Liver disease 1 Flashcards
List the different liver function tests
- Bilirubin
- Alkaline phosphatase
- Alanine Transaminase
- Gamma GT
What is hepatitis
- Inflammation of the liver
- Raised Transaminases
- Raised ALT, AST( released when the liver is damaged)
What does ALT stand for
Alanine transaminase
- An enzyme found mostly in the liver
- Released by liver cells when they are damaged
- An ALT test measures how much ALT is in the blood
What does AST stand for?
- Aspartate aminotransferase
- An enzyme that is normally present in liver & heart cells.
- Released into the blood when the liver or heart is damaged
What is Cholestasis?
- Obstructive
- Reduction or stoppage of bile flow
- Raised alkaline phosphatase
- Raised GGT
- To determine whether the patient has cholestasis or hepatitis, need to look at the ALT,AST &GGT
What is GGT?
- Gamma-glutamyl transferase
- Elevated levels may be due to liver diseases, such as hepatitis or cirrhosis, but they may also be due to other conditions eg congestive heart failure, diabetes or pancreatitis
- A low/normal GGT test result indicates that it’s unlikely that the person has liver disease or has consumed any alcohol
Outline what biliary disorders are and list them
- Diseases affecting bile ducts from small interlobular ducts down to common bile duct outlet in duodenum
1. ) Large duct obstruction-generally referred to extrahepatic BD
2. ) Primary sclerosing cholangitis -large and/or small BD
3. ) Primary biliary cirrhosis- small interlobular BD
Outline the various causes of abnormal liver enzymes
- Alcohol
- Medications
- NAFLD
- Viral hepatitis( chronic hep B& C)
- Haemochromatosis
Rarer causes=
- autoimmune hepatitis
- Primary biliary cirrhosis
- Alpha-1-antitrypsin deficiency
- Wilson’s disease
- Coeliac disease
- Sero-negative hepatitis
What investigations may be carried out when determining if a patient has liver disease?
- FBC
- INR
- U&E/LFTs
- Lipids
- Imaging( ultrasound& dopplers) on the hepatic& portal veins
- Immunology: autoantibodies, immunoglobulins
- Virology: hepatitis B surface antigen; hep C Ab
- Chemistry: ferritin; copper/caeruloplasmin
Which autoantibodies may be looked for when investigating liver disease?
- Antinuclear antibodies, smooth muscle antibodies
- Anti-mitochondrial abs
- Anti-endomyseal abs
List the possible causes of cirrhosis
- Alcohol
- Chronic viral hepatitis (hep B& hep C)
- Haemochromatosis
- Non-alcoholic steatohepatitiis
- Primary biliary cirrhosis
- Autoimmune hepatitis
- Primary sclerosing cholangitis
- Alpha-1-antitrypsin deficiency
- Wilson’s disease
- Drug induced
List the different types of viral hepatitis
Hepatitis..
A,B,C,D,E
Outline the characteristics of Hep A
-Faeco-oral route
-Self limiting in 99%
-No chronicity
-Hep A IgM= acute Hep A
-Hep A IgG= previous exposure
-Vaccination available
common in travel
Outline the serology of Hep B
- Hepatitis B surface antigen (HBsAg)= patient has hep B= refer patient!
- Hepatitis B surface antibody(HBsAb)= patient is immune to Hep B
- Hepatitis B core IgM= patient has acute Hep B
- Hepatitis B core IgG= patient has been exposed to Hep B (particularly in people undergoing chemo or immunosuppression)
Outline the immunoglobulins from greatest to least in number within our body
GAMED( IgG, IgA, IgM,IgE,IgD)
What immunoglobulin is produced when your body first starts fighting off an infection?
-Body first produces IgM to fight off the infection, until it starts producing IgGs which stay in the body for years
What i the relationship between the quantity of HBsAg in your blood and your symptoms
-The greater the quantity of HBsAg in your blood, the more likely it is for you to develop symptoms
what is the HBeAg a marker of?
viral replication
what does HBsAg indicate
infection
-(regardless of whether it is acute or chronic)
What does IgG-HBsAg indicate?
immunity (cure or vaccine)
Describe the window period that exists during the course of the infection
The time period when the IgM-HBcAg is fighting off the virus so well that the virus particles become so few that they aren’t detected on serology
- However the person still has Hep B infection as the body still hasn’t produced enough IGsAg
- Infected despite a negative HBsAg
How do you tell the difference between immunity via cure and immunity via vaccination in an IgG-HBsAg positive patient?
If the person was once infected then they would have antibodies against core antigen.
- Hep B virus vacicnation contains HBsAg only, so the body only produces antibodies against HBsAg and not HBcAg
- The exception is the window period i.e infected despite a negative HBsAg
How can you tell the difference between an acute and chronic Hep B infection using the serology indicating the antibodies against HBcAg
-If the abs against HBcAg are IgM, that means acute infection. If they’re IgG, that means chronic infection
State the disease manifestation of the immune tolerant phase (phase I) of chronic HBV infection
minimal inflammation as the body’s immune system fails to respond to the infection
State the management that should be followed for the following…
HBeAg +Ve
HBV DNA( copies mL) = <10^5
ALT normal
Follow, no treatment
State the management that should be followed for the following…
HBeAg +Ve
HBV DNA( copies mL) = >/= 10^5
ALT normal
Consider biopsy.
treat if diseased
State the management that should be followed for the following…
HBeAg +Ve
HBV DNA( copies mL) = <10^5
ALT elevated
TREAT
State the management that should be followed for the following…
HBeAg -Ve
HBV DNA( copies mL) = <10^4
ALT normal
Follow, no treatment
State the management that should be followed for the following…
HBeAg -Ve
HBV DNA( copies mL) = >/= 10^4
ALT normal
Consider biopsy.
Treat if diseased
State the management that should be followed for the following…
HBeAg -Ve
HBV DNA( copies mL) = >/= 10^4
ALT elevated
TREAT
What is HARVONI?
The first and only single-tablet regimen for the majority of HCV GT1 adult patients(excluding those who with decompensated cirrhosis or who are pre- or post liver transplant)
Outline the characteristics of Haemochromatosis
- Iron overload
- Autosomal recessive
- HFE gene
- Homozygote gene frequency~ 1 in 150
- Phenotypic frequency~4 in 100
What are the clinical features of Haemochromatosis?
- Cirrhosis
- Skin pigmentation
- Diabetes
- Cardiomyopathy
- Arthritis
- Pituitary failure
Explain how we diagnose haemochromatosis
- Raised ferritin
- Difficult to differentiate from alcoholic haemosiderosis
- HFE gene
- Liver biopsy& hepatic iron estimation
- Hepatic iron index= micromol iron per g dry weight/age
- HII>1.9 (diagnostic of haemochromatosis, reliably differentiates from alcoholic iron overload)
Outline the characteristics of primary biliary cholangitis
- different from primary biliary cirrhosis
- Middle aged female
- Itching,tiredness
- Cholestatic LFTs
- Not necessarily ‘cirrhotic’
- Raised IgM, psoitive anti-mitochondrial ab
- Liver biopsy( bile duct damage, granulomatous cholangitis)
- Treatment: Ursodeoxycholic acid, Obeticholic acid
Outline the progression of the changes toward cirrhosis in primary biliary cirrhosis
- Portal tract expansion with radiating septa& absence of bile duct( ductopaenia)
- Biliary interface activity with characteristic ‘halo’
- Cirrhosis with portal-portal pattern of bridging fibrous septa
Outline the characteristics of autoimmune hepatitis
Diagnosis:
- Raised IgG
- Positive anti-nuclear ab
- Positive smooth muscle ab
- Positive liver-kidney
- Liver biopsy: interface hepatitis; plasma cell infiltrates
- Treatment: prednisolone, azathioprine
Outline the characterstics of alpha-1-antitrypsin deficiency
-Associated with COPD Diagnosis: -alpha-1- antitrypsin level<25% -alpha-1-antitrypsin phenotype -Liver biopsy-PAS positive globules
Outline the characteristics of Wilson’s disease
-Autosomal recessive
-disorder of copper metabolism( Caeruloplasmin synthesis defective; reduced biliary copper excretion)
-Young adults/children
Clinical features=
-Liver cirrhosis
-Acute liver failure
-Neuropsychiatric disorders
-Kayser-Fleischer rings
How is Wilson’s disease diagnosed
- Low serum caeruloplasmin
- Reduced serum copper
- High urinary copper excretion
- Kayser-Fleischer rings
- Liver biopsy(liver copper>250micrograms/g liver dry weight)
- Treatment: penicillamine; transplantation
State the different chronicity stages of chronic HBV infection and link them to their disease state
Phase 1=immune tolerant phase;Minimal inflammation
Phase 2=Immune active;chronic active hepatitis
Phase 3=Non-replicative;cirrhosis/HCC
Resolved=Normal to cirrhosis/HCC
Describe the serology according to the different chronicity stages of HBV
Phase 1= HBsAg; HBeAg
Phase 2=continuation of phase 1 serology
Phase 3=Anti-HBe
Phase 4=Anti-HBs
Describe the changes in ALT level as a pt progresses through chronic HBV infection
Phase 1=stays low/o
Phase 2=increases and peaks in the middle of phase
Phase 3=stays at 0/low
Describe the changes in HBV DNA as a pt progresses through chronic HBV infection
Phase 1=very high i.e high viral load
Phase 2=gradually decreases
Phase 3=0
What does it mean when someone is HBeAg negative with a high viral load?
- Someone becomes HBeAg -ve when they ahve been infected/exposed during the perinatal period and remain infected unto above their 40s
- overtime the virus mutates to evade the immune system
- even when they lose HBeAg the mutated virus can carry on replicating; they may even have HBeAb
- The mutated virus can put people at higher risk of liver damage
What are the treatment options for Hep B
Antivirals:
- entecavir
- tenofovir
- lamivudine
- adefovir
- telbivudine
What are the treatment options for chronic hep C
-Harvoni= the first & only single tablet regimen for most HCV G1 adults
- Ledipasvir
- Sofosbuvir
When CAN’T harvoni be used for HCV G1 adults
-those pts with decompensated cirrhosis or who are pre or post liver transplant
What is the treatment for primary biliary cholangitis?
- Ursodeoxycholic acid
- Obeticholic acid
Outline the treatment in autoimmune hepatitis
- Prednisolone
- Azathioprine
What is primary sclerosing cholangitis(PSC) ?
- A long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts which normally allow bile to drain from the gallbladder.
- Ulcers
- Periductal fibrosis & epithelial atrophy
- Bile ducts replaced by fibrosis cords
How can we diagnose PSC?
- Liver biopsy (‘onion skin’ fibrosis)
- ERCP/MRCP
How is Wilson’s disease diagnosed
- Low serum caeruloplasmin
- Reduced serum copper
- High urinary copper excretion
- Kayser-Fleischer rings
- Liver biopsy( liver copper>250ug/g liver dry weight)
- Treatment (penicillamine; transplantation)
How can we treat Wilson’s disease
- penicillamine
- transplantation
Is there any association between Wilson’s disease and diabetes
There’s a strong association
Describe the course of NAFLD leading to liver failure
NAFLD—>NASH—>CIRRHOSIS—>LIVER FAILURE
What are the advantages of taking a liver biopsy
- Cannot differentiate between NASH and simple steatosis otherwise
- Diagnosis of NASH important prognostically
- Cirrhotic patients need to be screened for HCC
- Future therapies will be available
Outline the non-invasive markers of cirrhosis
Physical: -Tissue elastography eg fibroscan (to see if the liver is stiff) Biochemical: -enhanced liver fibrosis score (ELF) -NAFLD fibrosis score -Fibrotest -AST to platelet ratio (APRI)
State the steps of progression in non-alcoholic liver disease
- ) Steatosis
- )Steatohepatitis
- ) Fibrosis
- )Cirrhosis
What are key differences in the liver enzymes during progression of non-alcoholic liver disease compared to alcoholic liver disease ?
Non-alcoholic: increases ALT and sometimes AST
-Alcoholic: increases AST and ALT to a lesser degree ; AST:ALT ratio increases in alcoholic
