Hepatology I Flashcards
DM
The severity of cirrhosis can be graded using the []
The severity of cirrhosis can be graded using the Child-Pugh score.
What are the arrows pointing to? [1]
What pathology does this indicate? [1]
Mallory bodies are highly eosinophilic and thus appear pink on H&E stain. The bodies themselves are made up of intermediate keratin filament proteins that have been UBIQUINATED, or bound by other proteins such as heat shock protein
Found in ALCOHOLIC HEPATITIS
What are signs & symptoms of alcoholism associated with:
- CNS [6]
CNS:
- Reduced memory
- cortical atropy
- fits & falls
- wide based gait (cerebellar dysfunction)
- Korsakoffs (memory disorder that results from vitamin B1 deficiency and is associated with alcoholism)
- W.Enceph.
What are signs & symptoms of alcoholism associated with the blood [3]
- Increased MCV: non-megaloblastic macrocytic anaemia
- anaemia from marrow depression
- Folate deficiency: decreased intake; inhibits folate absorption
What are signs & symptoms of alcoholism associated with reproduction [4]
- testicular atrophy
- decreased testosterone and progesterone
- increased oestrogen
- fetal alcohol withdrawal
Which score is used to calculate risk of alcohol dependence? [1]
AUDIT
TOM TIP: Both the NFS and FIB-4 scores use the AST:ALT ratio to assess the severity of liver fibrosis.
The normal ratio is []/
A ratio [] in NAFLD suggests advanced fibrosis
. An AST:ALT ratio [] indicates alcohol-related liver disease rather than NAFLD.
TOM TIP: Both the NFS and FIB-4 scores use the AST:ALT ratio to assess the severity of liver fibrosis.
The normal ratio is less than 1.
A ratio greater than 0.8 in NAFLD suggests advanced fibrosis.
An AST:ALT ratio greater than 1.5 (meaning a disproportionately high AST) indicates alcohol-related liver disease rather than NAFLD.
Name 3 drugs that are associated with increasing risk factor for NAFLD [3]
Name a surgery that is associated associated as a risk factor for NAFLD [1]
Describe nutrition that is associated with increasing risk factor for NAFLD [2]
Drugs:
- Steroids
- Amiodarone
- Methotrexate
Weight reducing surgery:
- jejuno-ileal by pass
Nutrition
* Protein calorie malnutrition & TPN
Describe the treatment algorithm for NAFLD [6]
- Weight loss: diet & exercise
- Consider vitamin E
- Consider pioglitazone (reduces peripheral insulin resistance)
- Consider weight loss medication: orlistat
- Consider bariatric surgery if BMI > 35 and one other obesity co-morbid / BMI > 40.
- Liver transplant
BMJ BP
Describe the treatment for HBV [3]
Nucleoside analogues:
- Entecavir
- Tenofovir
AND
PEG-IFN (peginterferon alfa 2a)
If cirrhosis - just E & T
Describe HCV treatment:
- Length? [1]
- Therapies? [3]
8-12 weeks
Therapies:
- ARVs: aim sustained virological response (SVR; undetectable serum HCV RNA six months after the end of therapy)
- Combination dependent on genotype and stage of fibrosis
- currently a combination of protease inhibitors (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir) with or without ribavirin are used
Which gene is associated with haemochromatosis? [1]
Describe the inheritance pattern [1]
How does this gene mutation cause the pathogenesis of the disease? [5]
- human haemochromatosis protein (HFE) gene
- autosomal recessive
- HFE mutation causes decreased hepcidin activity (regulates iron stores); increased duodenal/jejunal iron absorption AND release of iron from bone marrow macrophages → iron deposition in cells → Fenton reaction and hydroxyl free radicals → DNA, lipid and protein damage → organ dysfunction
Fenton reaction:
Iron freely undergoes oxidation in cells from Fe2+ to Fe3+ as part of the Fenton reaction
In this process, hydroxyl free radicals are generated which then cause oxidative damage
Tx of Wilson’s diease? [3]
Copper chelation using either:
* Penicillamine
* Trientine
Zinc salts (inhibit copper absorption in the gastrointestinal tract)
Liver transplantation
If have high risk of HCC (have liver cirrhosis), what screening is undertaken to ID risk? [2]
- USS: 6 months
- test for AFP - tumour marker
The MELD Score is used to measure severity of? [1]
Cirrhosis
The Model of End-Stage Liver Disease (MELD)
Score measures the severity of cirrhosis based on five parameters: serum bilirubin, INR, sodium, creatinine and need for dialysis.
What is the first line treatment for hepatic encephalopathy? [1]
What is the secondory prophylaxis of hepatic encephalopathy? [1]
NICE recommend lactulose first-line
rifaximin for the secondary prophylaxis of hepatic encephalopathy
What is pneumonic for remembering the factors that influence Child-Pugh score? [5]
ABCDE
A - albumin
B - bilirubin
C - clotting
D - distention (ascites)
E - encephalopathy
What is the triad of hepatorenal syndrome? [3]
Cirrhosis
Ascites
AKI not attributable to any other cause.
How do you treat type 1 HRS? [3]
terlipressin, have a growing evidence base supporting their use. They work by causing vasoconstriction of the splanchnic circulation
volume expansion with 20% albumin
transjugular intrahepatic portosystemic shunt
(still have a v poor prognosis)
Describe the extra-hepatic symptoms of Wilsons disease [5]
Blue nails
Kayser fleischer ring
Haemolytic anaemia
Cardiomyopathy
Neurological:
- Cognitive decline
- Lack of co-ordination leading to PD like symptoms
- Dementia
- Pyschosis
-
What are the major clinical manifestations of haemochromatosis? [5]
Cirrhosis of the liver
Diabetes mellitus
Arthritis
Cardiomyopathy
Hypogonadotropic hypogonadism
Describe the impact of haemochromatosis on reproductive system [3]
Amenorrhoea
Erectile dysfunction
Testicular atrophy
Describe the presentation of Budd-Chiari syndrome [3]
abdominal pain: sudden onset, severe
ascites → abdominal distension
tender hepatomegaly
State the first and second line benzodiazepenes used to treat AWS [2]
1st line: Chlordiazepoxide
2nd line: Lorazepam - First line if cirrhotic.
Which drugs are used if seizures [1] and pyschotic symptoms [1] develop from AWS?
Seizures: IV Lorazepam
Pyschotic symptoms: Haloperidol (blocks D2 receptors)
Describe and explain treatment plan for hepatic encephalopathy [3]
1. Lactulose:
- Increases faecal bulk & peristalsis
- Also reduces colonic pH: reduces absorption of NH3
- dose varies from 15-50ml TDS
2. Phosphate enemas:
- fast acting osmotic laxative
- STAT if Ptx encephalopathic; after passing stools PRN BD
3. Rifaximin
- antibiotic: diminishes deaminating enteric bacteria to decrease production of nitrogenous compounds
- 550mg BD
When is rifaximin prescribed in HE? [1]
Only in recurrent HE
Tx for gastro-oesophageal varices? [2]
Terlipressin:
- contracts smooth oesophageal muscles; compression of the varices
- 1-2 mg for 4-6hrs until bleeding controlled
- Continue for 5day
Carvedilol:
- preffered due to mild anti-alpha 1 adrenergic activity (historically propanolol)
- used as prophylaxis
Describe IV NAC infusion regime in paracetamol OD [3]
First infusion:
- 150mg/kg: one hour
Second infusion:
- 50mg/kg: 4 hours
Third infusion (can repeat if need)
- 100mg/kg: 16 hours
Tx for Hep B? [2]
Which is safe in pregnancy? [1]
Tenofocir
- competitive inhibition: replaces the deoxyribonucleitde substrate in HBV DNA
- faster acting than entecavir
- safe in pregancy
Entecavir
- inhibits RT of Hep B DNA
- toxicity in pregnancy
Name three scoring systems used to assess NAFLD [3]
NICErecommends considering the use of which test to assess the risk of advanced liver fibrosis in people with suspected non-alcoholic fatty liver disease (NAFLD), prior to the other two? [1]
NAFLD Fibrosis Score (NFS)
Enhanced Liver Fibrosis (ELF) - NICE rec. as first line score
FIB-4
Why does Wilsons disease lead to haemolysis? [1]
The hemolysis in Wilson’s disease is due to deficiency of ceruloplasmin, the copper transport protein which results in exessive inorganic copper in the the blood circulation, much of it accumulates in red blood cells.
State two haemodynamic conseqeunces of:
- Acute liver failure [2]
- Chronic liver failure [5]
Acute liver failure:
* Cerebral oedema;
* Renal failure
Chronic liver failure:
Portal HTN:
* i) Ascites
* ii) Splenomegaly
* iii) Varices
* iv) Hepatic encephalopathy
Explain specific change in blood flow from portal hypertension contributes to hepatic encephalopathy [1]
Collaterals between splenic and renal veins: spleno-renal shunts: allow blood from bowel to bypass the liver and leak into systemic circulation, ammonia included (instead of being converted to urea and excreted). Goes to brain
What effect does portal HTN have on cell count? [1]
Why? [1]
Causes pancytopenia (red blood cells, white blood cells and platelets decreased) due to splenomegaly
How does portal hypertension lead to ascites? [5]
- Increased pressure in portal system causes fluid to leak out of the capillaries in the liver and into peritoneal cavity. Increase in pressure also causes release of splachnic vasodilators.
- Drop in circulating volume due to vasodilators on splachnic vessels and fluid forced out causes reduced pressure in kidneys
- Renin is released
- Aldosterone is secreted via RAAS
- Increased aldosterone increase Na+ and therefore fluid reabsorption
- Cirrhosis is causes low albumin levels, which decreases oncotic pressure
State 5 triggers for decompensated cirrhosis
How is spontaneous bacterial peritonitis diagnosed? [2]
Ascitic tap:
- WCC > 250 mm3 (neutrophils 80%)
- Gram -ve often
Tx of SBP? [2]
IV antibiotics: IV cefotaxime
Human albumin solution
Which drug classes can induce H.E? [3]
opiods, benzodiazepines, diuretics
Describe the treatment for hepatic encephalopathy [3]
Lactulose: laxative that reduces NH3 production in bowel
Phosphate enema (relieve constipation)
Rifaximin: modulates the gut flora resulting in decreased ammonia production
The [] blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease.
What is key about this? [1]
The enhanced liver fibrosis (ELF) blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease.
It is NOT used in patients with other causes of liver disease.
The enhanced liver fibrosis (ELF) test is a blood test that measures three molecules involved in liver matrix metabolism to give a score reflecting the severity of liver fibrosis.
Which immunoglobulins are specifically screened for in a liver screen? [3]
Which diseases do they indicate may be more likely?
IgA: ALD
IgM: Primary biliary cholangitis (PBC)
IgG: Autoimmune hepatitis
Which auto-antibodies are specifically screened for in a liver screen for:
- PBC [2]
- AIH [3]
- PSC [1]
PBC: -
- AMA (anti-mitochondiral antibody):
- AMA M2 antibody
AIH:
- ANA (Antinuclear antibody);
- SCM (smooth muscle antibody);
- SLA (soluble liver antigen)
PSC:
- ANCA (Antineutrophilic cytoplasmic antibody)
Describe the process of TIPS [2]
- shunt inserted into portal vein & into hepatic circulation
- reduces portal pressure
When is TIPS indicated? [2]
Treat bleeding in varices due to portal HTN
Ascites refractory to medical therapy
TIPS increases the risk of which pathology? [1]
Hepatic encephalopathy
State causes of acute liver failure [4]
- Drugs: paracetamol; alcohol
- Infection: Hep A / B / E
- Poor Nutrition
- Pregnancy
Describe the clinical features of someone suffering from acute liver failure [5]
- Jaundice
- coagulopathy: raised prothrombin time: INR >1.5
- Hypoalbuminaemia
- Hepatic encephalopathy
- Renal failure is common (‘hepatorenal syndrome’)
How do you manage Ptx with ALF? [6]
- Monitor for encephalopathy and conscious state.
- Administer N-acetylcysteine in all patients with acute liver failure, regardless of aetiology
- Insert a urinary catheter and monitor urine output hourly
- Blood glucose should be monitored by nursing staff every 2 hours for hypoglycaemia.
- Baseline tests depend on the history ie paracetamol levels following an overdose
- Arrange USS abdomen with Doppler of hepatic veins
Name three non-paracetamol medications can cause ALF [3]
Non-paracetamol medications: Statins, Carbamazepine, Ecstasy
How can ALF lead to death? [5]
Most cases of ALF are associated with a direct insult to the liver leading to massive hepatocyte necrosis
As the condition progresses it can lead to a hyperdynamic circulatory state with low systemic vascular resistance due to a profound inflammatory response
This causes poor peripheral perfusion and multi-organ failure
Patients also develop significant metabolic derangements (e.g. hypoglycaemia, electrolyte derangement) and are at increased risk of infection.
Marked cerebral oedema occurs, which is a major cause of morbidity and mortality in ALF.
Define Gilbert’s syndrome [1]
Gilbert’s syndrome is an autosomal recessive condition associated with intermittent raised unconjugated bilirubinaemia, resulting from a defective glucuronyl transferase. This is the enzyme involved in conjugation of bilirubin, and so the ability of patients to conjugate bilirubin is significantly reduced.
Gilbert’s syndrome is defined by which four characteristics? [4]
The condition is defined by the four following characteristics, necessary for diagnosis:
- unconjugated hyperbilirubinaemia
- normal liver function
- no haemolysis
- no evidence of liver disease
Expalin why in Gilbert’s syndrome, there is absence of bilirubin in the urine?
In unaffected individuals following conjugation, conjugated bilirubin is released into the bile and is either excreted in the faeces as stercobilin or reabsorbed in the circulation and excreted by the kidneys in the urine in the form of urobilinogen
In Gilberts: there is a defective glucuronyl transferase. This is the enzyme involved in conjugation of bilirubin, and so the ability of patients to conjugate bilirubin is significantly reduced. Unconjugated bilirubin is non-water-soluble; therefore, it cannot be excreted in the urine.
