1. PARENCHYMAL LIVER DISEASE Parenchymal liver disease may be classified as acute ( 6month) or on a histological basis. Parenchymal liver disease may be classified as acute ( 6month) or on a histological basis. Broadly however parenchymal liver disease can be classified into fatty liver, hepatitis, and cirrhosis. Broadly however parenchymal liver disease can be classified into fatty liver, hepatitis, and cirrhosis. Chronic Hepatitis Symptomatic, biochemical or aetiological evidence of continuing or relapsing hepatic disease for more than 6 months without steady improvement is called chronic hepatitis. Symptomatic, biochemical or aetiological evidence of continuing or relapsing hepatic disease for more than 6 months without steady improvement is called chronic hepatitis.

2. CIRRHOSIS OF LIVER Definition:- Cirrhosis is defined as diffused process characterized by fibrosis and conversion of normal liver architecture into structurally abnormal nodule. Cirrhosis is defined as diffused process characterized by fibrosis and conversion of normal liver architecture into structurally abnormal nodule. Cirrhosis is gradually progressive widespread death of liver cells assocoiated with inflammation and fibrosis leading to loss of normal lobular liver architecture. Cirrhosis is gradually progressive widespread death of liver cells assocoiated with inflammation and fibrosis leading to loss of normal lobular liver architecture.

3. Anatomical(Histological)Classification 1.Micronodular cirrhosis:- < 3mm in size. (Alcoholic) < 3mm in size. (Alcoholic) Characterized by regular connective tissue septa, regenerative nodules, and involvement of every lobule. Characterized by regular connective tissue septa, regenerative nodules, and involvement of every lobule. 2.Macronodular cirrhosis:- >3mm in size ( Viral Hepatitis) >3mm in size ( Viral Hepatitis) Connective tissue vary in thickness and nodules Connective tissue vary in thickness and nodules Show marked difference in size. Show marked difference in size.

4. 3.Intermediate mixed forms. (Alcoholic cirrhosis with time) (Alcoholic cirrhosis with time) Cirrhosis is defined by its pathological features on microscopy: (1) the presence of regenerating nodules of hepatocytes and (2) the presence of fibrosis, or the deposition of connective tissue between these nodules. Necrosis of hepatocytes Necrosis of hepatocytes Irreversible Irreversible Progressive disorder Progressive disorder Entire Liver is involved Entire Liver is involved

5. CAUSESCommon Alcohol Alcohol Hepatitis B +/- D Hepatitis B +/- D Hepatitis C Hepatitis COthers Biliary Obstruction Primary Biliary cirrhosis Primary Biliary cirrhosis Secondary Biliary cirrhoses (stones, stricture) Secondary Biliary cirrhoses (stones, stricture)

6. Metabolic Haemochromatosis Haemochromatosis Wilson’s disease Wilson’s disease a1-antitrysin deficiency a1-antitrysin deficiency Cystic fibrosis Cystic fibrosis Hepatic congestion Cardiac failure Cardiac failure Budd-chiari syndrome Budd-chiari syndromeIdiopathic

7. Alcoholic Liver Disease ALD comprises of 3 distinct forms of Liver diseases Hepatic steatosis/ fatty Liver Hepatic steatosis/ fatty Liver Alcoholic hepatitis Alcoholic hepatitis Cirrhosis Cirrhosis Dr S Chakradhar 7

8. Haemochromatosis Is defined as the excessive accumulation of body iron, most of which deposited in the parenchymal cell of various organ particularly liver & pancreas Is defined as the excessive accumulation of body iron, most of which deposited in the parenchymal cell of various organ particularly liver & pancreasTypes Hereditary/primary/idiopathic Hereditary/primary/idiopathic Secondary – occuring as a secondary complications to a variety of diseases Secondary – occuring as a secondary complications to a variety of diseases Dr S Chakradhar 8

9. Wilson’s Disease Is an autosomal recessive disorder of copper metabolism & is marked by accumulation of toxic levels of copper in many tissues in many tissues & organs principally the liver, brain & eye Is an autosomal recessive disorder of copper metabolism & is marked by accumulation of toxic levels of copper in many tissues in many tissues & organs principally the liver, brain & eye Dr S Chakradhar 9

10. Biliary cirrhosis Primary intrahepatic biliary cirrhosis An autoimmune disease marked by the slow progressive destruction of the small intrahepatic bile ducts. An autoimmune disease marked by the slow progressive destruction of the small intrahepatic bile ducts. Bile builds up in the liver and over time damages the tissue. Bile builds up in the liver and over time damages the tissue. This can lead to scarring, fibrosis and cirrhosis This can lead to scarring, fibrosis and cirrhosis Secondary biliary cirrhosis Results from obstruction to the major extra hepatic duct Results from obstruction to the major extra hepatic duct Dr S Chakradhar 10

11. Alpha1 antitrypsin deficiency Is an autosomal recessicve disorder marked by abnormally low levels of of α 1-antitrypsin in serum Predominantly synthesized in Hepatocytes & to less extent in macrophage Dr S Chakradhar 11

12. PATHOGENESIS Following liver injury cytokines produced by kupffer cells and hepatocytes activate the stellate cells. Following liver injury cytokines produced by kupffer cells and hepatocytes activate the stellate cells. Following activation the stellate cells becomes transformed into multifunctional cells, capable of collagen production, contraction and cytokine synthesis. Following activation the stellate cells becomes transformed into multifunctional cells, capable of collagen production, contraction and cytokine synthesis.

14. The net outcome is A fibrotic, nodular liver in which delivery of blood to hepatocytes is severely compromised, as is the ability of hepatocytes to secrete substances into plasma. A fibrotic, nodular liver in which delivery of blood to hepatocytes is severely compromised, as is the ability of hepatocytes to secrete substances into plasma. Disruption of the interface between the parenchyma and portal tracts obliterates biliary channels as well. Disruption of the interface between the parenchyma and portal tracts obliterates biliary channels as well. Thus, the cirrhotic patient may develop jaundice and even hepatic failure, despite having a liver of normal mass. Dr S Chakradhar 14

15. CLINICAL FEATURES Frequent complains include:- weakness, fatigue, muscle cramps, weight loss, weakness, fatigue, muscle cramps, weight loss, And non specific digestive symptoms - anorexia, vomiting, upper abdominal discomfort. And non specific digestive symptoms - anorexia, vomiting, upper abdominal discomfort. Hepatomegaly (decrease as the disease progress) – Non tender, hard, irregular Hepatomegaly (decrease as the disease progress) – Non tender, hard, irregular Jaundice Jaundice Ascites Ascites

16. Circulatory changes spider telangiectasia, palmar erythema, cyanosis, spider telangiectasia, palmar erythema, cyanosis, Endocrine changes Loss of libido, hair loss Loss of libido, hair loss Men: gynaecomastia, testicular atrophy, impotence Men: gynaecomastia, testicular atrophy, impotenceWomen: Breast atrophy, Breast atrophy, irregular menses, irregular menses, amenorrhoea amenorrhoea

17. Haemorrhagic tendency Bruises, purpura, epistaxis, menorrhagia Bruises, purpura, epistaxis, menorrhagia Portal hypertension Splenomegaly, collateral vessels, variceal bleeding, Splenomegaly, collateral vessels, variceal bleeding, Fetor hepaticus Fetor hepaticus Hepatic encephalopathy Hepatic encephalopathy Other features Pigmentation, digital clubbing, low-grade fever Pigmentation, digital clubbing, low-grade fever

18. COMPLICATION Hepatic encephalopathy Hepatic encephalopathy Portal hypertension Portal hypertension Ascites Ascites Renal failure Renal failure Hepatocellular carcinoma Hepatocellular carcinoma

19. Investigations TC, DC, ESR, Hb TC, DC, ESR, Hb Liver function test (LFT) Liver function test (LFT) Serum bilirubin - increased Serum bilirubin - increased Plasma Aminotransferase (ALT, AST) – low in established case Plasma Aminotransferase (ALT, AST) – low in established case Prothrombin time - prolonged Prothrombin time - prolonged Plasma alkaline phosphatase – increased in biliary cirrhosis Plasma alkaline phosphatase – increased in biliary cirrhosis Plasma albumin – Decreased Plasma albumin – Decreased Liver Biopsy – Diagnostic Liver Biopsy – Diagnostic USG of hepatobilliary system / CT USG of hepatobilliary system / CT Viral markers – Hbs Ag, antibody against HCV Viral markers – Hbs Ag, antibody against HCV

20. MANAGEMENT Main objective of treatment Treatment of any known (treatable) cause Treatment of any known (treatable) cause Prevention & correction of malnutrition Prevention & correction of malnutrition Management of chronic cholestasis Management of chronic cholestasis Treatment of complications Treatment of complications

21. No treatment can reverse cirrhosis or even ensure that no further progression occurs. Rx is symptomatic and supportive. Withdrawal or treatment of aetiological factors e.g. Alcohol consumption, drugs, Haemochromatosis. Withdrawal or treatment of aetiological factors e.g. Alcohol consumption, drugs, Haemochromatosis. No strenuous activity to reduce metabolism No strenuous activity to reduce metabolism Nutrition Nutrition High energy protein (in absence of encephalopathy) & CHO rich diet High energy protein (in absence of encephalopathy) & CHO rich diet Fat restriction (if Cholestasis) Fat restriction (if Cholestasis) Alcohol must be forbidden Alcohol must be forbidden Vitamin B-complex. Vitamin B-complex. Treatment of complications Treatment of complications Ascites – low salt diet, Diuretics Ascites – low salt diet, Diuretics Liver Transplant Liver Transplant 6 monthly USG and AFP to detect the development of hepatocellular carcinoma 6 monthly USG and AFP to detect the development of hepatocellular carcinoma

23. Patterns of Hepatic Injury Normal LiverApoptotic Body What is the name for it? Inflammation (Hepatitis) Fibrosis (Cirrhosis)

24. Portal HTN Cirrhosis Esophageal Varices Caput Medusa Splenomegaly