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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antibiotics

• Infections seem to predispose bleeds• Antibiotics seem to improve survival• Norfloxacin 400mg bd or ciprfloxacin

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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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