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Liver cirrhosis
Indika Bandara Gawarammana
• 6000 deaths a year in UK• Liver fibrosis is the final pathological
pathway in many CLD• Cirrhosis is the irreversible state of liver
fibrosis
Definition
• Histologically: diffuse process characterized by by fibrosis and a conversion of normal architecture into structurally abnormal nodules
• Histological classification micro, macro and mixed
• Aetiological classification
Pathogenesis
• Regardless of the aetiology, the cellular mechanisms are common
• Site of origin of may be different: viral hepatitis- periportal, alcohol- pericentral
Hepatic stellate cell ( HSC)
• Major cell in matrix synthesis and metabolism
• Plays the pivotal role in cirrhosis• In the normal liver HSC is situated in the
subendothelial space of Disse and are involved in retinoid storage
• After injury HSC proliferates, loose the retinoid droplets and are activated to a myelofibroblast like cell: “ activated HSC”
• Activated HSC acts as the major source of collagen, and non collagenous matrix proteins
• HSC also secrete matrixmetalloproteinases• Kupffer cells too have a role HSC activation
Contd.
• Parenchymal cell necrosis also aid activation
• Possibly via release of lipid peroxidases and insulin like growth factors
Once activated
• HSC expresses numerous cytokines and their receptors: TGF and PDGF
• They sustain activation, proliferation and fibrogenesis
• Activated HSC lays down the matrix, initially in the spaces of Disse
• Fibrous septae form which distort the liver parenchyma
• The vascular structures get linked and the architecture is distorted
• With advanced fibrosis parenchymal dysfunction and portal HT develops
Aetiology of cirrhosisDrugs and toxins Alcohol, methotrexate, isoniazid, methyldopa
infections Hepatitis B and C , Schistosoma japonicum
autoimmune PBC, autoimmune hepatitis, PSC
metabolic Wilson’s disease, haemochromatosis, alpha 1 antitrypsin, porphyria
Biliary obstruction Cystic fibrosis, atresia, strictures, gall stones
vascular Chronic right heart failure,Budd Chiari syndrome
miscellaneous Sarcoidosis, intestinal by- pass surgery for obesity
unknown cryptogenic
• Insight of this process offers hope of treatment: blocking the fibrogenic cxascade
Clinical presentation
• Non specific symptoms: lethargy, malaise, abd pain
• Specific: pruritus, jaunndice, ascites ect.• Signs of CLD• Most present when they develop
complications
investigations
• Routine• Ast/alt, albumin , PT
Aetiological diagnosis
Viral hepatitis Hepatitis B and C serology
PBC AMA, serum IgM level
Autoimmune hepatitis
Anti LKM antibody, anti smooth muscle antibody, IgG
Alpha 1 antitrypsin deficiency
Alpha 1 antitrypsin level, phenotype testing
Wilson’s disease Reduced serum Cu and Caeruloplasmin; increased 24 hr Cu excretion
haemochromatosis
s. ferritin, HFE
Hepatocellular carcinoma
Alpha feto protein level
diagnosis
• Ultimately a histological diagnosis• Ultrasound cheap, accurate, non invasive• CT complements US/S, in
Haemochromatosis there is a dramatic increase in hepatic density
• Liver biopsy : cornerstone
treatment
• Stop alcohol• Treat specific aetiology when possible• Treat complications
Complications of cirrhosis:oesophageal varices
• Due to rise in portal pressure portosystemic anastomoses form: most important is in the lower oesophagus
• 25- 40% develop a bleed, first bleed carries a mortality rate of 5-50%!
Management of variceal haemorrhage
• Initial resusitation• 2 large peripheral canulae• Cross match 6 units of blood• Correct PT and platelet count• Consider central venous access• Air way intubation sos
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oeso varices
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antibiotics
• Infections seem to predispose bleeds• Antibiotics seem to improve survival• Norfloxacin 400mg bd or ciprfloxacin
500mg bd for 7days is recommended
Prevention of rebleed
• Majority will rebleed with in 6 months• Band ligation to eradicate varices• Beta blockers• TIPPS• Liver transplantation
Primary prophylaxis against variceal bleeding
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d a ig n os iso f c irrh os is