13 - Hepatology Flashcards
1
Q
What are the functions of the liver?
A
2
Q
What are some causes of unconjugated hyperbillirubinaemia and conjugated hyperbilirubinaemia?
A
Unconjugated:
- Haemolytic disorders (e.g malaria)
- Drugs affecting liver (e.g paracetamol)
- Impaired conjugation (e.g Gilbert’s)
Conjugated
- Hepatocellular dysfunction (e.g viruses like hepatitis and CMV, liver metastases, a1-antitrypsin)
- Impaired hepatic secretion (e.g primary sclerosing cholangitis, CBD gallstones, Mirizzi syndrome)
3
Q
What are some drugs that cause drug induced jaundice?
A
4
Q
If a patient is jaundiced what investigations should you order?
A
- Liver screen (inc albumin and total protein)
- Paracetamol level
- Urine to check for billirubin in post-hepatic jaundice
- FBC, clotting, reticulocytes, malaria film, parasites, Coombs
- Blood cultures
- Hepatitis serology
- US of bile ducts
- Liver biopsy
5
Q
What is the definition of liver failure and what are some causes of this?
A
Development of coagulopathy (INR>1.5) and encephalopathy
If occurs in previously healthy liver it is acute liver failure, however more often occurs on top of cirrhosis so chronic liver failure
Causes: infections, drugs, toxins, vascular, alcohol, autoimmune conditions
6
Q
It is important to distinguish whether liver disease in a patient is acute or chronic. What questions should you ask the patient in the history to work this out?
A
- Any blood transfusions?
- Any IV drug use?
- Operations with dubious sterile procedures?
- Sexual exposure?
- Medications taken (prescribed/OTC)?
- FHx of liver disease, diabetes and IBD?
- Alcohol?
- Foreign travel?
- Obesity?
7
Q
What are some causes of acute liver failure?
A
- Drugs (e.g Paracetamol OD, halothane)
- Viral Hepatitis
- Amanita Phalloides mushroom
- Wilson’s disease
- Fatty liver of pregnancy
- Malignancy
8
Q
What are some signs of acute and chronic liver failure?
A
Acute: jaundice, hepatic encephalopathy, fetor hepaticus (sweet musty breath), asterix/flap, constructional apraxia
Chronicity: spider naevi, clubbing, ascites, palmar erythema
9
Q
What is hepatic encephalopathy and how is the severity of it graded?
A
Decline in brain function as a result of severe liver disease due to a build up of toxins (ammonia) in the blood stream and passes to the brain
10
Q
What are some blood investigations you should do in suspected acute liver failure?
IMPORTANT
A
- FBC: often thrombocytopenia if liver fibrosis
- LFTs: ALT raised if hepatocytes damaged, ALP and gamma-GT raised if ducts damaged, albumin may be decreased
- Clotting: INR often increased
- Paracetamol Level
- TFTs, Lipids and Glucose
- Rest of liver screen: see image
11
Q
What other investigations should you order for a patient with acute liver failure after bloods?
A
- Blood and urine cultures
- Abdominal US of liver and pancreas
- CXR
- Doppler US of hepatic vein if Budd-Chiari suspected
12
Q
What is included in an LFT panel?
A
Hepatocellular damage/Cholestasis:
- ALT
- ALP
- AST
- Gamma GT
Synthetic Function of Liver:
- Billirubin
- Albumin
- PT/INR
13
Q
What are some causes of an isolated ALP increase (no gamma GT increase)?
A
- Metastases or primary bone tumours
- Vitamin D deficiency
- Recent bone fractures
- Renal osteodystrophy
14
Q
What are some causes of an isolated rise of billirubin (no derangement of ALT/ALP)?
A
- Haemolysis
- Gilbert Syndrome
15
Q
What are some causes of the following:
ALT>AST
AST>ALT
A
- Chronic liver disease
- Cirrhosis and Acute alcoholic hepatitis
16
Q
If an LFT panel shows a cholestatic abnormality, what test is carried out next?
A
Need to do an US to look for any obstructive jaundice, which would have dilatation of the bile ducts
17
Q
What are some causes of hepatic and cholestatic derangement of LFTs?
A
Hepatic: ALT raised mostly
Cholestatic: ALP and gamma GT raised markedly and ALT/AST slightly raised
18
Q
What might you find on abdominal US with cirrhosis?
A
- Nodularity
- Coarse texture
- Splenomegaly
- Ascites
19
Q
What is the immediate management of acute liver failure?
A
- Refer to critical care and nearest liver transplant unit as may need transplant
- Place urinary and central venous catheter to measure urine output hourly
- Treat the cause if known (e.g paracetamol poisoning) and complications
- 10% glucose IV 1L/12h to reduce risk of hypoglycaemia, check BM every 1-4h
- Avoid sedatives
- Haemodialysis if renal failure develops
- Provide nutritional support
20
Q
What are some of the complications of acute liver failure and how are they managed?
A
- Cerebral oedema
- GI Bleeding/Varices
- Encephalopathy
- Hypogylcaemia
- Sepsis
- Renal failure
21
Q
What is the criteria for predicting poor outcome with paracetamol induced acute liver failure?
A
King’s College Criteria
If fulfill these criteria should promptly consider transplant!!!!
(pH<7.3, signs of grade III or IV encephalopathy, INR>6.5, plasma creatinine>300)
22
Q
What are some of the signs and symptoms of paracetamol overdose? (>12g/24 tablets)
A
- Initially nothing
- Nausea/vomiting
- RUQ pain
- Jaundice
- Encephalopathy
- AKI
23
Q
What are some investigations you should do for a patient coming in with paracetamol OD?
A
- Patient’s weight for treatment
- Paracetamol levels after 4h of ingestion and compare with treatment graph
- FBC and INR
- LFTs, U+Es, Phosphate
- VBG for pH, lactate, glucose, bicarbonate
24
Q
How is a paracetamol overdose managed initially?
A
<4hours since OD: activated charcoal
4 hours: take glucose, U+Es, LFT, INR, ABG, FBC, HCO3, paracetamol level
<10-12h after OD and paracetamol level over treatment line: 3 consecutive acetylcysteine IV infusions over 20 hours, checking paracetamol levels at end of 2nd infusion
>8-24h after OD and suspect large OD: acetylcysteine
25
What are some adverse reactions to N-acetylcysteine and how can you treat this adverse reaction?
**Adverse effects:** Nausea, vomiting, flushing, urticarial rash, angioedema, tachycardia, bronchospasm
**Treatment:** stop infusion, give H1 antihistamine, give salbutamol neb if required, restart when reaction settled, give antiemetics prophylactically next time
26
How is paracetamol overdose managed after acetylcysteine administration?
- Next day do INR, U+Es, LFTs. Continue Acetylcysteine until INR\<1.4
- Discuss with liver team and specialist liver unit guided by King's college criteria
27
What is hepatorenal syndrome? And what is the management?
Progressive renal failure associated with cirrhosis or acute liver failure
**Renal vasoconstriction** leads to renal failure. **Need liver transplant!**
Can treat temporarily with TIPPS, terlipressin, haemodialysis
28
What are some causes of chronic liver disease?
Eventually lead to cirrhosis:
**- Non-alcoholic steatohepatitis**
**- Viral hepatitis (Hep B and C)**
- Autoimmune hepatitis
- PBC
- PSC
- Haemochromatosis
- Wilsons
- Antil LKM
29
How does alcoholic liver disease progress?
**- Fatty liver:** reversible
**- Alcoholic Hepatitis**
**- Cirrhosis:** will show mallory bodies and neutrophil infiltrates on biopsy
30
What are some signs of alcohol withdrawal?
Starts 10-72h after last drink:
- Tachycardia
- Hypotension
- Tremor
- Confusion
- Seizures
- Delirium tremens
31
What medication should you give to a withdrawing alcoholic that is admitted as an inpatient?
- Chlordiazepoxide (benzodiazepine)
- Pabrinex or Oral Thiamine
32
How do you screen for unhealthy alcohol use quickly?
CAGE
- Ever felt you need to cut down on drinking?
- Have people annoyed you by criticising your drinking?
- Have you ever felt guilty about your drinking?
- Ever had an eye-opener in the morning?
33
How may a patient with alcoholic hepatitis present and how may their bloods present?
**_Patient:_** malaise, raised RR/HR/Temp, anorexia, tender hepatomegaly, jaundice, bleeding, ascites, encephalopathy
**_Bloods:_** increased INR, thrombocytopenia, increased AST, raised MCV, raised WCC, raised urea
34
What would indicate severe alcoholic hepatitis when looking at a patient?
- Jaundice
- Encephalopathy
- Bleeding
35
How should we manage alcoholic hepatitis?
**- Screen for infections** and ascitic tap
**- Stop alcohol consumption immediately** and give **chlordiazepoxide IV or lorazepam IM** for withdrawals
**- Vitamin K, Thiamine (or Pabrinex**)
**- Optimise nutrition**
**_- Consider steroids_** if severe disease
36
What score is used to assess mortality in alcoholic liver disease?
**Maddrey Score**
- Prothrombin time
- Billirubin
If Maddrey\>31 and encephalopathy give prednisolone!!!
37
What blood result can indicate hepatorenal syndrome developing?
Raising creatinine
38
What is NAFLD?
**Increased fat in hepatocytes** that cannot be attributed to other causes. Can be seen on **US**
**Can progress to cirrhosis** so need **biopsy and elastography.**
Raised ALT
39
How is NAFLD managed?
**- Control risk factors** e.g bariatric surgery for obesity, control diabetes
**- Address CVD risk**
**- Avoid alcohol**
**- Monitor for complications** e.g cirrhosis, NASH, DM
- If cirrhotic **screen for HCC** with US and AFP twice yearly
40
Apart from Hep B/Hep C, what are some other infective causes of hepatitis?
- EBV
- CMV
- Malaria
- Syphillis
- Yellow fever
41
What are the following for Hepatitis A:
- Spread
- Symptoms
- Diagnosis
- Treatment
- Very rare to develop chronic infection!
- Incubation 2-6 weeks
- Can get immunised IM as a child
42
What are the following for Hepatits B?
- Spread
- Symptoms
- Incubation
43
What are some antigens/antibodies tested for in a Hepatitis B infection and what do they mean?
**HBsAg:** present first 1-6months after exposure
**HBeAg:** *high infectivity*, 1-3 months adter acute illness
**HBcAb:** implies past infection
**HBsAb**: implies vaccination if no core antibody found too
Can also do liver biopsy and US elastography to look for liver damage
44
What does it mean if HbsAg persists for over 6 months?
Defines carrier status so chronic infection
45
How is hepatitis B managed?
**Aim is to clear HBsAg and prevent cirrhosis and HCC**
- Avoid alcohol
- Immunise sexual contacts
- Fluids and pain relief for acute
- Refer for antivirals and peginterferon alfa 2-a if chronic liver inflammation or cirrhosis. Can consider liver transplant to
46
What are some of the complications of hepatitis B?
- Acute liver failure
- Cirrhosis
- HCC
- Cholangiocarcinoma
- Membranous nephropathy
47
If someone has had exposure to Hep B what is the management?
- Can give vaccine if not already vaccinated up to 12 hours after exposure
- Hep B serology
48
What are the following for hepatitis C:
- Spread
- Symptoms
- Risk factors for progression
Incubation of 6-8 weeks
49
What investigations are done to diagnose Hep C?
**- Anti-HCV** confirms exposure
**- HCV-PCR** confirms ongoing infection
**- Liver biopsy or US elastography** if HCV-PCR positive to assess liver damage
**- Raised LFTs**
50
What are some complications of Hep C?
- Cirrhosis
- HCC
- Liver failure
- Glomerulonephritis
- Autoimmune hepatitis
- Polymyositis
51
How is Hep C managed?
**- Avoid alcohol**
**- Start antivirals** ledipasvir and sofosbuvir for 8-12 weeks
**- Test for HIV** and treat this as HIV increases rate of HCV induced liver cirrhosis
**- Tell patient they can catch it again,** there is no vaccine and no immunity from already having it
52
What is hereditary haemochromotosis?
**Autosomal recessive** disorder with a mutation of the HFE gene on chromosome 6, where there is **increased intestinal iron absorption** so **increased iron deposition** in joints, liver, heart, pancreas, pituitary, adrenals and skin
53
How may a patient with hereditary haemochromatosis present?
**Early:** asymptomatic, tiredness, arthralgia
**Late:** slate-grey skin, signs of chronic liver disease, hepatomegaly, cirrhosis, dilated cardiomyopathy, bronze DM, hypogonadism, pituitary dysfunction
54
What tests are done to diagnose herediary haemochromotosis?
**- Gold standard:** HFE genotyping (hepcidin protein)
**- Bloods**: raised LFT, raised ferritin (also raised in inflammation), raised transferrin saturation
**- Imaging:** chondrocalcinosis, liver and cardiac MRI have Fe overload
**- Liver biopsy:** Perl's stain shows iron loading
55
How is hereditary haemochromatosis managed?
**- Venesection** every 2-3 months for life
**- Desferrioxamine**
**- Monitor LFTs and glucose** (HbA1c may be falsely low due to venesection)
**- If cirrhotic screen for HCC** with US and AFP twice yearly
**- Avoid iron in diet and OTC vitamins**
56
What is the prognosis with hereditary haemochromotosis?
- If cirrhosis 30% chance of developing HCC
- With venesection life expectancy back to normal and can help improve cirrhosis
57
What is autoimmune hepatitis and who does it mainly affect?
Inflammatory autoimmune condition where **T-cells and auto-antibodies** direct **against hepatocyte surface antigens**
Usually affects **women** in bimodal distribution (10-30 and then \>40)
58
What is the typical presentation of autoimmune hepatitis?
**- Acute hepatitis**
**- Features of autoimmune disease:** fever, malaise, urticarial rash, polyarthritis, pleurisy, glomerulonephritis
**- Gradual jaundice**
**- Asymptomatic**
**- Amennorhea**
59
How is autoimmune hepatitis investigated and diagnosed?
**_Ix_**
**- LFTs:** bilirubin, ALT, ALP, AST raised
**- Hypergammaglobulinaemia:** especially IgG
**- Autoantibodies:** ANA, p-ANCA, anti-LKM1, anti-SMA
**- FBC:** anaemia, low platlets, low WCC due to hypersplenism
**- Liver biopsy:** mononuclear infiltrate of portal areas, necrosis and fibrosis
- **MRCP**: helps exclude PSC
**_Dx:_** based on biopsy, autoantivodies and IgG levels.
60
What are the two different classifications of autoimmune hepatitis?
**Class I:** in 80% of patients, ASMA and ANA auto antibodies
**Class II:** commoner in younger patients, more chance of progressing to cirrhosis, LKM1 antibodies
61
What are some diseases associated with autoimmune hepatitis?
- UC
- Pernicious anaemia
- Glomerulonephritis
- Autoimmune thyroid disease
- DM
- HLA A1, B8, DR3
62
How is autoimmune hepatitis managed to try and slow the progression of cirrhosis?
**_- Immunosuppresion_**: *Prednisolone* to induce then *Azathioprine* for maintenance of remission
**_Liver transplantation:_** if decompensated liver cirrhosis or failed to respond to medical therapy
63
What is primary biliary cholangitis?
Interlobular bile ducts are damaged by **autoimmune granulotamous inflammation** causing **cholestasis** which can lead to **fibrosis, cirrhosis and portal hypertension**
More common in women
64
What are some signs and symptoms of PBC?
**Symptoms:** asymptomatic incidental ALP rise, lethargy, sleepiness
**Signs:** jaundice, hepatosplenomegaly, xanthelasma, xanthoma, signs of cirrhosis
65
What are some tests used to diagnose PBC?
**Bloods:** raised ALP and gamma GT, raised AST/ALT in late disease, decreased albumin, raised bilirubin
**Autoantibodies:** AMA
**US**: exclude extrahepatic cholestasis
**Biopsy**: look for granulomas around bile ducts and cirrhosis
66
How is PBC treated?
**_Symptomatic:_**
* - Cholestyramine* for pruitis
* - Codeine phosphate* for diarrhoea
- Osteoporosis prevention
**_Specific:_**
- Fat soluble vitamins (A, D, K)
- High dose **ursodeoxycholic acid**
- Liver transplant for late stage disease
67
How do we monitor PBC patients?
- Regular LFT
- US and AFP twice yearly if cirrhotic
68
What is primary sclerosing cholangitis?
Progressive cholestasis with bile duct inflammation and strictures.
Occurs in intra and extrahepatic ducts
69
What are some of the signs and symptoms of PSC?
Usually in **males** and **occurs with IBD**
- Pruitis
- Ascending cholangitis
- Cirrhosis
70
What cancers are PSC associated with?
- Colon
- Bile duct
- Gall bladder
- Liver
Do colonscopy and US yearly and consider cholecystectomy
71
What tests are done to diagnose PSC?
**Bloods**: raised ALP and billirubin
**Autoantibodies:** ANA, SMA and ANCA positive but AMA -ve
**MRCP or ERCP**: beads on a string
**Liver biopsy:** fibrous obliterative cholangitis
72
How is PSC treated?
- Definitive is ***liver transplant***
- Ursodeoxycholic acid may improve LFT but no survival benefit
***- Colestyramine*** for itch
***- Abx*** for bacterial cholangitis
73
What is Wilson's disease?
**Autosomal recessive** disorder of copper excretion with **excess deposition in liver and CNS.**
**Treatable** cause of cirrhosis so test everyone with cirrhosis for it
Due to the fact **copper cannot be incorporated to caeruloplasmin** so cannot be excreted into bile
74
Where is copper absorbed in the body?
Small intestine
75
How does Wilson's disease present?
**- Liver disease:** *cirrhosis,* failure
- **CNS signs:** tremor, dysarthria, parkinsonism, dystonias
**- Mood:** depression, labile emotions
**- Cognition:** decreased memory
**- Kayser Fleischer rings:** in iris
76
What tests are done to diagnose Wilson's disease?
**- Urine 24h copper excretion:** raised
**- LFTs:** raised
**- Serum Cu**
**- Serum caeruloplasmin:** lowered
**- Molecular genetic testing**
**- Liver biopsy**
**- MRI:** look at basal ganglia
77
How is Wilson's disease treated?
**- Diet:** avoid food high in copper e.g liver, chocolate, mushrooms, shellfish
**- Lifelong penicilllamine:** chelating agent, will reverse cirrhosis
**- Screen siblings**
**- Liver transplant** if severe liver disease
78
What is cirrhosis and what are some of the causes of this? **(bold is most common)**
Irreversible liver damage, nodular regeneration surrounded by bands of fibrosis
- Infective (**HBV, HCV)**
- Autoimmune
- Metabolic disorders
**- Alcoho**l/Drugs
**- NAFLD**
79
When should you suspect cirrhosis?
In patients with **thrombocytopenia** or **clinical stigmata of chronic liver disease**
80
What are some of the signs a patient may display with cirrhosis?
- Jaundice
- Hepatosplenomegaly
- Leuconychia
- Clubbing
- Palmar erythrema
- Dupuytren's contracture
- Spider naevi
- Gynacoemastia
- Ascites
- Testicular atrophy
- Parotid swelling
- Asterixs/Hepatic flap
81
What are some complications of cirrhosis?
**- Hepatic failure:** coagulopathy, encephalopathy, hypoalbuminaemia, sepsis, spontaneous bacterial peritonitis, hypoglycaemia
**- Portal hypertension**: ascites, splenomegaly, oesophageal varices, caput medusa
**- HCC**
82
What are some tests you should do when you suspect liver cirrhosis?
**- Bloods:** LFTs, FBC (platelets and WCC may drop)
**- Autoantibodies:** help find cause
**- Viral serology:** help find cause
- **Caeruloplasmin and a1-antitrypsin levels**
**- FIBROSCAN US**: liver may be small
**- MRI**
**- Ascitic tap**: urgent MC+S to look for spontaneous bacterial peritonitis
**- Liver biopsy:** CONFIRM DIAGNOSIS
83
How is cirrhosis diagnosed?
**- History**
**- Exam**
**- Bloods**
**- USS:** Course texture, nodular, splenomegally, ascites, enlarged caudate lobe.
**- Fibroscan**
**- Liver biopsy**
84
If a patient has an endoscopy and is found to have varices, what is this diagnostic of?
Cirrhosis
85
What should you screen all patients with cirrhosis for?
**- Varices** to detect for primary prophylaxis to lower bleeding risk
- If ascites do **ascitic tap** for cell count and MC+S to check for spontaneous **bacterial peritonitis**
- Check **AFP and US** twice yearly for **HCC**
- Long term do **DEXA scan for osteoporosis**
86
How do you treat cirrhosis in general?
**TREAT UNDERLYING DISEASE** e.g penicillamine for Wilson's
## Footnote
- Good nutrition
- Avoid alcohol, NSAIDs, sedatives and opiates
- Colestyramine for itching
- US and AFP twice yearly for HCC
**_- Definitive:_** liver transplant
87
How are the following cirrhotic complications managed:
- Ascites
- Encephalopathy
- Spontaneous bacterial peritonitis
**_Ascites_**
## Footnote
* - Fluid restrict and low salt diet*
* - Spironolactone*
- If tense do *therapeutic paracentesis* with albumin infusion
- Take daily weight
**_Encephalopathy_**
- Prophylactic lactulose
**_SBP_**
- Consider if ascites and patient deteriorating quickly
- Commonly due to E.Coli and Klebsiella
* - Piperacillin with tazobactam*
88
What are some poor prognostic indicators with cirrhosis?
- Encephalopathy
- Na\<110
- Serum albumin \<25
- Raised INR
89
What are some indications for liver transplantation (both acute and chronic)?
**Acute:** King's college criteria
**Chronic:** advanced cirrhosis of any cause, HCC with 1 nodule\<5cm or \<5nodules \<3cm
90
What are some contraindications for liver transplantation?
- Extrahepatic malignancy
- Severe cardiorespiratory disease
- Systemic sepsis
- Continued alcohol use
- Unlikely to comply with drugs
91
How do we prioritise which patients get a liver transplant first?
**_UKELD score_**
Predicts mortality in end stage liver disease
**Looks at:** INR, Billirubin, Sodium and Creatinine
Can also look at Child Pugh and MELD score
92
What are the biggest issues cirrhosis causes and what factors can cause the cirrhosis to decompensated?
**Issues**: jaundice, encephalopathy, ascites
**Factors:** dehydration, constipation, alcohol use, infection, opiate overuse, GI bleed SO AVOID THESE
93
Cirrhosis causes portal hypertension. What are some signs of this?
- Ascites
- Encephalopathy
- Caput Medusa
- Varices
DIAGNOSE BY ENDOSCOPICALLY LOOKING FOR VARCIES OR LOOK FOR ASCITES
94
How can portal hypertension be managed?
- Avoid alcohol
- Endoscopic sclerotherapy or banding for varices
- Salt restrict
- TIPPS or DSRS
95
What veins do oesophageal varices form between?
Azygous and Short gastric veins
(don't forget varices at rectal and umbilical areas)
96
What are the reasons for malnutrition in chronic liver disease?
**_Impaired intake_**
- Lack of appetite and early sateity due to ascites. Liquid calories. Not wanting to eat due to oesophagitis
- Offer other ways of nutrition e.g NG
**_Impaired nutrient storage and synthesis_**
- Liver cannot store and synthesise micronutrients like water soluble vitamins. Thiamine deficiency
- Give Pabrinex or Oral thiamine
**_Impaired absorption_**
- Due to portal hypertension
97
What clinical guideline would you use to determine specific treatment for paracetamol overdose?
**TOXBASE -** use the normogram provided!
**- 3 consecutive acetyl cysteine infusions over 20 hours** if paracetamol levels over treatment line. Efficacy decreases after 8 hours.
98
How does acetly cysteine help with paracetamol OD?
It helps to **replenish glutathione** which helps to conjugate **NAPQI** to safe molecules that can be excreted
99
How do you conduct a MMSE?
- Orientation
- Attention and Calculation
- Recall
- Language
- Copying
100
What investigations should you do for a patient admitted with a paracetamol overdose?
**- Patient's weight** for treatment
**- Paracetamol levels** after 4h of ingestion and compare with treatment graph
**- FBC and INR**
**- LFTs, U+Es, Phosphate**
**- VBG** for pH, lactate, glucose, bicarbonate
101
What is needed before a safe discharge following a paracetamol OD?
- Psychiatric risk assessment
- Paracetamol levels below threshold
- LFTs returning to normal
102
How is malnutrition best managed?
- High calorie and fortified foods
- Nutritional supplements
- Support with eating e.g someone feeding, teeth in
- Treating any underlying conditions causing malnutrition e.g IBD
- Feeding tubes
