CT 3.1 Chronic Liver disease Flashcards
1
Q
what measures are looked at when assessing liver function
A
- serum bilirubin
- serum aminotransferase ALT - indicates hepatocellular inflammation
- serum alkaline phosphatase - biliary disease or non liver
- GGT biliary disease, alcohol or fatty liver
- globulins
- Prothrombin time PT - measure of extrinsic pathway
2
Q
what does raised IgG suggest in the context of liver disease
A
autoimmune hepatitis
3
Q
what does raised IgM suggest in the context of liver disease
A
primary biliary cholangitis/cirrhosis
4
Q
what does raised IgA suggest in the context of liver disease
A
alcoholic liver disease
5
Q
what investigations would you carry out for jaundice
A
biochemical profile
FBC
abdominal ultrasound
6
Q
where is alt found
A
predominantly liver
small amounts in heart and muscle
7
Q
where is ast found
A
liver, muscle and heart, kidney and brain
8
Q
elevation in ALP and GGT is suggestive of what
A
cholestasis
alcoholic damage
9
Q
where is ALP founf
A
liver
bone
placenta
10
Q
an isolated rise in ALP without elevation of GGT may indicate what
A
bone disease
11
Q
what are the functions of the liver
A
Storage of glycogen, release of glucose, and gluconeogenesis-
Protein synthesis (e.g. albumin and coagulation factors)-
Catabolism/breakdown of amino acids, and production of urea-
Detoxification of nitrogenous molecules from the GI tract- Drug and steroid metabolism-
Lipoprotein synthesis- Conjugation and excretion of bilirubin-
Production and excretion of bile salts- Participation in immune processes
12
Q
ANCA is positive in which liver pathology
A
primary sclerosing cholangitis
13
Q
anti-mitochondrial antibodies AMA are found in which condition
A
PBC
14
Q
which viruses can cause hepatitis
A
Hep A, B, C, D + E
- can only get D if have infection with B
Hep C can result in chronic infection and sometimes B can
CMV
herpes
EBV
varicella
mumps + rubella
yellow fever and adenovirus
15
Q
what are the other causes of hepatitis
A
acute:
alcohol
DILI drug induced liver injury
autoimmune
ischaemic hepatitis
chronic causes
- alcoholic
- NAFLD
- genetic: wilsons, haematochromatosis and alpha 1 antitrypsin deficiency
- PBC and PSC
16
Q
Investigations for Hepatitis virus A
A
mild increases in ALT and AST, increased bilirubin, presence of faecal hepatitis A
virus (HAV), anti-HAV IgM on bloods (which if found indicates the virus is active), and anti-HAV IgG
(which if found indicates the person has recovered/had a previous infection, or received a vaccine)
17
Q
what are the risk factors for acquiring Hep B and C infections
A
sexual activity, IV drug use, working in healthcare,
having CKD, and household contact (i.e. with close family).
transfusions (particularly those before 1991,
incubation period is >6 weeks
18
Q
what is the diagnostic marker for hep B infection
A
HBsAg
19
Q
what are the symptoms of viral hepatitis
A
fever, malaise, nausea, hepatomegaly, increase in
liver enzymes (e.g. ALT, AST etc. ALT will have a bigger increase than AST), large lymphocytes,
jaundice (due to a build-up of bilirubin in the blood), and dark urine (when soluble, conjugated
bilirubin leaks, is processed by the kidneys, and enters the urine)
20
Q
what are the causes of cirrhosis
A
Causes of cirrhosis are alcohol, hepatitis B, C, and B+D, NASH, NAFLD, drugs, autoimmune liver disease, cholestatic liver disease, metabolic liver disease and hepatic venous congestion
21
Q
what are the complications of cirrhosis
A
portal hypertension
oesophageal varices
hepatorenal syndrome
ascites
hepatic encephalopathy
22
Q
investigations for cirrhosis
A
fibroscan
acoustic radiation force impulse
23
Q
what classification systems are used for liver cirrhosis
A
child-pugh
MELD
24
Q
what are the consequences of hepatic failure
A
- Unable to filter toxins and drugs effectively
- Metabolism of nutrients reduced
- Reduced immunity (unable to help fight infection by removing bacteria from blood)
- Reduced production of clotting factors (so increased risk of clotting)
- Unable to store nutrients, so body may experience shortage
- Reduced protein production (e.g. albumin)
- Reduced bile production (so reduced absorption of fat soluble vitamins A, D, E, and K)
*
Consequences of hepatic failure can be cerebral oedema, bleeding, infections, kidney failure,
jaundice, ascites, melena, hypotension (due to reduced systemic vascular resistance), and
tachycardia
25
what are the risk factors for NAFLD
obesity, type 2 diabetes, hyperlipidaemia, sudden weight loss/starvation, and
jejunoileal bypass. It is usually asymptomatic, but can cause hepatomegaly, ALT and AST rise (ALT
more so), and increased echogenicity on ultrasound (more reflective/brighter than normal)
26
what is the investigation for NAFLD
enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis, and other
measures are FIB4 score or NALFD fibrosis score, and a FibroScan (liver stiffness measurement).
27
Management of NAFLD
weight loss (with consideration to gastric banding), and insulin-sensitising
drugs (e.g. metformin, pioglitazone) can be used
28
what is type I autoimmune hepatitis
presence of ANA and anti-smooth muscle antibodies SMA
affects both adults and children
29
what is type II autoimmune hepatitis
anti-liver/kidney microsomal type I antibodies LKM1
affects children only
30
what is type III autoimmune hepatitis
soluble liver-kidney antigen present
affects middle-aged adults
31
how does autoimmune hepatitis present
signs of chronic liver failure
or acute hepatitis symptoms eg fever and jaundice
amenorrheoa
32
what are phase I reactions in the liver
oxidation, reduction or hydrolysis of the drug to add functional chemical groups making it more polar. This is done by CYP450 enzymes
33
what are phase II reactions
conjugation, so the products of phase I are added to endogenous substances like glycine, glucuronic acid, sulphuric acid etc. This makes the products more water soluble,
meaning that they can be more easily excreted
34
what are phase III reactions
excretion, most commonly occurs via the kidneys, that can only occur if the product
is water soluble and of a relatively small size. If a molecule is highly polar and/or is large, it will
be removed via biliary excretion
35
what is acute liver failure
rapid onset of hepatocellular dysfunction leading to jaundice, coagulopathy (i.e.
impaired blood clotting due to deficiency/disruption in clotting factors), hypoalbuminaemia, hepatic
encephalopathy, asterixis (hepatic flap), spider naevi, and renal failure.
36
what are the causes of acute liver failure
paracetamol overdose, alcohol, viral hepatitis (usually A or B), and acute fatty liver of pregnancy
37
what drugs can cause acute liver failure
antibiotics (NSAIDs, nitrofurantoin, ciprofloxacin,
erythromycin, and anti-TB drugs isoniazid, rifampicin, and pyrazinamide), antidepressants
(amitriptyline, MAOIs), anaesthetics (halothane), statins, immunosuppressants (cyclophosphamide,
methotrexate), amiodarone, phenytoin, St John’s wort, and sodium valproate (mood stabiliser)
38
what is type A adverse drug reaction
(80% of cases which is predictable and dose
related, and is rarely dangerous, such as bleeding after warfarin, nausea from digoxin, dizziness from
beta blockers etc),
39
what is type B adverse drug reaction
(rarer, and is non-predictable and not dose-related, such as
hepatocellular injury caused by active metabolites of drugs)
40
what can precipitate an elevation of bilirubin in gilbert syndrome
stress
fasting
illness
exercise
does not require treatment
41
what is acute on chronic liver failure
syndrome characterised by acute decompensation of chronic liver disease, associated with organ failure and high short-term mortality. Cirrhosis, alcoholic
hepatitis and chronic viral hepatitis are the most common chronic liver diseases
42
what are triggers of acute on chronic liver failure
bacterial infections, alcohol, acute viral hepatitis and DILI
However usually the trigger is unknown. Triggers cause systemic inflammation
(i.e. high WCC, CRP etc), which is a hallmark of ACLF. Once ACLF has been activated, the symptoms
and pathophysiology of liver damage are similar to acute liver failure
43
what are the infective causes of hepatomegaly
Glandular fever: 90% of times caused by EBV. others include CMV + HHV6
Viral Hep, A,B,C (causes a smooth edged enlarged liver)
malaria w
abscesses
hydatid cysts
leishmania
44
what are the neoplastic causes of hepatomegaly
- liver on palpation may have a hard irregular edge
Leukaemia
Lymphoma
hepatocellular carcinoma
metastatic tumours
45
what are biliary causes of hepatomegaly
primary biliary cirrhosis
primary sclerosing cholangitis
extra-hepatic obstruction by cancers
Liver cirrhosis
46
what are the symtoms and signs of glandular fever
fever
lymphadenopathy
sore throat
palatal petechiae
splenomegaly
hepatomegaly
hepatitis
haemolytic anaemia due to cold agglutinins IgM
47
How is glandular fever caused by EBV confirmed
heterophil antibody test done in the second week of illness
48
how is glandular fever treated
supportive management with fluids. rest, avoid alcohol and analgesia
49
what are the metabolic causes of hepatomegaly
- wilson's disease
- haemochromatosis
- NAFLD
- amyloidosis
50
what is wilson's disease
accumulation of copper particularly in the liver (causes hepatitis and cirrhosis), brain (causes speech, behavioural and psychiatric problems, and basal ganglia
degeneration) and eyes (causes green-brown rings (Kayser-Fleischer rings) in the iris), due to a
defect in the ATP7B gene on chromosome 13
51
what are the investigations for wilsons disease
- decreased serum caeruloplasmin
- decreased total serum copper
- increased 24hr urinary Cu excretion
- genetic analysis
- liver biopsy
52
what is the management of wilsons disease
penicillamine (is a chelating agent which increases urinary excretion of copper)
53
what are the symptoms of haemochromatosis
- fatigue
- joint pain
- erectile dysfunction
- bronze skin pigmentation
- testicular atrophy and infertility
- hepatomegaly
heart failure
- condition in which there is an excess of iron stored in the body
treatment is venesection weekly and for maintenance a few times a year
transferrin sats + serum ferritin should be below 50% and 50
avoid vit C as it increases absorption of iron from diet
54
how is alcholic hepatitis managed
glucocorticoids
pentoxyphylline
55
what congenital conditions can result in hepatomegaly
haemolytic anaemia
ADPKD - causes liver cysts but in brain may lead to berry aneurysms and in heart mitral valve prolapse + aortic dissection
SCD
thalassemia
56
what is the management of ADPKD
tolvaptan ADH receptor antagonist
57
where can amyloidosis occur
◦
Kidneys = nephrotic syndrome, and renal failure
◦
GI system = macroglossia, malabsorption, and hepatosplenomegaly
◦
Neurological system = neuropathies
◦
Blood vessels = periorbital purpura ("racoon eyes")
◦
Joints = painful asymmetrical large joint inflammation
58
what would blood findings be in a patient with haemochromatosis
high transferrin sats
high serum ferritin
low TIBC
59
what is the normal pressure within the hepatic portal system
7mmHg
60
what are the pre-hepatic causes portal hypertension
blockage of the portal or splenic veins by thrombosis or invading tumour
61
what are the hepatic causes of portal hypertension
cirrhosis
Schistosoma
hereditary haemorrhagic telangiectasia/ osler-weber-rendu syndrome ( some blood vessels that have not developed properly and sometimes cause bleeding, known as arteriovenous malformations (AVMs).
HCC
sarcoidosis
62
what are the post-hepatic causes of portal hypertension
thrombosis of the hepatic vein or IVC and cardiac disease
63
what are the symptoms of hepatic encephalopathy
cerebral oedema, mental state changes (e.g. forgetfulness, confusion, irritability, disrupted sleep patterns, personality changes), asterixis/hepatic flap, constructional
apraxia (e.g. inability to draw a 5-pointed star), and coma
64
what is the management of hepatic encephalopathy
Management first-line is oral lactulose (helps excrete ammonia), with oral rifaximin
65
what is hepatorenal syndrome
rapid decline in kidney function and development of kidney
failure in somebody with liver cirrhosis. This is because the cirrhosis leads to splanchnic vasodilation
(i.e. dilation of the vessels that supply the stomach, intestines, spleen, pancreas and liver), which
reduces systemic blood pressure. The kidneys activate RAAS, but this constricts the afferent
arteriole, leading to further hypo-perfusion, and kidney failure
66
management of hepatorenal syndrome
Terlipressin which causes splanchnic vasoconstriction
volume expansion with 20% albumin
TIPS transjugular intrahepatic portosystemic shunt
liver transplant
67
what is the management of ascites
reducing dietary sodium
fluid restriction
spironolactone
oral cipro (reduce risk of bacterial peritonitis)
drain the fluid (abdominal paracentesis)
68
what is budd chiari syndrome
thrombosis in the hepatic vein
causes triad of
abdo pain,
tender hepatomegaly
ascites
investigated with doppler
management is anticoagulation and thrombolysis
69
Effect of Drugs on Liver Function and the Effect of Impaired Liver Function on Drug Metabolism and Excretion
Effects of Drugs on Liver Function:Hepatotoxic drugs (e.g., paracetamol in high doses, methotrexate, amiodarone, and statins) can cause:
Hepatocellular injury (elevated ALT/AST)
Cholestasis (elevated ALP and bilirubin)
Mixed patterns
Impaired Liver Function:Liver disease alters drug metabolism, leading to:
Reduced drug clearance: Drugs like benzodiazepines and opioids may accumulate.
Impaired conjugation: This affects drugs like morphine.
Increased drug sensitivity: Due to altered plasma protein binding (e.g., warfarin).
Altered excretion: Bile excretion may be impaired.
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Distinguishing Pre-hepatic, Hepatic, and Post-hepatic Jaundice
Pre-hepatic (Hemolytic):
Clinical Features: Mild jaundice without dark urine or pale stools
Biochemical Findings: Elevated unconjugated bilirubin; normal AST, ALT, and ALP
Causes: Hemolysis (e.g., G6PD deficiency, sickle cell disease)
Hepatic:
Clinical Features: Jaundice with variable dark urine and normal stool color
Biochemical Findings: Elevated AST/ALT, variable ALP; mixed bilirubin levels
Causes: Viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis
Post-hepatic (Obstructive):
Clinical Features: Jaundice, dark urine, pale stools, pruritus
Biochemical Findings: Elevated conjugated bilirubin and ALP; mildly elevated AST/ALT
Causes: Gallstones, cholangiocarcinoma, biliary stricture
71
Initial Investigations for Jaundice and Interpretation
Liver function tests (LFTs): ALT, AST, ALP, bilirubin
Full blood count (FBC): Check for anemia (hemolysis)
Coagulation profile: Assess liver synthetic function
Hepatitis serology (HAV, HBV, HCV)
Abdominal ultrasound: Detect biliary obstruction, hepatomegaly
72
Common Causes of Hepatomegaly and Appropriate Initial Investigations
Causes Based on Clinical Features:
Smooth, tender liver: Viral hepatitis, right heart failure
Nodular liver: Cirrhosis, malignancy
Massive hepatomegaly: Hepatocellular carcinoma, fatty liver disease
Initial Investigations:
LFTs
Imaging (ultrasound, CT abdomen)
Viral markers, tumor markers (AFP)
Liver biopsy in selected cases
73
Recognizing Chronic Liver Disease Manifestations (Including Liver Failure and Portal Hypertension)
Chronic Liver Disease Features:
Jaundice
Spider nevi, palmar erythema
Muscle wasting
Ascites
Splenomegaly
Portal Hypertension Features:
Esophageal varices
Caput medusae
Ascites
Liver Failure Signs:
Encephalopathy
Coagulopathy
Hypoalbuminemia
74
Causes of Acute and Acute-on-Chronic Hepatic Failure, Recognition, Investigation, and Management
Acute Hepatic Failure Causes:
Viral hepatitis (HAV, HBV)
Drug-induced (paracetamol overdose)
Autoimmune hepatitis
Acute-on-Chronic Hepatic Failure:
Decompensated cirrhosis triggered by infection, bleeding, or alcohol binge
Recognition:
Encephalopathy
Coagulopathy (INR >1.5)
Jaundice
Initial Management:
Supportive care (fluid balance, correction of coagulopathy)
Treat the underlying cause (e.g., NAC for paracetamol poisoning)
Monitor for complications (hepatic encephalopathy)
75
Discussing Options with Patients to Limit Risks of Liver Damage
Lifestyle Measures:
Alcohol cessation
Weight loss and management of metabolic syndrome
Avoidance of hepatotoxic drugs
Vaccinations:
Hepatitis A and B for at-risk populations
Education:
Safe practices to avoid viral transmission
76
Detection of Ascites Clinically
Clinical Methods:
Inspection: Abdominal distension, umbilicus eversion
Percussion: Shifting dullness, fluid wave test
Palpation: Assess for hepatomegaly, splenomegaly
77
Management of Hepatic Ascites
Lifestyle Modifications:
Sodium restriction
Fluid restriction
Medical Treatment:
Diuretics (spironolactone +/- furosemide)
Albumin infusion in selected cases
Procedural Treatment:
Large-volume paracentesis
Transjugular intrahepatic portosystemic shunt (TIPS)
78
Risk Factors for Chronic Liver Disease and Prevention Measures
Risk Factors:
Alcohol consumption
Viral hepatitis
Non-alcoholic fatty liver disease (NAFLD)
Autoimmune disorders
Preventive Measures:
Public health campaigns for vaccination and alcohol moderation
Screening for viral hepatitis
Management of metabolic syndrome
79
Distinguish between infectious and mechanical causes of biliary obstruction
Infectious Causes
Infectious causes are due to infections that directly or indirectly block bile flow by causing inflammation or fibrosis in the biliary tract.
Parasitic Infections:
Clonorchis sinensis (liver fluke)
Fasciola hepatica
Ascaris lumbricoides (worm migration into the bile ducts)
Bacterial Infections:
Ascending cholangitis (commonly caused by Escherichia coli, Klebsiella, or Enterococcus) leading to inflammation and obstruction.
Viral Infections:
Rare, but viral infections such as hepatitis can indirectly contribute by causing bile duct injury.
Mechanical Causes
Mechanical causes involve physical obstruction of the biliary ducts by structural anomalies, external compression, or intraductal material.
Gallstones (Choledocholithiasis): The most common cause, where stones migrate to the common bile duct.
Tumors:
Cholangiocarcinoma
Pancreatic carcinoma compressing the common bile duct
Ampullary carcinoma
Strictures:
Post-surgical or post-inflammatory scarring of bile ducts
Chronic pancreatitis-induced strictures
Congenital Abnormalities:
Biliary atresia
Choledochal cysts
External Compression:
Enlarged lymph nodes (e.g., from malignancies or infections)
Pancreatic pseudocysts
Trauma:
Iatrogenic injury (e.g., during gallbladder surgery)
Blunt abdominal trauma
Clinical Implications
Infectious Obstructions: Often present with fever, right upper quadrant pain, and jaundice (Charcot's triad) due to cholangitis.
Mechanical Obstructions: Present more with progressive jaundice, pale stools, dark urine, and may or may not involve fever.
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