Definition - Chronic liver disease is defined as liver injury occurring over more than 6 months duration
  • Consequences
  • Cirrhosis
  • Malignancy 

Cirrhosis of Liver
  • Cirrhosis results from the necrosis of liver cells followed by fibrosis and nodule formation.
  • This derangement produces the clinical features of portal hypertension and impaired liver cell function.

  • Alcohol consumption is the most common cause in western world while chronic viral hepatitis (Hep B and C) is the most common cause world-wide.
  • Other causes 
  • Non-alcoholic fatty liver disease
  • Immune 
  • Primary sclerosing cholangitis 
  • Autoimmune liver disease 
  • Biliary 
  • Primary biliary cirrhosis 
  • Cystic fibrosis 
  • Genetic 
  • Haemochromatosis 
  • α1-antitrypsin deficiency 
  • Wilson's disease 
  • Cryptogenic 

Infectious Diseases
Brucellosis , Echinococcosis , Schistosomiasis, Toxoplasmosis , Viral hepatitis [hepatitis B, C, D), cytomegalovirus; Epstein-Barr virus 

Inherited and Metabolic Disorders 
1-Antitrypsin deficiency, Biliary atresia, Familial intrahepatic cholestasis, Fanconi’s syndrome, Galactosemia, Gaucher’s disease, Glycogen storage disease, Hemochromatosis, Hereditary fructose intolerance, Hereditary tyrosinemia, Wilson’s disease

Drugs and Toxins
Alcohol, Amioradone, Arsenicals, Oral contraceptives, antineoplastic agents

Other Causes
Biliary obstruction (chronic), Cystic fibrosis, Graft-versus-host disease, Jejunoileal bypass, Nonalcoholic fatty liver disease, Primary biliary cirrhosis, Primary sclerosing cholangitis, Sarcoidosis 

Pathophysiology continued 
  • All causes of cirrhosis have activation of hepatic stellate cells and when activated, the quiescent fat-storing stellate cells become multifunctional cells, capable of collagen production, contraction and cytokine synthesis on interaction with other cells in the liver like damaged hepatocytes, kupffer cells, platelets and lymphocytes.
  • Destruction and distortion of liver architecture by fibrosis and nodule formation rather than lobule causes portal hypertension and portosystemic shunting.
  • Histologically classified as
  • Micronodular cirrhosis is characterised by small nodules about 1 mm in diameter and is seen in alcoholic cirrhosis
  • Macronodular cirrhosis is characterised by larger nodules of various sizes

    Clinical features 
    • Hepatomegaly (in early stages of cirrhosis) 
    • Jaundice 
    • Ascites 
    • Circulatory changes 
    • Spider telangiectasia, palmar erythema, cyanosis 
    • Endocrine changes 
    • Loss of libido, hair loss 
    • Men: gynaecomastia, testicular atrophy, impotence 
    • Women: breast atrophy, irregular menses, amenorrhoea 
    • Haemorrhagic tendency 
    • Bruises, purpura, epistaxis, menorrhagia 
    • Portal hypertension 
    • Splenomegaly, collateral vessels, variceal bleeding, fetor hepaticus 
    • Hepatic (portosystemic) encephalopathy 
    • Other features 
    • Pigmentation, digital clubbing , parotomegaly, dupuytren’s contracture
    • Cirrhosis may be entirely asymptomatic found incidentally at surgery or may be associated with minimal features such as isolated hepatomegaly.
    •  Frequent complaints include weakness, fatigue, muscle cramps, weight loss and non-specific digestive symptoms such as anorexia, nausea, vomiting and upper abdominal discomfort.

    • Ascites
    • Spontaneous bacterial peritonitis -  The diagnosis is established by a positive ascitic fluid bacterial culture and/or an elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count (≥250 cells/mm3).
    • Hepatorenal syndrome: The hepatorenal syndrome is characterized by a generally benign urine sediment, a very low rate of sodium excretion, and a progressive rise in the plasma creatinine concentration.
    • Variceal hemorrhage
    • Hepatopulmonary syndrome:  The hepatopulmonary syndrome (HPS) is considered to be present in patients with the following triad:
    • Liver disease
    • Increased alveolar-arterial gradient while breathing room air
    • Evidence for intrapulmonary vascular abnormalities, referred to as intrapulmonary vascular dilatations (IPVDs)
    • Other pulmonary syndromes
    • Hepatic hydrothorax
    • Portal hypertension associated pulmonary hypertension (portopulmonary hypertension)

    Complications continued…….
    • Cardiomyopathy
    • Hepatic encephalopathy
    • Hepatocellular carcinoma

    • Liver function tests
    • USG
    • Liver biopsy
    • Cause specific tests
    • Hepatitis B : HBsAg and HBeAg and/or HBV DNA
    • Hepatitis C:  Anti-HCV and HCV RNA
    • Hepatitis D (delta): HBsAg and anti-HDV
    • Primary biliary cirrhosis: Mitochondrial antibody, elevated IgM levels, and compatible histology
    • Primary sclerosing cholangitis: P-ANCA, cholangiography
    • Alcoholic liver disease: History of excessive alcohol intake and compatible histology
    • Antitrypsin disease : Reduced 1 antitrypsin levels
    • Wilson’s disease: Decreased serum ceruloplasmin and increased urinary copper; increased hepatic copper level
    • Hemochromatosis: Elevated iron saturation and serum ferritin; genetic testing for HFE gene mutations

    • Includes treatment of the known cause, maintenance of nutrition, and management of complications
    • Alcohol should be absolutely forbidden
    • Management of complications like
    • Variceal bleeding
    • Ascites
    • Hepatic encephalopathy (lactulose)
    • Liver transplantation : usually performed in patients with cholestasis type of cirrhosis like PBC, alcoholic cirrhosis, hep. C and rarely in metabolic conditions like alpha1 anti-trypsin deficiency, hemochromatosis

    Liver transplant contd………

    Child Pugh score of 7 or more
    MELD score is preferred these days. Its cut off value is variable but 10 is considered by many.
    Cardiopulmonary disease that cannot be corrected and is a prohibitive risk for surgery.
    Malignancy outside of the liver within five years of evaluation (not including superficial skin cancers) or not meeting oncologic criteria for cure.
    Active alcohol and drug use. Most programs require a minimum period of abstinence of at least six months with participation in a structured rehabilitation and abstinence program and adequate social support to help maintain sobriety.
    AIDS and sepsis


    Highly variable and depends on severity of liver damage
    Criteria used are Child-Pugh criteria and MELD (Model for end stage liver disease) scoring system

    MELD = 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4