肝 硬 化 肝 硬 化 Liver CirrhosiLiver Cirrhosi

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肝 硬 化 肝 硬 化 Liver CirrhosiLiver Cirrhosi

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Rukun He MD 2008-04-21

Cirrhosis

is the end result of a variety of disease causing chronic liver injury. It is an irreversible disturbance of entire hepatic architecture by three characteristics :

1, Bridging fibrous septa

2, Parenchymal nodules ( micronodules or macronodules )

3, Disturbance of liver circulation.

New Unit (pseudo-lobules)

Classification

• Portal ( B or C-hepatitis or Alcoholic )

• Post-necrotic( Viruses or chemical )

• Biliary ( primary or secondary )

• Others

Etiology

Multiples factors

1 、 viral hepatitis

2 、 alcoholism 3 、 toxication carbon tetrachloride

4 、 malnutrition deficiency of choline

Hepatitis Virus and liver cirrhosis

In china, up to 70% of liver cirrhosis is correlated with B or C- Hepatitis

Alcoholism and liver cirrhosisIn western countries, around 70% of liver cirrhosis correlated with alcoholic consumption

mechanismsmechanisms

Recurrent liver injury and repair Recurrent liver injury and repair lead to the reconstruction of lobules.lead to the reconstruction of lobules.

Hepatocellular deathHepatocellular death

Hepatocellular nodulHepatocellular nodular regenerationar regeneration

Progressive fibrosisProgressive fibrosis

Severe architectural Severe architectural disturbance, a new undisturbance, a new un

it ( pseudo-lobules ) it ( pseudo-lobules ) tto be formedo be formed

Cytokine :

TNFα ；

IL-1 、 IL-6 ；

TGFβ ；

Disruption of the extracellular matrix

Toxin stimulate

The fatty storage cells may converte to myofibroblast-like cells and Fibrosis results.

Fibrosis of space of Disse

Reconstruction of liver lobules may cause

1, disturbance of intra-liver circulation

2, hepatic artery-to-portal vein vascular shunts develop

3, fibrocytes proliferation

4, pseudo-lobules.

Portal cirrhosis

During the early stages, the liver may be larger and fatty grossly.

With advancing disease the liver tends to decrease gradually in size and progressively to become nodularity, which is the most characteristic feature, on the surface or in the section.

The liver may be small , hard and the liver weight may be decrease under 1,000g.

nodularity is the most characteristic feature

Nodules ( portal cirrhosis),

the diameter is 5mm or so, the largest one is less than 1 cm

Intervening connective tissue is thin and consistent

Post-necrotic liver cirrhosis

1, severe hepatitis cause massive or sub-

massive liver necrosis;

2, toxication : ( carbon tetrachloride )

The liver is asymmetrically small, sometimes it may be conspicuously deformed especial in the left lobe. The size of nodules is variable and it may reach to 3 cm, even 5 cm.

Nodules are circumscribed by fibrotic tissue and composed of liver cells organized in irregular plates, sometimes with atypic nuclei .

The vasculature of the liver is greatly distorted

Biliary cirrhosisSecondary biliary cirrhosis follows prolonged extrahepatic or intrahepatic obstruction of the biliary tract. The bile stasis is striking.

The liver is usually enlarged and green.

In the early stages the capsular is smooth, later a fine granules are present on the surface or in the section.

Bile ducts proliferate, connective tissue is abundant around the bile ducts. Swollen and necrosis of hepatocytes and intralobular bile stasis present . Bile lake may be formed

Clinic features of cirrhosis

• Portal hypertension

• Liver failure

• Liver cell carcinoma.

Portal hypertensionis elevation of portal venous pressure above the upper limit of normal of 12 mmHg.

The causes of portal hypertension are :

• obstruction to the outflow of blood from the portal system

• transmission of arterial pressure to the portal circulation through arteriovenous fistulas

• reduced the blood vessels in the liver

Hepatic artery Portal vein

Splenomegaly is caused by passive venous congestion

Ascites1, increase transudation of fluid across the peritoneal membrane, particularly over the surface of liver;

2, decrease in serum albumin level

Development of portosystemic venous anastomoses, bypassing the obstructed portal circulation

Anastomoses between lower esophagus & stomach veins

hemorrhoid

Caput medusae

Chronic Liver Failure

Decreased synthesis of albumin

Decreased level of coagulation factors,resulting in a bleeding tendence

Hepatic encephalopathy1,ammonia,2,amides like octopamine which acts as false neurotransmiters

Spider nevus gynecomastia

Spider nevi

Gynecomastia & atrophy of testis

hyperestrogenism

jaundice

Type

Pathogenesis

Nodules

Septal

Clinic features

Incidence of HCC

Time-table

Portal cirrhosis

Severe chronic hepatitis or alcoholism

Micronodules

Small and consistence

Portal hypertension

Low

Longer, 10 years more

Post-necrotic cirrh

Massive necrosis by virus or chemical

Macro or mix nodul

Big & variable

Liver failure

High

Shorter

Primary malignant tumor of the liverPrimary malignant tumor of the liverPrimary malignant tumor of the liverPrimary malignant tumor of the liver

Primary malignant tumors of the liver include :• Liver cell carcinoma ( hepatocellular carcinoma )• Cholangiocarcinoma ( adenocarcinoma of bile ducts

)• Angiosarcoma ( malignant tumor of vascular endoth.

)• Hepatoblastoma ( primary liver tumor in childhood )

Primary liver carcinoma Primary liver carcinoma Primary liver carcinoma Primary liver carcinoma

Hepatocellular carcinoma derive from hepatocytes

Early stage : The diameter of nodule is less than 3 cm

and total number of nodules is no more

than 2.

The patients are without any symptoms but the Alpha Fetal Protein ( AFP ) in the serum is positive.

Advanced HCC :

There are three macroscopic appearance :

Solitary massive type ( unifocal )

Multiple nodules type ( multifocal )

Diffuse infiltrative type.

Most of them complicate with liver cirrhosis.

Histology :

Hepatocellular carcinoma

Cholangiocarcinoma

Mixed

Trabecular variant

Bile thrombus

cholangiocarcinoma

1, Intra-liver metastasis

Satellite Nodules

2, Outside of liver metastasis

Lymphatic spread to the hepatic hilus LN

Hematogenous spread to every where

such as lungs,brain & bone etc.

Seeding of carcinoma to the surface of

organs in peritoneal cavity

Clinical manifestations

Hepatomegaly and pain

Liver dysfunction : jaundice, ascites, spider nevus,

hemorrhage & hepatic encephalopathy,

increased ALT and AST in the serum

AFP increase in the serum

Cachexia

Viral Hepatitis, B/C Type

Aflatoxin B1

DENA ( diethonitrosamine )

Clonorchis ( fluke )

Etiological factorsEtiological factors

How to understand the relationship among viral hepatitis, liver cirrhosis and hepatocellular carcinoma ?