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B.J. WALELENGN. TENDEAN WENASF. WIBOWO
GASTROENTEROHEPATOLOGY DIVISION
INTERNAL MEDICINE DEPARTMENT
SAM RATULANGI UNIVERSITY
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Cirrhosis is a diffuse process characterized byfibrosis and the conversion of normal liver
architecture into structurally abnormalnodules.
End stage of chronic liver damage resultingfrom several different causes.
Leading to altered hepatic function andportal hypertension.
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World prevalence : 100 (25-400) / 100,000 796,000 deaths from cirrhosis (2001)
UK : 3000 deaths from cirrhosis or chronicliver disease every year (40% due to alcoholrelated disease)
Italy : 15,000 died from cirrhosis (1992) 28deaths /100,000. Most frequent causes : HCV,alcohol, HBV
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USA : 5.5 million prevalence, rate2030/100,000 (1998). Mortality 25,000 (9.3 /
100,000) annually. Most common causes : HCV (57%), alcohol
(24%), Non alcoholic fatty liver disease(9.1%), hepatitis B (4.4%)
INDONESIA 4%
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MAIN ETIOLOGIC FACTORS IN CIRRHOSIS
Hepatitis C virus Biliary disease(PBC, PSC, Intrahepatic or extrahepaticbiliary obstruction)
Hepatitis B or B/D virus Venous Outflow obstruction(Budd Chiari, veno-occlusive disease,cardiac failure)
Alcohol Drugs (amiodarone, methotrexate) andtoxins
Autoimmune hepatitis Intestinal bypassMetabolic disorders(hemochromatosis, Wilsons disease,alpha-1 antitrypsin deficiency, NASH,diabetes, glycogen storage diseases,abetalipoproteinemia, porphyria)
Cryptogenic cirrhosis
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In the Western World the most commonetiology of cirrhosis is HCV, followed by
alcohol abuse. Other important factors are hepatitis B
infection and NASH. Autoimmune, metabolic, biliary, genetic
disorders account for the largest remainingproportion of cirrhosis.
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Progressive accumulation of collagentypes I and III in the liver parenchyma
Alteration of :The exchange between hepatocytes and plasma
Regulation of intrahepatic resistance to blood flow
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Active fibrogenesis
Activation and proliferation ofhepatic stellate cells (extracellular
matrix in fibrotic liver)
TGF-PDGF
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Micronodular
Nodules < 3 mm
Alcoholic cirrhosis, hemochromatosis, bile ductobstruction
Macronodular
Nodules of variable size > 3 mm
Chronic viral hepatitis, autoimmune hepatitis
Mixed
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Compensated cirrhosis
Asthenia, malaise, right upper quadrant
abdominal discomfort, sleep disturbances Physical signs secondary to alterations of
estrogen metabolism : palmar erythema, spiderangiomata
Hepatomegaly with increased liver consistency
Splenomegaly and collateral circulation on theabdominal wall
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Decompensated cirrhosis
Ascites, gastrointestinal hemorrhage, jaundice,
portosystemic encephalopathy : main signs ofdecompensation
Malnutrition and muscle wasting
Hypotension and tachycardia due to
hyperdynamic circulation secondary to portalhypertension.
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CLINICAL FINDINGS
Asthenia Splenomegaly
Malaise Abdominal wall collaterals
RUQ abdominal discomfort General deterioration, muscle wasting
Loss of libido Jaundice
Sleep disturbances Ascites
Palmar erythema Ankle edema
Dupuytrens contracture Flapping tremor
Spider nevi Bradylalia
White nails Mental state alteration (coma)
Gynecomastia Fetor hepaticus
Hair loss Gastrointestinal hemorrhage
Hepatomegaly Hypotension, tachycardia
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LABORATORY FINDINGS ULTRASONOGRAPHIC
FINDINGS
ENDOSCOPIC FINDINGS
AST : ALT ratio > 1 Liver nodular surface Esophageal varices
Low platelet count Reduced portal flow
velocity
Gastric varices
Hypoalbuminemia Portal vein diameter >13mm
Congestive gastropathy
Hypergammaglobulinemia Lack (or reduction
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Liver biopsy is the gold standard Compensated cirrhosis : clinical, biochemical,
USG, endoscopic findings When a precise definition of stage of fibrosis
or grading of inflammation is required, liverbiopsy is needed.
Signs of decompensation : ascites, varicealbleeding, encephalopathy
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Ascites Spontaneous bacterial peritonitis
Variceal hemorrhage Hepatic encephalopathy Hepatocellular carcinoma Hepatorenal syndrome
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BLEEDING FROM ESOPHAGEAL VARICES
Incidence per year :
2% in patients without varices at diagnosis 5% in those with small varices
15% in those with medium-large varices Major indicators of the risk of bleeding Child-Pugh class
Ascites
Red wheal marks
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Increased risk of bleeding with increased
portal pressure
Ruptured esophageal varices : 60-70% ofall upper GI bleeding in cirrhosis
Reduction of HVPG
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COMPLICATIONS
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DEVELOPMENT OF ASCITES AND
ENCEPHALOPATHY
Ascites develops after HVPG has increased to morethan 12 mmHg
Incidence : 5% per year Ascites and variceal bleed : the most frequent mode
of transition from compensated to decompensatedcirrhosis Incidence of encephalopathy : 2-3% per year
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Ascites
Sodium and fluid restriction
Diuretics : furosemide, spironolactone Albumin infusion
Therapeutic paracentesis
TIPS
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Portal hypertension, esophageal varices andvariceal bleeding
Reduce pressure with beta blockers
Active bleeding : vasopressin, somatostatin
Endoscopic and surgical management
TIPS
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Spontaneous bacterial peritonitis
Antibiotics : treatment and prophylaxis
Hepatic encephalopathy
Treat precipitating causes
Correction of hypokalemia
Dietary protein reduction
Antibiotics
Lactulose to reduce ammonia level
Bleeding tendencies Vitamin K, fresh frozen plasma for bleeding due to
hypoprotrombinemia
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Specific treatment :
Phlebotomy for hemochromatosis
D-penicillinamine for Wilsons disease
Avoidance of alcohol for alcohol-induced cirrhosis
Combination of pegylated interferon alpha and ribavirinfor chronic hepatitis C infection
Lamivudine and adefovir dipivoxil for chronic hepatitis Binfection
Corticosteroids for autoimmune hepatitis
Ursodeoxycholic acid for PBC
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Screening for hepatocellular carcinoma with
serial ultrasound examinations and serum
AFP in cirrhosis patients Vaccination against hepatitis A and B Avoidance of alcohol and other hepatotoxins
Liver transplantation in end-stage cirrhosis ifthe patient is an appropriate candidate.
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Compensated cirrhosis
10-year survival rate : 90%
Median survival after decompensation : 2 years 10-year transition rate to decompensation : 50%
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Decompensated cirrhosis Median survival after first variceal hemorrhage : 1
year
Survival after development of ascites : 2 years Median survival after encephalopathy or jaundice is
shorter than that of bleeding or ascites.
Most common causes of death : Bleeding Liver failure with hepatic coma
Sepsis
Hepatorenal syndrome.
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STAGES OF CIRRHOSIS PROGRESSION
1%
4.4%
7%3.4%
6.6%
20%
7.6% 4%
57%
Stage 0
Stage 1
Stage 2
Stage 3
No varicesNo ascites
VaricesNo ascites
Ascites +
Varices
Bleeding +Ascites
Death
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Consider in patients with end-stage liver
disease with :
Life threatening complication of hepaticdecompensation
Quality of life decreasing to unacceptable levels
Will result in irreversible damage to the centralnervous system
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End stage cirrhosis of all causes Alcoholic cirrhosis Chronic viral hepatitis
Fulminant hepatitis Biliary cirrhosis Cryptogenic cirrhosis Hepatic vein thrombosis Primary hepatocellular malignancies
Hepatic adenomas
Most common indication for liver transplant (40%) :hepatitis C and alcoholic liver disease
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ABSOLUTE RELATIVE
Uncontrolled extrahepatobiliaryinfection
Age>70
Active, untreated sepsis Prior extensive hepatobiliary surgery
Active substance or alcohol abuse Portal vein thrombosis
Advanced cardiopulmonary disease Renal failure
Extrahepatobiliary malignancy Previous extrahepatic malignancy
Metastatic malignancy to the liver Severe obesity
AIDS Severe malnutrition / wastingLife-threatening systemic diseases HIV seropositivity
Inability to comply withimmunosuppression protocol
Severe hypoxemia secondary to right-to-left intrapulmonary shunts
Uncontrolled psychiatric disorder
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ETIOLOGY PERCENTAGE
Hepatitis C 36%
Alcohol 14%
Cryptogenic 11%
Alcohol and viral hepatitis 7%
PSC 7%
PBC 6%
Hepatitis B 4%
Metabolic (e.g. Wilsons, hemochromatosis) 4%
Autoimmune hepatitis 4%
Secondary biliary cirrhosis
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Highest priority : fulminant hepatic failure MELD (model for end stage liver disease)
score : bilirubin, creatinine, INR Child-Turcotte-Pugh score : encephalopathy
stage, ascites, bilirubin, albumin, PT
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Cadaver : Head trauma / brain dead Hemodynamic stability Adequate oxygenation
Absence of bacterial or fungal infection Absence of abdominal trauma Absence of hepatic dysfunction Serologic exclusion of hepatitis B and C and HIV
Living donor Transplantation of the right lobe of the liver from a healthy
adult into an adult recipient Left lobe for small children
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Immunosuppresive therapy minimizing rejection,significant side effects Cyclosporine Tacrolimus : more effective but more toxic than
cyclosporine Combinations of cyclosporine or tacrolimus with
prednisone and azathioprine, all at reduced doses, areprefereble regimens.
OKT3 (monoclonal antibodies to T cells) Mycophenolate
Balance immunosuppression and immunologiccompetence
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Management of postoperative complications(cardiovascular, pulmonary, renal, etc)
Transplant rejection : starting 1-2 weeks aftersurgery, treat with IV methylprednisoloneboluses.
Recurrence of primary disease
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