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PBL Y2 S4 > Case 5 - Hepatitis > Flashcards

Case 5 - Hepatitis Flashcards

1
Q

What is stored in the liver?

A

Glycogen, B12, Vitamin A

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2
Q

What does the liver detoxify?

A

Xenobiotics (ammonia, drugs etc.)
Steroids
Thyroid hormone
Metabolites

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3
Q

What does the liver synthesise?

A

Albumin, clotting factors, binding proteins, non-essential amino acids

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4
Q

What cell is responsible for phagocytosis in the liver?

A

Kupffer cells

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5
Q

What is the blood supply of the liver? Include the flow rate

A

➢75% from portal vein: rich in absorbed nutrients, recycled bile acids/ salts, about 1300 ml/min

➢ 25% from hepatic artery: regular systemic arterial blood, about 500ml/min

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6
Q

What cells line the sinusoids?

A

Fenestrated endothelial cells

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7
Q

What are the functions of zone I (periportal) of the liver?

A

Close to portal venule and oxygenated blood, so getting most oxygen to the cells. Functions:
* Amino acid catabolism
* Gluconeogenesis
* Cholesterol synthesis

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8
Q

What are the functions of zone II and III (pericentral)?

A

Zone III = functions that require the least oxygen so:
* Lipid synthesis
* Ketogenesis
* Glutamine synthesis
* Drug metabolism

Zone II = mix of zone I and III

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9
Q

With liver fibrosis, where are fibrotic changes most likely to occur?

A

Around the central veins (where there is least oxygen) as the cells there are less able to regenerate.

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10
Q

What type cells are hepatocytes?

A

polarised epithelial cells

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11
Q

What are the modifications of the epithelium to allow substances to pass from the blood to the interstitial fluid?

A

The endothelia is fenestratred, i.e. there are holes in the cell to allow substances to pass (‘Space of Disse’ in the liver).

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12
Q

Are the sinusoidal and canalicular membanes apical or basolateral?

A

Sinusoidal = apical
Canalicular = basolateral

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13
Q

How much bile is secreted per day from the liver? How much reaches the duodenum?

A

1000ml/day is secreted by the liver, however only around 500ml/day reaches the duodenum (as it is concentrated by the gall bladder)

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14
Q

What does bile include?

A
  • Bilirubin (conjugated)
  • Bile acids / salts (+ phospholipids and cholesterol)
  • Metabolites of hormones and drugs
  • Heavy metal ions
  • HCO3- to neutralise acid and water
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15
Q

Compare the structure of bile acids and bile salts

A

Bile salts = conjugated, i.e. with taurine, glycine, sulphate, glucuronate (water-soluble)

Bile acids = unconjugated (BA-), proton attached. pKa around 5

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16
Q

What are secondary bile acids?

A

Bile acids that have been modified by the terminal ileum and colon. Can be conjugated to lower the dissociation constant

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17
Q

What type transporters are responsible for importing/exporting bile salts? How do they work?

A

APC transporters (ATP-binding cassete) - utilise ATP hydrolysis to pump

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18
Q

Give 2 examples of APC transporters for bile and one for cholesterol

A

Bile:
- BSEP (bile salt export pump)
- MRP2 (multidrug resistance-associated protein 2)

Cholesterol = ABCA1

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19
Q

How is unconjugated bile reabsorbed?

A

Most bile is conjugated but becomes unconjugated as it moves through the intestine. It is then reabsorbed passively

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20
Q

How is conjugated bile reabsorbed?

A

Mainly reabsorbed in the terminal ileum via ASBT (sodium bile salt cotransporter, active uptake), once it has entered the cell it then leaves via OST (organic solute transporter)

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21
Q

What is the average daily excretion of bile acids? What is it compensated by?

A

600mg/d, compensated by the synthesis of new bile acids

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22
Q

After recycled bile salts arrive at the liver, what are the 3 routes of uptake?

A
  • Simple diffusion of unconjugated neutral BAH
  • NTCP = Co-transport with Na+
  • OATP = exchange with Cl-
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23
Q

Give some examples of organic ions that may be excreted by the liver into the bile

A

Thyroid and steroid hormones, prostaglandins, drugs (statins), toxins

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24
Q

How are organic ions excreted by the liver?

A
  • OATP; basolateral uptake with exchange with Cl-
  • Conjugation with glucuronate or sulphate
  • Apical secretion via MRP2
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25
Q

Give some examples of organic cations excreted by the liver

A

Cytotoxic drugs, local anaesthetics, antibiotics

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26
Q

How are organic cations excreted by the liver?

A

Small cations = via facilitated diffusion of OCT1/3, then exchanged with H+ via MATE1
Bigger cations = OATP then MDR1

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27
Q

What transporter secretes cholesterol?

A

ABCG5/8

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28
Q

What produces bilirubin? Where is it transported to after it is produced?

A

RBC broken down by phagocytosis into haem and globin. Haem is then broken down into unconjugated bilirubin + iron. It is then bound to albumin and transported to the liver

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29
Q

How is bilirubin taken up by the liver? Where does it go after this?

A

After arriving with albumin, it is taken up by OATP. It is then conjugated with glucuronate in the ER (to become water soluble) and secreted by MRP2 into the bile = excreted

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30
Q

Why are faeces brown and urine yellow?

A

Bilirubin is deconjugated by bacteira in the SI, which converts it to urobilinogen. - Some of this is converted to stercobilin which is brown, hence faeces
- Some urobilinogen is reabsorbed into the blood and excreted as urobilin by the kidneys (yellow)

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31
Q

What is ketogenesis? What is it stimulated by?

A

Using acetyl-CoA to produce emergency fuel.
Promoted by surplus of mobilised FA in starvation or T1DM (as ketogenesis is suppressed by insulin)

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32
Q

What can surplus ammonia arrive to the liver as?

A

glutamate, glutamine or alanine (then de- or transaminated to dispose N as urea)

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33
Q

Which GLUT transporters are present in the adipose tissue and liver?

A

GLUT4 = adipose (target of insulin)
GLUT2 = liver

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34
Q

What traps glucose in a cell?

A

Phosphorylation (as the ionic phosphate cannot cross the membrane spontaneously) via hexokinase (liver) or glucokinase (other tissues). Uses ATP

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35
Q

What is the rate limiting step of glycolysis?

A

Phosphofructokinase-1 (PFK1): phosphorylates F6P to F1,6, biphosphate (this step requires ATP, very slow)

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36
Q

How much energy does glycolysis produce?

A

2 ATP per molecule glucose

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37
Q

What are the 2 main storages of glycogen in the body? How much (g) can they store?

A

Skeletal muscle = 400g
Liver = 100g

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38
Q

Why is glycogen branched?

A

More free ends mean it is more mobile / efficient to use as fuel

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39
Q

How does glucagon lead to its effects on glycogen metabolism?

A

1: glucagon increases cAMP which activates protein kinase A
2: PKA phosphorylates glycogen synthase directly and glycogen phosphorylase indirectly (via phosphorylase kinase)
3: Leads to glycogen breakdown (glycogenolysis) and inhibits glycogen formation (inhibits glycogenesis)

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40
Q

How does glucagon regulate gluconeogenesis?

A
  • represses pyruvate kinase = increases PEP availability by preventing pyruvate formation
  • Increases expression of PEP carboxykinase, promoting oxaloacetate to be converted into PEP
  • Represses formation of F2, 6BP
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41
Q

How do catecholamines affect glucose production?

A

increase glucose production by cAMP activation of glycogen phosphorylase and gluconeogenesis.

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42
Q

What regulates phosphofructokinase-1 (PFK1)?

A

Activated by= allosterically by AMP (low levels in the cell) and F2,6BP
Inhibited by = ATP and citrate

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43
Q

How is F2, 6BP activated? What regulates this?

A

By PFK2 enzyme, which is inhibited by glucagon (when blood sugar is low) and stimulated by insulin (well fed state)

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44
Q

What is the role of pyruvate dehydrogenase complex (PDC)?

A

Contains E1, E2 and E3 for oxidative carboxylation of pyruvate into acetyl CoA, so then acetyl CoA can enter the TCA cycle

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45
Q

Why is oxygen required for the TCA cycle?

A

For oxidation (recycling) of the reduced cofactors (NADHH+ and FADH2)

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46
Q

How much ATP does the TCA cycle produce?

A

28 ATP per glucose (and 2 GTP)

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47
Q

What regulates lipogenesis?

A
  • Availability of substrate: i.e. carbohydrate rich meals provide pyruvate/ acetyl-CoA and NADPH
  • Insulin: stimulates
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48
Q

What is responsible for catalysing acetyl CoA –> Malonyl-CoA?

A

Acetyl-Coa-decarboxylase (ACC)

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49
Q

What regulates ACC enzyme?

A

ACC is inhibited by:
- Fatty acyl CoA (negative feedback)
- AMP
- Glucagon
- AMPK

ACC is stimulated by:
- Citrate
- Insulin

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50
Q

How much energy does beta-oxidation of FA produce?

A

Long chain FA are broken down 2 carbon atoms at a time, per 2-carbon unit it produces:
- one FADH2 = 2 ATP
- one NADH = 3 ATP
- one acetyl CoA = 12 ATP

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51
Q

What causes the ‘fruity’ breath noticed in T1DM patients? What is this a sign of?

A

Sign of serious ketoacidosis. Caused by spontaneous production of acetone (volatile) from acetoacetate

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52
Q

How can type 1 diabetes lead to ketoacidosis?

A

1: lack of insulin = loss of repression of hormone-sensitive lipase in adipocytes = TG is hydrolysed and FA is released
2: limited ability of liver to oxidise FA, so liver produces ketone bodies
3: leads to increased ketone bodies in blood (ketonemia) and in urine (ketouria)
4: Acidity of ketone bodies lowers blood pH = ketoacidosis

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53
Q

How can untreated T1D lead to hyperglycaemia?

A

Glucagon promotes gluconeogenesis in the liver, raising blood glucose levels

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54
Q

What is the reaction that catabolism of amino acids begins with?

A

Transaminase reaction, i.e. removal of a-amino group (transferred to a-ketoglurate)

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55
Q

What 2 liver transaminases are measured in a liver function test? Which is more sensitive and specific?

A
  • Alanine transaminase (ALT) = more specific (only found in hepatocytes)
  • Aspartate transaminase (AST) = more sensitive (as is in higher amounts, but is also present in heart, muscle and RBCs)
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56
Q

What is the role of AST?

A

Catalyzes the conversion of aspartate and a-ketoglutarate to oxaloacetate and glutamate

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57
Q

What are the 2 routes for how ammonia can enter the liver?

A

1- as glutamine, then releases 2 ammonia molecules by glutaminase and then glutamate decarboxylase
2- ammonia may be delivered by alanine-glucose shuttle; alanine delivers ammonia via ALT and resulting pyruvate goes into gluconeogenesis = glucose

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58
Q

How much ATP does it cost for ammonia and CO2 to be converted into urea?

A

4 ATP

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59
Q

What is the effect of malonyl- CoA on beta oxidation?

A

Inhibits beta oxidation, i.e. reduces breakdown of FA

60
Q

How can the AST/ ALT ratio indicate what the likely cause of liver damage is?

A

AST < ALT = chronic liver damage, viral hepatitis
AST > ALT = cirrhosis or acute alcoholic hepatitis

61
Q

What measures can be taken to assess injury to bile canaliculi (i.e. obstruction in biliary system)?

A

Alkaline phosphatase and bilirubin

62
Q

What measures can provide an indication for the synthetic function of the liver?

A

INR / prothrombin time and albumin

63
Q

What can an isolated increase in ALP indicate?

A

Bone breakdown, i.e. bone metastases/ cancer

64
Q

What can cause a decrease in albumin?

A
  • Chronic liver disease/ cirrhosis = liver produces less albumin
  • Excessive loss in urine can indicate nephrotic syndrome / chronic kidney disease
65
Q

What can cause an increase in prothrombin time?

A
  • Chronic liver disease/ cirrhosis - liver isnt producing clotting factors
  • Anti coagulation
  • Vitamin K deficiency
66
Q

Give the 3 types of jaundice and their cause

A

1: pre-hepatic = excessive RBC breakdown (haemolysis), so becomes. too much for the liver to breakdown and conjugate
2: Hepatic = dysfunction of hepatocytes, so liver loses ability to conjugate
3: Post-hepatic (obstructive) = liver conjugates bilirubin normally but obstruction of biliary drainage means it isn’t secreted

67
Q

For pre-hepatic jaundice, give the:
- Type of bilirubin present
- Effect on urine
- Effect on ALT and ALP
- Examples

A

High unconjugated bilirubin:
- Urine is normal
- ALT and ALP normal
- Examples = haemolytic anaemia, Gilberts syndrome

68
Q

For hepatic jaundice, give the:
- Type of bilirubin present
- Effect on urine
- Effect on ALT and ALP
- Examples

A

High unconjugated and conjugated bilirubin (mixed):
- Dark urine
- ALT very high, ALP high/normal
- Examples = hepatitis, alcoholic liver disease, cirrhosis, primary sclerosing cholangitis

69
Q

For post-hepatic jaundice, give the:
- Type of bilirubin present
- Effect on urine
- Effect on ALT and ALP
- Examples

A

High conjugated bilirubin:
- Dark urine
- ALT high/normal, ALP very high
- Examples= pancreatic cancer, gall stones

70
Q

How can you differentiate between hepatic and post-hepatic jaundice?

A

Post hepatic jaundice likely to have pale and fatty stools, as the obstruction to bile flow is preventing fat absorption. Also post hepatic has no unconjugated bilirubin

71
Q

Why is urine normal colour for pre-hepatic jaundice?

A

Unconjugated bilirubin isnt water soluble, so doesnt enter urine

72
Q

Why can premature infants be seen with jaundice?

A

Change in fetal haemoglobin to adult haemoglobin but if the liver isn’t fully functional the bilirubin produced cannot be exported out of the body = jaundice.

73
Q

What can cause hepatitis?

A

Infectious = viral, fungal, bacterial, parasitic
Non-infectious = alcohol, drugs, autoimmune, metabolic (i.e. fatty liver disease, metabolic syndrome)

74
Q

What causes liver damage from viral hepatitis?

A

Immune-mediated, i.e. the immune response mounted against the virus (the virus themselves are non-cytopathic)

75
Q

How does viral hepatitis lead to inflammation and/or necrosis of the liver?

A

1: Virally infected hepatocytes present MHC1 (antigens) on its surface
2: Recognised by CD8+ T cells (cytotoxic), leading to apoptosis of hepatocytes (mainly in portal tracts and lobules)
3: leads to inflammation and possibly necrosis (‘fuminant hepatitis’)

76
Q

How does viral hepatitis present initially and later on (symptoms)?

A

Intitial: fever, malaise, fatigue, nausea (may have low appetite and itching)
Progression: jaundice, dark urine, pale stools from cholestasis, hepatomegaly, pain

77
Q

What causes the abdominal pain of viral hepatitis?

A

When the liver becomes inflamed and enlarged, it stretches the capsule which contains stretch receptors. Thus pain is only felt when it gets bigger

78
Q

Upon examination, what are some typical signs you will see in a patient with viral hepatitis? Include findings from screening tests

A
  • Very high ALT and AST (but ALT>AST)
  • High atypical lymphocytes
  • Increased bilirubin and ALP
  • RUQ tenderness
  • Hepatomegaly
  • Increased urobilinogen in the urine sample (it has been redirected to kidneys)
79
Q

Why does viral hepatitis lead to type 2 jaundice?

A

Mixed bilirubin types:
- Hepatocytes are damaged so they are less able to conjugate the bilirubin = leads to high levels of unconjugated bilirubin
- Hepatocytes also form the lining of bile ducts so conjugated bilirubin is also leaked out (leads to dark urine)

80
Q

What is classed as a chronic viral hepatitis infection?

A

persistance of the virus in the blood stream > 6 months

81
Q

What would you test for in a viral hepatitis screen?

A
  • Hep A antibody (IgM)
  • Hep B surface antigen
  • Hep C antibody
  • Consider Hep E IgM
82
Q

How does viral hepatitis cause cirrhosis?

A

On-going cycles of inflammation with immune responses to the viral infection of hepatocytes = liver attempts to heal but is fibrotic tissue (=liver fibrosis)

As there are progressively less liver cells present, the liver cannot carry out its function = cirrhosis (can take 20-30 yrs)

83
Q

What factors can accelerate cirrhosis from viral hepatitis?

A

Alcohol
HIV
Diabetes
Steatohepatitis (advanced stage of non-alcoholic fatty liver disease)

84
Q

What investigations may be performed to diagnose fibrosis/ cirrhosis?

A
  • Liver biopsy: gold-standard, but invasive
  • APRI score: platelet count and AST
  • Fibrotest: serum markers such as bilirubin, GGT, Apo-A1
  • Ultrasound elastography (fibroscan)
85
Q

How does an ultrasound elastography test for fibrosis?

A

Fibroscan sends ultrasound waves through the liver. The waves are reflected more quickly as liver stiffness increases (with fibrosis). Threshold to where this is considered cirrhotic. Can repeat the test

86
Q

How can cirrhosis progress?

A

1- Risk of becoming decompensated liver disease (start to develop ascites or jaundice), 50% 5 year survival
2- Then may = hepatocellular carcinoma

87
Q

List the complications of cirrhosis and why they are caused

A

Fibrotic tissue leads to portal hypertension, which can cause:
- Ascites: fluid collection in abdomen due to fluid backflow
- Varices / variceal bleeding
- Encephalopathy: build up of neurotoxins in the brain, leads to confusion, may see a liver flap on examination
- Subacute bacterial peritonitis
- Splenomegaly

88
Q

What is a varices? Give examples of where they may occur

A

Dilated veins where there are anastomoses between the portal and systemic systems, due to increased pressure in the portal vein. Risk of bleeding as they can rupture easily.
Examples:
- Periumbilical = around umbilicus
- Lower oesophageal
- Perianal

89
Q

For Hepatitis A, give its:
- Type of virus (RNA/DNA)
- Route of transmission (give ex)
- Symptoms/ chronic infection risk
- Incubation period

A
  • RNA (picornavirus)
  • Faecel oral transmission, i.e. contaminated food and water, travelling to endemic countries (Sub-Saharan, India), associated with poor sanitation
  • No chronic infection but tends to be symptomatic in adults (jaundice, nausea) - mild or subclinical infection in children
  • IP = 30 days (4-6wks)
90
Q

What are some complications of Hepatitis A?

A
  • Prolonged cholestasis (rare)
  • Fulminant liver disease
  • liver failure
91
Q

How can Hepatitis A be prevented?

A

Improve sanitation
Vaccines

92
Q

How is hepatitis A diagnosed?

A

Measure HAV antibodies:
- HAV IgM = active
- HAV IgG = recovery or vaccinated

93
Q

For Hepatitis E, give its:
- Type of virus (RNA/DNA)
- Route of transmission (give ex for genotype)
- Symptoms/ chronic infection risk
- Incubation period

A
  • RNA (Herpevirus)
  • Faecel oral OR blood/bodily fluids: genotype 1,4 = water borne, genotype 3,4 = zoonotic (undercooked meat, pork)
  • Risk of chronic infection for immunocompromised
  • High mortality in cirrhotics and pregnancy (and immunocompromised)
  • IP= 40 days
94
Q

What are the complications of Hepatitis E? How can infection be prevented?

A

Complications - acute neurological syndromes
Prevention = improve sanitation, vaccine available in china

95
Q

How is Hepatitis E diagnosed with serology?

A

HEV IgM = current infection
HEV IgG = recovered
HEV RNA blood = if present indicates chronic infection

96
Q

For Hepatitis B, give its:
- Type of virus (DNA/ RNA)
- Route of transmission with examples

A

DNA virus (multiple subtypes). Blood/bodily fluids:
- Contact with infected blood, i.e. unsterile tattoos, shaving
- unprotected sex
- mother to baby, highest risk of chronic infection

97
Q

What does the outcome of infection of hepatitis B depend on?

A

Maturity of your immune system, strongly determined by your age. Chronic infection is highly likely if you’re infected as a baby (>90%) but very small if infected as an adult (<5%)

98
Q

Where are the endemic areas of Hep B? what is the prevalence in the UK?

A

Asia, China, Middle East
UK = 0.3%

99
Q

What is the screening programme for Hep B?

A

Identify anyone at risk of it, i.e. drug users
- Antenatal clinics; screen mothers for HBV
- Prisons
- GUM clinics
- Community drug services

100
Q

How would you treat a woman who was pregnant if they tested positive for HBV?

A

Can either:
- Vaccinate the baby
- Give Hep B immunoglobulin to baby
- Treat the mother if high HBV in her blood

101
Q

Where is GGT (Gamma-glutamyl transferase) found and what is its role?

A
  • Found in many cells/ tissues, but large quantities in the liver = localised to hepatocytes and epithelium of small bile ducts.
  • Transfer gamma-glutamyl peptides to other peptides and amino acids
102
Q

What can increase activity of GGT?

A

Alcohol, carbamezpine, barbituates, glucocorticoids

103
Q

What does increased GGT indicate?

A

Acute and chronic hepatitis
Cholestasis
Chronic alcoholism (can be used as a recent drinking indicator in alcoholics)
Pancreatic biliary tract cancers

104
Q

What 3 antigens are present with Hep B? What do they indicate?

A
  • Hep B surface antigen (HBsAg) = indicates current infection
  • Hep B e antigen (HBeAg) = secreted by infected cells to indicate active infection, higher levels = higher infectivity
  • Hep B core antigen (HBcAg)
105
Q

What antibodies can we secrete after exposure to Hep B?

A
  • Hep B e Antibody (Anti-HBe)
  • Hep B core antibody (Anti-HBc), i.e. IgM anti-HBc or IgG anti-HBc
  • Hep B surface antibody (Anti-HBs) – in response to HBsAg
106
Q

How can you tell if someone has been vaccinated by Hep B or have been exposed to the virus?

A

Vaccination only includes Hep B surface antigen, so if they has been vaccinated and not infected they would only have anti-HBs
If previously infected they would have anti-HBs AND IgG anti-HBc

107
Q

Describe the typical serologic course of Hepatitis B

A

HBsAg = first detected
HBeAg next detected
Then the body would make antibodies so:
- IgM anti-HBc increases
- IgG anti-HBc increases and remains high
- Anti-HBs will increase after IgM falls, and will remain high

108
Q

How is hepatitis B diagnosed?

A

HBV sAg negative and Core AB (IgM/ IgG anti-HBc) negative = no exposure

HBV sAg negative and anti-HBc positive = previous exposure to infection

HBV sAg positive and anti-HBc positive = current (on-going) chronic infection

(essentially = antibody- previous exposure, antigen= ongoing infection)

109
Q

Describe what happens during the course of Hep B after infection during birth (in reference to ALT and HBV DNA)

A

1: immune tolerant phase: Immature immune system, high HBV DNA, normal ALT (hepatocytes not destroyed yet)
2: As the immune system matures (>20y/o), ALT and HBV DNA fluctuates (active immune system = destruction of hepatocytes)
3: Cycles of inflammation and repair = fibrosis
4: Age 40, infection becomes inactive carrier (normal ALT)
5: reactivation: HBeAg-negative chronic hepatitis, very unpredictable, can occur if patient becomes immunocompromised (i.e. takes corticosteroids)
6: some may clear virus (and produce anti-HBs) but may have severe fibrosis

110
Q

Why is chronic HBV harder to treat than other hepatitis infections?

A

Part of the HBV lifecycle is in the cytosol where it inserts covalently closed circular DNA (cccDNA) into the host genome. This acts as a viral reservoir, so the only way to get rid is to destroy the whole hepatocyte

111
Q

What treatments may be given for chronic HBV infections?

A
  • Antiretrovirals, i.e. tenofovir and entecavir (‘nucleoside analogues’)
  • pegylated interferon
112
Q

How do tenofovir and entecavir treat chronic hepatitis B? How is it given?

A

Block hepatitis B DNA polymerase to switch off replication (but cannot eradicate cccDNA). Given once a day LIFELONG - may clear the virus eventually but after many years of treatment

113
Q

How does pegylated interferons treat chronic hepaitits B? How is it given?

A

Given as an injection once a week, stimulates immune system to recognise infected cells and destroy them, also inhibits some stages of viral replication

114
Q

What does presence of anti-HBc IgG vs IgM indicate?

A

Previous or ongoing infection (need HBV sAg to confirm if ongoing)
IgM = within last 6 months

115
Q

For Hepatitis D, give its:
- Type of virus
- Route of transmission

A

Defective RNA virus, transmitted via blood and bodily fluids but requires Hep B machinery to replicate = uses its surface antigen for its viral envelope

116
Q

How can hepatitis D be acquired?

A

‘Simultaneous: infected with HBV and HDV at once, so can clear HDV if you clear HBV
‘Superinfection’: have chronic HBV and acquire HDV. Dangerous, as ca lead to acute liver injury

117
Q

What are the endemic regions of HDV?

A

Meditteranean basin, Turkey, Russia, Central Asia, S. America

118
Q

What are the complications of hepatitis D?

A

Severe hepatitis
70% develop cirrhosis
Lifetime risk of HCC doubles

119
Q

How is hepatitis D diagnosed?

A

If any are present;
- HDV IgM
- HDV IgG
- HDV RNA

120
Q

How can hepatitis D be treated?

A

If clear HBV sAg then can eradicate HDV. Give pegylated interferon for >48 weeks, but outcomes are poor

121
Q

For Hepatitis C, give its:
- Type of virus
- Route of transmission
- IP

A
  • RNA (Flavivirus) - 6 subtypes
  • Blood and bodily fluids, mainly poor sterilisation. Transmission via sex or mother to baby is rare
  • IP = 2 weeks to 6 months
122
Q

What is the risk of hepatitis C? i.e. chronic infections etc.

A
  • 75% develop chronic infections, irrespective of age and immune status
  • 1 in 5 develop cirrhosis or HCC
123
Q

Where is prevalence of hepatitis C highest? What is the prevalence in the UK?

A

Egypt (& Africa), Pakistan, Middle East
UK = 0.44%

124
Q

How is Hepatitis C diagnosed?

A

If HCV AB positive but HCV RNA negative = previous exposure
If HCV AB positive and HCV RNA positive = chronic infection

125
Q

What are poor prognostic factors of treating Hep C?

A
  • Cirrhosis
  • Non-causacian
  • HIV co-infected
  • Steatosis
    Also depends on genotype
126
Q

What drugs may be used to treat hepatitis C? Why is Hep C curable?

A

Direct Acting Antivirals (DAA) for 8-12wk:
- NS3/4 protease inhibitors
- NS5A inhibitors
- NS5B polymerase inhibitors

Curable as the lifecycle of HCV occurs in the cytoplasm

127
Q

For the DAA’s used to treat Hep C, what do the common names end in?

A

‘previr’ = NS 3/4 protease inhibitor
‘asvir’ = NS5A inhibitor
‘buvir’ = NS5B polymerase inhibitor

128
Q

What might DAA’s be supplemented with if the patient with Hep C has cirrhosis?

A

Ribavirin

129
Q

Who is screened in the UK for hepatitis C?

A

Those at high risk of infection (e.g., injection drug users), if had a medical treatment abroad which seemed unsterile etc.
Prisoners = aim to eradicate in prisons by 2030!

130
Q

Histologically, how does hepatitis C appear?

A
  • Portal tract is full of lymphocytes
  • May not be able to see the boundary between portal tract and the hepatocellular lobule (interface hepatitis)
  • Round white globules = fatty change (steatosis - hepatocytes become full of fat)
131
Q

How is death caused from lethal alcohol toxcity?

A

Respiratory depression

132
Q

What are the 4 stages of alcoholic liver disease? State whether they are reversible and what changes are noted

A

1: fatty change= reversible, globules formed
2: alcoholic hepatitis= reversible, expansion of lymphocytes ,may see Mallory’s hyalline
3: Pericellular fibrosis= reversible up to a point Scarring occurs, typically around a central vein in each lobule. Hepatocytes become surrounded by fibrotic tissue (instead of vasculature)
4: Cirrhosis= irreversible, lobules surrounded by fibrous tissue

133
Q

What is Mallory’s hyaline?

A

When cytoskeletal particles have aggregated in severely damaged hepatocytes. Seen in alcoholic hepatitis

134
Q

What is non-alcoholic fatty liver disease?

A

Fatty change in people who have metabolic syndromes (obesity, T2D, hyperlipidaemia). It has similar changes to alcoholic liver disease.

Includes = Non-alcoholic steatohepatitis (NASH)

135
Q

What are the 2 types of cirrhosis? What are they typically caused by?

A

Micronodular: <0.3cm, typically alcohol issues
Macronodular: >0.3cm, typically viral

136
Q

Why does ammonia (and other neurotoxic substances) build up in hepatic encephalopathy?

A

Functional liver impairment = liver normally breaks down ammonia (produced from intestinal bacteria)
AND
Collateral vessels between the portal and systemic circulation mean ammonia can bypass the liver and enters systemic circulation directly

137
Q

Compare acute vs chronic hepatic encephalopathy. Give some other symptoms

A

Acute= reduced consciousness and confusion
Chronic = changes to personality, mood and memory

Other symptoms = anxiety, cognitive impairment, difficulty concentrating, slurred speech

138
Q

What is the role of ALT?

A

Converts alanine and a-ketoglutarate into glutamate and pyruvate

139
Q

How do cholangiocytes (epithelial cells lining bile ducts) secrete bile?

A
  • secondary active transport of Cl- and HCO3- via CFTR
  • Paracellular Na+ transport with isosmotic flow
140
Q

What increases bile secretion?

A

Secretin, VIP, glucagon, CCK

141
Q

What can you use / measure to identify cause of ascites?

A

serum-ascites albumin gradient (SAAG) , i.e. serum albumin concentration/ ascitic albumin concentratoin

If SAAG > 11g/L= Transudate Cause e.g. Portal Hypertension
If SAAG < 11g/L= Exudate Cause ,e.g. inflammation, pancreatitis

142
Q

What cell is activated if hepatocyte proliferation is severely impaired?

A

Oval cells = small population of cells (intrahepatic progenitor cells) involved i liver regeneration

143
Q

What cell converts haem to bilirubin?

A

Hepatocytes

144
Q

What cell is the major cell type involved in liver fibrosis?

A

Hepatic stellate cells

145
Q

What is kernicterus?

A

High bilirubin levels in the baby can lead to neurotoxicity (pre hepatic jaundice) = rises to toxic levels in the brain

146
Q

What does Hep B eAg and HBV e antibody indicate ?

A

High viral replication rate, so current infection (if high = highly infectious!)

If HBV e antibody = previous infection was highly infectious/ replicative at one point but they have cleared it now

PBL Y2 S4 (9 decks)

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