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 cirrhosis
Drugs and toxins
infections autoimmune metabolic Biliary obstruction vascular miscellaneous unknown

Alcohol, methotrexate, isoniazid, methyldopa

Hepatitis B and C , Schistosoma japonicum PBC, autoimmune hepatitis, PSC Wilsons disease, haemochromatosis, alpha 1 antitrypsin, porphyria Cystic fibrosis, atresia, strictures, gall stones Chronic right heart failure,Budd Chiari syndrome Sarcoidosis, intestinal by- pass surgery for obesity 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 PBC Autoimmune hepatitis Alpha 1 antitrypsin deficiency Wilsons disease Hepatitis B and C serology AMA, serum IgM level Anti LKM antibody, anti smooth muscle antibody, IgG Alpha 1 antitrypsin level, phenotype testing

Reduced serum Cu and Caeruloplasmin; increased 24 hr Cu excretion

haemochromatos s. ferritin, HFE is

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

UGI bleeding

UGIE available?

yes: UGIE

not available terlipressin, octreotide

oeso varices

gastric varices

band ligation/ sclerotherapy

gastro- oesophgeal

isolated gastric varices portal hypertensive gastropathy

uncontrolled

controlled

blood, vaso and thenTIPPS

baloon tamponade

eradication programme

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

daignosis of cirrhosis

UGIE

no varices

grade 1 varices

grade ii, iii varices

reUGIE in 3-4 yrs

UGIE in 1 yr

propranolol 80-160mg/day

band ligation if intolerant