¥μ“¡√–¥—∫ HBsAg
√–À«à“ß°“√√—°…“¥â«¬¬“Õ‘π‡μÕ√å‡øÕ√Õπæ∫«à“°“√∑’Ë¡’√–¥—∫ HBsAg ≈¥≈ß¡“°°«à“
0.5 log IU/mL ∑’Ë —ª¥“Àå∑’Ë 12 À≈—ß°“√√—°…“ ·≈– ≈¥≈ß¡“°°«à“ 1 log IU/mL ∑’Ë
—ª¥“Àå∑’Ë 24 À≈—ß°“√√—°…“ “¡“√∂∑”𓬰“√μÕ∫ πÕßμàÕ¬“„π√–¬–¬“«‰¥â‡ªìπ
Õ¬à“ߥ’ πÕ°®“°π’Ȭ—ßæ∫«à“°≈ÿà¡∑’Ë¡’√–¥—∫ HBsAg μË”°«à“ 1,500 IU/mL ∑’Ë —ª¥“Àå∑’Ë
12 À≈—ß°“√√—°…“¡’‚Õ°“ ‡°‘¥ HBsAg loss „π√–¬–‡«≈“ 4 ªï‰¥â∂÷ß 35%12 „πÕ’°
°“√»÷°…“Àπ÷Ëß°Áæ∫«à“°“√∑’Ë¡’ HBsAg μË”°«à“ 10 IU/mL ¡’√–¥—∫ HBsAg ≈¥≈ß
®“°°àÕπ√—°…“¡“°°«à“ 1 log IU/mL ·≈– 2 log IU/mL À≈—ß°“√√—°…“¥â«¬
peginterferon alfa-2a ®–‡°‘¥ HBsAg Loss À≈—ß°“√√—°…“ 3 ªï ∂÷ß 52%, 30%
·≈– 42.3% μ“¡≈”¥—∫13
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12
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