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Pathology Lecture 7 – Liver pathology CCL07 – Conditions of the liver 1. Alcoholic liver disease Pathological changes to the liver occur progressively through the spectrum of ALD Alcoholic fatty liver disease  Soft, pale yellow liver  ‘Spongy’ appearance due to fat-filled vacuoles  Hepatomegaly Alcoholic steatohepatitis  Hepatocyte necrosis with focal reticulin collapse  Mallory’s hyaline bodies (intracellular eosinophilic i.e. red aggregates of cytokeratines)  Focal neutrophil infiltrate

Alcoholic fibrosis  ‘Chicken-wire’ fibrosis (network of intra-lobular connective tissue surrounding cells & venules)  Result of cytokines/chemokines from Kuppfer cells stimulating collagen production via hepatic stellate cells Alcoholic cirrhosis  Attempted hepatocyte regeneration  Formation of non-functioning regenerative micronodules  Interrupted bile flow  Deranged blood flow with abnormal anastomoses  Portal hypertension

Causes of hepatic decompensation – mnemonic: HEPATICUS Haemorrhage/hypoglycaemia/HCC Electrolyte imbalance Protein load/Paracetamol OD Alcohol Trauma Infection/ischaemia (portal vein thrombosis; Budd-Chiari syndrome) Constipation Uraemia Sedatives/shunts/surgery

Complications of decompensation  Hepatic encephalopathy o Drowsy  coma o Confusion o Constructional apraxia  Portal hypertension o Ascites o Bleeding (haemorrhage, haemorrhoids) o Caput medusae o Diminished liver o Enlarged spleen  Hyperoestrogenaemia

Portal hypertension complications 1. Enlargement of collateral veins - Gastro-oesophageal junction with varices & haematemesis - Periumbilical region with prominent subcutaneous veins (caput medusa) - Splanchnic vascular congestion with ascites 2. Splenomegaly +/- hypersplenism o Hypersplenism = ↑rate of RBC, leukocyte +/- platelet destruction

3. Non-alcoholic fatty liver disease (NAFLD) Primary NAFLD Identical histological findings to ALD (inc Mallory hyaline bodies), but not associated with alcohol use.  More associated with micro-vesicular steatosis & nuclear vacuolisation  Considered part of metabolic (insulin resistance) syndrome Metabolic syndrome diagnostic criteria -

Central obesity Impaired glucose tolerance (T2DM) Dyslipidaemia Hypertension Metabolic syndrome  NAFLD  NASH  ‘Cryptogenic’ cirrhosis (with no steatosis)

Secondary NAFLD - Drugs e.g. amiodarone, steroids, tamoxifen - Surgical procedures e.g. extensive bowel resection, gastroplasty - TPN

4. Acute hepatitis Acute-onset inflammation of hepatocytes with associated necrosis. Causes 1. Infectious agents e.g. HAV, HBV, HCV, delta HV 2. Autoimmune hepatitis due to T-cell mediated autoimmunity 3. Drug-induced due to direct drug-toxicity, immune-mediated injury 4. Idiopathic

Clinical sequence i. Pre-icteric phase - Fever, nausea, vomiting, epigastric pain, myalgia, hepatic tenderness ii.

Icteric phase a. Jaundice, ‘dark urine + pale stools’, peripheral blood lymphocytosis

Outcomes  Complete recovery  Chronic hepatitis  Cirrhosis  Massive liver necrosis +/- HCC Hep A 

Acute, benign & self-limiting

Hep B     

Can lead to rapid death due to fulminant/massive liver cell necrosis Generally chronic, associated with cirrhosis, HCC Endemic in SE Asia Presence of lymphocytes “Ground glass-like” cytoplasm

Hep C   

Less likely to cause death short-term; more associated with chronic deaths High incidence of progression to chronic hepatitis (80%) Associated with carrier status & drug abuse

Hep D  

Incomplete virus  requires Hep B surface antigens for proliferation Always occurs in tandem with Hep B

Autoimmune hepatitis   



Most common demographic  young women Classified under type I, IIa, IIB and III according to presence/absence of specific autoantibodies Large numbers of lymphocytes present  T-cell mediated autoimmune reaction o Focal lymphocytic infiltrate o Absence of neutrophils/macrophages NB: anti-smooth muscle antibody + antinuclear antibody = hallmark diagnostic

Sequence from hepatitis to cirrhosis

5. Cirrhosis Liver damage characterised by diffuse distortion of hepatocyte architecture, bridging fibrosis (subdividing parenchyma) and regenerative nodules. Clinical features of cirrhosis – Mnemonic: ABCDEFGHI PS Asterixis/ascites Bruit/bruising (purpura, epistaxis) Cachexia/Caput medusa Dermatogenic symptoms Edema/encephalopathy Fetor hepaticus Gynaecomastia/testicular atrophy/impotence/irregular menses/amenorhoea Hepato-renal/-pulmonary syndrome/hepatomegaly Icterus Palmar erythema/portal hypertension Spider naevi

Types of cirrhosis i. Macronodular (nodules >3mm diameter) - Chronic active viral hepatitis B&C - Drugs ii. Micronodular (nodules