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Flashcards in Lecture 23 Deck (53):

What is one of the most common causes of chronic liver disease?

Chronic viral hepatitis
-can lead to potential progression to cirrhosis and other risks and other complications


When can acute liver failure occur

In someone who has acute liver injury
-e.g. acute hepatitis
-drug overdose
-chronic liver disease/cirrhosis --> then develops acute injury on top of that


Case 1:

68 year old lady
1973: operation for endometriosis
Complicated by peritonitis
Further laparotomy; given blood transfusion (due to bleeding during surgery)
8 wks later - nausea, anorexia, vomiting "looking yellow"
AST and ALT >1000 U/L (normal 0-40 U/L) for 2 weeks; elevated bilirubin for 1 week (jaundice)
Admitted to hospital for dehydration (anorexia and vomiting) - given intravenous fluids
Symptoms resolved completely after 1 month


Liver tests: Transaminases

AST: aspartate Transaminase/aminotransferase
ALT: alanine transaminase/aminotransferase
When elevated:
- hepatic inflammation= hepatocellular injury


Liver tests: GGT and ALP

Cholestatic enzymes:
GGT: gamma-glutamyl transferase
ALP: alkaline phosphatase
When elevated- cholestasis i.e.
1. bile stasis (fat in liver causing bile to flow slowly) -bile flows slowly through liver
2. obstruction (tumour/stones) mechanical stopping bile flow


Liver tests: Bilirubin

When bilirubin elevated causes Jaundice (symptom/sign of hyperbiliaremia)
-yellow sclera, yellow skin
Liver diseases are the most common reason for an increased bilirubin count, but it isnt the only reason/cause
-Haemolysis (excessive breakdown of RBC, resulting elevated bilirubin)
Can be due to biliary obstruction (of bile flow. Bile cannot leave liver, accumulated and spills into circulation) or hepatocellular injury (damage to hepatocytes, inflammation of hepatocytes, results in hepatocytes undergoing Lysis, then bile/bilirubin into circulation)


Liver tests: Albumin and clotting factors

Produced by liver
-liver makes proteins such as Albumin and Clotting factors
When abnormal (in clotting factors/albumin), suggests impaired synthesis by liver i.e. liver not functioning properly
-not able to make normal amounts of albumin/clotting factors


When interpreting abnormal liver tests:

1. Is the pattern of abnormality mostly: (hepato recognition to figure out underlying cuase)
-Hepatocellular (Transaminases significantly elevated re to other enzymes)
-Cholestatic (GGT or ALP predomianntly elevated- more tan transaminases)
-mixed (both Transaminases and Cholestatic enzymes equally or similarily elevated without preferance for one of the other)
2. Is there Jaundice?
-depending on whether cholestasis problem or hepatocellular problem, may indicate underlying condition
3. Is Liver Synthetic function impaired?
-Prothrombin ratio (measure of clotting time)


Case 1:
Well until 1993; presented with tiredness
-abnormal AST and ALT 200-300 U/L; serum albumin and prothrombin ratio normal
-tested positive for hepatitis C active infection

Elevated Transaminases
-Not jaundice
-normal synthetic function
Elevated AST and ALT - think viral causes (more common Hep A B C)
-Hep C not recognised until 1989, therefore anyone who received blood transfusion prior to 1990's was at risk of acquiring Hep C (non A non B transfusion related hepatitis)


Hepatitis in medical context

Hepatitis ="titis"- inflammation (of liver)
-doesn't infer particular eateology
-most patients refer hepatitis to "infection"
-incorrect as doesn't necessarily mean it is viral in eateology


Hepatitis B and C

(Hep A is self-limiting infection. most imunnosupressed/ elderly patients (not people who are healthy, therefore not a chronic infection/hepatitis))
-can cause acute and (subsequently) chronic viral hepatitis (if not cleared)
-acute infection -first 6 months
-if still infected after six months - chronic
Both are transmitted via blood (risk factors to vary)
Hepatitis B R.f.:
1. child hood/birth (mother with Hep B can transfer to baby)
2. Country with endemic of hep B. acquired as child via horizontal transmission.
3. Adult: most commonly acquired through sexual transmission
4. Adult: second common injecting drug use
Hep C R.f.:
1. Most common: injecting drug use
- for hep C sexual transmission not particularly high risk factor
2. Blood transfusion (contaminated blood -prior to 1990s (prior to Hep C awareness) or -acquired in a country which has no proper screening for Hep C)
Both Important causes of chronic liver disease and cirrhosis (due to potential for causing chronic infection)
- Majority of people infected with Hep C will develop chronic infection (wont be able to clear infection once infected with the disease)
Vaccine available for hepatitis B but not C


Risk factors for Hepatitis B

Hepatitis B R.f.:
1. child hood/birth (mother with Hep B can transfer to baby)
2. Country with endemic of hep B. acquired as child via horizontal transmission.
3. Adult: most commonly acquired through sexual transmission
4. Adult: second common injecting drug use
-vaccine available


Risk factors of Hepatitis C

Hep C R.f.:
1. Most common: injecting drug use (~60^ of HCV cases)
2. Sexual: Risk is extremely low in monogamous long-term relationships (even in partner has Hep C) and absence of HIV
-If person infected with Hep C was co-infected with HIV, increased risk of sexual transmission
- for hep C sexual transmission not particularly high risk factor
3. Blood transfusion
a) Recieved unscreened blood products/donated organs
-pre 1992 in Western countries
-In countries with no universal HCV screening
-contaminated blood -prior to 1990s (prior to Hep C awareness) or -acquired in a country which has no proper screening for Hep b) Vertical (mother to baby)
-risk (for baby) also low (unlike Hep B) but can be much higher if mother HIV positive
4. Occupational
-Medical treatments in countries with poor sterile practice (people who deal with needles/needle stickinjuries) (countries which dont sterilise medical equipment, or reuse certain needles or medical equipment
-Tattooing or body piercing with non-sterile equipment (not so much any more)


What is one of the particular issues and problems/risks of Hepatitis C?

- Majority of people infected with Hep C will develop chronic infection (wont be able to clear infection once infected with the disease)
- No vaccination


Acquiring Hepatitis B

1. Sexual intercourse
2. Injecting drug use
-most adults who are healthy will be able to clear Hep B acutely
-But if acquire Hep B as a child/baby, unlikely to clear infection acutely
Therefore most commonly seen Chronic Hep B cases, are people who have acquired Hep B:
1. During Childhood
2. At birth
-Now Hep B vaccination to decrease rates


Hepatitis C (HCV)

Single-stranded RNA virus (different to hep B)
-discovered in 1989, diagnostic tests available soon after
-many cases of post-transfusional hepatitis, previously known as "non-A non-B hepatitis", were due to HCV
Spread by blood
Exists as different strains known as genotypes
Majority of people infected are unable to eliminate the virus
-up to 85% of people acutely infected will end up with chronic infection


Case 1:
1995: decided to have treatment
-Interferon for 6 months

Many side effects
Treatment failed
Remained infected with Hepatitis C


Treatment for HCV

HCV treatment has evolved over the years
Regimens were Interferon based
*Cytokine produced by lymphocytes in response to viral infection (in natural immune response. physiological cytokine)
* Our body makes it "endogenous"
* In HCV treatment "exogenous" Interferon is used to increase interferon response (to increase immune response against virus)
* Causes "flu-like" symptoms (headache, fever, muscle aches, tiredness) - related to interferon release


Interferon treatment for HCV

Interferon has been the cornerstone of HCV treatment for almost 2 decades
-given as subcutaneous injection (like insulin)
-initially interferon alone i.e. mono-therapy
- moved on to interferon with Ribavirin (treatment combo)
-moved on to pegylated interferon with ribavirin
--Pegylation - addition of polyethylene glycol (PEG) molecule to prolong half-life i.e. stays in body for longer (and concentration remains more stable)



addition of polyethylene glycol (PEG) molecule to prolong half-life i.e. stays in body for longer (and concentration remains more stable)
-e.g. PEgylation of interferon with Ribavirin


Problems with interferon

1. Sub-optimal cure rates: with newer regimes, cure rates were better but still only 50-80% depending on genotype
2. Problematic side-effects (flu like symptoms)
3. Long duration - 6 to 12 months depending on genotype (longer treatment vs most viral infection treatments)


Breakthrough HCV treatment

In the last few years, new groups of drugs known as direct-acting antiviral agents (very soon interferon wont be used. good as previously top indication for liver transplantation was Hep C, now better drugs, most people will be cured, --> unlikely to develop complications from chronic liver disease and unlike to require liver transplant)
-taken as tablets
-significantly better cure rates
-cure rates of >90% could be achievable without interferon - just taking a short course of tablets


Case 1:
1999: presented with Melaena

Passage of dark/black bowel motions
-related to bleedings on upper GI tract
-Spurting varices (actively bleeding, usually aggressive and life threatening)
-varices are under high pressure, develops due to complication of portal hypertension
1. Try and inject adrenalin directly into varices (usually doesn't work) just below where hole is
2. Banding - suck varices through middle of cap into endoscope (buldges towards you into cap), strings on side attached to rubber band, then rubber band deployed to strangle bottom of varices to stop from bleeding


Portal Circulation

The portal vein conducts venous blood from entire Gi tract + and Spleen --> to the liver
Venous blood passes through liver through hepatic veins and to IVC inferior vena cava then back to heart
-portal cirulation affected if pressure in liver increases
-can result in portal hypertension


Portal hypertension

High pressure in portal vein
Difficult from blood in portal circulation to return to the right heart
-body adapts if portal hypertension is long term/long period of time. instead of pushing blood through portal vein (which are increasing becoming increasingly resistant/ increasing in pressure)- forms collaterals
Porto-systemic collaterals begin to form
-these are alternative vessels that enlarge to try and divert blood from portal circulation back to the right heart (bi-passing portal vein)
-called varices
-typically form in oeosphagus or stomach. can also form in Mesentery. Also around Small and Large intestine, around kidneys and pancreas
-Bleeding oesophagus: blood which normally flows from oesophagus has to go through portal vein. But if pressure is high, additional veins form around the oesophagus, and try to carry blood back into IVC without going through Portal Vein


Location of Porto systemic Collaterals/Varices

Typically form in Oesophagus or Stomach
Can also form in Mesentery
-Also small and Large intestine - around kidneys and pancreas


Oesophageal and Gastric Varices

-varices most commonly present in oesophagus and stomach with bleeding
Can rupture and bleed because of high pressure
-after ruptured will bleed profusely due to high pressure
1. Esophageal varices EV: (GO junction)
-nobly columns
-typically begin/form at GO gastro-oesophageal junction (bottom of food pipe), and move upwards as columns of blood vessels
2. Gastric Varices GV: (Fundus)
-typically in Fundus/top of stomach
-Swollen Vessels- look like lumps
-can bleed as well


Treatment for GI bleeding and/or suspected Varices

Endoscopy with Teloscope (down to distal oesophagus)
1. Adrenalin Injection
2. Rubber Band ligation system
- varices identified
-sucked up into scope/plastic transparent cap (with rubber bands sitting ontop of cap)
3. Rubber bands deployed to tie onto varices, to stop them from bleeding or rupturing
4. Often can required several treatments of bands, before varices eradicated
-Banding doesn't mean that varices cannot reform (similar to hemorrhoids)
-If underlying problem (portal hypertension) is not addressed or treated, New varices will form over time
(non-permanent solution, more a temporary fix)


Causes of Portal Hypertension

1. Pre-hepatic (occur before liver)
-Portal vein Thrombosis (if doesnt dissolve, become a clot, can increase PV pressure. Occurs before liver, doesnt involve the liver)
2. Intra hepatic (most common)
-Cirrhosis (problem inside of liver. Scarring of liver = stiff liver = difficult for blood to flow through it)
3. Post-hepatic (problem lies beyond liver)
-Hepatic vein (thrombosis) (clot, causing pressure to rise inside liver and in portal vein)
-Right sided heart failure (pressure in right side of heart elevated, due to heart failure, either due to valvular disease or ischaemic heart disease. Then the pressure required for the liver/portal vein to push blood back into heart is increased, causing portal hypertension)


Portal hypertension Values

Normal portal blood flow:
Pressure 12mmHg (due to liver stiffness)
Formation of porto-systemic collaterals i.e. varices (to try compensate for increased portal pressure)


Liver Cirrhosis

-can be caused by anything that leads to chronic injuring of the liver
Irreversible scarring of liver
Advanced liver disease
Liver initially enlarged (swollen), then progressively shrinks
Surface becomes irregular and nodular
Nodules- normally liver surface should be smooth and shiny


Fibrosis and cirrhosis of the Liver

Prolonged or repeated liver inflammation leads to fibrosis -i.e. scarring
-fibrosis= initial scarring. Is reversible to a certain extent.
Fibrosis is potentially reversible if liver allowed time to regenerate by removing cause of inflammation
If not, eventually fibrosis becomes irreversible
Irreversible scarring = cirrhosis
Initially, cirrhosis is mild - liver functions normally (blood tests may appear normal as liver is still able to function normally)
Cirrhosis can progress and eventually liver no longer functions normally (eventually liver function will become abnormal)


Case 1: 2001: problems with concentration and judgement
-awake at night and sleepy during the day
-had to stop work and driving was difficult
-confused and disorientated on several occasions
Diagnosed with hepatic encephalopathy
Started on lactulose
-partial improvement

Hepatic Encephalopathy
-well recognised complication of liver disease


Hepatic Encephalopathy HE

Result of chronic liver failure
Due to build up of toxins that cross the Blood-brain barrier
Early symptoms: (subtle and difficult to detect)
-mood and personality change
-inverted (minor) sleep pattern (sleep-wake reversal) (little harder to sleep at night, and sleeping more during the day)
Late symptoms: (progresses and not treated)
-confusion and bizarre behaviour
-drowsiness and coma


Mechanism of HE Hepatic Encephalopathy

Chronic liver failure i.e. functioning poorly
Liver unable to detoxify substances produced by bacterial metabolism

-blood not detoxified by the liver
Build up of Ammonia in the blood
-Ammonia is toxic to the brain
-passes blood-brain barrier and disturbs normal brain function
In addition, porto-systemic collaterals(varices) shunt blood from portal circulation back to right heart, bypassing the liver
-by blood bypassing liver, it isnt detoxified at all by the liver

Therefore not only do you have a) a build up of ammonia b) you also have a good proportion of the blood that doesn't even go through the liver, then there is no detoxification


Treatment of HE Hepatic Encephalopathy

Lactulose (drug)
-Used to manage HE symptoms but not definitive treatment (not solution to problem, but is a medication to manage the symptoms)
-normally used as a laxative to treat constipation (by acting as a osmotic laxative)
-Non-absorbed disaccharide
-In patients with hepatic encephalopathy:
Mechanism of action of lactulose in treating HE is not completely understood
1. Decreases ammonia generation by bacteria (in bowel)
2. Converts ammonia to a non-absorbable molecule (non-soluble/ not fatty molecule, therefore unable to cross blood brain barrier/doesnt enter circulation, therefore cannot reach or affect brain)
3. Increases bowel transit (increasing stool movement in bowel, less time for bacteria to produce ammonia)
Variable improvement


Case 1:
2002: abdominal distension
Diagnosed with ascites.
Not responsive to diuretics
2003: waitlisted for liver transplantation

Abdominal distention has many causes
-one of causes is ascites - accumulation of peritoneal fluid
-used to treat ascites
-treat fluid overload (e.g. in heart failure)



Ascites is fluid in the peritoneum causing abdominal distention
Number of causes; including portal hypertension (+ cancer/malignancy which has spread to peritoneum and caused ascites)
-elevated hydrostatic pressure in portal vein (too much fluid in portal vein, causing fluid to shift out of circulation --> into peritoneum)
-low oncotic pressure in portal vein(due to fallen albumin protein levels) (due to impaired liver function --> low serum albumin)
(less able to hold on to fluid in circulation)
NB. Hydrostatic pressure- exerted by fluid
NB. Oncotic pressure-exerted by proteins


Hydrostatic pressure

exerted by fluid


Oncotic pressure

exerted by proteins


Major points

Liver Cirrhosis- long term damage to chronic liver disease (progressive/repeated injury to liver)
Fibrosis of liver =/= doe NOT mean cirrhosis
-liver has an amazing regenerative power (binge drink, lil inflammation and/fibrosis. abstain from alcohol 5-10 years, fibrosis may be reversible)
Cirrhosis is when the fibrosis/scarring has become irreversible
Cirrhosis is the most common cause of portal hypertension
-Portal hypertension can present as:
1. Varices
2. Ascites (stomach distended with fluid due to hypertension)
3. Hepatic encephalopathy (disturbed cognitive function or sleep pattern)
4. Hypersplenism (splenomegaly, low platelet count) - spleen swollen (venous blood flow from spleen --> portal vein --> liver). therefore if portal vein pressure is high then spleen can become swollen. --> Platelets that go through the spleen become destroyed at a higher rate
Initially patients with cirrhosis can have good liver function (albumin/clotting factors will be normal)
-liver has enormous reserve capacity (as dont need all of liver to perform daily activites/sustin normal life)
-can perform its duties even when 70-80% is damaged
Hepatic Encephalopathy is an indication of advanced cirrhosis with liver failure (can give hepatic flap)
Blood vessels ontop of chest = spider nevi
The only definitive treatment for liver failure is liver transplantation
The other important complication of cirrhosis is hepatocellular carcinoma (primary liver cancer)



splenomegaly, low platelet count) - spleen swollen (venous blood flow from spleen --> portal vein --> liver). therefore if portal vein pressure is high then spleen can become swollen. --> Platelets that go through the spleen become destroyed at a higher rate


Case 2:
41 year old woman
10days of:
-nausea and anorexia
-upper abdominal pain
-abdominal distention
Hb, Platelets, WCC normal
ALP and GGT normal
Bilirubin 50
AST 241
ALT 217
Albumin 30
Prothrumbin Ratio 1.7

Past medical history:
1. Ulcerative colitis
-diagnosed 1993. (reasonably well controlled)
-Prednisone 1-2 months each year
-well on no medications for past 6 months
-occasional loose motions
2. Asthma
3. 6 months post-partum
-normal vaginal delivery
-1 months ago, had tubal ligation
Social and Family history:
-No alcohol
-Married with 2 children
-Breastfeeding her 6 month old son
-No family history of note
Physical examination:
-Low grade temperature
-Mild Jaundice
-No signs of chronic liver disease (ascites, encap
-Grossly distended abdomen with shifting dullness (suspected ascites)
-JVP normal
-Milk ankle oedema


Signs of Chronic liver disease

Encephalopathy (gives hepatic flap)
BV ontop of chest (spider nevi)


Hb, Platelets, WCC normal
ALP and GGT normal
Bilirubin 50
AST 241
ALT 217
Albumin 30
Prothrumbin Ratio 1.7

Raised Bilirubin = Jaundice
Transaminases: AST and ALT elevated in 200's . Normal is less than 40
Low Albumin
Prothrombin ratio Elevated= disturbed clotting
-taking longer (elevated) to clot blood , compared to normal person


Prothrumbin ratio

elevated= impaired clotting
-taking longer (elevated) to clot blood , compared to normal person


Case 2 Impression

Normally well person
Became acutely unwell and developed sudden ascites
Evidence of liver inflammation (elevated transaminases) and jaundice (elevated bilirubin)
Blood tests indicate impaired liver function (low albumin, prothrumbin high)


Case 2 Ultra sound

ascites- fluid surrounding liver
doppler of veins = blood flow through vein.
-Left hepatic vein- has flow through
-Right hepatic vein - not seen well
-Middle hepatic vein - only little flow through
Venous supply through liver: Portal vein, enters liver, branches into segments, hepatic veins take blood from small vessels in liver and take into IVC


Budd Chiari Syndrome

Acute thrombosis (clot) in hepatic veins
Outflow of blood from liver is obstructed (blood cannot flow out of liver, and becomes acutely swollen)
Liver becomes acutely congested, hepatocellular damage (due to liver swelling)
-Acute liver damage +
Acute Portal hypertension occurs with ascites developing


Presentation of Budd Chiari Syndrome

Acute rapidly progressive severe
-havent had time for body to adapt to sudden rise of abdominal pressure
Upper abdominal pain
Hepatomegaly (enlarged, swollen liver)
Ascites (rapid onset)
Hepatic Encephalopathy in fluminant cases (drowsy and coatosed rapidly)
-NB. Fulminant - very severe and sudden



very severe and sudden


Budd-Chiari Syndrome cuases

75% - no obvious cause (of clot of hepatic veins)
25% - cause identified
-external compression e.g. tumour
Polycythaemia vera
-bone marrow makes too many RBC
*Pregnancy, post partum
*Oral contracetpive pill ( asked about blood clotting problems)
-clotting disorders
Paroxysmal nocturnal haemoglobinuria
-genetic mutation -defect in RBC membrane - immune destruction of RBC
* Hepatocellular carcinoma (caused by complication of tumour. tumour causing compression and disruption of blood flow, can lead to thrombis)


Management of Budd Chiari

1. Portocaval shunting is often performed to divert blood flow (bypass area of obstruction in vein/swollen liver)
-Trans-jugular Intrahepatic Porto-Systemic Shunt (TIPSS) (sometimes done in people with portal hypertension, to Reduce resistance of blood flow through liver) surgical (done with other causes of portal hypertension as well)
2. Anticoagulation (treat clot- thin blood and dissolve clot)
3. Diuretics (treat manage ascites via giving diuretics)