Review Article
Bile Acid Diarrhea
™“≠≥√ߧå μ√’ ÿ«√√≥«—≤πå
√—μπ“ ∫ÿ≠»‘√‘®—π∑√å
Àπ૬‚√§√–∫∫∑“߇¥‘πÕ“À“√·≈–μ—∫ §≥–·æ∑¬»“ μ√å«™‘√欓∫“≈
○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○
¿“«–∑âÕ߇ ’¬‡√◊ÈÕ√—߇ªìπªí≠À“∑’Ëæ∫‰¥â∫àÕ¬„π‡«™ªØ‘∫—μ‘ ‚¥¬π‘¬“¡¢Õß
¿“«–∑âÕ߇ ’¬‡√◊ÈÕ√—ߧ◊Õ ¡’Õ“°“√∂à“¬Õÿ®®“√–‡À≈« ‚¥¬¡’°“√‡æ‘Ë¡¢÷Èπ¢Õß®”π«π§√—Èß
¢Õß°“√∂à“¬Õÿ®®“√–√à«¡¥â«¬À√◊Õ‰¡à°Á‰¥â ‡ªìπ‡«≈“π“π°«à“ 4 —ª¥“Àå “¡“√∂·¬°
μ“¡°≈‰°°“√‡°‘¥‚√§®“°≈—°…≥–¢ÕßÕÿ®®“√–‚¥¬·∫à߇ªìπ 4 ≈—°…≥–§◊Õ osmotic
diarrhea, fatty diarrhea, inflammatory diarrhea ·≈– secretory diarrhea
¿“«–∑âÕ߇ ’¬‡√◊ÈÕ√—ßπ—Èπ‡°‘¥‰¥â®“°À≈“¬ “‡Àμÿ °“√„™â·π«∑“ß°“√«‘π‘®©—¬
·≈–¥Ÿ·≈√—°…“¿“«–∑âÕ߇ ’¬‡√◊ÕÈ √—ß1 ‚¥¬°“√´—°ª√–«—μ·‘ ≈–μ√«®√à“ß°“¬Õ¬à“ß≈–‡Õ’¬¥
√à«¡°—∫°“√ àßμ√«®∑“ßÀâÕߪؑ∫—μ‘°“√‡∫◊ÈÕßμâπ ¡—°®– “¡“√∂«‘π‘®©—¬∂÷ß “‡Àμÿ¢Õß
¿“«–∑âÕ߇ ’¬‡√◊ÈÕ√—ß„πºŸâªÉ«¬ à«π„À≠à‰¥â ·μà®–¡’ºŸâªÉ«¬ à«πÀπ÷Ëß∑’ˉ¡à “¡“√∂À“
“‡Àμÿ‰¥â ®÷ß¡—°®–∂Ÿ°®—¥Õ¬Ÿà„π°≈ÿà¡∑’ˉ¡à∑√“∫ “‡Àμÿ™—¥‡®π ‡™àπ functional diarrhea ‚√§≈”‰ â·ª√ª√«π (irritable bowel syndrome; IBS) ·≈–¿“«–°“√¥Ÿ¥´÷¡
°√¥πÈ”¥’º‘¥ª°μ‘ ‡ªìπμâπ
¿“«–∑âÕ߇ ’¬‡√◊ÕÈ √—ß®“°°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º¥‘ ª°μ‘ (bile acid malabsorption; BAM) æ∫‰¥â‰¡àπâÕ¬ ·μà¡—°®–‰¡à‰¥â√—∫°“√«‘π‘®©—¬ (‡π◊ËÕß®“°°“√μ√«®∑“ß
ÀâÕߪؑ∫—μ‘°“√¬ÿà߬“° À√◊Õ·æ∑¬å‰¡àμ√–Àπ—°∂÷ß) ·≈–¡—°®–∂Ÿ°«‘π‘®©—¬‡ªìπ‚√§
Õÿ®®“√–√à«ß∑’ˉ¡à¡’ “‡Àμÿ (functional diarrhea) À√◊Õ ‡ªìπ‚√§≈”‰ â·ª√ª√«π
·∫∫Õÿ®®“√–√à«ß (diarrhea-predominant irritable bowel syndrome; IBS-D)
§«“¡º‘¥ª°μ‘¢Õß°“√¥Ÿ¥´÷¡°√¥πÈ”¥’ “¡“√∂∑”„À⇰‘¥¿“«–∑âÕ߇ ’¬‡√◊ÕÈ √—߉¥â
2 ≈—°…≥– ®“° 4 ≈—°…≥–¢â“ßμâπ ‰¥â·°à fatty diarrhea ·≈– secretory diarrhea
16
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
‚¥¬ fatty diarrhea À√◊Õ steatorrhea §◊Õ Õ“°“√∂à“¬‡À≈«‚¥¬¡’≈—°…≥–Õÿ®®“√–
‡ªìπ¡—π °“√¢“¥°√¥πÈ”¥’∑”„Àâ°“√¬àÕ¬·≈–¥Ÿ¥´÷¡‰¢¡—πº‘¥ª°μ‘ æ∫„πºŸâªÉ«¬∑’ˉ¥â
√—∫°“√ºà“μ—¥≈”‰ â‡≈Á° à«π ileum ¡“°°«à“ 100 ‡´Áπ쑇¡μ√2 À√◊Õ¡’°“√μ—¥≈”‰ â‡≈Á°
à«π terminal ileum à«π„π°≈ÿ¡à secretory diarrhea ®–¡’≈°— …≥–∂à“¬‡À≈«‡ªìππÈ”
´÷Ë߇°‘¥®“°°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º‘¥ª°μ‘∑’Ë≈”‰ â‡≈Á° ∑”„Àâ¡’°√¥πÈ”¥’∑’ˉ¡à∂Ÿ°¥Ÿ¥´÷¡
à«π‡°‘πºà“π‰ª¬—ß≈”‰ â„À≠à¡“°°«à“ª°μ‘ °√¥πÈ”¥’ à«π‡°‘ππ’È®–°√–μÿâπ‡´≈≈å„π
≈”‰ â„À≠à„ÀâÀ≈—Ëß “√πÈ”ÕÕ°¡“∑”„À⇰‘¥Õ“°“√∂à“¬‡À≈«
°≈à“«‚¥¬ √ÿª§◊Õ Õ“°“√∂à“¬‡À≈«∑’ˇ°‘¥®“°°√¥πÈ”¥’ ‡°‘¥‰¥â„π 2 ≈—°…≥–
À“°°√¥πÈ”¥’„π≈”‰ ⢓¥ ®–∑”„Àâ∂à“¬‡À≈«‡ªìπ¡—π À“°¡’°√¥πÈ”¥’ à«π‡°‘π≈ß¡“∑’Ë
≈”‰ â„À≠à ®–∑”„Àâ∂à“¬‡À≈«‡ªìππÈ”
√’√«‘∑¬“æ◊Èπ∞“π¢Õß°“√ √â“ß·≈–¥Ÿ¥´÷¡°√¥πÈ”¥’2
πÈ”¥’ √â“ߢ÷πÈ ®“°μ—∫ ·≈–À≈—ßË ÕÕ°¡“¬—ß∑àÕπÈ”¥’ ª√–°Õ∫¥â«¬ “√μà“ßÊ À≈“¬
™π‘¥ ‰¥â·°à
- øÕ ‚ø‰≈ªî¥
- ‚§‡≈ ‡μÕ√Õ≈
- ∫‘≈‘√Ÿ∫‘π
- °√¥πÈ”¥’
- ‰∫§“√å∫Õ‡πμ
°√¥πÈ”¥’ ´÷Ë߇ªìπ à«πª√–°Õ∫À≈—°„ππÈ”¥’ ¡’Àπâ“∑’ËÀ≈“¬Õ¬à“ß §◊Õ °√–μÿâπ
„À⇰‘¥°“√‰À≈¢ÕßπÈ”¥’·≈– “√μà“ßÊ ®“°μ—∫ÕÕ°¡“„ππÈ”¥’ ‡™à𠂧‡≈ ‡μÕ√Õ≈
øÕ ‚ø‰≈ªî¥ ™à«¬„π°“√¬àÕ¬·≈–¥Ÿ¥´÷¡‰¢¡—π ™à«¬„π°“√¥Ÿ¥´÷¡«‘μ“¡‘π∑’Ë≈–≈“¬„π
‰¢¡—π ‰¥â·°à «‘μ“¡‘π ‡Õ ¥’ Õ’ ‡§ ™à«¬§«∫§ÿ¡ ¡¥ÿ≈¢Õß‚§‡≈ ‡μÕ√Õ≈„π√à“ß°“¬
™à«¬∑”≈“¬‡™◊ÈÕ·∫§∑’‡√’¬„π≈”‰ ⠙૬ªÑÕß°—π°“√‡°‘¥π‘Ë«·§≈‡´’¬¡„π∂ÿßπÈ”¥’ ·≈–
π‘Ë«ÕÁÕ°´“‡≈μ„π‰μ ‡ªìπμâπ
°√¥πÈ”¥’∂Ÿ° √â“ß‚¥¬‡´≈≈åμ—∫ ‚¥¬ √â“ß®“° “√μ—Èßμâπ §◊Õ ‚§‡≈ ‡μÕ√Õ≈
À≈—ËßÕÕ°¡“√«¡„ππÈ”¥’ ·≈–®–∂Ÿ°‡°Á∫‰«â∑’Ë∂ÿßπÈ”¥’„π¢≥–Õ¥Õ“À“√ ·μà‡¡◊ËÕ√—∫
Bile Acid Diarrhea
17
ª√–∑“πÕ“À“√®–‡°‘¥°“√°√–μÿâπ cholecystokinin ®“°≈”‰ â‡≈Á°∑”„À⇰‘¥°“√∫’∫
μ—«¢Õß∂ÿßπÈ”¥’·≈–°“√§≈“¬μ—«¢ÕßÀŸ√Ÿ¥∑’˪≈“¬∑àÕπÈ”¥’ (sphincter of Oddi) πÈ”¥’
®÷߉À≈≈ß¡“∑’Ë≈”‰ â‡≈Á° ‡æ◊ËÕ∑”Àπâ“∑’Ëμà“ßÊ ¢â“ßμâπ À≈—ß®“°π—Èπ √âÕ¬≈– 95 ¢Õß°√¥
πÈ”¥’®–∂Ÿ°¥Ÿ¥´÷¡°≈—∫‰ª¬—ßÀ≈Õ¥‡≈◊Õ¥¥” à«πæÕ√å∑—≈‡¢â“ Ÿàμ—∫ (enterohepatic circulation) ‚¥¬∑—Èß«‘∏’ passive ·≈– active transportation ∑’Ë≈”‰ â‡≈Á° à«π ileum
‚¥¬μ—∫®–º≈‘μ°√¥πÈ”¥’¢÷Èπ„À¡à‡æ’¬ß√âÕ¬≈– 5 ‡∑à“π—Èπ
°√¥πÈ”¥’®–À≈—ËßÕÕ°¡“„À¡à‡¡◊ËÕ¡’°“√°√–μÿâπ®“°¡◊ÈÕÕ“À“√ ‚¥¬®–‡°‘¥°“√
‰À≈‡«’¬π‡™àππ’È 2-3 §√—ÈßμàÕ¡◊ÈÕÕ“À“√ √«¡‡ªìπ 6-10 §√—ÈßμàÕ«—π ‡°‘¥°“√¥Ÿ¥´÷¡°√¥
πÈ”¥’ 10-30 °√—¡μàÕ«—π ¡’°√¥πÈ”¥’‡æ’¬ß 0.2-0.6 °√—¡∑’ˉ¡à∂Ÿ°¥Ÿ¥´÷¡·≈–∂Ÿ°¢—∫ÕÕ°
¡“∑“ßÕÿ®®“√– À“°°“√¥Ÿ¥´÷¡°≈—∫¢Õß°√¥πÈ”¥’≈¥≈ß¡“°®πμ—∫‰¡à “¡“√∂ √â“ß
°√¥πÈ”¥’∑¥·∑π‰¥â∑—π ®–∑”„Àâ√à“ß°“¬¢“¥°√¥πÈ”¥’„π°“√™à«¬¬àÕ¬‰¢¡—π (form
micelle) ‡ªìπº≈„À⇰‘¥Õ“°“√∑âÕ߇ ’¬·∫∫ stetorrhea ´÷Ëßæ∫‰¥â„πºŸâªÉ«¬∑’Ë¡’°“√
μ—¥≈”‰ â‡≈Á° à«π ileum ‡°‘π 100 ‡´Áπ쑇¡μ√ ·μà∂â“°“√¥Ÿ¥´÷¡°≈—∫¢Õß°√¥πÈ”¥’
≈¥≈߉¡à¡“°π—° ·≈–μ—∫¬—ß “¡“√∂ √â“ß°√¥πÈ”¥’∑¥·∑π‰¥â∑—π °Á®–‰¡à‡°‘¥¿“«–
°“√¢“¥°√¥πÈ”¥’À√◊Õ‰¡à‡°‘¥ steatorrhea ·μà®–‡°‘¥ªí≠À“ °“√¡’πÈ”¥’ à«π‡°‘π∑’ˉ¡à
“¡“√∂¥Ÿ¥´÷¡®“°≈”‰ â‡≈Á°ºà“π‰ª∑’Ë≈”‰ â„À≠àª√‘¡“≥¡“°¢÷Èπ °√¥πÈ”¥’™π‘¥À≈—°∑’Ë
∑”„À⇰‘¥Õ“°“√∂à“¬‡À≈«≈—°…≥–π’È ‰¥â·°à ™π‘¥ dihydroxy bile acid ´÷ËßÀ“°¡’
§«“¡‡¢â¡¢âπμË”®–≈¥°“√¥Ÿ¥´÷¡¢Õß “√πÈ”∑’Ë≈”‰ â„À≠à ·μàÀ“°¡’§«“¡‡¢â¡¢âπ Ÿß®–
°√–μÿâπ°“√À≈—Ëß “√πÈ”¡“°¢÷Èπºà“π°“√À≈—Ëߧ≈Õ‰√¥å ‚¥¬√«¡§◊Õ¡’º≈∑”„À⇰‘¥°“√
¥Ÿ¥´÷¡πÈ”∑’Ë≈”‰ â„À≠à≈¥≈ß °√–μÿâπ°“√À≈—Ëß “√πÈ”·≈–‡°≈◊Õ·√ஓ°≈”‰ â„À≠à ‡ªìπ
“‡Àμÿ∑”„À⇰‘¥Õ“°“√∂à“¬‡À≈«™π‘¥ secretory diarrhea
°≈‰°°“√‡°‘¥‚√§2
„π∫∑§«“¡π’È®–°≈à“«∂÷ß°≈‰°°“√‡°‘¥‚√§∑âÕ߇ ’¬‡√◊ÈÕ√—ß™π‘¥ secretory
diarrhea ®“°¿“«–°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º‘¥ª°μ‘ ‡π◊ËÕß®“°‡ªìπ¿“«–∑’Ë«‘π‘®©—¬¬“°
·≈–‡°‘¥‰¥â®“°À≈“¬ “‡Àμÿ à«π fatty diarrhea ¡—°‰¡à¡’ªí≠À“„π°“√«‘π‘®©—¬
‡π◊ÕË ß®“° ¡’Õ“°“√™—¥‡®π Õÿ®®“√–‡ªìπ¡—π ¡—°‡°‘¥„πºŸªâ «É ¬∑’¡Ë ª’ √–«—μμ‘ ¥— ≈”‰ â‡≈Á° à«π
18
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
ileum ÕÕ°¡“° ·≈–¡—°¡’Õ“°“√®“°°“√¢“¥ “√Õ“À“√Õ◊ËπÊ √à«¡¥â«¬ (short bowel
syndrome)
1. Enterohepatic circulation
¡’°“√≈¥≈ߢÕß°“√¥Ÿ¥´÷¡°√¥πÈ”¥’∑’Ë≈”‰ â°≈—∫‰ª∑’Ëμ—∫ (¥Ÿ¥´÷¡°≈—∫πâÕ¬
°«à“√âÕ¬≈– 95) ·μàμ—∫¬—ß “¡“√∂ √â“ß°√¥πÈ”¥’™¥‡™¬‰¥â º≈§◊Õ √à“ß°“¬‰¡à¢“¥
°√¥πÈ”¥’ ·μà∑”„Àâ¡’°√¥πÈ”¥’ºà“π‰ª∑’Ë≈”‰ â„À≠à¡“°¢÷Èπ °√¥πÈ”¥’¡’º≈μàÕ‡´≈≈凬◊ËÕ∫ÿ
≈”‰ â„À≠à‡ªìπº≈„À⇰‘¥ secretory diarrhea μ“¡¡“ “‡Àμÿ‡ªìπ‰¥â∑—Èß®“°√Õ¬
‚√§„π≈”‰ â‡≈Á° À√◊Õ≈”‰ â‡≈Á° à«π ileum ∂Ÿ°μ—¥·μà‰¡à‡°‘π 100 ‡´Áπ쑇¡μ√
2. Ileal bile acid transport
°“√¥Ÿ¥´÷¡°√¥πÈ”¥’∑’Ë∫√‘‡«≥ terminal ileum ‡°‘¥∑’Ë∫√‘‡«≥ brush border ºà“π∑“ß apical sodium bile acid transporter (ASBT) ‚¥¬®–¥Ÿ¥´÷¡°√¥
πÈ”¥’™π‘¥ conjugated form ‡ªìπÀ≈—° À“°¡’¿“«–∫“ßÕ¬à“ß ‡™àπ ·∫§∑’‡√’¬„π
≈”‰ â‡≈Á°‡®√‘≠º‘¥ª°μ‘ (small intestinal bacterial overgrowth; SIBO)
·∫§∑’‡√’¬„π≈”‰ â‡≈Á°®–‡ª≈’ˬπ°√¥πÈ”¥’®“° conjugated form ‰ª‡ªìπ deconjugated form ¡’º≈∑”„Àâ°“√¥Ÿ¥´÷¡¢Õß°√¥πÈ”¥’≈¥≈߉¥â
3. Negative feedback2,3
°“√ √â“ß°√¥πÈ”¥’®“°μ—∫∂Ÿ°§«∫§ÿ¡‚¥¬ cytochrome P-450 7A1
(CYP7A1) ‡ªìπÀ≈—° ´÷Ëß®–¡’negative feedback ‚¥¬ºà“π°≈‰°§◊Õ ‡¡◊ËÕ°√¥πÈ”¥’
ºà“π‰ª¬—ß≈”‰ â‡≈Á° à«π terminal ileum ·≈–∂Ÿ°¥Ÿ¥´÷¡°≈—∫·≈â« ®–‰ª®—∫°—∫
Farnesoid X receptor (FXR) ∑’ËÕ¬Ÿà∑’Ë∫√‘‡«≥ ileal enterocytes °√–μÿâπ„À⇰‘¥
°“√ √â“ߌÕ√å‚¡π (enteric hormone) ∑’ˇ√’¬°«à“ Fibroblast growth factor-19
(FGF19) ´÷ßË ®–À≈—ßË ÕÕ°¡“¬—ßÀ≈Õ¥‡≈◊Õ¥¥”æÕ√å∑≈— ·≈–‰ª®—∫°—∫ receptor ∑’‡Ë ´≈≈åμ∫—
¡’º≈¬—∫¬—Èß CYP7A1 ·≈–≈¥°“√ √â“ß°√¥πÈ”¥’ ´÷Ë߇ªìπ°≈‰°§«∫§ÿ¡°“√ √â“ß°√¥
πÈ”¥’„πª√‘¡“≥∑’ˇÀ¡“– ¡ À“°¡’°“√ √â“ß FGF19 ≈¥≈ß (∑—ÈßÊ ∑’Ë≈”‰ ≡ࡒ§«“¡º‘¥
Bile Acid Diarrhea
19
ª°μ‘·≈– “¡“√∂¥Ÿ¥´÷¡°√¥πÈ”¥’°≈—∫‰ª∑’Ëμ—∫‰¥â‡ªìπª°μ‘) ®–∑”„À⢓¥°≈‰°¬—∫¬—Èß
°“√ √â“ß°√¥πÈ”¥’∑’ˇÀ¡“– ¡ μ—∫ √â“ß°√¥πÈ”¥’¡“°º‘¥ª°μ‘ ∑”„Àâ°√¥πÈ”¥’¡’
ª√‘¡“≥¡“°‡°‘π°«à“∑’Ë®–¥Ÿ¥´÷¡°≈—∫‰¥âÀ¡¥∑’Ë≈”‰ â‡≈Á° ®÷ß¡’°√¥πÈ”¥’ à«π‡°‘πºà“π‰ª
¬—ß≈”‰ â„À≠à ∑”„À⇰‘¥Õ“°“√∂à“¬‡À≈« ∑—Èß∑’ˉ¡à¡’§«“¡º‘¥ª°μ‘¢Õß≈”‰ â à«π„¥‡≈¬
´÷Ëß°“√ √â“ß FGF19 ∑’Ë≈¥≈ßπ’È Õ“®‡ªìπ°≈‰°„π°“√‡°‘¥ BAM ™π‘¥ª∞¡¿Ÿ¡‘ À√◊Õ∑’Ë
‡√’¬°«à“ primary bile acid diarrhea À√◊Õ idiopathic bile acid malabsorption
(I-BAM)4
°“√·∫àß™π‘¥¢Õß¿“«–°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º‘¥ª°μ‘
°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º‘¥ª°μ‘ “¡“√∂·∫à߉¥â‡ªìπ 3 ™π‘¥5 ‰¥â·°à
™π‘¥∑’Ë 1 ™π‘¥∑ÿ쑬¿Ÿ¡‘∑’ˇ°‘¥®“°æ¬“∏‘ ¿“æ∑’Ë≈”‰ â‡≈Á° à«π ileum ‡™àπ
°“√μ—¥≈”‰ â‡≈Á° à«π ileum (Ileal resection) À√◊Õ¡’°“√Õ—°‡ ∫¢Õß ileum ‡™àπ„π
‚√§ Crohnûs disease
™π‘¥∑’Ë 2 ™π‘¥ª∞¡¿Ÿ¡‘ À√◊Õ ‰¡à∑√“∫ “‡Àμÿ (primary or idiopathic bile
acid malabsorption) ¡’°“√≈¥°“√ √â“ß FGF19 ∑”„À⢓¥°≈‰°¬—∫¬—Èß°“√ √â“ß
°√¥πÈ”¥’∑’ˇÀ¡“– ¡
™π‘¥∑’Ë 3 ™π‘¥∑ÿ쑬¿Ÿ¡‘∑’ˇ°‘¥®“°‚√§μà“ßÊ ¢Õß√–∫∫∑“߇¥‘πÕ“À“√∑’ˉ¡à„™à
à«π¢Õß ileum ‚¥¬μ√ß ‡™àπ ¿“«–À≈—ßμ—¥∂ÿßπÈ”¥’ (cholecystectomy) ¿“«–À≈—ß
μ—¥‡ âπª√– “∑‡«°— (vagotomy) ¿“«–·∫§∑’‡√’¬„π≈”‰ â‡≈Á°‡®√‘≠º‘¥ª°μ‘ (small
intestinal bacterial overgrowth) §«“¡º‘¥ª°μ‘¢Õß≈”‰ âÀ≈—ß©“¬· ß (radiation enteropathy) ‚√§ Celiac disease ‚√§μ—∫ÕàÕπÕ—°‡ ∫‡√◊ÈÕ√—ß ·≈–Õ◊ËπÊ
æ∫¿“«–°“√¥Ÿ ¥ ´÷ ¡ °√¥πÈ” ¥’ º‘ ¥ ª°μ‘ § √—È ß ·√°„πºŸâ ªÉ « ¬∑’Ë ‡ ªì π ‚√§¢Õß
≈”‰ â‡≈Á° à«π ileum „πªï §.». 19676 ´÷Ëßμ√ß°—∫™π‘¥∑’Ë 1 ¢â“ßμâπ À≈—ß®“°π—Èπ®÷ß¡’
°“√æ∫¿“«–°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º¥‘ ª°μ‘„πºŸªâ «É ¬∑’‰Ë ¡à¡æ’ ¬“∏‘ ¿“æ¢Õß≈”‰ â‡≈Á° à«π
ileum „πªï §.». 19767 ´÷Ëßμ√ß°—∫™π‘¥∑’Ë 2 ¢â“ßμâπ ·≈–Õ∏‘∫“¬®“°°“√ √â“ߢÕß
FGF19 ∑’Ë enterocyte ¢Õß≈”‰ â à«π ileum ≈¥≈ß À≈—ß®“°π—Èπ®÷߉¥â¡’°“√·∫àß
¿“«–π’ȇªìπ 3 ™π‘¥ ¥—ß°≈à“«5
20
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
°“√«‘π‘®©—¬8
°“√μ√«®æ∫°√¥πÈ”¥’ à«π‡°‘π„πÕÿ®®“√–Õ“®‡ªìπ«‘∏’∑’Ë·¡à𬔠·μà‡ªìπ°“√
μ√«®∑’Ë¡’‡©æ“– ∂“π∑’Ë«‘®—¬„À≠àÊ ·≈–‰¡à·æ√àÀ≈“¬ ªí®®ÿ∫—π¡’«‘∏’μ√«®∑’Ëßà“¬·≈–
‡™◊ËÕ∂◊Õ‰¥â¡“°°«à“ „π°“√μ√«®«à“¡’°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º‘¥ª°μ‘À√◊Õ‰¡à ‰¥â·°à
1. SeHCAT test
SeHCAT test À√◊Õ 75Se-homocholic acid taurine test ‡√‘Ë¡„™â§√—Èß
·√°„πªï §.».19819 ´÷Ëß “¡“√∂∑”‰¥âÀ“°¡’Àπ૬‡«™»“ μ√å𑫇§≈’¬√å∑’Ë¡’ gamma
camera ‚¥¬À≈—°°“√§◊Õ „Àâ√—∫ª√–∑“𷧪´Ÿ≈¬“ SeHCAT ∑’Ë∫√√®ÿ°√¥πÈ”¥’∑’Ë¡’
radioisotope labeled ·≈– “¡“√∂ºà“π enterohepatic circulation ‡À¡◊Õπ
°√¥πÈ”¥’∑’Ë √â“ß®“°μ—∫ª°μ‘ À≈—ß®“°π—Èπ„Àâ∑”°“√ ·°π¥Ÿª√‘¡“≥ SeHCAT ∑’Ë
– ¡§â“ßÕ¬Ÿà„π√à“ß°“¬À≈—ß 7 «—π ´÷Ëߧπª°μ‘À“°¡’°“√¥Ÿ¥´÷¡°√¥πÈ”¥’§àÕπ¢â“ߥ’®–
¡’ª√‘¡“≥ SeHCAT À≈߇À≈◊ÕÕ¬Ÿà¡“°°«à“√âÕ¬≈– 15 „π√“¬∑’˺‘¥ª°μ‘®–‡ ’¬°√¥
πÈ”¥’ÕÕ°‰ª∑“ßÕÿ®®“√– ∑”„Àâ¡’ª√‘¡“≥§ß‡À≈◊Õ„π√à“ß°“¬πâÕ¬ §◊Õ¡’§à“πâÕ¬°«à“
√âÕ¬≈– 10 ´÷ßË ∑”𓬰“√μÕ∫ πÕßμàÕ°“√√—°…“¥â«¬¬“°≈ÿ¡à bile acid sequestrants
·¡â«à“®–‡ªìπ°“√μ√«®∑’ˉ¡à´—∫´âÕπ ª≈Õ¥¿—¬ ·≈–√“§“‰¡à·æß ·μà°“√μ√«®π’È°Á¬—ß
‰¡à “¡“√∂ àßμ√«®‰¥â„πÀ≈“¬Ê ª√–‡∑» √«¡∂÷߬—߉¡à‡ªìπ∑’Ë√—∫√Õß„π À√—∞Õ‡¡√‘°“
SeHCAT test ¡’§«“¡‰«√âÕ¬≈– 80-90 ¡’§«“¡®”‡æ“–√âÕ¬≈– 70-10010-12
2. 7α-OH-4-cholesten-3-one (C4) test13-15
7α-OH-4-cholesten-3-one À√◊Õ¬àÕ«à“ C4 ‡ªìπ “√μ—ßÈ μâπ¢Õß°“√ √â“ß°√¥
πÈ”¥’ ´÷Ëß “¡“√∂«—¥√–¥—∫¢Õß “√π’È„π‡≈◊Õ¥‰¥â ‚¥¬«‘∏’ high-performance liquid
chromatography (HPLC) ‚¥¬¡’À≈—°°“√ §◊Õ À“°¡’°“√¥Ÿ¥´÷¡¢Õß°√¥πÈ”¥’≈¥≈ß
®–∑”„Àâ¡’°“√ √â“ß°√¥πÈ”¥’™¥‡™¬ ∑”„Àâ¡’°“√ √â“ß “√μ—Èßμâπ™π‘¥π’È¡“°¢÷Èπ °≈à“«
‚¥¬ √ÿª§◊Õ À“°¡’°“√ √â“ß°√¥πÈ”¥’®“°‡´≈≈åμ—∫¡“°¢÷Èπ “√π’È (C4) μâÕß¡’√–¥—∫
‡æ‘Ë¡¢÷Èπ·ª√º—πμ“¡°—π„π°√–· ‡≈◊Õ¥
Bile Acid Diarrhea
21
¢âÕ®”°—¥¢Õß°“√μ√«®π’ȧ◊Õ „™â‡«≈“μ√«®π“π μâÕß„™â‡∑§π‘§°“√μ√«®
摇»… ·≈–¬—߉¡à‡ªìπ∑’Ë·æ√àÀ≈“¬ ·μà “¡“√∂„™â‰¥â„π∫“ߪ√–‡∑» ‡™àπ „πª√–‡∑»
À√—∞Õ‡¡√‘°“∑’ˉ¡à¡’°“√μ√«® SeHCAT test
§«“¡™ÿ°
¿“«–°“√¥Ÿ¥´÷¡°√¥πÈ”¥’º¥‘ ª°μ‘‡√‘¡Ë ¡’°“√√“¬ß“π‡æ‘¡Ë ¡“°¢÷πÈ „πÀ≈“¬Ê °“√
»÷°…“ ‚¥¬æ∫∫àÕ¬„πºŸâªÉ«¬‚√§ Crohnûs disease ‚¥¬‡©æ“–À“°¡’°“√μ—¥
≈”‰ â‡≈Á° à«π ileum ´÷Ëß¿“«–π’È„πÕ¥’μ¡—°‰¡à‰¥â√—∫°“√«‘π‘®©—¬ ·μàÀ≈—ß®“°¡’°“√
μ√«®æ‘‡»… ‡™àπ SeHCAT test ∑”„Àâ “¡“√∂«‘π‘®©—¬¿“«–π’ȉ¥â¡“°¢÷Èπ
¡’°“√»÷°…“«‘®—¬À≈“¬™‘Èπ∑’Ë√“¬ß“π∂÷ß¿“«– BAM „πºŸâªÉ«¬∑âÕ߇ ’¬‡√◊ÈÕ√—ß
‚¥¬°“√»÷°…“∑’Ë„À≠à∑’Ë ÿ¥π—Èπ¡’®”π«πºŸâªÉ«¬ 304 √“¬ ‡ªìœ°“√»÷°…“¢Õß Smith
·≈–§≥–16 „™â§à“ SeHCAT test ∑’ËπâÕ¬°«à“√âÕ¬≈– 10 ‡ªìπ‡°≥±å°“√«‘π‘®©—¬¿“«–
BAM ·∫àߺŸâªÉ«¬‡ªìπ 4 °≈ÿà¡ °≈ÿà¡·√°‰¥â·°àºŸâªÉ«¬ Crohnûs disease ∑’Ë¡’°“√
ºà“μ—¥≈”‰ â à«π ileum æ∫¿“«– BAM √âÕ¬≈– 97 (36 ®“° 37 √“¬) °≈ÿà¡∑’Ë 2 ºŸâªÉ«¬
Crohnûs disease ∑’ˉ¡à‰¥â√—∫°“√ºà“μ—¥≈”‰ â æ∫¿“«– BAM √âÕ¬≈– 54 (24 ®“° 44
√“¬) °≈ÿà¡∑’Ë 3 ºŸâªÉ«¬∑’ˉ¥â√—∫°“√ºà“μ—¥°√–‡æ“–·≈–/À√◊Õºà“μ—¥∂ÿßπÈ”¥’ (vagotomy
and pyloroplastywith/without cholecystectomy) æ∫¿“«–BAM √âÕ¬≈– 58
(15 ®“° 26 √“¬) ·≈–„π°≈ÿà¡∑’Ë 4 ºŸâªÉ«¬≈”‰ â·ª√ª√«π∑’Ë¡’Õ“°“√∑âÕ߇ ’¬‡¥àπ (diarrhea-predominant irritable bowel syndrome; IBS-D) æ∫¿“«– BAM √âÕ¬≈–
33 (65 ®“° 197 √“¬) ‚¥¬‡ªìπ°“√»÷°…“„πºŸâªÉ«¬ IBS-D ∑’Ë¡’®”π«πºŸâªÉ«¬¡“°
∑’Ë ÿ¥∑’Ë¡’°“√∑” SeHCAT test
Wedlake ·≈–§≥–17 ‰¥â∑”°“√»÷°…“·∫∫ systematic review „πªï §.».
2009 √«∫√«¡°“√«‘π‘®©—¬¿“«– BAM „πºŸâªÉ«¬ IBS-D ∑’ˉ¥â√—∫°“√μ√«® SeHCAT
test ∑—Èß ‘Èπ®“° 18 ß“π«‘®—¬ ®”π«πºŸâªÉ«¬√«¡ 1,223 √“¬ (μ“√“ß∑’Ë 1) ´÷Ëß®“°°“√
»÷°…“π’È À“°·¬°μ“¡§à“ SeHCAT test ∑’Ë®ÿ¥μ—¥μà“ßÊ „π°“√«‘π‘®©—¬¿“«– BAM
®–æ∫«à“ „π°≈ÿà¡∑’Ë SeHCAT test πâÕ¬°«à“√âÕ¬≈– 5 ¡’§«“¡™ÿ°¢Õß¿“«– BAM
§‘¥‡ªìπ√âÕ¬≈– 10 ·μà∂ⓇªìπºŸâªÉ«¬∑’Ë SeHCAT test ¡’§à“πâÕ¬°«à“√âÕ¬≈– 10 ´÷Ëß
22
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
μ“√“ß∑’Ë 1 °“√»÷°…“·∫∫ systematic review‚¥¬ Wedlake ·≈–§≥–17 ‡°’ˬ«°—∫¿“«– bile acid malabsorption ‚¥¬°“√μ√«® SeHCAT test „πºŸâªÉ«¬ IBS-D
®”π«πºŸâªÉ«¬∑’Ë¡’º≈ SeHCAT test
º‘¥ª°μ‘∑’Ë®ÿ¥μ—¥μà“ßÊ (§π)
°“√»÷°…“‚¥¬ (ªï §.».)
®”π«πºŸâªÉ«¬
(§π)
Merrick (1885)
Sciarretta (1986)
Sciarretta (1987)
Williams (1991)
Ford (1992)
Galatola (1992)
Eusufzai (1993)
Sciarretta (1994)
Brydon (1996)
Rudberg (1996)
Sinha (1998)
Rossel (1999)
Smith (2000)
Ung (2000)
Fernandez-Banares (2001)
Wildt (2003)
Muller (2004)
Fernandez-Banares (2007)
43
13
38
181
74
98
24
31
46
20
17
150
197
36
23
133
37
62
√«¡
1,223
πâÕ¬°«à“
√âÕ¬≈– 5
23
3
3
1
13
43
πâÕ¬°«à“
√âÕ¬≈– 10
πâÕ¬°«à“
√âÕ¬≈– 15
5
6
12
39
15
56
11
18
13
3
6
12
65
13
15
21
15
28
339
60
20
8
9
30
24
163
Bile Acid Diarrhea
23
‡ªìπ§à“¡“μ√∞“π∑’Ë„™â„π°“√«‘π‘®©—¬ ¡’®”π«πºŸâªÉ«¬ IBS-D 1,073 √“¬ μ√«®æ∫º≈
∫«° 339 √“¬ §‘¥‡ªìπ√âÕ¬≈– 32 ·≈–„π°≈ÿà¡∑’Ë¡’§à“ SeHCAT test πâÕ¬°«à“√âÕ¬≈–
15 æ∫«à“¡’°“√»÷°…“«‘®—¬Õ¬Ÿà 7 ™‘È𠉥âº≈∫«° 163 √“¬ ®“° 618 √“¬ §‘¥‡ªìπ√âÕ¬≈–
26
®“°°“√»÷°…“π’È Õ“®æÕ √ÿª‰¥â«à“ ºŸâªÉ«¬ ”‰ â·ª√ª√«π∑’Ë¡’Õ“°“√∑âÕ߇ ’¬
‡¥à𠧫√‰¥â√—∫μ√«®‡æ◊ËÕ«‘π‘®©—¬·¬°‚√§°—∫¿“«– BAM ÕÕ°°àÕπ ‡π◊ËÕß®“°æ∫¿“«
°“√≥奟¥´÷¡°√¥πÈ”¥’º‘¥ª°μ‘∂÷ßÀπ÷Ëß„π “¡¢ÕߺŸâªÉ«¬°≈ÿà¡π’È
°“√√—°…“
·∫à߇ªìπ 2 ™π‘¥μ“¡ “‡Àμÿ∑’Ë∑”„À⇰‘¥Õ“°“√∑âÕ߇ ’¬ §◊Õ √à“ß°“¬¢“¥°√¥
πÈ”¥’ ·≈– °√¥πÈ”¥’‡°‘π
1. °“√√—°…“¿“«–¢“¥°√¥πÈ”¥’
°“√√—°…“¿“«–¢“¥°√¥πÈ”¥’ ∑’Ë∑”„À⇰‘¥°“√¬àÕ¬‰¢¡—πº‘¥ª°μ‘ ∑”„À⇰‘¥
Õ“°“√∂à“¬‡À≈«‡ªìπ¡—π∑”‰¥â‚¥¬°“√„Àâ°√¥πÈ”¥’™¥‡™¬ ‰¥â·°à ¬“„π°≈ÿà¡ Bile acid
replacement ‚¥¬¬“„π°≈ÿà¡π’È∑’Ë¡’°“√„™â∫àÕ¬∑’Ë ÿ¥ ‰¥â·°à ursodeoxycholic acid
(UDCA) ·μà∑’Ë¡’°“√„™â√—°…“Õ“°“√∑âÕ߇ ’¬®–‡ªì𬓄π°≈ÿà¡ Ox bile ·≈–¬“„À¡à∑’Ë
¡’°“√»÷°…“‡æ‘Ë¡¢÷Èπ‡√◊ËÕ¬Ê ‰¥â·°à cholylsarcosine
1.1 Ursodeoxycholic acid (UDCA)
‡ªìπ bile acid therapy ∑’Ë¡’°“√„™â·æ√àÀ≈“¬¡“°∑’Ë ÿ¥2 ‚¥¬‡√‘Ë¡·√°‰¥â√—∫
°“√¬Õ¡√—∫‚¥¬Õߧ尓√Õ“À“√·≈–¬“¢Õߪ√–‡∑» À√—∞Õ‡¡√‘°“ (US FDA) ‡æ◊ËÕ„™â
„π°“√√—°…“π‘Ë«„π∂ÿßπÈ”¥’ μàÕ¡“®÷߉¥â√—∫¢âÕ∫àß™’È„π°“√√—°…“‚√§ primary biliary
cirrhosis ´÷Ëß “¡“√∂™–≈Õ°“√‡°‘¥æ—ߺ◊¥„πμ—∫·≈–≈¥Õ—μ√“°“√쓬‰¥â UDCA
“¡“√∂™¥‡™¬®”π«π°√¥πÈ”¥’‰À≈‡«’¬π„π√à“ß°“¬‰¥â∂÷ß√âÕ¬≈– 40 ”À√—∫°“√√—°…“
short bowel syndrome à«π„À≠à®–‡ªìπ°“√»÷°…“„π·ßà¢Õß°“√≈¥ cholestasis
®“°°“√„Àâ parenteral nutrition18 ·μà„π·ßà¢Õß°“√≈¥ steatorrhea ¬—߉¡à¡’°“√
»÷°…“∑’°Ë ≈à“«∂÷ß¡“°π—° §ß¡’·μà°“√»÷°…“„π·¡«∑’‰Ë ¥â√∫— °“√μ—¥ ≈”‰ â jejunoileal re24
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
section (√âÕ¬≈– 85 ¢Õߧ«“¡¬“«≈”‰ â‡≈Á°) ·≈–„Àâ UDCA ¢π“¥ 15 ¡‘≈≈‘°√—¡
μàÕ°‘‚≈°√—¡ ‡ªìπ‡«≈“ 6 —ª¥“Àå æ∫«à“∑”„ÀâÕ“°“√∂à“¬‡À≈«≈¥≈ß ∑—Èß®”π«π§√—Èß
·≈–≈—°…≥–Õÿ®®“√–19
1.2 Ox bile extracts
°—¥®“°πÈ”¥’¢Õß«—« ‡ªìπ mixture of natural conjugated bile acids
‚¥¬¡’ «à πª√–°Õ∫À≈—°§◊Õ taurocholic acid ´÷ßË ¡’°“√»÷°…“À≈“¬°“√»÷°…“20-23 „π
ºŸâªÉ«¬ short bowel syndrome æ∫«à“≈¥Õ“°“√∂à“¬‡À≈«∑’ˇªìπ·∫∫ fat malabsorption ‰¥â ‚¥¬„πÕ¥’쇙◊ËÕ«à“°“√„Àâ°√¥πÈ”¥’„πºŸâªÉ«¬ short bowel syndrome
∑’¬Ë ß— ¡’≈”‰ â„À≠à‡À≈◊ÕÕ¬ŸÕà “®∑”„Àâ∂“à ¬‡À≈«‡ªìππÈ”¡“°¢÷πÈ ·¡âÕ“°“√∂à“¬‡ªìπ¡—π®–¥’¢π÷È
·μஓ°°“√»÷°…“ à«π„À≠àæ∫«à“°“√¥Ÿ¥´÷¡‰¢¡—π¥’¢πÈ÷ ·≈–‰¡à‡æ‘¡Ë ª√‘¡“≥¢ÕßÕÿ®®“√–
1.3 Cholylsarcosine
‡ªìπ synthetic conjugated bile acid ∑’ˇ√‘Ë¡¡’°“√»÷°…“¡“°¢÷Èπ„π
¡πÿ…¬åμß—È ·μàªï §.».199323-27 °“√»÷°…“‚¥¬ Gruy-Kapral C ·≈–§≥–23 „πºŸªâ «É ¬
4 √“¬∑’Ë¡’°“√„À⬓π’È„π¢π“¥ 2 °√—¡μàÕ¡◊ÈÕÕ“À“√æ∫«à“¡’°“√¥Ÿ¥´÷¡‰¢¡—π‡æ‘Ë¡¢÷Èπ®“°
65.5 ‡ªìπ 94.5 °√—¡μàÕ«—π ·≈–Õ“°“√∂à“¬‡À≈«‡ªìπ¡—π¥’¢÷Èπ ‚¥¬‰¡à∑”„ÀâÕ“°“√∂à“¬
‡À≈«‡ªìππÈ”‡æ‘¡Ë ¢÷πÈ ·μà„π∫“ß°“√»÷°…“25 æ∫«à“ºŸªâ «É ¬∫“ß√“¬∑’¬Ë ß— ¡’≈”‰ â„À≠àÕ¬ŸÕà “®
¡’Õ“°“√∂à“¬‡À≈«‡æ‘Ë¡¢÷Èπ πÕ°®“°π’Ȭ—߇√‘Ë¡¡’°“√»÷°…“„À¡àÊ „π√Ÿª·∫∫¬“ entericcoated cholylsarcosine ∑’ˇ™◊ËÕ«à“∑”„À⇰‘¥Õ“°“√√–§“¬‡§◊ÕßμàÕ°√–‡æ“–Õ“À“√
πâÕ¬°«à“·∫∫¥—È߇¥‘¡∑’ˇªìπ™π‘¥·§ª´Ÿ≈27
2. °“√√—°…“¿“«–°√¥πÈ”¥’‡°‘π
°“√√—°…“À≈—°¢ÕßÕ“°“√∑âÕ߇ ’¬∑’ˇ°‘¥®“°√¥πÈ”¥’‡°‘π‡π◊ËÕß®“°°“√¥Ÿ¥´÷¡
°√¥πÈ”¥’º‘¥ª°μ‘ ‰¥â·°à °“√„À⬓°≈ÿà¡ bile acid sequestrants ∑’Ë®–‰ª®—∫°—∫
°√¥πÈ”¥’ à«π‡°‘π„π≈”‰ â∑’Ë®–ºà“π‰ª¬—ß≈”‰ â„À≠à·≈–°√–μÿâπ„À⇰‘¥Õ“°“√∑âÕ߇ ’¬
¬“„π°≈ÿà¡π’ȉ¥â·°à cholestyramine, colestipol ·≈– colesevelam
2.1 Cholestyramine À√◊Õ Colestyramine
‡ªì𬓰≈ÿà¡ bile acid sequestrants ∑’Ë®—∫°—∫°√¥πÈ”¥’ ‚¥¬‡ªìπ≈—°…≥–
Bile Acid Diarrhea
25
¢Õ߇√´‘π ‰¥â¡°’ “√„™â√°— …“ºŸªâ «É ¬∑’¡Ë Õ’ “°“√∑âÕ߇ ’¬À≈—ß°“√ºà“μ—¥≈”‰ â‡≈Á° à«π ileum
¡“μ—Èß·μàªï §.».196928 ´÷ËßÀ“°¥Ÿº≈°“√μÕ∫ πÕßμàÕ°“√√—°…“®“°°“√»÷°…“¢Õß
Wedlake ·≈–§≥–17 „πºŸâªÉ«¬ IBS-D ∑’Ëæ∫¿“«– BAM æ∫«à“¡’°“√»÷°…“«‘®—¬∂÷ß
15 ™‘Èπ∑’Ë»÷°…“∂÷ߪ√– ‘∑∏‘¿“æ¢Õ߬“·≈–æ∫«à“„π°≈ÿà¡∑’Ë¡’§à“ SeHCAT test μË”
°«à“®–¡’º≈°“√μÕ∫ πÕߥ’°«à“„π°≈ÿà¡∑’Ë¡’§à“ SeHCAT test Ÿß°«à“Õ¬à“ß¡’π—¬
”§—≠∑“ß ∂‘μ‘ (p=0.007) °≈à“«§◊Õ „π°≈ÿà¡∑’Ë¡’§à“ SeHCAT test πâÕ¬°«à“√âÕ¬≈–
5 ¡’°“√„À⬓ 24 √“¬ ¡’°“√μÕ∫ πÕß 23 √“¬ §‘¥‡ªìπ√âÕ¬≈– 96 à«π„π°≈ÿà¡∑’Ë¡’§à“
SeHCAT test πâÕ¬°«à“√âÕ¬≈– 10 ¡’°“√μÕ∫ πÕß 122 √“¬®“° 152 √“¬ §‘¥
‡ªìπ√âÕ¬≈– 80 ·≈–„π°≈ÿà¡∑’Ë¡’§à“ SeHCAT test πâÕ¬°«à“√âÕ¬≈– 15 ∂÷ß·¡â®–¡’
°“√μÕ∫ πÕßμàÕ¬“πâÕ¬∑’Ë ÿ¥§◊Õ 52 ®“° 74 √“¬ °Á¬—ߧ‘¥‡ªìπ√âÕ¬≈– 70
·¡â«à“°“√μÕ∫ πÕßμàÕ¬“ cholestyramine ®–§àÕπ¢â“ߥ’®“°º≈°“√
»÷°…“«‘®¬— À≈“¬™‘πÈ 5,29 ·μà°¡Á ¢’ Õâ ®”°—¥„π·ßà¢Õß°“√√—∫ª√–∑“𬓠´÷ßË ∑”„À⺪Ÿâ «É ¬‰¡à
“¡“√∂√—∫ª√–∑“πμàÕ‡π◊ËÕ߉¥â ®“°≈—°…≥–¢Õß√ ·≈–‡π◊ÈÕ·ªÑß∑’ˇªìπ‡√´‘π æ∫«à“ºŸâ
ªÉ«¬∑’Ë°‘𬓰≈ÿà¡π’È„π°“√√—°…“‰¢¡—π„π‡≈◊Õ¥ Ÿß‡°‘π§√÷ËßÀπ÷ËßÀ¬ÿ¥¬“¿“¬„π 1 ªï30 ´÷Ëß
Õ¥§≈âÕß°—∫Õ’°ß“π«‘®—¬Õ’°™‘ÈπÀπ÷Ëß∑’Ë»÷°…“„π°“√√—°…“ºŸâªÉ«¬ idiopathic BAM ∑’Ë
μâÕßÀ¬ÿ¥¬“ 6 √“¬®“° 16 √“¬∑’Ëμ‘¥μ“¡°“√√—°…“®π§√∫31 ‚¥¬º≈¢â“߇§’¬ß∑’Ëæ∫
∫àÕ¬‰¥â·°à ∑âÕߺŸ° ∑âÕßÕ◊¥ ª«¥‡°√Áß∑âÕß ·≈–§≈◊Ëπ‰ â ¥—ßπ—Èπ®÷ß∑”„Àâ¡’°“√§‘¥§âπ
¬“„π√Ÿª·∫∫ enterocoated tablets ´÷Ëß®–‰ª·μ°μ—«„π≈”‰ â„À≠à ∑”„Àâ√—∫
ª√–∑“πßà“¬¢÷Èπ ·μà°Á‡ªìπ‡æ’¬ß°“√»÷°…“¢π“¥‡≈Á°32 ·≈–‰¡à‰¥â¡’°“√∑”¬“√Ÿª·∫∫π’È
ÕÕ°¡“«“ߢ“¬®√‘ß ¢π“¥¬“¢Õß cholestyramine ∑’Ë„™â√—°…“¿“«– BAM ¬—߉¡à‰¥â
¡’¢π“¥·π–π”∑’ˇÀ¡“– ¡ ¢π“¥¬“¡’μ—Èß·μà 2 °√—¡ °àÕππÕπ §√—È߇¥’¬« ‡æ‘Ë¡®π∂÷ß 4
°√—¡ «—π≈– 3 §√—Èß
2.2 Colestipol
¡—°„™â‡ªìπ¬“≈¥‰¢¡—π ¬—ß‰¡à¡’°“√»÷°…“„À≠àÊ ∑’Ë¡’º≈μàÕ¿“«– BAM À√◊Õ
Õ“°“√∂à“¬‡À≈« à«π„À≠à®–‡ªìπ°“√»÷°…“¢π“¥‡≈Á°·≈–„™â∑¥·∑π„π°√≥’∑’˺ŸâªÉ«¬
√—∫ª√–∑“𬓠cholestyramine ‰¡à‰¥â ‡™àπ °“√»÷°…“„πºŸâªÉ«¬ collagenous colitis 27 √“¬33 ∑’Ëæ∫ SeHCAT test πâÕ¬°«à“√âÕ¬≈– 10 ®”π«π 12 √“¬ (§‘¥‡ªìπ
26
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
√âÕ¬≈– 44) ¡’°“√„À⬓ colestipol 3 √“¬ ·≈–„À⬓ cholestyramine 24 √“¬
æ∫«à“„π°≈ÿà¡∑’ˉ¥â√—∫°“√«‘π‘®©—¬ BAM ¡’Õ“°“√∂à“¬‡À≈«¥’¢÷Èπ ·μà„π°“√»÷°…“π’ȉ¡à
‰¥â√–∫ÿ√“¬≈–‡Õ’¬¥«à“„π√“¬∑’ˉ¥â colestipol ∑—Èß 3 √“¬¡’º≈ SeHCAT test ‡ªìπ
Õ¬à“߉√ πÕ°®“°π’Ȭ—߇§¬¡’°“√»÷°…“°“√„™â¬“‡æ◊ËÕªÑÕß°—πÕ“°“√∂à“¬‡À≈«À≈—ß®“°
°“√©“¬· ß∫√‘‡«≥Õÿâ߇™‘ß°√“π æ∫«à“‰¡à¡’§«“¡·μ°μà“ß®“°¬“À≈Õ° ·μà¡’º≈¢â“ß
‡§’¬ß¡“°°«à“34
2.3 Colesevelam
‡ªì𬓰≈ÿà¡ bile acid sequestrants ∑’Ë¡’§«“¡ “¡“√∂„π°“√®—∫°—∫°√¥
πÈ”¥’¡“°°«à“ cholestyramine ‚¥¬‡√‘Ë¡·√°„™â„π°“√√—°…“¿“«–‚§‡≈ ‡μÕ√Õ≈„π
‡≈◊Õ¥ Ÿß ·≈–μàÕ¡“¡’°“√„™â„π BAM ·≈– IBS-D ¡“°¢÷È𠇙àπ °“√»÷°…“¢Õß
Suwebatu T. Odunsi-Shiyanbade ·≈–§≥–35 „πºŸâªÉ«¬ IBS-D 24 √“¬ ¡’ 12
√“¬‰¥â colesevelam ‡∑’¬∫°—∫Õ’° 12 √“¬ ∑’ˉ¥â¬“À≈Õ° æ∫«à“®”π«π°“√∂à“¬‰¡à
·μ°μà“ß°—π ·μà¡’·π«‚πâ¡¥’°«à“„π·ßà¢Õß stool consistency (p=0.12) ·≈– ease
stool passage (p=0.048) ·μà„π°“√»÷°…“π’È¡’°“√μ√«®æ∫¿“«– BAM ®“°°“√
μ√«®«—¥√–¥—∫ 7α C4 ‡æ’¬ß 4 „π 24 √“¬
°“√»÷°…“«‘®—¬Õ’°™‘ÈπÀπ÷ËߢÕß Puleston ·≈–§≥–36 ‡ªìπ°“√»÷°…“¢π“¥
‡≈Á° ∑”„πºŸâªÉ«¬ BAM 4 √“¬ ∑’ˉ¡à “¡“√∂√—∫ª√–∑“π cholestyramine ‰¥â ·μà
“¡“√∂√—∫ª√–∑“π colesevelam ‰¥â‚¥¬∑’ËÕ“°“√∑âÕ߇ ’¬¥’¢÷Èπ∑—Èß 4 √“¬ ·≈–‰¡à¡’
º≈¢â“߇§’¬ß √–¬–‡«≈“∑’Ë√—∫ª√–∑“π¬“Õ¬Ÿà√–À«à“ß 2-7 ‡¥◊Õπ ´÷Ë߬“π’ȇªìπ√Ÿª·∫∫¬“
‡¡Á¥¢π“¥ 625 ¡‘≈≈‘°√—¡ √—∫ª√–∑“πßà“¬°«à“ cholestyramine ·≈–¢π“¥∑’Ë„™â§◊Õ
1.25-3.75 °√—¡μàÕ«—π „πºŸâªÉ«¬∑’ˉ¡à “¡“√∂√—∫ª√–∑“𬓠cholestyramine ‰¥â °Á
æ∫«à“∂Ⓡª≈’Ë¬π¡“‡ªì𬓠colesevelam °Á “¡“√∂√—∫ª√–∑“π‰¥â¥37’ ·μà¡’¢âÕ®”°—¥
§◊Õ¬—߉¡à¡’°“√»÷°…“„À≠àÊ ∑’ˇªìπ·∫∫ double-blind À√◊Õ randomized studies
∑”„À⬓π’Ȭ—߉¡à‰¥â√—∫°“√√—∫√Õß„π°“√√—°…“¿“«– bile acid malabsorption
°“√„À⬓„π°≈ÿ¡à bile acid sequestrants π—πÈ Õ“®¡’º≈‰ª®—∫μ—«°—∫ “√Õ◊πË Ê
‰¥â ®÷ß¡’¢âÕ·π–π”«à“À“°μâÕß√—∫ª√–∑“π¬“Õ◊Ëπ√à«¡¥â«¬ „Àâ√—∫ª√–∑“π¬“π—Èπ 1
™—Ë«‚¡ß°àÕπ À√◊Õ 5-6 ™—Ë«‚¡ßÀ≈—ß√—∫ª√–∑“𬓰≈ÿà¡ bile acid sequestrants ·≈–
Bile Acid Diarrhea
27
‡π◊ËÕß®“°¬“°≈ÿà¡π’ÈÕ“®¡’º≈μàÕ°“√¥Ÿ¥´÷¡«‘μ“¡‘π∑’Ë≈–≈“¬„π‰¢¡—π §◊Õ «‘μ“¡‘π‡Õ ¥’ Õ’
‡§ ®÷ß·π–π”„Àâμ√«®À“¿“«–°“√¢“¥«‘μ“¡‘π¥—ß°≈à“«‡ªìπ√–¬–
°“√√—°…“Õ◊ËπÊ
ºŸâªÉ«¬„π°≈ÿà¡ BAM ™π‘¥∑ÿ쑬¿Ÿ¡‘ ‡™àπ „π™π‘¥∑’Ë 1 ·≈– 3 Õ“®¡’°“√√—°…“
‡©æ“–∫“ßÕ¬à“ß∑’˙૬≈¥Õ“°“√∑âÕ߇ ’¬‰¥â ‡™àπ „π°≈ÿà¡∑’ˉ¥â√—∫°“√ºà“μ—¥≈”‰ â à«π
ileum ‡°‘π 100 ‡´Áπ쑇¡μ√ Õ“®‡°‘¥¿“«– short bowel syndrome ∑”„Àâ¡’°“√
¥Ÿ¥´÷¡‰¢¡—πº‘¥ª°μ‘®“° bile acid pool ∑’Ë≈¥≈ß ®π∑”„À⇰‘¥Õ“°“√∑âÕ߇ ’¬∂à“¬
‡ªìπ¡—π (steatorrhea) √à«¡¥â«¬ „Àâ√—°…“‚¥¬°“√√—∫ª√–∑“πÕ“À“√‰¢¡—πμË”√à«¡°—∫
°“√„Àâ medium-chain triglycerides29 §«∫§Ÿà‰ª°—∫°“√„Àâ cholylsarcosine ´÷Ëß
‡ªìπ bile acid analogue ∑’ˉ¥â°≈à“«·≈â«¢â“ßμâπ
„π°≈ÿࡺŸâªÉ«¬ Crohnûs disease °“√„À⬓°≈ÿࡧÕ√åμ‘‚§ ‡μ’¬√Õ¬¥åÕ“®
∑”„Àâ¿“«– BAM ¥’¢÷Èπ ®“°°“√‡æ‘Ë¡¢Õß apical membrane sodium bile acid
transporter (ASBT) ∑’Ë∫√‘‡«≥ terminal ileum ∑”„Àâ “¡“√∂¥Ÿ¥´÷¡°√¥πÈ”¥’‰¥â
¡“°¢÷Èπ38
„π°√≥’∑¿Ë’ “«– BAM ‡°‘¥√à«¡°—∫ SIBO „Àâ°“√√—°…“‚¥¬°“√„À⬓ªØ‘™«’ π–
39
√à«¡¥â«¬ ‡ªìπμâπ
√ÿª
ºŸªâ «É ¬∑’¡Ë “¥â«¬Õ“°“√∂à“¬‡À≈«‡√◊ÕÈ √—ßÕ“®¡’ “‡Àμÿ∑‡’Ë °’¬Ë «¢âÕß°—∫°√¥πÈ”¥’‚¥¬
·∫∫·√°‡ªìπ¿“«–¢“¥°√¥πÈ”¥’ à«π„À≠à‡°‘¥®“°°“√μ—¥≈”‰ â‡≈Á° à«π terminal ileum ‡°‘π 100 ‡´Áπ쑇¡μ√ ®–∑”„Àâ¡’°“√¬àÕ¬‰¢¡—πº‘¥ª°μ‘ ∑”„Àâ∂à“¬‡À≈«‡ªìπ¡—π
à«π·∫∫∑’Ë Õ߇°‘¥®“°¿“«–¥Ÿ¥´÷¡°√¥πÈ”¥’º‘¥ª°μ‘ ∑”„Àâ¡’°√¥πÈ”¥’ à«π‡°‘πºà“π
‰ª¬—ß≈”‰ â„À≠à·≈–°√–μÿâπ„À⇰‘¥°“√∂à“¬‡À≈«‡ªìππÈ” ´÷Ëß¿“«–π’È¡—°®–‰¡à‰¥â√—∫°“√
«‘π‘®©—¬ À√◊Õ¡’°“√«‘π‘®©—¬μË”°«à“§«“¡‡ªìπ®√‘ß „πºŸâªÉ«¬∑’ˇªìπ‚√§≈”‰ â·ª√ª√«π∑’Ë
¡’Õ“°“√∑âÕ߇ ’¬‡¥àπ°Á “¡“√∂æ∫¿“«–π’È∂÷ßÀπ÷Ëß„π “¡ ´÷ËßÕ“®«‘π‘®©—¬‚¥¬„Àâ°“√
√—°…“·≈â«¥Ÿº≈°“√μÕ∫ πÕßμàÕ¬“ (therapeutic trial) ‚¥¬°“√„À⬓„π°≈ÿà¡ bile
28
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
acid sequestrants ´÷ËßÀ“°‰¥âº≈¥’°Á®–™à«¬«‘π‘®©—¬¿“«–π’ȉ¥â ·μàÀ“°Õ¬Ÿà„π ∂“π∑’Ë
∑’Ë “¡“√∂ àßμ√«® SeHCAT test ´÷Ë߇ªìπ¡“μ√∞“π„π°“√«‘π‘®©—¬¿“«–π’È ‡™àπ„π
ª√–‡∑»·∂∫¬ÿ‚√ª °Á§«√®–‰¥â√—∫°“√ àßμ√«®‡æ◊ËÕ®–™à«¬„π°“√«‘π‘®©—¬·≈–∑”π“¬
°“√μÕ∫ πÕßμàÕ°“√√—°…“‰¥â¥’¢÷Èπ
‡Õ° “√Õâ“ßÕ‘ß
1. Fine KD, Schiller LR. AGA technical review on the evaluation and management
of chronic diarrhea. Gastroenterology 1999;116:1464-86.
2. Mark F, Lawrence SF, Lawrence JB, eds. Sleisenger and Fordtranûs gastrointestinal and liver disease. Ninth Edition ed: Elsevier Science; 2010.
3. Walters JRF, Tasleem AM, Omer OS, Brydon WG, Dew T, le Roux CW. A new
mechanism for bile acid diarrhea: defective feedback inhibition of bile acid
biosynthesis. Clin Gastro Hepatol 2009;7:1189-94.
4. Hofmann AF. Chronic diarrhea caused by idiopathic bile acid malabsorption: an
explanation at last. Expert Rev Gastroenterol Hepatol 2009;3:461-4.
5. Fromm H, Malavolti M. Bile acid-induced diarrhoea. Clin Gastroenterol 1986;
15:567-82.
6. Hofmann AF. The syndrome of ileal disease and the broken enterohepatic circulation: cholerheic enteropathy. Gastroenterology 1967;52:752-7.
7. Thaysen EH, Pedersen L. Idiopathic bile acid catharsis. Gut 1976;17:965-70.
8. Walters JR, Pattni SS. Managing bile acid diarrhoea. Therap Adv Gastroenterol
2010;3:349-57.
9. Boyd GS, Merrick MV, Monks R, Thomas IL. Se-75-labeled bile acid analogs,
new radiopharmaceuticals for investigating the enterohepatic circulation. J Nucl
Med 1981;22:720-5.
10. Merrick MV, Eastwood MA, Ford MJ. Is bile acid malabsorption underdiagnosed?
An evaluation of accuracy of diagnosis by measurement of SeHCAT retention.
BMJ 1985; 290:665-8.
Bile Acid Diarrhea
29
11. Sciarretta G, Vicini G, Fagioli G, Verri A, Ginevra A, Malaguti P. Use of 23selena-25-homocholyltaurine to detect bile acid malabsorption in patients with
ileal dysfunction or diarrhea. Gastroenterology 1986;91:1-9.
12. Fellous K, Jian R, Haniche M, Marteau P, Messing B, Rian JD, et al. Mesure de
lûabsorptioniléale des selsbiliaires par le test à lûhomotaurocholatemarqué au
sélelnium 75. Validation et signification clinique. Gastroenterol Clin Biol 1994;
18:865-72.
13. Sauter GH, Munzing W, von Ritter C, Paumgartner G. Bile acid malabsorption
as a cause of chronic diarrhea: diagnostic value of 7alphahydroxy-4-cholesten-3one in serum. Dig Dis Sci 1999;44:14-19.
14. Brydon WG, Nyhlin H, Eastwood MA, Merrick MV. Serum 7 alpha-hydroxy-4cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention
in the assessment of bile acid induced diarrhoea. Eur J Gastroenterol Hepatol
1996;8:117-23.
15. Sciarretta G, Fagioli G, Furno A, Vicini G, Cecchetti L, Grigolo B, et al. 75SeHCAT
test in the detection of bile acid malabsorption in functional diarrhoea and its
correlation with small bowel transit. Gut 1987;28:970-5.
16. Smith MJ, Cherian P, Raju GS, Dawson BF, Mahon S, Bardhan KD. Bile acid
malabsorption in persistent diarrhoea. J R Coll Physicians Lond 2000;34:448-51.
17. Wedlake L, AûHern R, Russell D, Thomas K, Walters JR, Andreyev HJ. Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed
by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel
syndromeé. Aliment Pharmacol Ther 2009;30:707-17.
18. de Marco G, Sordino D, Bruzzese E, di Caro S, Mambretti D, Tramontano A, et
al. Early treatment with ursodeoxycholic acid for cholestasis in children on
parenteral nutrition because of primary intestinal failure. Aliment Pharmacol
Ther 2006;24:387-94.
19. Kouti V, Papazoglou L, Flaskos J, Angelopoulou K, Karkavelas G, Rallis T.
Ursodeoxycholic acid promotes intestinal adaptation in a cat model of short
bowel syndrome. Fundam Clin Pharmacol 2011;25:734-42.
30
®ÿ≈ “√ ¡“§¡·æ∑¬å√–∫∫∑“߇¥‘πÕ“À“√·Ààߪ√–‡∑»‰∑¬, 惻®‘°“¬π-∏—𫓧¡ 2555
20. Fordtran JS, Bunch F, Davis GR. Ox bile treatment of severe steatorrhea in an
ileectomy-ileostomy patient. Gastroenterology 1982;82:564-8.
21. Djurdjeviç D, Popoviç O, Neciç D, Hranisavljeviç S. Ox bile treatment of severe
steatorrhea in a colectomy and ileectomy patient. Gastroenterology 1988t;95:1160.
22. Little KH, Schiller LR, Bilhartz LE, Fordtran JS. Treatment of severe steatorrhea
with ox bile in an ileectomy patient with residual colon. Dig Dis Sci 1992;37:92933.
23. Gruy-Kapral C, Little KH, Fordtran JS, Meziere TL, Hagey LR, Hofmann AF.
Conjugated bile acid replacement therapy for short-bowel syndrome. Gastroenterology 1999;116:15-21.
24. Schmassmann A, Fehr HF, Locher J, Lillienau J, Schteingart CD, Rossi SS, et al.
Cholylsarcosine, a new bile acid analogue: metabolism and effect on biliary
secretion in humans. Gastroenterology 1993;104:1171-81.
25. Heydorn S, Jeppesen PB, Mortensen PB. Bile acid replacement therapy with
cholylsarcosine for short-bowel syndrome. Scand J Gastroenterol 1999;34:818-23.
26. Popoviç OS, Jojiç N, Neciç D. Cholylsarcosine for bile acid deficiency caused by
ileal resection. Dig Dis Sci 1999;44:1931-2.
27. Fürst T, Bott C, Stein J, Dressman JB. Enteric-coated cholylsarcosine
microgranules for the treatment of short bowel syndrome. J Pharm Pharmacol
2005;57:53-60.
28. Hofmann AF, Poley JR. Cholestyramine treatment of diarrhea associated with
ileal resection. N Engl J Med 1969;281:397-402.
29. Westergaard H. Bile Acid malabsorption. Curr Treat Options Gastroenterol 2007;
10:28-33.
30. Hiatt JG, Shamsie SG, Schectman G. Discontinuation rates of cholesterol-lowering medications: implications for primary care. Am J Manag Care 1999;5:437-44.
31. Rossel P, Jensen HS, Qvist P, Arveschoug A. Prognosis of adult-onset idiopathic
bile acid malabsorption. Scand J Gastroenterol 1999;34:587-90.
32. Jacobsen O, Hojgaard L, Hylander ME, Wielandt TO, Thale M, Jarnum S, et al.
Effect of enterocoated cholestyramine on bowel habit after ileal resection: a
Bile Acid Diarrhea
31
s33.
34.
35.
36.
37.
38.
39.
32
double blind crossover study. Br Med J (Clin Res Ed) 1985;290:1315-8.
Ung KA, Gillberg R, Kilander A, Abrahamsson H. Role of bile acids and bile acid
binding agents in patients with collagenous colitis. Gut 2000;46:170-5.
Stryker JA, Chung CK, Layser JD. Colestipol hydrochloride prophylaxis of diarrhea during pelvic radiotherapy. Int J Radiat Oncol Biol Phys 1983;9:185-90.
Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio
IA, et al. Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam,
on intestinal transit and bowel function. Clin Gastroenterol Hepatol 2010;8:15965.
Puleston J, Morgan H, Andreyev J. New treatment for bile salt malabsorption.
Gut 2005;54:441-2.
Knox JF, Rose D, Emmons J, et al. Colesevalam for the treatment of bile acid
diarrhea induced diarrhea in Crohnûs disease: patients intolerant of cholestyramine.
Gastroenterology 2004;5:W1399.
Jung D, Fantin AC, Scheurer U, Fried M, Kullak-Ublick GA. Human ileal bile
acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid
receptor. Gut 2004;53:78-84.
Roberts SH, James O, Jarvis EH. Bacterial overgrowth syndrome without ùûblind
loopé: A cause for malnutrition in the elderly. Lancet 1977;2:1193-5.
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