Chronic Liver Diseases Flashcards by Rachel Agnew

What is the minimum clinical duration for chronic liver disease?

6 months

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What is the outcome for chronic liver disease?

Progression to cirrhosis

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What is the pathology of chronic liver disease?

Recurrent inflammation and repair with fibrosis and regeneration

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What is the flow of chronic liver disease?

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

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The activation of which cells initiates fibrosis?

Hepatic stellate cells

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What activates the quiescent hepatic stellate cells?

Inflammatory cells

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What would usually happen to an activated hepatic stellate cell?

Resolution =

Becomes apoptotic

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What prevents the apoptosis of activated hepatic stellate cells?

TIMP

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What is NAFLD?

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

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What is NASH?

Non-Alcoholic Steato-Hepatitis

Fat and inflammation

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

1st Hit = Excess fat accumulation

2nd Hit = Intrahepatic oxidative stress

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

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

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

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

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What are the risk factors for NAFLD/NASH?

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

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What is the management for NAFLD - simple steatosis?

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

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What is the management for NAFLD - NASH?

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

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What are the auto-immune liver diseases?

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

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What is the immunological aetiology of primary biliary cholangitis?

T cell mediated

CD4 cells reactive to M2 target

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What immunological components are the hallmark of primary biliary cholangitis?

Antimitochondrial antibodies

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What is the pathogenesis of primary biliary cholangitis?

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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What are the symptoms of primary biliary cholangitis?

Usually asymptomatic
Fatigue
Itch without a rash
Xanthesalma and xanthomas

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In which group is primary biliary cholangitis more common?

Middle aged women

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What is needed for a diagnosis of primary biliary cholangitis?

2 from:
Positive AMAs
Cholestatic LFTs
Liver Biopsy

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What is the treatment for primary biliary cholangitis?

Urseo deoxyxcholic acid

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What is autoimmune hepatitis?

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

What is the classification of Type 2 autoimmune hepatitis?

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

What is the classification of Type 1 autoimmune hepatitis?

``` Commoner in adults +ve ASMA in majority +ve ANA in some +ve AMA Increased IgG ```

In what group is Type 1 autoimmune hepatitis more common?

Females | 10-20, 45-70

What are the associated extra hepatic manifestations of autoimmune hepatitis?

``` Autoimmune thyroiditis Graves Disease Chronic UC Pernicious anaemia SLE Autoimmune haemolysis Diabetes PSC ```

What is the clinical presentation of autoimmune hepatitis?

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

How is autoimmune hepatitis diagnosed?

``` Elevated AST and ALT Elevated IgG Presence of autoimmune antibodies Liver biopsy Rule out differential ```

What is the differential for autoimmune hepatitis?

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

What is the histology of autoimmune hepatitis?

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

What is the proposed pathogenesis for autoimmune hepatitis?

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

What is the treatment for autoimmune hepatitis?

Immunosupression = Corticosteroids and Azathioprine | Predinsone (30mg daily then taper to 10mg daily maintenance until end point) + azathioprine (50-100mg daily)

What is the prognosis for autoimmune hepatitis?

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

What is primary sclerosing cholangitis?

Autoimmune destructive disease of large and medium sized bile ducts

In which group is primary sclerosing cholangitis more common?

Males | 40% also have UC

What is the clinical presentation of primary sclerosing cholangitis?

Recurrent cholangitis | Pruritus +/- fatigue

What is the diagnosis for primary sclerosing cholangitis?

Imaging of biliary tree (ERCP)

What is the treatment for primary sclerosing cholangitis?

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

What is haemochromatosis?

Mono-genetic autosomal recessive disease of iron over-load | Increased iron absorption leads to deposition in joints, liver, heart, pancreas, pituitary, adrenals and skin

In which group is haemochormatosis more common?

Middle aged men

What is the clinical presentation of haemochromatosis?

Cirrhosis Cardiomyopathy Pancreatic failure Bronzed diabetic

What are the most common mutations responsible for haemochromatosis?

``` Gene = HFE Mutations = C282Y, H63D ```

What is the treatment for haemochromatosis?

Venesection

What is Wilson's Disease?

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

What causes Wilson's Disease?

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

What is the clinical presentation of Wilson's Disease?

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

What is the treatment for Wilson's Disease?

Copper chelation drugs

What is Alpha 1 Antitrypsin Deficiency?

Autosomal recessive disorder leading to excess styptic activity

What causes Alpha 1 Antitrypsin Deficiency?

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

What is the cancel presentation of Alpha 1 Antitrypsin Deficiency?

``` Lung = emphysema Liver = Deposition of mutant protein, cell damage, cirrhosis ```

What is the treatment for Alpha 1 Antitrypsin Deficiency?

Supportive management

What is Budd-Chiari?

Thrombosis of the hepatic veins

What causes Budd-Chiari?

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

What is the clinical presentation of Budd-Chiari?

``` Acute = Jaundice, tender hepatomegaly Chronic = Ascites, portal hypertension ```

What is the treatment for Budd-Chiari?

Recanalisation | TIPSS

What is methotrexate?

Drug used to treat rheumatoid arthritis and psoriasis

How does methotrexate cause chronic liver disease?

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

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

Stop the drug

What is the cause of cardiac cirrhosis?

``` Secondary to high right heart pressures = Incompetent tricuspid valve Congenital Rheumatic fever Constrictive pericarditis ```

What is the clinical presentation of cardiac cirrhosis?

CCF, with too much ascites and/or liver impairment

What is the treatment for cardiac cirrhosis?

Treat the cardiac condition