2. 肝 硬 化 Liver Cirrhosis Rukun He MD 2008-04-21

3. 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)

4. Classification Portal ( B or C-hepatitis or Alcoholic ) Post-necrotic ( Viruses or chemical ) Biliary ( primary or secondary ) Others

5. Etiology Multiples factors 1 、 viral hepatitis 2 、 alcoholism 3 、 toxication carbon tetrachloride 4 、 malnutrition deficiency of choline

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

7. Alcoholism and liver cirrhosis In western countries, around 70% of liver cirrhosis correlated with alcoholic consumption

8. mechanisms Recurrent liver injury and repair lead to the reconstruction of lobules. Hepatocellular death Hepatocellular nodular regeneration Progressive fibrosis Severe architectural disturbance, a new unit ( pseudo-lobules ) to be formed

9. 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.

10. Fibrosis of space of Disse

20. 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.

21. 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.

22. nodularity is the most characteristic feature

23. Nodules ( portal cirrhosis), the diameter is 5mm or so, the largest one is less than 1 cm Intervening connective tissue is thin and consistent

24. Post-necrotic liver cirrhosis 1, severe hepatitis cause massive or sub- massive liver necrosis; 2, toxication : ( carbon tetrachloride )

25. 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.

26. 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

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

28. 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.

29. 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

30. Clinic features of cirrhosis Portal hypertension Liver failure Liver cell carcinoma.

31. Portal hypertension is 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

32. Hepatic arteryPortal vein

33. Splenomegaly is caused by passive venous congestion Ascites 1, increase transudation of fluid across the peritoneal membrane, particularly over the surface of liver; 2, decrease in serum albumin level

34. Development of portosystemic venous anastomoses, bypassing the obstructed portal circulation Anastomoses between lower esophagus & stomach veins hemorrhoid

35. Caput medusae

36. Chronic Liver Failure Decreased synthesis of albumin Decreased level of coagulation factors,resulting in a bleeding tendence Hepatic encephalopathy 1,ammonia, 2,amides like octopamine which acts as false neurotransmiters

37. Spider nevus gynecomastia Spider nevi Gynecomastia & atrophy of testis hyperestrogenism jaundice

38. 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

39. Primary 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 )

40. 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.

41. 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.

44. Histology : Hepatocellular carcinoma Cholangiocarcinoma Mixed

45. Trabecular variant

46. Bile thrombus

47. cholangiocarcinoma

48. 1, Intra-liver metastasis

49. Satellite Nodules

50. 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

51. 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

52. Viral Hepatitis, B/C Type Aflatoxin B 1 DENA ( diethonitrosamine ) Clonorchis ( fluke ) Etiological factors

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