Metabolic and Alcoholic Liver Disease

14/05/2013 by admin | Gastroenterology

Alcoholic liver disease:

    1. o Relationship between chronic liver disease and alcohol use is complex
    2. o Excess alcohol = chronic liver disease
    3. o However personal susceptibility varies and alcohol-related pathology is increasingly seen in individuals who drink minimal amounts of alcohol (=non-alcoholic steatohepatitis = NASH)
    4. o Of all the people who drink excess alcohol – only 20% develop chronic liver disease
    5. o Exact pathophysiology not understood – thought to be due to the acetaldehyde derivatives in alcohol
  1. 3 pathological forms of alcoholic liver disease:
    1. o Fatty liver: occurs in 50% of heavy drinkers – reversal on alcohol cessation. No encephalopathy, no hyperbili or jaundice, rised AST/LDH, normal INR, good prognosis
    2. o Acute alcoholic hepatitis: occurs in 40% of heavy drinkers, may have encephalopathy, raised bilirubin, very high AST/LDH, prolonged INR, moderate prognosis. Symptoms vary (mildsevere), may have an overlying bruit, may have a large spleen. often have a long history of alcohol use and then suddenly become jaundiced, anorexic, have nausea, malaise, fever, neutrophil leucocytosis
    3. o Cirrhosis: needs >30units/week. A man consuming 2.5bottles wine/day over 22 years has a 50% chance of cirrhosis! Does have encephalopathy, raised bilirubin, no change to AST/LDH (only in acute change), prolonged INR, poor prognosis, decompensate = GI bleeding, ascites
  2. Ix:
    1. o Random ethanol level taken on admission
  3. Mx:
    1. o Address challenge of total abstinence from alcohol – 5 year survival doubles in patient stops drinking (from 35%–>70%)
    2. o Biopsy for degree of fibrosis
    3. o Prednisolone for severe alcoholic hepatitis
    4. o HCC occurs in 15% with alcoholic cirrhosis – surveillance may reduce this



  1. Primary iron overload (total body iron >5g). Normal stores 3-4g
  2. In most cases, overload due to increased GI absorption
  3. The excess iron is deposited in several organs = damage
  4. Incidence: mutation in the HFE gene is cause of haemochromatosis (C282Y), and is v common in white people
  5. Prevalence: 1/150 in populations with strong celtic ancestry – despite this symptomatic presentations are rare
  6. Pathophysiology:
    1. o C282Y mutation in HFE gene prevents cell surface expression of protein – how this leads to demonstrable increase in GI iron absorption in no known.
    2. o Excess iron is absorbed and deposited in liver, pancreas, heart, joints. Leads to liver fibrosis and risk of hepatoma
  7. p/c: bronzed skin, DM, cardiac failure, joint involvement (=pyrophosphate arthropathy, can be v disabling).
  8. Ix:
    1. o LFTs: non-specific hepatitis
    2. o Iron indices:
    1. o Transferrin saturations >80%
    2. o Ferritin levels very high 1000-2000ug/L (normal <300ug/L)
    3. o Liver biopsy = characteristic distribution or iron and provides and provides information on staging (degree of fibrosis)
    4. o Genetic mutation analysis: 90% of white people with haemochromatosis are homozygous for C282Y in HFE.
  1. Mx:
    1. o Venesection: 500g whole blood removed weekly until excess iron is removed (may take 12-18 months), thereafter remove 500g every 3 months indefinitely.
    2. o Surveillance of hepatoma: in those patients with cirhhosis before a diagnosis was made = high risk of hepatoma. Complete regular AFP measurements and liver USS to assess.
    3. o Screening 1st degree relatives: by HFE mutation analysis


Wilson’s disease:

  1. Rare (1-3/mil), autosomal recessive disorder of copper metabolism = overload
  2. Arises when mutation in gene for copper transport protein (ATP7B C13q14.3) leads to failure of biliary excretion and thus progressive accumulation.
  3. p/c: hepatic (=acute hepatitis/fulminant liver failure/chronic liver disease) and neurological damage (=extrapyramidal disturbance/psychosis), haematological damage (=acute intravascular hamolysis) seen in children and young adults, M=F, Kayser-Fleisher rings may be identified by slip lamp examination
  4. Ix:
    1. o Copper studies: low serum copper, ceruloplasmin (low in 80%), 14-h urinary copper increased
    2. o Liver biopsy: defines degree of fibrosis as well as quantifies copper load
    3. o Cerebral CT/MRI
  5. Mx:
    1. o Liver disease: penacilliamine is used to chelate copper – which is then excreted in the urine. Transplantation?
    2. o Neurological damage: is permanent
    3. o Screening of first degree relatives 
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