Chronic Liver Disease II Flashcards
1
Q
Remind yourself of some causes of chronic liver disease- highlighting the most common
*This deck provides more in depth information about each of the causative conditions
A
- Alcoholic liver disease
- Non-alchoholic fatty liver disease
- Hep b
- Hep C
- Autoimmune hepatitis
- Primary biliary sclerosis
- Primary sclerosing cholangitis
- Alpha-1 antitrypsin deficiency
- Haemochromatosis
2
Q
Remind yourself of the symptoms of chronic liver disease
**For each of the diseases that we discuss in this deck, we will discuss symptoms related to each of the diseases but remember that each of the diseases cause chronic liver disease and hence may have symptoms of chronic liver disease or cirrhosis
A
- Fatigue
- Anorexia
- Weight loss
- Nausea & vomitting
- Abdo tenderness
- Loss of sex drive
- Pruritis
- Forgetfulnes, confusion
- Frequent nose bleeds
- Bleeding gums
- Easy bruising
- ….
3
Q
Remind yourself of the clinical signs/stigmata of chronic liver disease
**For each of the diseases that we discuss in this deck remember that they all cause chronic liver disease and hence could present with symptoms of chronic liver disease/cirrhosis
A
Hands
- Asterixis
- Leuconychia
- Terry’s nails
- Clubbing
- Palmar erythema
- Dupuytren’s contracture
Face
- Xanthelasma
- Scleral icterus & yellow skin
Chest
- Gynaecomastia
- Spider naevi
Abdomen
- Ascites
- Caput medusa
- Bruising
- Hepatomegaly
Legs
- Peripheral oedema
4
Q
What is NAFLD?
A
Fat is deposited in liver cells. Initially does not cause problems however it can interfere with functioning of liver cells and lead to hepatitis and cirrhosis. Forms part of the metabolic syndrome.
5
Q
State the 4 stages of NAFLD
A
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis
- Fibrosis
- Cirrhosis
*once person reaches NASH stage, prognosis worsens as ~40% go on to develop fibrosis
6
Q
State some risk factors for NAFLD
A
Same as for CVD & diabetes:
- Obesity
- Poor diet & low activity
- T2DM
- High cholesterol
- Smoking
- Hypertension
- Age (middle-age onwards)
7
Q
What investigations would you do if you susupect NAFLD, include:
- Bedside
- Bloods
- Imaging
*For each, indicate why you are doing the test
A
Bedside
- BMs: check diabetes
- BMI
Bloods
- FBC: platelets, decresed WCC, anaemia
- U&Es: hyponatraemia, urea & creatinine may be off
- LFTs:abnormal
- TFTs: may be abnormal in liver problems
- Coagulation studies
- Non-invasive liver screen
- ELF blood test
Imaging
- Liver ultrasound: can confirm diagnosis of steatosis but does indicate severity, function of liver or if there is fibrosis.
- Fibroscan: measures stiffness of liver to give an indication of fibrosis. Performed if the ELF blood test or NAFLD fibrosis score indicates fibrosis
8
Q
Discuss the recommended investigations for assessing fibrosis in NAFLD
A
- ELF blood test
- If ELF blood test not available, can use NAFLD fibrosis socre
- Fibroscan
9
Q
What is the ELF blood test?
How is it used to indicate fibrosis?
A
- Enhanced liver fibrosis blood test
- Measures markers (HA, PIIINP and TIMP-1) and uses an alogrithm to indicate degree of fibrosis of liver:
- <7.7= none to mild
- >/=7.7 - 9.8= moderate
- >/= 9.8= severe
10
Q
What is the NAFLD fibrosis score?
What is it used for?
A
Uses an alogrithm which is based on:
- BMI
- Age
- Liver enzymes
- Platelets
- Albumin
- Diabetes
Helpul in ruling out fibrosis but not helpful at assessing severity when present
11
Q
The ELF test is the first line investigation for assessing fibrosis in NAFLD; however, what is the current issue (2020) with this test?
A
Not currently available in many areas
12
Q
Discuss the management of NAFLD
A
NAFLD management
- Weight loss
- Exercise
- Stop smoking
- Control of diabetes, blood pressure, cholesterol
- Avoid alcohol
- If they have fibrosis:
- Vitamin E
- Or pioglitazone
^^^Both known to improve NAFLD
If pt develops cirrhosis, treat and manage their cirrhosis as already discussed in Chronic Liver Disease I
13
Q
Remind yourself what tests are involved in the non-invasive liver screen
A
Non-invasive liver screen aim is to determine cause of abnormal LFTs/liver disease:
- Hep B & C serology
-
Autoantibodies
- ANA: autoimmune hepatitis
- SMA: autoimmune hepatitis (70%)
- AMA: primary biliary cholangitis (95%)
- LKM-1 (autoimmune hepatitis)
- Immunoglobulins
- Caeruloplasmin (Wilson’s disease)
- Alpha-1 antitrypsin deficiency (alpha-1 antitrypsin deficiency)
- Ferritin, trasnferrin saturation, TIBC (haemochromatosis)
- Alpha-feto protein (hepatocellular carcinoma)
- Viral screen for EBC, CMV etc..
- Coeliac serology
- Serum protein electrophoresis (help confirm alpha-1 antitrypsin deficiency)
14
Q
What is haemochromatosis?
What gene is mutated and where is this gene found?
What is the inheritence pattern?
A
- Fe storage disorder that results in excessive total body Fe and hence the deposition of Fe in tissues including liver, heart, pancreas etc….
- Mutated HFE gene on chromosome 6 (other genes can also cause condition)
- Autosomal recessive
15
Q
Discuss the pathophysiology of haemochromatosis
A
- Mutated HFE gene (and hence protein)
- HFE usually interacts with transferrin receptor and reduces its affinity for Fe bound transferrin. Mutated HFE protein can’t bind to transferring receptor and hence can’t exert negative effect on binding; consequently too much Fe taken up into cells
16
Q
At what age does haemochromatosis usually present?
Why does it often present later in females?
A
- Present >40yrs (when Fe overload becomes symptomatic)
- Menstruation acts to regularly elimate Fe from body
17
Q
State some symptoms of haemochromatosis
A
- Chronic tiredness
- Joint pain
- Pigmentation (bronze/slate grey discolouration)
- Hair loss
- Erectile dysfunction
- Ammenorrhoea
- Cognitive symptoms (mood & memory disturbance)
18
Q
The main diagnostic test to confirm haemochromatosis is a serum ferritin level; discuss whether serum ferritin is a specific test and any additional tests you can do to make results conclusive
A
- Ferritin is an acute phase reactant hence it can be elevated in inflammatory conditions
- Perform both serum ferritin & transferrin saturation to determine if serum ferritin is elevated due to excess Fe or due to inflammation
**Transferrin saturation is considered most useful marker
19
Q
Following serum ferritin & transferrin saturation tests, what other tests can you do to aid diagnosis of haemochromatosis?
A
- Genetic testing
- Liver biopsy with Perl’s stain (can establish Fe concenration in parenchymal cells. Used to be gold standard but now replaced by genetic testing)
- CT abdomen (non-specific increase in attenuation in liver)
- MRI (look for Fe depositis in liver & heart)
20
Q
Discuss the management of haemochromatosis
A
- Venesection
- Monitoring serum ferritin
- Avoid alcohol
- Genetic counselling
- Monitoring & treatment of complications
21
Q
State some potential complications of haemochromatosis
A
- T1DM
- Liver cirrhosis
- Endocrine & sexual problems (e.g. hypogonadism, impotence, amenorrhoea, infertility)
- Cardiomyopathy
- Hepatocellular carcinoma
- Hypothyroidism
- Chrondocalcinosis/pseudogout
22
Q
What is primary biliary cirrhosis?
A
Condition where immune system attacks small bile ducts within the liver; first ducts to be affected are the interlobar ducts- also known as Canals of Hering. This causes cholestasis; back pressure and overall disease process ultimately leads to fibrosis, cirrhosis & liver failure
*chronic autoimmune granulomatous inflammation
23
Q
Who is PBC more common in; men or women?
State some risk factors for PBC
A
- More common in middle aged women
- Risk factors:
- Female
- Other autoimmune diseases (e.g. thyroid, coeliac)
- Rheumatoid conditions (e.g. RA, Sjogrens, systemici sclerosis)
- Smoking
- 45-60
24
Q
State some symptoms & signs of primary biliary cirrhosis
A
- Fatigue
- Pruritis
- GI disturbance & abdo pain
- Jaundice
- Pale stools
- Xanthoma & xanthelasma
- Hepatosplenomegaly
- Signs of liver cirrhosis
*NOTE: pt often asymptomatic and diangosed after incidental finding of raised ALP
25
For each of the following symptoms of primary biliary cirrhosis, explain why they ocur:
* Pruritis
* Jaundice
* Xanthelasma & xanthoma
* Steatorrhoea
Bile acids, bilirubin & bile salts are usually excreted through bile ducts into intestines hence when there is an obstruction they build up in the blood:
* Pruritis: build up of bile acids in blood
* Jaundice: build up of bilirubin in blood
* Xanthelasma & xanthoma: build up of cholesterol in blood
* Steatorrhoea: lack of bile acids in intestine (greasy/fatty stools) and lack of bilirubin in stool (pale)
26
Discuss what the results of the following investigations would be in someone with PBC:
* ALP, AST, ALT, bilirubin
* Autoantibodies
* ESR & IgM
* Liver enzymes
* **ALP = first liver enzyme to be raised**
* ALT & AST & bilirubin may be raised later in disease
* Autoantibodies:
* **AMA (anti-mitochondrial antibodies)** is most specific to PBC
* **ANA (anti-nuclear antibodies)** raised in about 35% pts
* **Smooth muscle antibodies** *(30%)*
* **ESR & IgM raised**
27
Following blood tests, what other imaging and tests could you do to help confirm PBC?
Liver biopsy
## Footnote
*\*Oxford handbook says it s*
28
Discuss the treatment for PBC
* **1st line= Ursodeoxycholic acid**: *reduce intestinal absoprtion of cholesterol (helps to improve symptoms & slow disease progression)*
* **Colestyramine**: *bile acid sequestrant- prevents bile acid absorption in gut to help reduce plasma bile acids and hence reduce itching*
* **Fat soluble vitamin prophylaxis**
* **Osteoporosis prevention**
* **Liver transplant**
* **Immunosupression with steroids** *(considered in some pts\_)*
* **Regular monitoring**
29
Disease course and symptoms of PBC vary significantly; state soem potential complications of PBC
Most important are:
* Advanced liver cirrhosis
* Portal hypertension
Others are:
* Symptomatic pruritis
* Fatigue
* Steatorrhea
* Distal renal tubular acidosis
* Hypothyroidism
* Osteoporosis
* Hepatocellular carcinoma
30
What is primary sclerosing cholangitis?
Inflammation of intrahepatic and extrahepatic ducts become strictured and fibrotic- leading to obstruction of bile flow out of liver and into intestine.
* Sclerosis: thickening & hardening of bile ducts
* Cholangitis: inflammation of bile ducts
Chronic bile obstruction leads to liver inflammation, fibrosis and cirrhosis
Cause is unclear but likely to be combination of genetic, autoimmune, intestinal microbiome & environmental factors.
31
State some risk factors for primary sclerosing cholangitis (PSC)
* **Male**
* 30-40yrs
* **Ulcerative colitis**
* Crohn's (less common in crohn's than in UC)
* **HIV**
* Family history
32
State some symptoms &signs of PSC
* Jaundice
* Chronic upper right quadrant pain
* Pruritis
* Fatigue
* Hepatomegaly
33
For a pt with PSC state what the following blood tests would show:
* ALP
* AST & ALT
* Bilirubin
* ALP= raised
* AST & ALT: raised as disease progresses
* Bilirubin: raised
34
Discuss whether autoantibodies can be used to support a diagnosis of PSC
No antibodies highly specific to PSC hence aren't very helpful in diagnosis but they can indicate if there is an autoimmune elemetn to disease and hence whether it will respond to immunosupression:
* p-ANCA: raised in up to 94%
* ANA: raised in up to 77%
* aCL: raised in up to 63%
35
What is the gold standard for diagnosing PSC?
MRCP (magentic resonance cholangiopancreatography)= MRI scan of liver, bile ducts & pancreas. It will show bile duct lesions or strictures
36
State some potential complications of PSC
* Acute bacterial cholangitis
* Cholangiocarcinoma
* Colorectal cancer
* Cirrhosis
* Biliary strictures
* Fat soluble vitamin deficiencies
37
Discuss the management of PSC
* **Liver transplant can be curative** *(but associated with it's own problems)*
* **Colestyramine:** *bile acid salt sequestrant to prevent bile acid absorption in intestines and hence reduce plasma bile acids and reduce pruritis*
* **ERCP** (endoscopic retrograde cholangio-pancreatography) can be used to dilate & stent any strictures
* **Monitoring for complications e.g. cholangiocarcinoma, cirrhosis, varices etc…**
38
Describe ERCP (endoscopic retrograde cholagnio-pancretography)
* Insert camera down throat
* Go down to duodenum
* Go through sphincter of Oddi into ampulla of Vater
* Then enter bile ducts and use x-rays and inject contrast to identify any strictures
* Strictures can be dilated & stented during same procedure
39
What is the recommended weekly alcohol intake for men and for women?
* No more than 14 units per week
* If drinking 14 units, this should be spread over 3 or more days (no more than 5 units per day)
40
What questions can you use to quickly screen for harmful alcohol use?
Use CAGE questions:
* **C-** have you ever thought you shut cut down?
* **A-** do you get annoyed at others commenting on your drinkin?
* **G-** do you ever feel guilty about drinking?
* **E-** do you ever drink in the morning to either help you hangover or nerves?
41
Alongide your CAGE questions, what other screening tools can you use to assess whether someone's alcohol consumption is harmful?
* AUDIT questionnaire (alcohol use disorder identification test)
* 10 questions with multiple choice answers
* Score of 8 or more indicates harmful use
42
What is meant by alcoholic liver disease?
Chronic liver disease caused by long term excessive consumption of alcohol
43
Describe the stepwise progression of alcoholic liver disease
1. **Alcohol related fatty liver**: *drinking leads to build up of fat in liver; if stop drinking this reverses in ~2 weeks*
2. **Alcoholic hepatitis**: *inflammation of liver which is usually reversible with permanent abstinence*
3. **Cirrhosis**: *liver made up of scar tissue with nodule formation. Irreversible. Stop drinking to prevent further damage*
44
The onset and progression of alcoholic liver disease varies betwen people; what does this suggest?
There may be a genetic predisposition to alcohol having harmful effects on the liver
45
State some potential complications of excessive alcohol consumption
* Alcoholic liver disease- has complications such as cirrhosis & hepatocellular carcinoma
* Alcohol dependence & withdrawal
* Wernicke-Korsakoff syndrome
* Pancreatitis
* Alcoholic cardiomyopathy
46
How may someone with alcoholic liver disease present?
Present with symptoms & signs of chronic liver disease
_Symptoms_
* Fatigue
* Nausea & vomitting
* Anorexia
* Pruritis
* Easy bruising
_Signs_
* Asterixis
* Leuconychia
* Palmar erythema
* Dupuytren's contracture
* Jaundice
* Gynaecomastia
* Ascites
* Caput medusa
* Spider neavi
47
Discuss what the results of the following blood tests may show in alcoholic liver disease:
* FBC
* LFTs
* Clotting
* U&Es
* FBCs
* Macrocytic anaemia
* Thrombocytopenia
* LFTs
* Raised ALT and AST
* AST raised more than ALT
* Low albumin
* Elevated bilirubin
* Clotting
* Elevated prothrombin time
* U&Es
* Deranged in hepatorenal syndrome
48
Discuss what imaging techniques you may use to investigate someone with suspected alcoholic liver disease
* Ultrasound
* Fibroscan
* Endoscopy: *check for oesophageal varices*
* CT & MRI: *fatty liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes, ascites*
* Liver biopsy: *can be used to confirm diagnosis of alcoholic related hepatitis or cirrhois. NICE reccomends in pts where steroid treatment is being considered*
49
Dicsus the general management of alcoholic liver disease
* Stop drinking alcohol permanently
* Consider detoxication regime
* Nutritional support with vitamines (particularly thiamine) & high protein diet
* Steroids improve short term outcomes in severe alcoholic hepatits
* Treat complications of cirrhosis
* Refer for liver transplant in severe disease
50
What is sometimes given in the acute phase of alcoholic hepatitis?
What tool can be used to assess who would benefit from the above?
* **Glucocorticoids** (e.g. PO prednisolone) may given during acute episode
* Can use **Maddrey's discriminant function** to help determine who would benefit from steroids (uses prothrombin time & bilirubin concentration to calculate)
*\*\*NOTE: pentoxyphylline is also sometimes used. STOPAH study compared the two common treatments for alcoholic hepatitis, pentoxyphylline and prednisolone. It showed that prednisolone improved survival at 28 days and that pentoxyphylline did not improve outcomes. (Directly copied from passmed)*
51
How long must someone abstain from alcohol for before they can be referred for liver transplant?
3 months
52
When someone is alcohol dependent and stops drinking there is a risk of them developing withdrawal symtpoms; the symptoms can vary greatly. Different symptoms occur at different times after alcohol consumption ceases; state the symptoms at:
* 6-12 hrs
* 12-24hr
* 24-48hrs
* 24-72hrs
* 6-12hrs: **tremor, sweating, headahce, craving, anxiety**
* 12-24hrs: **hallucinations**
* 24-48hrs: **seizures**
* 24-27hrs: **delerium tremens**
53
Explain what delirium tremens is, include:
* Pathophysiology
* What is happening in terms of excitability of brain
* Symptoms & signs
_Medical emergency associated with alcohol withdrawal._
* **Alcohol stimulates GABA receptors** and **inhibits glutamate/NMDA receptors**- this has overall inhibitory effect on brain
* Chronic alcohol use results in **GABA receptors being downregulated and glutamate/NMDA receptors being upregulated**- this is bodys attempt to balance out the effects of alcohol.
* When alcohol is removed from system, **GABA underfunctions & glutamate/NMDA overfunctions** causing an **extreme excitability of brain with excess adrenergic activity**
_Symptoms & signs:_
* Acute confusion
* Severe agitation
* Delusions or hallucinations
* Tremor
* Tachycardia
* Hypertension
* Hyperthermia
* Ataxia
* Arrhythmias
54
What vitamin deficiency does excessive alcohol consumption lead to?
Thiamine (vitamin B1)
55
Explain why alcoholics have thiamine (vit B1) deficiency
* Thiamine poorly absorbed in presence of alcohol
* Alcoholics tend to have poor diets & rely on alcohol for their calories
56
State two conditions that arise from thiamine deficiency in alcoholics
State which comes first
State if they are reversible or irreversible
* **Wernicke's encephalopathy**- *reversible. But is a medical emergency that has high mortality if untreated*
* **Korsakoffs syndrome:** *irreversible & pts require full time institutional care*
*\*Wernicke's comes first*
57
What is the triad of symptoms in Wernicke's encephalopathy?
* **Confusion**
* **Occulomotor disturbances** e.g. nystagmus, lateral rectal palsies etc...
* **Ataxia**
58
What is Korsakoff's syndrome?
* Memory impairement (retrograde & anterograde)
* Behavioural changes
*(Dementia caused by thiamine deficiency)*
59
What scoring systems can be used to score pts on their withdrawal symptoms and guide treatment for alcohol withdrawal?
* CIWA-Ar (clinical institute withdrawal assessment- alcohol revised) tool.
* GMAWS in UHL
60
State two medications we can use to treat alcohol withdrawal
* **Chlordiazepoxide ("librium")**: *benzodiazepine hence binds to GABA and increases Cl- conductance to have inhibitory effect on brain*
* **IV high dose B vitamins (pabrinex):** *to prevent Wernicke's encephalopathy & Korsakoffs*
61
What % of people will relpase soon after starting treatment for alcohol withdrawal?
50%
62
What should IV pabrinex be followed by?
Regular lower dose oral thiamine
63
What drug can be used to treat chronic alcohol dependence?
## Footnote
*\*HINT: causes extremely unpleasant effects after alcohol consumption*
Disulfiram
64
Hepatitis is inflammation of liver; state some causes of inflammation of liver
* Alcoholic hepatitis
* Non-alcoholic fatty liver disease
* Viral hepatitis
* Autoimmune hepatitis
* Drug induced hepatitis (e.g. paracetamol overdose)
65
State some signs & symptoms of hepatitis
* Abdo pain
* Fatigue
* Pruritis
* Muscle & joint aches
* Nausea & vomitting
* Jaundice
* Fever (viral)
66
What would be the results of the following tests in hepatitis:
* ALT & AST
* ALP
* Bilirubin
* ALT & AST= high
* ALP= should be less of a rise compared to AST & ALT
* Bilirubin= high (can rise as a result of inflammation of liver cells)
67
What is the most common viral hepatitis world-wide?
Hepatitis A (but realatively rare in UK)
68
For hepatitis A, describe:
* DNA or RNA
* Transmission
* Spontaneous recovery or progression
* Vaccination
*
* RNA
* Faecal-oral route (usually contaminated water or food)
* Resolves without treatment in 1-3 months
* Vaccination is available
69
Discuss the management of hepatitis A
Resolves without treatment in 1-3 months hence management is **analgesia**
70
For hepatitis B, describe:
* DNA or RNA
* Transmission
* Spontaenous recovery or progression
* Vaccination
* **DNA**
* **Direct contact with blood or bodily fluids** *(this includes vertical transmission)*
* **Most people fully recover in 2 months** however 10% go on to become chronic hepatits B carriers *(virus DNA incorporated into their own DNA so they continue to produce viral proteins)*
* **Vaccination is available (inject hep B surface antigen; 3 doses at different intervals)**
71
For hepatitis B, state which antibodies you can test for and what a positive result in each one means
* **Surface antigen (HBsAg)**: active infection
* **E antigen (HBeAg):** marker of viral replication and implies high infectivity
* **Core antibodies (HBcAb)**: past or current infection
* **Surface antibody (HBsAb)**: implies vaccination or past or current infection
* **Hepatitis B virus DNA (HBV DNA):** direct count of viral load
72
Hepatitis core antibodies (HBcAb) imply past or current infection; explain how we can use further immunoglobulin tests to distinguish if this is an acute infection or previous infection
We can measure IgM and IgG versions of HbcAb:
* IgM high= active infection
* IgG high= past infection
73
Discuss the management of hepatitis B
* Stop smoking & alcohol
* Educate about transmission
* Test for complications e.g. fibroscan for cirrhosis
* Anti-viral medication to slow progression & reduce infectivity
* Liver transplant (end stage liver disease)
74
For hepatitis C, describe:
* DNA or RNA
* Transmission
* Spontaneous recovery or progression
* Vaccination
* RNA
* Transmission: blood & bodily fluids
* 1 in 4 make spontaneous recovery, 3 in 4 develop chronic hepatitis
* No vaccine
75
If we do a hepatitis C antibody test and find out someone is + for hepatitis C; what test do we do next and why?
* Hepatitis C antibody is screening test
* If positive we do **hepatitis C RNA testing** to **confirm diagnosis, calculate viral load and assess individual for viral gentotype to guide treatment**
76
Discuss the management of hepatitis C
* Direct acting antivirals can sucessfully cure infection in over 90%- take for 8-12 weeks
* Stop smoking & alcohol
* Educate about transmission
* Test for complications
* Liver trasnplant for end-stage liver disease
77
For hepatitis D, describe:
* DNA or RNA
* Transmission
* Co-infection required
* Treatment
* RNA
* Blood & bodily fluids
* Needs hepatitis B co-infection as hepatitis D attaches itself to surface antigen of hepatitis B and cannot survive without this protein
* No specific treatment. It increases complications & severity of hepatitis B
78
For hepatitis E, describe:
* DNA or RNA
* Transmission
* Resolve or progress
* Vaccination?
* RNa
* Faecal-oral
* Normally produces mild illness that is cleared within a month and no treatment required; rarely it progresses to chronic hepatitis- more so in immunocompromised
* No vaccine
79
All hepatitis infections are notifiable diseases; true or false?
TRUE
80
Which two antibodies/antigens would you test for if you are screening for hepatitis?
If these two came back positive, what further tests would you do to confirm if the pt is having an active hep B infection?
To screen for hepatitis:
* HBsAg (surface antigen)
* HBcAb (core antibodies)
If HBsAg +ve means they have active infection. If HBcAB is +ve means have current or past infection. If the above two are +ve pt must have active infection hence check:
* HBeAg
* HBV DNA
... to test for viral replication, viral load & infectivity
81
Autoimmune hepatitis is a rare cause of hepatitis; true or false?
True
82
Discuss the pathophysiology of autoimmune hepatitis
* T cell mediated immune response against liver cells
* Exact cause unknown but it may be associated with genetic predisposition triggered by environmental factors such as viral infection
83
Describe the two types of autoimmune hepatitis, include:
* Age of onset
* Present acutely?
* Autoantibodies
Two types have different ages of onset & autoantibodies:
_Type 1_
* **Adults** (late 40/50's)
* Less acute course compared to type 2
* Autoantibodies: **ANA, ASMA, anti-SLA/LP** (anti-soluble liver antigen)
_Type 2_
* **Teens or early twenties**
* Acute hepatitis
* Autoantibodies: **anti-LKM1** (anti-liver kidney microsomes-1), **anti-LC1** (anti-liver cytosol antigen type 1)
84
How can we confirm a diagnosis of autoimmune hepatitis?
Liver biopsy
85
Discuss the management of autoimmune hepatitis
* _Remission:_ **high dose steroids** e.g. prednisolone which are **reduced over time as other immunosupressants- particularly azathioprine- are introduced**
* _Maintaining remission:_ **i****mmunosupressant therapy usually required life-long**
* **Liver transplant** (however autoimmune hepatitis can re-occur in new liver)
86
State some conditions associated with autoimmune hepatitis
Other autoimmune conditions including:
* Ulcerative colitis
* Autoimmune thyroiditis
* Diabetes
* Primary sclerosing cholangitis
* Pernicious anaemia
87
Discuss the pathophysiology of alpha-1 antitrypsin deficiency- include how it causes liver & lung disease
* Inherited deficiency of alpha-1 antitrypsin (a protease inhibitor)
* Alpha-1 antitrypsin would usually inhibit proteases such as elastase- which digests connective tissues- and hence protect tissues
* Leads to an excess of proteases that attack liver and lung tissue causing cirrhosis and pulmonary basal emphysema
88
State the inheritence pattern of alpha-1 antrypsin deficiency
Autosomal recessive
89
What chromosome is the alpha-1 antitrypsin gene found on?
Chromosome 14
90
Which tissue is primarily affected first in alpha-1 antitrypsin deficiency; liver or lung?
* Pulmonary basal emphysema **after 30yrs old**
* Liver cirrhosis **after 50 yrs old**
91
Discuss how you diagnose alpha-1 antitrypsin deficiency
* Blood test: low serum alpha-1 antitrypsin
* Liver biopsy
* Genetic testing for A1AT gene
* High resolution CT thorax to diagnose pulmonary emphysema
92
What would a liver biopsy of a pt with alpha-1 antitrypsin deficiency show? (2)
* **Cirrhosis**
* **Acid-Schiff-positive staining globules***(staining of breakdown products of proteaeses)*
93
Discuss the management of alpha-1 antitrypsin deficiency
* Stop smoking *(smoking dramatically accelerates emphysema)*
* Symptomatic management
* Organ transplant
* Monitor for complications e.g. hepatocellular carcinoma
94
Do NICE reccomend the use of replacement alpha-1 antitrypsin?
No, however research and debeate is ongoing
95
What is Wilson's disease, include:
* Inheritance pattern
* Mutated gene
* What chromosome gene is found on
* Function of this protein and hence consequence of it's mutation
Autosomal recessive condition in which there is a mutation in 'Wilson disease protein' on chromosome 13; this protein is responsible for various functions including the removal of excess copper in the liver
96
Discuss how a pt with Wilson's disease might present
All problems are due to abnormall copper deposition:
* **Hepatic problems**
* **Neurological problems**
* Concentration difficulties
* Dysarthria
* Dystonia
* Parkinsonism
* **Psychiatric problems**
* Depression
* **Haemolytic anaemia**
* **Renal tubular acidosis**
* **Osteopenia**
* * Psychosis
97
What might you find on clinical examination of someone with Wilson's disease
* **Kayser-Fleischer ring** *(brownish circle surrounding iris due to deposition of copper. Usually visible to naked eye but proper assessment is made using slit lamp examination)*
* **Blue lunulae (nails)**
* **Grey skin**
98
Discuss how Wilson's disease is diagnosed
* **Initial investigation: serum caeruloplasmin**: *if low suggestive of Wilson's disease.*
* **Gold standard= liver biopsy**
* **24hr urinary copper assay:** *high*
* **Serum copper:** *low*
* **MRI brain**
99
Is low caeruloplasmin specific to Wilson's disease?
No, it can be low in conditions such as protein deficiency states e.g. nephrotic syndrome, malabsorption etc... HOWEVER, oxford handbook says is \<140mg/L is it pathognomonic of Wilson's disease
100
Discuss the management of Wilson's disease
* **Copper chelation with:**
* **Penicillamine**
* **Trientene**
* Avoid foods high copper e.g. liver, chocolate, nuts, mushrooms
* Liver transplant
101
What is budd-chiari syndrome?
Defined as/synonymous with **hepatic venous outflow tract obstruction**; venous obstruction can be located at any level from the small hepatic veins to the junction of the inferior vena cava (IVC)with the right atrium.
102
State some causes of budd-chiari syndrome
Budd-Chiari syndrome, or hepatic vein thrombosis, is usually seen in the context of underlying haematological disease or another procoagulant condition. Causes include:
* polycythaemia rubra vera
* thrombophilia: activated protein C resistance (factor V Leiden), antithrombin III deficiency, protein C & S deficiencies
* pregnancy
* combined oral contraceptive pill: accounts for around 20% of cases
103
Describe typical presentation of budd-chiari syndrome (triad)
* **abdominal pain**: sudden onset, severe
* ascites → **abdominal distension**
* **tender hepatomegaly**
104
What is the investigation of choice in budd-chiari syndrome?
Abdominal ultrasound with Doppler flow studies
