6. Management of Cirrhosis of the Liver

8/2/2019 6. Management of Cirrhosis of the Liver

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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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6. Management of Cirrhosis of the Liver

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