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Chronic Liver Diseases Flashcards

1
Q

What is the minimum clinical duration for chronic liver disease?

A

6 months

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2
Q

What is the outcome for chronic liver disease?

A

Progression to cirrhosis

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3
Q

What is the pathology of chronic liver disease?

A

Recurrent inflammation and repair with fibrosis and regeneration

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4
Q

What is the flow of chronic liver disease?

A

Cause ->
Recurrent inflammation, process of fibrosis ->
Compensated cirrhosis ->
Decompensated cirrhosis, chronic liver failure, acute on chronic liver failure

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5
Q

The activation of which cells initiates fibrosis?

A

Hepatic stellate cells

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6
Q

What activates the quiescent hepatic stellate cells?

A

Inflammatory cells

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7
Q

What would usually happen to an activated hepatic stellate cell?

A

Resolution =

Becomes apoptotic

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8
Q

What prevents the apoptosis of activated hepatic stellate cells?

A

TIMP

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9
Q

What is NAFLD?

A

Non-Alcoholic Fatty Liver Disease
Fatty liver or steato-hepatitis in the absence of other causes
Fat only

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10
Q

What is NASH?

A

Non-Alcoholic Steato-Hepatitis

Fat and inflammation

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11
Q

What is the “two hit paradigm” for the pathogenesis of NASH?

A

1st Hit = Excess fat accumulation

2nd Hit = Intrahepatic oxidative stress

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12
Q

What can cause the “second hit” for the pathogenesis of NASH?

A

Oxidative stress and lipid peroxidation
Pro-inflmmatory cytokine release (TNFa)
Lipopolysaccharide
Ischaemia-reperfusion injury

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13
Q

What is the one hit hypothesis for the pathogenesis of NASH?

A

aka Skinny NASH
Triglyceride benign
Hepatocytes can generate TNFa
Oxidative stress at centre of disease

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14
Q

What are the risk factors for NAFLD/NASH?

A

Metabolic syndrome = Type II diabetes, obesity, low HDL, hypertension, triglycerides
Insulin resistance is universal

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15
Q

What is the management for NAFLD - simple steatosis?

A 
Diagnosis = US 
Risks = Increased CVD, no progression of liver problems
Treatment = Weight loss and exercise
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16
Q

What is the management for NAFLD - NASH?

A 
Diagnosis = Liver biopsy 
Risks = Progression to cirrhosis 
Treatment = Weight loss, exercise, experimental treatments
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17
Q

What are the auto-immune liver diseases?

A 
Primary Biliary Cholangitis (Cirrhosis) 
Auto-immune Hepatitis 
Primary Sclerosing Cholangitis 
Alcohol related liver disease 
Drug reactions
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18
Q

What is the immunological aetiology of primary biliary cholangitis?

A

T cell mediated

CD4 cells reactive to M2 target

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19
Q

What immunological components are the hallmark of primary biliary cholangitis?

A

Antimitochondrial antibodies

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20
Q

What is the pathogenesis of primary biliary cholangitis?

A

Interlobular bile ducts are damaged by chronic autoimmune granulomatous inflammation
This causes cholestasis which may lead to fibrosis, cirrhosis and portal hypertension

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21
Q

What are the symptoms of primary biliary cholangitis?

A

Usually asymptomatic
Fatigue
Itch without a rash
Xanthesalma and xanthomas

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22
Q

In which group is primary biliary cholangitis more common?

A

Middle aged women

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23
Q

What is needed for a diagnosis of primary biliary cholangitis?

A

2 from:
Positive AMAs
Cholestatic LFTs
Liver Biopsy

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24
Q

What is the treatment for primary biliary cholangitis?

A

Urseo deoxyxcholic acid

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25
Q

What is autoimmune hepatitis?

A

Inflammatory liver disease of unknown cause characterised by suppressor T cell defects with autoantibodies directed against hepatocyte surface antigens

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26
Q

What is the classification of Type 2 autoimmune hepatitis?

A 
Commoner in children and young adults 
More likely to progress to cirrhosis 
Less treatable 
\+ve LKM-1 antibodies
\+ve AMA
27
Q

What is the classification of Type 1 autoimmune hepatitis?

A 
Commoner in adults 
\+ve ASMA in majority 
\+ve ANA in some
\+ve AMA 
Increased IgG
28
Q

In what group is Type 1 autoimmune hepatitis more common?

A

Females

10-20, 45-70

29
Q

What are the associated extra hepatic manifestations of autoimmune hepatitis?

A 
Autoimmune thyroiditis 
Graves Disease 
Chronic UC 
Pernicious anaemia 
SLE
Autoimmune haemolysis 
Diabetes 
PSC
30
Q

What is the clinical presentation of autoimmune hepatitis?

A 
Hepatomegaly, splenomegaly 
Jaundice 
Stigmata of chronic liver disease 
Elevated AST, ALT 
Elevated prothrombin time 
Malaise, fatigue, lethargy, nausea, abdo pain, anorexia
31
Q

How is autoimmune hepatitis diagnosed?

A 
Elevated AST and ALT 
Elevated IgG 
Presence of autoimmune antibodies 
Liver biopsy 
Rule out differential
32
Q

What is the differential for autoimmune hepatitis?

A 
Wilson's Disease 
Alpha 1 Antitrypsin Deficiency 
Viral Hepatitis (A, B, C) 
Drug induced 
NASH 
PBC 
PSC 
Autoimmune cholangitis
33
Q

What is the histology of autoimmune hepatitis?

A

Chronic hepatitis with marked piecemeal necrosis and lobular involvement
Numerous plasma cells
Interface hepatitis = HALLMARK

34
Q

What is the proposed pathogenesis for autoimmune hepatitis?

A

Genetically predisposed individual with exposure to an environmental agent triggers the autoimmune pathogenic process

35
Q

What is the treatment for autoimmune hepatitis?

A

Immunosupression = Corticosteroids and Azathioprine

Predinsone (30mg daily then taper to 10mg daily maintenance until end point) + azathioprine (50-100mg daily)

36
Q

What is the prognosis for autoimmune hepatitis?

A

Development of cirrhosis and varies in ~50%
Some have spontaneous resolution
Typically long term survival
Poor prognosis if ascites or hepatic encephalopathy present

37
Q

What is primary sclerosing cholangitis?

A

Autoimmune destructive disease of large and medium sized bile ducts

38
Q

In which group is primary sclerosing cholangitis more common?

A

Males

40% also have UC

39
Q

What is the clinical presentation of primary sclerosing cholangitis?

A

Recurrent cholangitis

Pruritus +/- fatigue

40
Q

What is the diagnosis for primary sclerosing cholangitis?

A

Imaging of biliary tree (ERCP)

41
Q

What is the treatment for primary sclerosing cholangitis?

A

Liver transplant for end stage
Maintain bile flow
Monitor for cholangiocarcinoma and colorectal cancer

42
Q

What is haemochromatosis?

A

Mono-genetic autosomal recessive disease of iron over-load

Increased iron absorption leads to deposition in joints, liver, heart, pancreas, pituitary, adrenals and skin

43
Q

In which group is haemochormatosis more common?

A

Middle aged men

44
Q

What is the clinical presentation of haemochromatosis?

A

Cirrhosis
Cardiomyopathy
Pancreatic failure
Bronzed diabetic

45
Q

What are the most common mutations responsible for haemochromatosis?

A 
Gene = HFE 
Mutations = C282Y, H63D
46
Q

What is the treatment for haemochromatosis?

A

Venesection

47
Q

What is Wilson’s Disease?

A

Mono-gentic autosomal recessive disease of biliary copper excretion
Copper overload in liver and CNS

48
Q

What causes Wilson’s Disease?

A

Loss of function or loss of protein mutations in caeruloplasmin (copper binding protein)
Loss of copper regulation = massive tissue deposition

49
Q

What is the clinical presentation of Wilson’s Disease?

A

Kaiser Fleisher rings
Neuro = chorea atheitoid movements
Hepatic = Cirrhosis, sub-fulminant liver failure
Usually present with either neurological or hepatic signs (rarely both)

50
Q

What is the treatment for Wilson’s Disease?

A

Copper chelation drugs

51
Q

What is Alpha 1 Antitrypsin Deficiency?

A

Autosomal recessive disorder leading to excess styptic activity

52
Q

What causes Alpha 1 Antitrypsin Deficiency?

A

Mutations in the A1AT genes at multiple sites = variable phenotype
Loss of protein function, so excess tryptic activity

53
Q

What is the cancel presentation of Alpha 1 Antitrypsin Deficiency?

A 
Lung = emphysema 
Liver = Deposition of mutant protein, cell damage, cirrhosis
54
Q

What is the treatment for Alpha 1 Antitrypsin Deficiency?

A

Supportive management

55
Q

What is Budd-Chiari?

A

Thrombosis of the hepatic veins

56
Q

What causes Budd-Chiari?

A

Congenital webs
Hypercoaguable states: protein C or S deficiency, the Pill, pregnancy)
Tumour

57
Q

What is the clinical presentation of Budd-Chiari?

A 
Acute = Jaundice, tender hepatomegaly 
Chronic = Ascites, portal hypertension
58
Q

What is the treatment for Budd-Chiari?

A

Recanalisation

TIPSS

59
Q

What is methotrexate?

A

Drug used to treat rheumatoid arthritis and psoriasis

60
Q

How does methotrexate cause chronic liver disease?

A

Dose dependant liver toxin
Progressive fibrosis
No clinical signs, so must monitor fibrosis

61
Q

What is the treatment for chronic liver disease due to methotrexate?

A

Stop the drug

62
Q

What is the cause of cardiac cirrhosis?

A 
Secondary to high right heart pressures = 
Incompetent tricuspid valve 
Congenital 
Rheumatic fever 
Constrictive pericarditis
63
Q

What is the clinical presentation of cardiac cirrhosis?

A

CCF, with too much ascites and/or liver impairment

64
Q

What is the treatment for cardiac cirrhosis?

A

Treat the cardiac condition

GI (24 decks)

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