CHAPTER I INTRODUCTION Approximately 90% of patients with cirrhosis will have developed esophageal varices within 10 years.

Esophageal variceal haemorrhage is a devastating complication of cirrhosis with mortality as high as 2550%. ed sign and variceal si!e "medi#m to large grade$ on endoscopy are representative for %leeding ris& of esophageal varices. 'everity of liver f#nction reserve and presence of ascites are also important ris& factors for variceal %leeding. "1(2$ )he %leeding ris& decreases over time from the time that varices are identified* most %leeding episodes occ#r within the first 2 years after identification of varices. +nce %leeding occ#rs( spontaneo#s cessation of %leeding occ#rs in only #p to ,0% of individ#als( and the %leeding is associated with the mortality of 20% or more at - wee&s. ".(,$ /atients who s#rvived an episode of ac#te variceal hemorrhage have a high ris& of re%leeding and death. )he median re%leeding rate in #ntreated individ#als is aro#nd -0% within 102 years of the index %leeding( with a mortality of ..% . )herefore( care sho#ld %e ta&en to prevent rec#rrent %leeding prior to discharge from the hospital for patients who have recovered from an episode of variceal %leeding. "5(-$ )his paper will mainly disc#ss the esophageal varices as the complication of hepatic cirrhosis.

CHAPTER II ANATOMY (7) )he liver is located in the right #pper 1#adrant( from the fifth intercostal space in the midclavic#lar line down to the right costal margin. )he liver weighs approximately 1200 g in men and 1,00 g in women. )he s#rfaces of the liver are smooth and convexin the s#perior( anterior( and right lateral regions. 3ndentations from the colon( right

&idney( d#oden#m ( and stomach are apparent on the posterior s#rface. )he line %etween the vena cava and gall%ladder divides the liver into right and left lo%es. Each lo%e has an independentvasc#lar and d#ct s#pply. )he liver is f#rther divided into eight segments( each containing a pedicle of portal vessels( d#cts( andhepatic veins. )he portal veno#s system extends from the intestinal capillaries to the hepatic sin#soid. )his veno#s system carries the %lood from the a%dominal gastrointestinal tract( the pancreas( gall%ladder( and spleen %ac& to the heart "co#rsing thro#gh the liver$. )he largest vessel in this system is the portal vein( which is formed %y the #nion of the splenic vein and s#perior mesentric veins. )he left gastric and right gastric veins and the posterior s#perior pancreaticod#odenal veins drain directly into the portal vein. )he portal vein r#ns posterior to the pancreas( and its extrahepatic length may %e anywhere from 59 cm. At the porta divides into the left portal veins the liver( and hepatis( right within the cystic vein into anch. the it and

typically drains right hepatic %r

6ig 1. Anatomy of hepar and system portal

)he portal vein s#pplies 40% of the %lood flow to the liver( %#t only ,0% of the liver oxygen s#pply. )he remainder of the %lood comes from the hepatic artery( and %lood from %oth of these vessels mixes in the sin#soids. )he liver receives a tremendo#s vol#me of %lood( on the order of 1.5 liters per min#te. )he d#al %lood s#pply allows the liver to remain relatively resistant to hypoxemia. 5nli&e the systemic vasc#lat#re( the hepatic vasc#lar system is less infl#enced %y vasodilatation and vasoconstriction. )his is %eca#se the sin#soidal press#res remain relatively constant despite changes in %lood flow. A classic example is hepatic vein occl#sion res#lting in high sin#soidal press#re and extracell#lar extravasation of fl#id. )o maintain a constant inflow of %lood to the liver( hepatic artery %lood flow is inversely related to portal vein flow. )his appears to %e hormonally mediated rather than ne#rally mediated( since it persists in the transplanted liver.

CHAPTER III
3

A. CIRRHOSIS HEPATIS

1. Definition 7irrhosis is a complication of many liver diseases that is characteri!ed %y a%normal str#ct#re and f#nction of the liver. )he diseases that lead to cirrhosis do so %eca#se they in8#re and &ill liver cells( and the inflammation and repair that is associated with the dying liver cells ca#ses scar tiss#e to form. )he liver cells that do not die m#ltiply in an attempt to replace the cells that have died. )his res#lts in cl#sters of newly0formed liver cells "regenerative nod#les$ within the scar tiss#e.

2. Epidemio o!" 7hronic liver disease and cirrhosis res#lt in a%o#t .5(000 deaths each year in the 5nited 'tates. 7irrhosis is the ninth leading ca#se of death in the 5nited 'tates and is responsi%le for 1.2% of all 5' deaths. 9any patients die from the disease in their fifth or sixth decade of life. Each year( 2000 additional deaths are attri%#ted to f#lminant hepatic fail#re "6:6$. 6:6 may %e ca#sed viral hepatitis "eg( hepatitis A and ;$( dr#gs "eg( acetaminophen$( toxins "eg( Amanita phalloides, the yellow death0cap m#shroom$( a#toimm#ne hepatitis( <ilson disease( or a variety of less common etiologies. 7ryptogenic ca#ses are responsi%le for one third of f#lminant cases. /atients with the syndrome of 6:6 have a 50020% mortality rate #nless they are salvaged %y liver transplantation.

#. Etio o!" 3n western co#ntries the ca#ses of liver cirrhosis are common d#e to alcoholism( while in 3ndonesia( especially d#e to infection with hepatitis ; or 7 vir#s. )he res#lts in 3ndonesia
4

said the most common ca#se of liver cirrhosis are hepatitis ; vir#s ".00,0%$( hepatitis 7 vir#s ".00,0%$( and #n&nown ca#ses "10020%$. As for some of the etiology of liver cirrhosis incl#de= a$ Alcohol is a very common ca#se of cirrhosis( partic#larly in the <estern world. )he development of cirrhosis depends #pon the amo#nt and reg#larity of alcohol inta&e. 7hronic( high levels of alcohol cons#mption in8#re liver cells. %$ >onalcoholic fatty liver disease ">A6?@$ refers to a wide spectr#m of liver diseases that( li&e alcoholic liver disease( ranges from simple steatosis( to nonalcoholic steatohepatitis ">A':$( to cirrhosis. All stages of >A6?@ have in common the acc#m#lation of fat in liver cells. )he term nonalcoholic is #sed %eca#se >A6?@ occ#rs in individ#als who do not cons#me excessive amo#nts of alcohol( yet( in many respects( the microscopic pict#re of >A6?@ is similar to what can %e seen in liver disease that is d#e to excessive alcohol. >A6?@ is associated with a condition called ins#lin resistance( which( in t#rn( is associated with the meta%olic syndrome and dia%etes mellit#s type 2.+%esity is the most important ca#se of ins#lin resistance( meta%olic syndrome( and type 2 dia%etes. >A6?@ is the most common liver disease in the 5nited 'tates and is responsi%le for 2,% of all liver disease. 3n fact( the n#m%er of livers that are transplanted for >A6?@0related cirrhosis is on the rise. /#%lic health officials are worried that the c#rrent epidemic of o%esity will dramatically increase the development of >A6?@ and cirrhosis in the pop#lation. c$ 7ryptogenic cirrhosis "cirrhosis d#e to #nidentified ca#ses$ is a common reason for liver transplantation. 3t is termed cryptogenic cirrhosis %eca#se for many years doctors have %een #na%le to explain why a proportion of patients developed cirrhosis. @octors now %elieve that cryptogenic cirrhosis is d#e to >A': "nonalcoholic steatohepatitis$ ca#sed %y long standing o%esity( type 2 dia%etes( and ins#linresistance. )he fat in the
5

liver of patients with >A': is %elieved to disappear with the onset of cirrhosis( and this has made it diffic#lt for doctors to ma&e the connection %etween >A': and cryptogenic cirrhosis for a long time. +ne important cl#e that >A': leads to cryptogenic cirrhosis is the finding of a high occ#rrence of >A': in the new livers of patients #ndergoing liver transplant for cryptogenic cirrhosis. 6inally( a st#dy from 6rance s#ggests that patients with >A': have a similar ris& of developing cirrhosis as patients with long standing infection with hepatitis 7 vir#s. "'ee disc#ssion that follows.$ :owever( the progression to cirrhosis from >A': is tho#ght to %e slow and the diagnosis of cirrhosis typically is made in patients in their sixties. d$ 7hronic viral hepatitis is a condition where hepatitis ; or hepatitis 7vir#s infects the liver for years. 9ost patients with viral hepatitis will not develop chronic hepatitis and cirrhosis. 6or example( the ma8ority of patients infected with hepatitis A recover completely within wee&s( witho#t developing chronic infection. 3n contrast( some patients infected with hepatitis ; vir#s and most patients infected with hepatitis 7 vir#s develop chronic hepatitis( which( in t#rn( ca#ses progressive liver damage and leads to cirrhosis( and( sometimes( liver cancers. e$ 3nherited "genetic$ disorders res#lt in the acc#m#lation of toxic s#%stances in the liver which lead to tiss#e damage and cirrhosis. Examples incl#de the a%normal acc#m#lation of iron "hemochromatosis$ or copper "<ilsonAs disease$.

3n hemochromatosis( patients inherit a tendency to a%sor% an excessive amo#nt of iron from food. +ver time( iron acc#m#lation in different organs thro#gho#t the %ody ca#ses cirrhosis( arthritis( heart m#scle damage leading to heart fail#re( and testic#lar dysf#nction ca#sing loss of sex#al drive. )reatment is aimed at preventing damage to organs %y removing iron from the %ody thro#gh %loodletting "removing %lood$. 3n <ilson disease( there is an inherited a%normality in one of the proteins that controls
6

copper in the %ody. +ver time( copper acc#m#lates in the liver( eyes( and %rain. 7irrhosis( tremor( psychiatric dist#r%ances and otherne#rological diffic#lties occ#r if the condition is not treated early. )reatment is with oral medication that increases the amo#nt of copper that is eliminated from the %ody in the #rine. f$ /rimary %iliary cirrhosis "/;7$ is a liver disease ca#sed %y an a%normality of the imm#ne system that is fo#nd predominantly in women. )he a%normal imm#nity in /;7 ca#ses chronic inflammation and destr#ction of the small %ile d#cts within the liver. )he %ile d#cts are passages within the liver thro#gh which %ile travels to the intestine. ;ile is a fl#id prod#ced %y the liver that contains s#%stances re1#ired for digestion and a%sorption of fat in the intestine( as well as other compo#nds that are waste prod#cts( s#ch as the pigment %ilir#%in. ";ilir#%in is prod#ced %y the %rea&down of hemoglo%in from old red %lood cells.$. Along with the gall%ladder( the %ile d#cts ma&e #p the%iliary tract. 3n /;7( the destr#ction of the small %ile d#cts %loc&s the normal flow of %ile into the intestine. As the inflammation contin#es to destroy more of the %ile d#cts( it also spreads to destroy near%y liver cells. As the destr#ction of the hepatocytes proceeds( scar tiss#e "fi%rosis$ forms and spreads thro#gho#t the areas of destr#ction. )he com%ined effects of progressive inflammation( scarring( and the toxic effects of acc#m#lating waste prod#cts c#lminates in cirrhosis. g$ /rimary sclerosing cholangitis "/'7$ is an #ncommon disease fo#nd fre1#ently in patients with #lcerative colitis . 3n /'7( the large %ile d#cts o#tside of the liver %ecome inflamed( narrowed( and o%str#cted. +%str#ction to the flow of %ile leads to infections of the %ile d#cts and 8a#ndice and event#ally ca#ses cirrhosis. 3n some patients( in8#ry to the %ile d#cts "#s#ally as a res#lt of s#rgery$ also can ca#se o%str#ction and cirrhosis of the liver.
7

h$ A#toimm#ne hepatitis is a liver disease ca#sed %y an a%normality of the imm#ne system that is fo#nd more commonly in women. )he a%normal imm#ne activity in a#toimm#ne hepatitis ca#ses progressive inflammation and destr#ction of liver cells "hepatocytes$( leading #ltimately to cirrhosis. i$ 3nfants can %e %orn witho#t %ile d#cts "%iliary atresia$ and #ltimately develop cirrhosis. +ther infants are %orn lac&ing vital en!ymes for controlling s#gars that leads to the acc#m#lation of s#gars and cirrhosis. +n rare occasions( the a%sence of a specific en!yme can ca#se cirrhosis and scarring of the l#ng "alpha 1 antitrypsin deficiency$. 8$ ?ess common ca#ses of cirrhosis incl#de #n#s#al reactions to some dr#gs and prolonged expos#re to toxins( as well as chronic heart fail#re "cardiac cirrhosis$. 3n certain parts of the world "partic#larly >orthern Africa$( infection of the liver with a parasite "schistosomiasis$ is the most common ca#se of liver disease and cirrhosis.

$. P%t&o!ene'i'
6ig 2. 'tages of liver damage

?iver responds the cell damage %y forming extracell#lar matrix containing collagen( glycoproteins( and proteogli&ans. 'tellate cell extracell#lar matrix play a role in shaping this.
8

3n an ac#te in8#ry( stellate cells reshaping the extracell#lar matrix is th#s fo#nd to swelling of the liver. :owever( there are several factors that ca#se para&rine stellate cells into collagen0 prod#cing cells. /ara&rine factors may %e released %y hepatocytes( B#pffer cells( and sin#soidal endothelial response to prolonged in8#ry. 6or example( elevated levels of the cyto&ine transforming growth facto %eta 1 ")C60%eta1$ was fo#nd in patients with chronic hepatitis 7 and cirrhosis patients. )C60%eta1 then activates stellate cells to prod#ce collagen type 1 and #ltimately shrin&ing the si!e of the liver. 3ncreased deposition of collagen in the perisin#soidal and red#ced the si!e of hepatic endothelial fenestra ca#se &apilerisasi "s#ch as capillary endothelial pore si!e$ of the sin#soid. 'tellate cell in prod#cing the collagen to contract large eno#gh to s#ppress local presence perisin#soidal stellate cell contractility &apilarisasi and that ca#ses a lot of emphasis on the veins in the liver that disr#pts the %lood flow to the liver cells and liver cells event#ally die. :epatocyte death in large n#m%ers will ca#se a lot of damaged liver f#nction that ca#ses many clinical symptoms. /ress#re on the veins in the liver can lead to portal hypertension. /ortal hypertension is a ma8or ca#se of the state of the clinical manifestations.

(. Si!n %nd '"mtom'(12) 9any people with cirrhosis have no symptoms d#ring the early phases of the disease. 'ymptoms are ca#sed %y either of 2 pro%lems. Crad#al fail#re of the liver to carry o#t its nat#ral f#nctions and distortion of the liverAs #s#al shape and si!e %eca#se of scarring )he most common symptoms of cirrhosis are tiredness "fatig#e$ or even exha#stion( wea&ness( na#sea( loss of appetite leading to weight loss( loss of sex drive. 'ymptoms may not appear #ntil complications of cirrhosis set in. 9any people do not &now they have cirrhosis #ntil they have a complication. )he symtoms are fever( vomiting( diarhhea( 8a#ndice ( yellowing of the s&in and eyes from deposition of %ilir#%in in these tiss#es.
9

;ilir#%in is a prod#ct of the %rea&down of old %lood cells in the liver. 3tching can %e happen from deposition in the s&in of prod#cts of the %rea&down of %ile. ;eside that( from fl#id retention ca#ses a%dominal swelling( edema( and diffic#lty %reathing. ;eca#se one of the f#nctions of the liver is secreting hormones( so in cirrhosis hepatic gynecomastia( scrotal swellin( and the a%normal menstr#al periods can %e fo#nd in this disease. ;leeding from g#ms or nose and easy %r#sing are often happend d#e to impaired prod#ction of clotting factors in cirrhosis.

CHAPTER III ). ESOPHA*EA+ ,ARICES

10

1. Definition Esophageal varices are a%normal( enlarged veins in the lower part of the esophag#s D the t#%e that connects the throat and stomach. Esophageal varices occ#r most often in people with serio#s liver diseases. Esophageal varices develop when normal %lood flow to yo#r liver is slowed. )he %lood then %ac&s #p into near%y smaller %lood vessels( s#ch as those in yo#r esophag#s( ca#sing the vessels to swell. 'ometimes( esophageal varices can r#pt#re( ca#sing life0 threatening %leeding.

2. Epidemio o!i Altho#gh varices can occ#r anywhere along the gastrointestinal tract t#%#lar( varices often occ#r in a few centimeters of the distal end of the esophag#s. Approximately 50% of patients with cirrhosis have gastroesophageal varices. Castric varices occ#r in 50..% of cases of portal hypertension. )he fre1#ency of esophageal varices ranged %etween .0040% in patients with cirrhosis( and 90.-% of patients with high0ris& varices. "11$

.. Etio o!" Esophageal varices are most often a complication of cirrhosis D irreversi%le scarring of the liver. +ther diseases and conditions also can ca#se esophageal varices. 7a#ses can incl#de= a$ 'evere liver scarring "cirrhosis$. A n#m%er of liver diseases can res#lt in cirrhosis( s#ch as hepatitis infection( alcoholic liver disease and a %ile d#ct disorder called primary %iliary cirrhosis.

11

%$ ;lood clot "throm%osis$. A %lood clot in the portal vein or in a vein that feeds into the portal vein called the splenic vein can ca#se esophageal varices. c$ A parasitic infection. 'chistosomiasis is a parasitic infection fo#nd in parts of Africa( 'o#th America( the 7ari%%ean( the 9iddle East and 'o#theast Asia. )he parasite can damage the liver( as well as the l#ngs( intestine and %ladder. d$ A syndrome that ca#ses %lood to %ac& #p in yo#r liver. ;#dd07hiari syndrome is a rare condition that ca#ses %lood clots that can %loc& the veins that carry %lood o#t of yo#r liver $. P%t&o!ene'i' 7irrhosis( the end stage of chronic liver disease( is the most common ca#se of portal hypertension. /ortal veno#s press#re "/$ is the prod#ct of vasc#lar resistance " $ and %lood flow "E$ in the portal %ed "+hmFs law* 6ig. 1$. 3n cirrhosis( %oth intrahepatic vasc#lar resistance and portal flow are increased. /ortal hypertension leads to the formation of portosystemic collaterals. :owever( d#e to their higher resistance and increased portal veno#s inflow( these collaterals are #na%le to decrease the hypertension. /ortal hypertension is %est assessed "indirectly$ #sing the wedged hepatic veno#s press#re "<:G/$ meas#rement. A press#re difference %etween the portal and systemic circ#lation "the hepatic veno#s press#re gradient( :G/C$ of 1012 mm:g is necessary "%#t not s#fficient$ for varices to form. )he normal :G/C is .5 mm:g. 'ingle meas#rements are #sef#l for determining the prognosis of %oth compensated and decompensated cirrhosis( while repeat meas#rements are #sef#l for monitoring the response to pharmacological therapy and the progression of liver disease."10$ Garices r#pt#re if the wall tension %ecomes too great. )he li&elihood that a varix will r#pt#re and %leed increases with increasing si!eHdiameter of the varix and with increasing variceal press#re( which is again proportionate to the :G/C. 7onversely( varices do not
12

%leed if the :G/C is %elow 12 mm:g. )he ris& of re%leeding decreases significantly with red#ctions in :G/C greater than 20% from %aseline. "11$

(. Si!n %nd '"mtom' Esophageal varices #s#ally donAt ca#se signs and symptoms #nless they %leed. 'igns and symptoms of %leeding esophageal varices incl#de= 'hoc&( in severe cases Gomiting %lood ;lac&( tarry or %loody stools

-. Ri'. f%/to0 An international normali!ed ratio "3> $ score I 1.5( a portal vein diameter of I 1. mm( and throm%ocytopenia have %een fo#nd to %e predictive of the li&elihood of varices %eing present in cirrhotics. 3f none( one( two( or all three of these conditions are met( then J 10%( 2050%( ,0-0%( and I 90% of the patients are estimated to have varices( respectively. )he presence of one or more of these conditions represents an indication for endoscopy to search for varices and carry o#t primary prophylaxis against %leeding in cirrhotic patients. "10(11$

CHAPTER I, DISCUSSION

13

Esophageal varices are the ma8or complication of portal hypertension. 3t is detected in a%o#t 50% of cirrhosis patients( and approximately 515% of cirrhosis patients show newly formed varices or worsening of varices each year K15L. As other parenchyma tiss#e( the liver normally contains epithelial component "hepatocytes$( endothelial layer "of the liver characteri!ed %y the presence fenestra$( tiss#e macrophages "B#pffer cells$( and perivasc#lar mesenchymal cells called stelata cells. 'telata cells that are normally involved in the storage of fat and vitamin A will %e transformed into cells that resem%le miofi%ro%las in case of in8#ry in the liver. )his led a change in the extracell#lar matrix( the prod#ction of collagen %ecome increase and forming tiss#e fi%rosis. 7ontraction of activated stellate cells is promoted %y increased vasoconstrictor endothelin and a red#ction in the vasodilator nitric oxide within the liver. )herefore( intrahepatic resistance increases. 3n contrast to its intrahepatic levels( nitric oxide concentrations are elevated in the peripheral and splanchnic circ#lation. )his res#lts in decreased systemic and splanchnic vasc#lar resistance( th#s increasing portal %lood flow."1,$

7irrhosis
3ncreased splanchnic M peripheral >+ @ecreased systemic M splanchnic vasc#lar resistance 3ncrease portal %lood flow 'odi#m retention @ecreased intrahepatic >+ 3ncreased intrahepatic resistance

7ollateral s
9aintains portal hypertension

/ortal hypertension is associated with %oth increased portal inflow and increased
6ig .. )he pathogenesis of oesophageal varices o#tflow resistance. )he portal hypertension is directly related to portal inflow andHor o#tflow 14

resistance(as determined %y +hmFs law Nportal press#re O portal veno#s inflow o#tflow resistance.P /ortal veno#s inflow is affected %y hyperdynamic circ#lation( which is characteri!ed %y systemic and splanchnic vasodilatation( low systemic resistance( plasma vol#me expansion( and high cardiac index. 'planchnic vasodilatation contri%#tes to increasing s#%stantial %lood vol#me which ret#rns to portal veno#s system. /eripheral vasodilatation activates endogeno#s ne#roh#moral systems that ca#se sodi#m retention( which leads to expansion of the plasma vol#me( followed %y an increase in the cardiac index."1.$ +ne of the potential for comm#nication %etween circ#lation splancnic intraa%dominal and systemic veno#s circ#lation is thro#gh the esophag#s. 3f the portal veno#s %lood flow to the liver is hampered %y cirrhosis or other ca#ses( portal hypertension that occ#r trigger the formation of collateral %ypass channels in a meeting place for portal and systemic systems. )herefore( the portal %lood flow diverted thro#gh the stomach into the coronary veno#s plex#s of s#%epithelial and s#%m#cosal esophageal veins( then into the a!ygos vein and s#perior vena cava. 3ncreased press#re in the esophageal plex#s ca#ses them to dilate and winding serpentine &nown as varices. /atients with cirrhosis are experiencing varices at a rate of 5% 015% per year( so that the veins fo#nd in approximately two0thirds of all patients with cirrhosis. "1.$

15

6ig ,. Esophageal varices

#pt#red varices occ#r when the strain in the wall of varices is too %ig. /ossi%le wall varices "varix$ will have a tear in line with the magnit#de H diameter varix variseal and with increased press#re( which again is e1#ivalent to the :G/C. <all varices will not tear if :G/C press#re less than 12 mm:g. 3n ideal circ#mstances( patients with &nown varices sho#ld receive treatment to red#ce their ris& of %leeding. )he non0selective Q0

%loc&ers "e.g.( propranolol 10 mg ( timolol or nadolol20 mg$ and nitrates "e.g. isosor%ide mononitrate "39>$ 20 mg ;@$ have %een eval#ated for primary prophylaxis. >on0 selective Q0%loc&ers "%#t not cardioselective Q0%loc&ers li&e atenolol$ are preferred %eca#se they decrease %oth cardiac o#tp#t %y Q1 %loc&ade and splanchnic %lood flow %y %loc&ing vasodilating Q2 receptors at splanchnic vasc#lat#re. )he effectiveness of this treatment has %een shown %y a n#m%er of different st#dies."15(1-$ Endoscopic variceal %and ligation may %e an alternative for patients who cannot tolerate( or have contraindications to %eta0%loc&ers. )he %est approach for patients with ac#te variceal %leeding is the com%ination of vasoactive dr#gs and endoscopic therapy. )erlipressin is administered as 2mg 3G %ol#s and 1mg every six ho#rs for 205 days. 'omatostatin is given as an 3G 250mcg %ol#s followed %y 250mcgHho#r inf#sion and octreotide is administered as a %ol#s in8ection of 50mcg followed %y an inf#sion at a rate of 50mcgHho#r. 'omatostatin or octreotide therapy sho#ld %e maintained for 5 days to prevent early re0%leeding. egarding

16

endoscopic therapy( EG? is preferred %#t sclerotherapy may %e #sed depending on the endoscopistFs experience and the partic#lar circ#mstances fo#nd d#ring endoscopy. "14(12$ )he first0line treatment for prevention of rec#rrent variceal haemorrhage is %eta%loc&ers( endoscopic variceal ligation or the com%ination of %eta0%loc&ers and endoscopic variceal ligation. )3/' or s#rgical sh#nt appears to %e more appropriate for patients who are non0compliant or refractory to pharmacological and endoscopic therapy."19$

A+*ORITHM1 PRIMARY PROPHY+A2IS O3 ,ARICEA+ )+EED

?arge varices "Crade .$ '#spected ac#te variceal %leeding "AG;$ or moderate varices "Crade 2$ with endoscopic red wale signs or 7hildFs 7 es#scitation( 3G access( CR9 cirrhosis

)erlipressin H +ctreotide H 'omatostatin for 205 days Anti%iotic /rophylaxis for 4 days in patients with cirrhosis ;eta0%loc&er therapy "propranolol 10 mg ( timolol or nadolol20 mg$ and Endoscopy service nitrates "e.g. #navaila%le isosor%ide mononitrate "39>$ 20 mg ;@$$ ;alloon tamponade if active %leeding )ransfer to endoscopy centre EG? if %eta0%loc&er 5rgent Endoscopy contraindicated or intolerant +esophageal varices 3f 7hildFs 7 cirrhosis consider EG? preferred* liver transplant sclerotherapy if EG? evaluation diffic#lt Castric varices

3n8ection with cyanoacrylate

/ersistent active %leeding

/ersistent active %leeding

A+*ORITHM1 MANA*EMENT O3 ACUTE ,ARICEA+ )+EEDIN*

>+ SE'

)3/' or s#rgical intervention

;eta0%loc&ers( EG? or %oth

17

epeat endoscopic therapy )3/' or s#rgical sh#nt

CHAPTER , CONC+USION 7irrhosis is a condition that is defined histopathologically and has a variety of clinical manifestations and complications( some of which can %e life0threatening( portal hypertension
18

is directly responsi%le for the two ma8or complications of cirrhosis( variceal hemorrhage. Gariceal hemorrhage is an immediate life0threatening pro%lem with a 20.0% mortality associated with each episode of %leeding. 3n normal condition( the liver has system receives %lood from the mesenteric veins( stomach( lymph nodes( and pancreas enter thro#gh the hepatic artery and portal vein. ;lood sent to the liver via the portal triad consisting of a %ranch of the portal vein( hepatic artery and %ile d#ct. )hen it will contino#s to the lo%#l liver sin#soid space. ;lood that has filtered into the central vein and then into the hepatic vein larger toward the inferior vena cava. 3n cirrhosis( the presence of fi%rotic tiss#e in the sin#soids interfere the normal %lood flow to the liver lo%#l( it will ca#se the portal hypertension that can develop into varices. )here are treatments to stop %leeding in s#ch as vaso0active dr#gs( vasopressin( somatostatin( octreotide( endoscopic sclerotherapy and %anding, and endoscopic variceal ligation. T0;loc&ers and endoscopic variceal %and ligation are the treatments to prevent %leeding.

RE3ERENCES

19

1.

. @e 6ranchis and 9. /rimignani( N>at#ral history of portal hypertension in patients with cirrhosis(P Clinics in Liver Disease( vol. 5( no. .( pp. -,5--.( 2001.

2.

7. 9er&el( 9. Uoli( '. 'iringo et al.( N/rognostic indicators of ris& for first variceal %leeding in cirrhosis= a m#lticenter st#dy in 411 patients to validate and improve the >orth 3talian Endoscopic 7l#% ">3E7$ index(P American Journal of Gastroenterology( vol. 95( no. 10( pp. 29152920( 2000.

..

C. @FAmico and . @e 6ranchis( N5pper digestive %leeding in cirrhosis. /ost0therape#tic o#tcome and prognostic indicators(P Hepatology( vol. .2( no. .( pp. 599-12( 200..

,.

>. 7ar%onell( A. /a#wels( ?. 'erfaty( +. 6o#rdan( G. C. ?Vevy( and

. /o#pon(

N3mproved s#rvival after variceal %leeding in patients with cirrhosis over the past two decades(P Hepatology(vol. ,0( no. .( pp. -52-59( 200,. 5. C. @FAmico( ?. /agliaro( W. ;osch( and @. /atch( N/harmacological treatment of portal hypertension= an evidence0%ased approach(P Seminars in Liver Disease( vol. 19( no. ,( pp. ,45 505( 1999. -. W. ;osch and W. 7. CarcVXa0/agVan( N/revention of variceal re%leeding(P The Lancet( vol. .-1( no. 9.-1( pp. 95295,( 200.. 4. Anatomy of :epar and /ortal Gein. Availa%le at = http=HHhop&ins0 gi.orgHC@?Y@isease.aspxZ7#rrent5@GO.1[C@?Y7atY3@O;;5.2@2A0,.7;0,1-70 96@20A04A7-,2-9-1[C@?Y@iseaseY3@OE19@;E,A0EE020,;@E096690 A2.412.,@E,A . Accessed on 2 8an#ary 201. 2. 7irrhosis of liver. Availa%le at = http=HHwww.liver.caHliverYdiseaseHad#ltYliverYdiseasesHcirrhosisYofYtheYliver.aspx. Accesed on 2 8an#ary 201.. 9. 7irrhosis. Availa%le at= http=HHwww.liverfo#ndation.orgHa%o#ttheliverHinfoHcirrhosisH.

Accesed on 2 8an#ary 201..

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10. @ite( /.( et al. <orld Castroenterology +rgani!ation /ractice C#ideline= Esophageal Garices. 2002. 11. @om%ro 9 ( CriffithFs 509in#te 7linical 7ons#lt( /hiladelphia = ?ippincott <illiams [ <il&ins( 200-. 12. 7irrhosis symtoms. Availa%le at = http=HHwww.emedicinehealth.comHcirrhosisHpage.Yem.htm\cirrhosisYsymptoms . Accesed on 2 8an#ary 201.. 1.. A. W. 'anyal( W. ;osch( A. ;lei( and G. Arroyo( N/ortal hypertension and its complications(P Gastroenterology( vol. 1.,( no. -( pp. 14151422( 2002. 1,. Cressner A9(<eis&irchen . 9odern pathogenetic concepts of liver fi%rosis s#ggest iol !ed"

stellate cells and )C60Y as ma8or players and therape#tic targets. J Cell 200-*10=4-99.

15. ?e%rec @( /oynard )( :illon /( ;enhamo# W0/ "1921$. ]/ropranolol for prevention of rec#rrent gastrointestinal %leeding in patients with cirrhosis= a controlled st#dy]. # $ngl J !ed #4( "2.$= 1.411.4,. 1-. )alwal&ar WA( Bamath /' "200,$. ]An evidence0%ased medicine approach to %eta0 %loc&er therapy in patients with cirrhosis]. Am J !ed11- "11$= 4594--. 14. Cros!mann W( Carcia0)sao C( ;osch W( et al" "2005$. ];eta0;loc&ers to /revent

Castroesophageal Garices in /atients with 7irrhosis]. # $ngl J !ed #(# "21$= 225, 22-1. 12. Barsan :A( 9orton '7( 'he&elle /C( et al. 7om%ination endoscopic %and ligation and sclerotherapy compared with endoscopic %and ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage= a meta0analysis. Dig Dis Sci. 2005*50"2$=.990,0-.

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19. osch W( Beller 6'. )rans8#g#lar intrahepatic portosystemic sh#nt= present stat#s( comparison with endoscopic therapy and sh#nt s#rgery( and f#t#re prospectives. %orld J Surg. 2001*25".$=..40,5.

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