cirrhosis of liver.2003 all

CIRRHOSIS OF LIVERCIRRHOSIS OF LIVER

Dr. Mizanur Rahman Chowdhury

EpidemiologyEpidemiology

40% cases asymptomatic

It is the 12th leading cause of death in

United States.

Approximately 30,000 to 50,000 deaths

per year

Additional 10,000 deaths due to liver

cancer secondary to cirrhosis

CirrhosisCirrhosis

Definition: It is the end stage of liver disease characterized by

Bridging fibrous septa in the form of delicate bands or broad scar linking portal tracts with one another and portal tracts with terminal hepatic vein

Parenchymal nodules containing hepatocytes encircled by fibrosis

Disruption of architecture entire of liver

Normal LiverNormal Liver

Normal Liver HistologyNormal Liver Histology

CV

PT

Histological classificationHistological classification

Micronodular Cirrhosis :Thick regular septa and regenerating small nodules varying little in size and involvement of every lobule, mainly seen in alcoholic cirrhosis.

Size of the nodule is less than 1cm

Histological classificationHistological classification

Micronodular Cirrhosis

Micronodular cirrhosis:Micronodular cirrhosis:

Histological classificationHistological classification

Macronodular Cirrhosis :Septa and nodules of variable size and normal lobules in larger nodules, mainly seen in post necrotic cirrhosis.

Size of the nodule is more than 1cm

Histological classificationHistological classification

Macronodular Cirrhosis

Histological classificationHistological classification

Macronodular Cirrhosis

Aetiological classification Aetiological classification

Viral: Chronic Hepatitis B, Hepatitis C infection.

Alcohol

Non alcoholic fatty liver

Metabolic disorder: Haemochromatosis, Wilson’s disease,Alpha-1 antripsin deficiency.

Autoimmune Hepatitis

Primary biliary cirrhosis

Aetiological classification Aetiological classification

Prolong cholestasis

Hepatic venous outflow obstruction: Constrictive pericarditis, Veno occlusive disease, Budd chairi syndrome.

Drugs: Methotraxate, Amioderone.

Cryptogenic: Unknown origin.

Etiology of CirrhosisEtiology of Cirrhosis

Alcoholic liver disease 60-70%

Viral hepatitis 10%

Biliary disease 5-10%

Primary hemochromatosis 5%

Cryptogenic cirrhosis 10-15%

Wilson’s, 1AT def rare

Pathogenesis of cirrhosisPathogenesis of cirrhosis

Hepatocellular death

Regeneration

Progressive fibrosis

Normal liver consists of I, III , IV Collagen in portal tracts and around central veins. A delicate reticulin network of IV collagen in the space of disse “( b/w sinusoidal endothelial cell and hepatocyte.) In cirrhosis there is deposition of type I, III and other components of ECM are deposited in all portion of lobule .

Pathogenesis of cirrhosisPathogenesis of cirrhosis

The induction of fibrosis occurs with activation of hepatic stellate cells, resulting in formation of increased amounts of collagen & other components of extracellular matrix.

Stimuli : o1.Chr.inflammation – cytokines like TNF, Lymphotoxin, IL-1

o 2.Cytokine production by injured Kupffer cells, endothelial cells, hepatocytes, bile duct epithelial cells

Pathogenesis of cirrhosisPathogenesis of cirrhosis

o 3.Disruption of ECM

o 4.Direct stimulation of stellate cells by toxins

On the other hand portal hypertension developed in following way

Pathogenesis of cirrhosisPathogenesis of cirrhosis

Necrosis of hepatic parenchyma due to some injury Collapse of hepatic lobule

Formation of diffuse fibrous septa

Nodular regrowth of liver cells

Altered hepatic vasculature

Portal blood flow is impaired

Development of portal hypertension

Cirrhosis of liver

CirrhosisCirrhosis

Fibrosis

Regenerating Nodule

Liver Biopsy – CirrhosisLiver Biopsy – Cirrhosis

Liver Biopsy – Cirrhosis:Liver Biopsy – Cirrhosis:

Alcoholic cirrhosisAlcoholic cirrhosis

Ethyal alcohol is a common cause of acute/chronic liver disease.

Paterns of alcoholic liver disease:1. Fatty change2. Acute Hepatitis3. Chronic hepatitis with fibrosis4. Cirrhosis, Chronic liver failure

All are reversible except cirrhosis stage

Pathogenesis of Alcoholic cirrhosisPathogenesis of Alcoholic cirrhosis

Acetaldehyde – metabolite – hepatotoxic

Diversion of metabolism – fat storage

Oxidation of ethanol NAD to NADH. NAD is required for the oxidation of fat..

Increased peripheral release of fatty acids

Inflammation, Portal bridging fibrosis

Stimulates collagen synthesis – fibrosis

Micronodular cirrhosis

Alcoholic Liver DamageAlcoholic Liver Damage

Alcoholic Fatty LiverAlcoholic Fatty Liver

Alcoholic Fatty LiverAlcoholic Fatty Liver

Alcoholic Fatty LiverAlcoholic Fatty Liver

Clinical Feature of cirrhosisClinical Feature of cirrhosis

Symptoms: Non specific symptoms: weakness, fatigue, anorexia JaundiceAbdominal distensionSwelling if legsLoss of libido in males and amenorrhoea

in females.Low grade feverLess commonly symptoms of complication

such as epistaxis, heamatemesis, melaena, menorrhagia.

Clinical Feature of cirrhosisClinical Feature of cirrhosis

Clinical Feature of cirrhosisClinical Feature of cirrhosis

Signs:

Jaundice

Fetor hepaticus

Pedal oedema

Generalized wasting

Hands: Leuconychia, clubbing, Jaundice, Flapping tremor, palmar erythema, dupuytren’s contructure

Clinical Feature of cirrhosisClinical Feature of cirrhosis

Parotid enlargement in alcoholic cirrhosis

Loss of secondary sexual hair, axillary and pubic

Gynaecomastia in males and breast atrophy in females.

Testicular atrophy in males.skin: spider naevi in the upper limbs and chest, generalized pigmentation, purpura, bruising

Clinical Feature of cirrhosisClinical Feature of cirrhosis

Abdomen :

Dilated abdominal vessels, caput medusa

Ascitis

Splenomegaly

Hepatomegaly

Haemorrhoid

Palmar erythemaPalmar erythema

Clinical Feature of cirrhosisClinical Feature of cirrhosis

Ascitis in CirrhosisAscitis in Cirrhosis

Porta-systemic anastomosis: Porta-systemic anastomosis: Prominent abdominal veins.Prominent abdominal veins.

Gynaecomastia in cirrhosisGynaecomastia in cirrhosis

Splenomegaly in cirrhosisSplenomegaly in cirrhosis

Submucosal veins in the esophagus become dilated. These Submucosal veins in the esophagus become dilated. These are known as esophageal varices. Varices are seen here in are known as esophageal varices. Varices are seen here in the lower esophagus as linear blue dilated veins. There is the lower esophagus as linear blue dilated veins. There is hemorrhage around one of them. Such varices are easily hemorrhage around one of them. Such varices are easily eroded, leading to massive gastrointestinal hemorrhageeroded, leading to massive gastrointestinal hemorrhage

Lab investigationsLab investigations

Liver function: serum albumin and prothrombin are the best indicator of liver functions. o Albumin is less than 28 g/loProthrombin time increase according to the

severity of the diseaseoSerum bilirubin is elevated

Liver biochemistry: this can be normal depending on the severity of the cirrhosisoALP is elevatedoALT is elevated

Lab investigationsLab investigations

Serum electrolytes: A low sodium indicate severe disease due to defect in the free water clearance or excess diuretic therapy.

Serum Creatinine: An elevation concentration of more than 130micromol/l indicate worse prognosis

In addition Alpha feto protein more than 200ng/ml strongly suggest that hepato cellular carcinoma

Lab investigationsLab investigations

Other test to identify the cause

Viral marker : HBsAg,Anti HCV

Alpha-1 antitripsin

Serum copper, Caeruloplasmin

Serum immunoglobulin

Auto antibody

Iron indices,ferritin

ImagingImaging

Ultrasonogram examinition:◦Liver may show coarse ecotexture◦Dilated portal veins◦Splenomegaly◦Ascitis

CT scan may show hepatosplenomegaly and dilated collaterals are seen in chronic liver disease

Upper GI endoscopy: Oesophageal varices may seen

LIVER BIOPSY IS CONFIRMATORY

Prognosis of CirrhosisPrognosis of Cirrhosis

Poor prognostic indicator of cirrhosis: Blood tests

low Serum albumin is( <28 g/l)Low Sodium is (<125mmol/l)Prolong prothrombin time(> 6sec)Serum Creatinine is (> 130micromol/l)

ClinicalPersistent jaundiceAscitisFailure of response to therapyHemorrhage from the varices,particolarly with

poor liver function

Prognosis of CirrhosisPrognosis of Cirrhosis

Neuropsychiatric complications developing with progressive liver failure

Persistent hypertension

Small liver

Aetiology eg.alcoholic cirrhosis if the patient continue to drink alcohol

Prognosis of CirrhosisPrognosis of Cirrhosis

Prognosis can be assessed by using CHILD-PUGH CLASSIFICATION

Prameter

Ascitis None Mild Moderate/ Severe

Enchaphalopathy

None Mild Marked

Bilirubin <2mg/dl 2-3mg/dl >3mg/dl

Albumin >3.5g/dl 2.8-3.5g/dl <2.8g/dl

Prothrombin time

<4 4-6 >6

Prognosis of CirrhosisPrognosis of Cirrhosis

Score5-6 grade A (well-compensated disease)

Score 7-9 grade B (Significant functional compromise)

Score 10-15 grade C (Decompensated disease)

Complication of cirrhosisComplication of cirrhosis

1. Ascitis2. Spontaneous bacterial

peritonitis3. Heamatemesis4. Enchaphalopathy5. Hepatocellular carcinoma6. Hepato renal syndrome 7. Increased susceptibility of

infection

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