Causes of Chronic Liver Disease Flashcards by Alison Gourlay

What defines chronic liver disease?

Duration greater than 6 months

- can present after the 6 months

How well did you know this?

Not at all

Perfectly

What is the pathology of chronic liver disease?

recurrent inflammation and repair with fibrosis and regeneration

How well did you know this?

Not at all

Perfectly

What cells initiate the inflammatory response in the liver in response to damage?

Hepatic Stellate Cells

How well did you know this?

Not at all

Perfectly

What do Hepatic Stellate Cells turn into before turning into fibrosis?

Hepatic Myofibroblast

How well did you know this?

Not at all

Perfectly

What is the progression of Hepatic Stellate Cells producing fibrosis?

QUIESCENT HSC
ACTIVATED HSC
APOPTOTIC HSC

How well did you know this?

Not at all

Perfectly

What are the causes of chronic liver disease?

Alcohol
NAFLD
Hepatitis C 
Primary Biliary Cholangitis
Autoimmune Hepatitis
Hepatitis B
Haemochromatosis
Primary Sclerosing Cholangitis
Wilsons Disease
alpha 1anti-trypsin
Budd-Chiari
Methotrexate

How well did you know this?

Not at all

Perfectly

What is Non Alcoholic Fatty Liver Disease (NAFLD)?

Fatty Liver or steato-hepatitis in absence of other cause

In obese = 60% have it

How well did you know this?

Not at all

Perfectly

What is the pathogenesis of NAFLD?

“2 Hit” Paradigm
“First hit” – Excess fat accumulation
“Second hit” – Intrahepatic oxidative stress
Lipid peroxidation
TNF-alpha, cytokine cascade
Ischeamia reperfusion injury

How well did you know this?

Not at all

Perfectly

What can generate TNFa?

Hepatocytes

How well did you know this?

Not at all

Perfectly

What is the treatment for simple steatosis?

weight loss and exercise

increased CVS risk

How well did you know this?

Not at all

Perfectly

What is the diagnosis and treatment for NASH?

Diagnosis = liver biopsy
Weight loss & exercise
Other treatments experimental

How well did you know this?

Not at all

Perfectly

What is a risk of NASH?

progression to cirrhosis

How well did you know this?

Not at all

Perfectly

Name some Autoimmune liver diseases?

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

How well did you know this?

Not at all

Perfectly

What causes Primary Biliary Cirrhosis (PBC)?

Autoimmune component 1960s,1970s-1980s AMAs M1-M9

1980s target M2-E2 E3 subunits of PDC-E2 n inner leaflet of mitochondrial membrane
T-cell mediated, CD4 cells reactive to M2 target, why loss of tolerance

How well did you know this?

Not at all

Perfectly

What are the symptoms of PBC?

Fatigue
Itch without rash
Xanthesalma and xanthomas - hypercholesterolemia
Normally middle aged women

How well did you know this?

Not at all

Perfectly

How is PBC diagnosed?

2 of 3:
Positive AMA
Cholestatic LFTs
Liver Biopsy

How well did you know this?

Not at all

Perfectly

How is PBC treated?

Urseo deoxycholic acid

What are the consequences of PBC?

Most will not develop symptoms in their life time
The majority with PBC symptoms do not develop liver failure
- Itch can be particularly problematic.
Many developing liver failure will be unfit for transplant

Describe auto-immune hepatitis?

Affects women more than men (3.6:1)
If untreated approximately 40% die within 6 months
40% develop cirrhosis

Describe type 2 auto-immune hepatitis?

Children & young adults
LKM-1
Exclusive
AMA

Describe type 1 auto-immune hepatitis?

Adult (teenagers + above)
ANA
ASMA - anti smooth muscle antibody
SLA severity

IgG –positive
AMA –positive
pANCA –positive

What extrahepatic manifestations are associated with Type 2 auto-immune hepatitis?

Autoimmune thyroiditis, graves disease, chronic UC

Less commonly with RA, pernicious anemia, systemic sclerosis, ITP, SLE

What is the clinical presentation of auto-immune hepatitis?

Hepatomegaly
Jaundice
Stigmata of chronic liver disease
Splenomegaly
Elevated AST and ALT
Elevated PT
Non-specific symptoms: malaise, fatigue, lethargy, nausea, abdominal pain, anorexia

How is auto-immune hepatitis?

Elevated AST and ALT
Elevated IgG
Presence of autoimmune antibodies
Liver biopsy – confirms diagnosis

What is the pathology of auto-immune hepatitis?

Chronic hepatitis with marked piecemeal necrosis and lobular involvement Numerous plasma cells Interface hepatitis: hallmark finding

What are the genetic predisposing factors of auto-immune hepatitis?

HLA-DR3: early onset, severe form HLA-DR4: caucasian, late onset, better response to steroids, higher incidence of extrahepatic manifestations IgG: part of the IgG molecule (mainly the heavy chain) T-Cell receptors

What drugs can cause auto-immune hepatitis?

``` Oxyphenisatin Methyldopa Nitrofurantoin Diclofenac Minocycline statins ```

What is the treatment of auto-immune hepatitis?

``` Corticosteroids Azathioprine Children: azathioprine or 6MP Combination Therapy Prednisone + Azathioprine Prednisone: start at 30mg daily and taper down to 15mg at week 4, then maintain on 10mg daily until therapy endpoint Azathioprine 50-100mg daily MUST GIVE STEROIDS OR THEY WILL DIE ```

What are the typical consequences of auto-immune hepatitis?

40% of all pts with AIH develop cirrhosis 54% develop esophageal varices within 2 years Poor prognosis if has presence of ascites or hepatic encephalopathy 13-20% of patients can have spontaneous resolution Of patients who survive the most early and active stage of disease, approximately 41% of them develop inactive cirrhosis.

Describe Primary Sclerosing Cholangitis?

Autoimmune destructive disease of large and medium sized bile ducts. M:F 4:1, 40% also have Colitis (mainly UC) Commonest liver disease in Scandinavia. Clinical: recurrent cholangitis Diagnosis: imaging of biliary tree Treatment: maintain bile flow, monitor for cholangiocarcinoma and colo-rectal cancer

What are the three features of the "bronzed diabetic"?

Cirrhosis cardiomyopathy Pancreatic failure

Describe Haemochromotosis?

Genetic Iron overload syndrome Mono-genetic autosomal recessive disease of Iron over load, C282Y or H63D, mutations in HFE gene. Gene carrier frequency 10%, genetic haemochromatosis 1 in 200 but partial penetrance. Cirrhosis, cardiomyopathy, Pancreatic failure Treatment: Venesection

Describe Wilsons Disease?

Lenticulo-hepatic degenerationMono-genetic autosomal recessive disease. loss of function or loss of protein mutations in caeruloplasmin Causes massive brain and liver damage

What is the clinical presentation of Wilsons Disease?

Neurological- chorea-atheitoid movements Hepatic – cirrhosis or sub-fulminant liver failure Kaiser Fleisher rings

What is the treatment of Wilsons Disease?

copper chelation drugs

Describe Alpha 1 anti-trypsin deficiency?

Genetic, Mutations in the A1AT genes, multiple sites, causes variable phenotype Protein Function lost meaning excess tryptic activity Trypsin destroys lung membrane and causes liver damage

What are the clinical features and treatment of Alpha 1 anti-trypsin deficiency?

Lung emphyesma Liver deposition of mutant protein, cell damage Treatment is supportive

Describe Budd-Chiari?

``` Thrombosis of the hepatic veins Congenital webs Thrombotic tendency, protein C or S deficiency Clinical: - Acute- Jaundice, tender hepatomegaly - Chronic- Ascites Diagnosis: U/S visualisation of hepatic veins Treatment: recanalization or TIPS ```

What can the drug Methotrexate do to the liver?

cause progressive fibrosis

Describe cardiac cirrhosis?

``` Secondary to High right heart pressures Incompetent tricuspid valve Congenital malformation Rheumatic fever Constrictive pericarditis Clinical: CCF, with too much ascites and or liver impairment Treatment: Treat the cardiac condition ```