Chronic liver diseases Flashcards
how do you define chronic liver disease?
= duration of greater than 6 months
what is the outcome of chronic liver disease?
= progression to cirrhosis
what is the pathology of chronic liver disease?
= recurrent inflammation and repair with fibrosis and regeneration
what are the causes of chronic liver disease?
- alcohol
- hep C
- primary biliary cholangitis
- auto-immune hepatitis
- hep B
- NAFLD
- haemochromatosis
- primary sclerosis cholaningitis
- Wilsons disease
- alpha 1 anti-trypsin
- budd-chiari
- methotrexate
what is the histopathology of non-alcoholic fatty liver disease?
= maladaption of oxidative stress
what is non-alcoholic fatty liver disease associated with?
- diabetes
- obesity
- fatty liver disease
describe the 2 hit pathogenesis in non-alcoholic fatty liver disease?
First hit
= excess fat accumulation
= hepatocytes can generate TNFa
Second hit = intra-hepatic oxidative stress = lipid per-oxidation = TNF-alpha, cytokinie cascade = lipopolysaccharide - ischeamia re-perfusion injury
how do you diagnose and treat simple steatosis?
= diagnosed by ultrasound
Treatment
- weigh loss
- exercise
how is Non-Alcoholic Steatohepatitis diagnosed and treated?
= diagnosed by liver biopsy
treatment
- weight loss
- exercise
- other experimental treatment
what are the 3 auto-immune liver diseases?
1) primary biliary cholangitis
2) auto-immune hepatitis
3) primary sclerosing cholangiis
what is the typical presentation for primary biliary cholangitis?
- middle aged women
- asympatomatic/incidental
- fatigue
- itch without rash
- Xanthelasma
- xanthomas
how do you diagnose primary biliary cholangitis?
- positive AMA
- cholestatic LFTs
- liver biopsy
how do you treat primary biliary cholanigits?
- urseo deoxycholic acid
what are the 2 types of auto-immune hepatitis?
type 1 = adult = ANA = ASMA = SLA severity
Type 2 = children & young adults = LKM-1 = exclusive = AMA
what is type 1 auto-immune hepatitis associated with?
- extra-hepatic manifestations
= auto-immune thyroiditis
= graves disease
= chronic UC
- less commonly with; = RA = pernicious anaemia = systemic sclerosis = ITP = SLE
how do you present with auto-immune hepatitis?
- hepatomegaly
- jaundicee
- stigmata of chronic liver disease
- splenomegaly
- elevated AST and ALT
- elevated PT
- non-specific symptoms;
= malaise
= fatigue
= lethargy
= nausea
= abdominal pain
= anorexia
how do you diagnose auto-immune hepatitis?
- Elevated AST and ALT
- Elevated IgG
- Rule out other causes:
= Wilsons disease
= Alpha 1 antitrypsin deficiency
= Viral hepatitis (A, B, C)
= Drug induced liver disease (alcohol, minocycline, nitrofurantoin, INH, PTU, methyldopa, etc)
= NASH
= PBC, PSC, autoimmune cholangitis - Presence of autoimmune antibodies
- Liver biopsy
what is chronic hepatitis marked by histologically?
= piecemeal necrosis and lobular involvement
= numerous plasma cells
describe the pathogenesis of interface hepatitis?
= Genetically predisposed individual with exposure to an environmental agent triggers the autoimmune pathogenic process
= Genetic predisposing factors:
- 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
= environmental triggers
= drugs; Oxyphenisatin Methyldopa Nitrofurantoin Diclofenac Minocycline statins
how do you treat interface 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
what is primary sclerosing cholangitis?
Autoimmune destructive disease of large and medium sized bile ducts.
what is primary sclerosis cholangitis associated with?
= colitis (mainly ulcerative colitis)
how do you diagnose primary sclerosin cholangitis?
imaging of biliary tree
how do you treat primary sclerosing cholangitis?
= bile flow
= monitor for cholaniocarcinoma
= colorectal cancer
what is haemochromatosis?
= autosomal recessive disease of iron overload
- C282Y
- H63D
- mutations in HFE ene
what can haemeochromatosis cause?
- cirrhosis
- cardiomyopathy
- pancreatic failure
- the bronzed diabetic
how do you treat haemochromatosis?
= venesection
what is Wilsons disease?
= autosomal recessive disorder where there is a loss of function or loss of protein mutation in caeruloplasmin
(copper binding protein, loss of copper regulation massive tissue deposition of copper)
how do you presenting with wilsonsn disease?
Neurological
= chorea-atheitoid movementts
Hepatic
= cirrhosis
= sub-fulminant liver failure
Kaiser Flisher rings
how do you treat Wilsons disease?
= copper chelation drugs
what is alpha 1 anti-trypsin deficiency?
Genetic, Mutations in the A1AT genes, multiple sites, causes variable phenotype
Protein Function lost excess tryptic activity
how do you present with alpha 1 anti-trypsin deficiency?
- lung emphsema
- liver deposition of mutant protein, cell damage
how do you manage alpha 1 anti-trypsin deficiency?
= supportive management
what is Budd-chiari syndrome?
= thrombosis of hepatic vein
= so blood cant drain out of liver
- congenital webs
what deficiency causes budd-chiari syndrome?
= Protein C or S deficiency
how do you present with budd-chiarir syndrome?
- jaundice
- tender hepatomegaly
- ascites
how do you diagnose budd-chiari?
= U/S visualisation of hepatic veins
how do you treat budd-chiari syndrome?
= recanalization or TIPS
what is methotrexate used to treat?
= rheumatoid arthritis and psoriasis
what can methotrexate cause?
- fibrosis
what is cardiac cirrhosis secondary to?
= high right heart pressure
what could cause cardiac cirrhosis?
Incompetent tricuspid valve
Congenital
Rheumatic fever
Constrictive pericarditis
how do you present wit cardiac cirrhosis?
- CCF
- too much ascites or liver impairment
how do you treat cardiac cirrhosis?
= treat cardiac condition
