professor of internal medicine
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Liver cirrhosisLiver cirrhosis
Usama Ahmed Arafa, MDUsama Ahmed Arafa, MD
Professor of Internal MedicineProfessor of Internal Medicine
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Definition
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Liver cirrhosis is characterized by:Liver cirrhosis is characterized by:
11-- Hepatocellular necrosisHepatocellular necrosis
22-- Hepatic fibrosisHepatic fibrosis22-- Hepatic fibrosisHepatic fibrosis
33-- Regeneration nodulesRegeneration nodules
44-- Loss of architectureLoss of architecture
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Normal Liver
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Cirrhosis
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Normal Liver Histology
CV
PT
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Cirrhosis
Fibrosis
Regenerating Nodule
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Etiology
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Common causesCommon causes
•• Chronic viral hepatitis: C, B Chronic viral hepatitis: C, B ±± DD•• AlcoholAlcohol•• SchistosomiasisSchistosomiasis (fibrosis not true LC)(fibrosis not true LC)
Less Common causesLess Common causesLess Common causesLess Common causes
•• Biliary cirrhosis: Biliary cirrhosis: -- primary primary -- secondarysecondary•• Autoimmune hepatitis Autoimmune hepatitis •• Hereditary: Hereditary: -- HaemochromatosisHaemochromatosis -- Wilson's Wilson's
disease disease -- Alpha Alpha 1 1 antitrypsin deficiencyantitrypsin deficiency
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•• Drugs (e.g. methotrexate) Drugs (e.g. methotrexate) •• Cystic fibrosis Cystic fibrosis •• NonNon--alcoholic fatty liver disease alcoholic fatty liver disease
(NAFLD) (NAFLD) •• Glycogen storage diseaseGlycogen storage disease•• Glycogen storage diseaseGlycogen storage disease•• VenoVeno--occlusive disease occlusive disease •• Hepatic venous congestion Hepatic venous congestion •• BuddBudd--Chiari syndrome Chiari syndrome •• Idiopathic (cryptogenic)Idiopathic (cryptogenic)
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Pathogenesis
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•• Chronic injury to the liver results in Chronic injury to the liver results in inflammation, necrosis and, eventually, inflammation, necrosis and, eventually, fibrosis. fibrosis.
•• Fibrosis is initiated by activation of the Fibrosis is initiated by activation of the stellate cells.stellate cells.
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•• In the space of In the space of DisseDisse, the normal matrix is , the normal matrix is replaced by collagen. replaced by collagen. SubendothelialSubendothelial fibrosis fibrosis leads to loss of the endothelial fenestrations, leads to loss of the endothelial fenestrations, and this impairs liver function.and this impairs liver function.
•• There is accumulating evidence that liver There is accumulating evidence that liver fibrosis is reversible.fibrosis is reversible.
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•• Pathogenesis of fibrosis Pathogenesis of fibrosis
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Pathological Types
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Micronodular cirrhosisMicronodular cirrhosis:: Regenerating nodules Regenerating nodules
are usually less than are usually less than 3 3 mm in size. This type is mm in size. This type is often caused by alcoholic or biliary cirrhosis.often caused by alcoholic or biliary cirrhosis.
Macronodular cirrhosisMacronodular cirrhosis:: The nodules are of The nodules are of Macronodular cirrhosisMacronodular cirrhosis:: The nodules are of The nodules are of
variable size and normal acini may be seen within variable size and normal acini may be seen within the larger nodules. This type is often seen the larger nodules. This type is often seen following previous hepatitis.following previous hepatitis.
A mixed picture:A mixed picture: with small and large nodules is with small and large nodules is
sometimes seen.sometimes seen.
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Micronodular cirrhosis
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Micronodular cirrhosis:
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Macronodular Cirrhosis
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Symptoms and Signs
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AA-- General manifestationsGeneral manifestations
•• WastingWasting
•• Parotid enlargementParotid enlargement•• Parotid enlargementParotid enlargement
•• Hyperkinetic circulationHyperkinetic circulation
•• Increased susceptibility to infectionIncreased susceptibility to infection
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BB-- Skin Skin manifestationsmanifestations
•• Spider Spider angiomataangiomata
•• Palmar erythemaPalmar erythema
•• LeuconychiaLeuconychia•• LeuconychiaLeuconychia
•• DupuytrenDupuytren’’ss contracturescontractures
•• XanthomasXanthomas
•• Alternation of body hair distributionAlternation of body hair distribution
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CC-- Endocrinal Endocrinal manifestationsmanifestations
•• GynecomastiaGynecomastia
•• Testicular atrophyTesticular atrophy
•• Amenorrhea in femalesAmenorrhea in females•• Amenorrhea in femalesAmenorrhea in females
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GynecomastiaGynecomastia in cirrhosisin cirrhosis
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DD-- Abdominal Abdominal manifestationsmanifestations
•• Hepatomegaly then shrinkage laterHepatomegaly then shrinkage later
•• SplenomegalySplenomegaly
•• Prominent abdominal veinsProminent abdominal veins•• Prominent abdominal veinsProminent abdominal veins
•• Peptic ulcer diseasePeptic ulcer disease
•• Chronic pancreatitisChronic pancreatitis
•• SteatorrheaSteatorrhea
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PortosystemicPortosystemic anastomosis: anastomosis: Prominent abdominal veins.Prominent abdominal veins.
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EE-- DecompensationDecompensation
•• JaundiceJaundice
•• AscitisAscitis
•• Bleeding tendencyBleeding tendency•• Bleeding tendencyBleeding tendency
•• Hepatic encephalopathyHepatic encephalopathy
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Physical signs in liver cirrhosis.
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InvestigationsInvestigations
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Investigations for severityInvestigations for severity
Liver function. Liver function. Serum albumin and prothrombin Serum albumin and prothrombin time are the best indicators of liver function. time are the best indicators of liver function.
■■ Liver biochemistry. Liver biochemistry. In most cases there is a slight In most cases there is a slight ■■ Liver biochemistry. Liver biochemistry. In most cases there is a slight In most cases there is a slight elevation in the serum ALP and serum elevation in the serum ALP and serum aminotransferases.aminotransferases.
■■ Serum electrolytes. Serum electrolytes. A low sodium indicates severeA low sodium indicates severe
liver disease.liver disease.
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Investigations for the etiologyInvestigations for the etiology
•• Viral markers Viral markers
•• Serum autoantibodies Serum autoantibodies
•• Iron indices and ferritin Iron indices and ferritin
•••• Iron indices and ferritin Iron indices and ferritin
•• Copper, ceruloplasmin Copper, ceruloplasmin
•• AlphaAlpha1 1 antitrypsin antitrypsin
(Serum copper and alpha(Serum copper and alpha1 1 antitrypsin should always beantitrypsin should always be
measured in young cirrhotics)measured in young cirrhotics)
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OthersOthers
•• Ultrasound examination.Ultrasound examination.
•• CT scan.CT scan.
•••• MRI scan.MRI scan.
•• Endoscopy.Endoscopy.
•• Liver biopsy.Liver biopsy.
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Management
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►►Management is that of complications. Management is that of complications.
►►Patients should have Patients should have 66--monthly monthly ultrasound and serum AFP to detect the ultrasound and serum AFP to detect the development of a hepatocellular development of a hepatocellular carcinoma as early as possible.carcinoma as early as possible.carcinoma as early as possible.carcinoma as early as possible.
►►There is no treatment that will arrest or There is no treatment that will arrest or reverse the cirrhotic changes although reverse the cirrhotic changes although progression may be halted by correcting progression may be halted by correcting the underlying cause.the underlying cause.
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►►Patients with compensated cirrhosis Patients with compensated cirrhosis should lead a normal life. should lead a normal life.
►►The only dietary restriction is to reduce The only dietary restriction is to reduce salt intake. salt intake.
►►Aspirin and NSAIDs should be avoided.Aspirin and NSAIDs should be avoided.
►►Alcohol should be avoided.Alcohol should be avoided.
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LIVER TRANSPLANTATIONLIVER TRANSPLANTATION
►►This is an established treatment for aThis is an established treatment for anumber of liver diseases. number of liver diseases.
►►Shortage of donors is a major problem Shortage of donors is a major problem in all developed countries.in all developed countries.
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Course and PrognosisCourse and Prognosis
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Child's-Pugh classification
Score 1 2 3• Ascites None Mild Moderate/severe
• Encephalopathy None Mild Marked
• Bilirubin < 2 mg/dL 2-3 >3
• Albumin > 3.5 (g/dL) 3.5-2.8 < 2.8
• Prothrombin time < 4 seconds 4-6 > 6• Prothrombin time < 4 seconds 4-6 > 6
(Scores) 1-year survival 5 years 10 years
Child's A (< 7) 82 45 25
Child's B (7-9) 62 20 7
Child's C (10+) 42 20 0
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COMPLICATIONS AND EFFECTS OF CIRRHOSISOF CIRRHOSIS
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►►Portal hypertension and gastrointestinal Portal hypertension and gastrointestinal haemorrhagehaemorrhage
►►AscitesAscites
►►PortosystemicPortosystemic encephalopathyencephalopathy
►►Renal failure (Renal failure (hepatorenalhepatorenal syndrome)syndrome)►►Renal failure (Renal failure (hepatorenalhepatorenal syndrome)syndrome)
►►HepatopulmonaryHepatopulmonary syndromesyndrome
►►Hepatocellular carcinomaHepatocellular carcinoma
►►BacteraemiasBacteraemias, , infectionsinfections
►►MalnutritionMalnutrition
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Ascites in Cirrhosis
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Hepatocellular Carcinoma