Chronic Liver Disease Flashcards
List 7 key functions of the liver
Synthesis of clotting factors (except factor 8)
Glucose homeostasis (gluconeogenesis, glycogen storage)
Albumin synthesis
Conjugation and clearance of bilirubin
NH3 metabolism (urea cycle)
Drug metabolism and clearance
Immune (dealing with gut-derived bacteria and bacterial products)
Describe the liver enzyme pattern seen in hepatocellular injury or necrosis
ALT, AST elevation
Very high ALTs in acute viral hepatitis, acute drug toxicity, ischaemia
Describe the liver enzyme pattern seen in intra- or extra-hepatic cholestasis
ALP, GGT elevation
Minor elevation of transaminases
Typical of biliary obstruction, liver infiltration, cholestatic reactions to drugs
Which is more liver-specific: ALT or AST?
ALT predominantly from the liver
AST from many sites
What forms of liver disease tend to present with a mixed picture in terms of the liver enzyme pattern?
Alcoholic liver disease
Fatty liver disease
List 5 symptoms of CLD
Fatigue Weight loss (muscle) or gain (ascites) Bleeding (haematemesis from varices) Abdominal distension (ascites) Confusion (encephalopathy)
List 3 clinical signs of CLD
Spider naevi
Splenomegaly
Jaundice
What pattern of liver enzymes is typically seen in CLD?
Low albumin
Raised bilirubin
AST>ALT (AST not routine)
NB LFTs may be normal
Describe the coagulopathy seen in CLD
Prolonged INR (or high normal 1.2-1.3) Low platelets (or normal, e.g. under 200)
80 year old woman presents with abnormal LFTs (ALT 54, AST 58, ALP 200)
40 years earlier had severe hepatitis with hepatic failure (encephalopathy and peripheral oedema) after trip to QLD, managed at Fairfield Hospital in ICU
Negative viral and AI serology at the time and made a full recovery
PHx: HTN, mitral valve prolapse
Rx: verapamil, esomeprazole, frusemide
SHx: lives alone (widowed) nearby children
No alcohol (current or past)
No FHx of liver disease
O/E: 3 spider naevi, no other peripheral signs of liver disease, no palpable hepato-splenomegaly, no ascites or oedema, loud pan-systolic murmur consistent with MR
Ix?
Ix: FBE, LFTs, coags
What do we look for O/E in CLD?
Stigmata of CLD
Signs of underlying aetiology
Signs of decompensation
Stigmata of CLD
Clubbing Leuconychia Palmar erythema Spider naevi Gynaecomastia
Signs of liver decompensation
Jaundice
Ascites/oedema
Bruising
Signs of underlying aetiology for CLD
Dupuytren’s contracture (EtOH)
Parotidomegaly (EtOH)
What is clubbing? Mechanism in CLD?
Increase in soft tissue of distal fingers/toes
Arterial hypoxaemia due to pulmonary AV shunt?
What is leuconychia? Mechanism in CLD?
Opacification of the nail bed
Hypoalbuminaemia or compression of capillary flow by EC fluid
Mechanism of palmar erythema in CLD
May be due to excess oestrogens and altered micro-vasculature
4 causes of Dupuytren’s contracture
CLD due to alcohol
Manual labour
Anti-epileptics
DM
Mechanism of parotidomegaly in alcoholism
Fatty infiltration due to alcohol toxicity +/- malnutrition
Describe the characteristic appearance of a spider naevus
Central arteriole with radiating small vessels
Blanches on compression
Where are spider naevi typically seen?
SVC distribution
What number of spider naevi is abnormal?
> 2 abnormal
What are multiple spider naevi pathognomonic of?
Cirrhosis
Mechanism of gynaecomastia in CLD
Imbalance of oestrogen:testosterone OR secondary to medication (spironolactone)
Mechanism of jaundice in decompensated CLD
Reduced bilirubin processing and excretion (including gall stones, HCC or portal vein thrombosis)
Mechanism of ascites in decompensated CLD
Abdominal free fluid due to combination of reduced oncotic pressure (low albumin) and increased portal pressure
Mechanism of coagulopathy in decompensated CLD
Reduced clotting factors,thrombocytopaenia
ALP 170 U/L GGT 88 U/L ALT 54 U/L AST 58 U/L Bilirubin 17 umol/L Albumin 36 g/L INR 1.1 Platelets 125 x 10^9/L What do these results suggest? What further tests would help?
Mixed elevation of liver enzymes AST>ALT suggests possible cirrhosis Normal synthetic function Possible portal HTN (low platelets) Further Ix: hepatitis serology, ANCA, ANA, AMA, ASMA, ALKM, liver U/S, consider liver biopsy
What does a positive ANCA and ANA indicate?
??
What is looked for on liver U/S in CLD?
Hepatic echogenicity Any focal lesions Liver and spleen size Portal vein diameter and flow Presence or absence of ascites
Describe the sonographic appearance of a cirrhotic liver
Coarsened hepatic echogenicity
How might liver biopsy be performed?
Via intercostal approach
Describe the histopathological progression of CLD
F0: normal
F1: peri-portal fibrosis, no septa
F2: peri-portal fibrosis with a few septa
F3: numerous septa, no architectural distortion
F4: architectural distortion and nodule formation
When is staging fibrosis useful?
If it would alter Mx
Liver biopsy often useful in this case
What are the risks of liver biopsy and how common are these?
Minor complications (e.g. pain): 14% Major complications (e.g. haemorrhage/perforation): 0.2-1.0% Mortality: 0.009%-0.2%
What alternative is there to liver biopsy and when is this indicated?
FibroScan
For patients with HCV (remains a research tool for other conditions)
What is FibroScan and how does it work?
Transient elastography: probe induces an elastic wave through the liver, velocity of wave is evaluated in a region located located from 2.5cm to 6.5cm below the skin surface
What measurement does FibroScan provide?
Liver Stiffness Measurement (LSM): absent or mild fibrosis, significant fibrosis, severe fibrosis, cirrhosis
Median LSM >13 kPa suggests cirrhosis
ARFI
Acoustic Radiation Force Imaging
What is ARFI?
High power ultrasonic waves are used to displace tissue for the purpose of tissue characterisation and measurements
Acoustic waves displace energy into the tissue; this energy generates a force that causes displacement of the tissue
These motions are used to derive information about the tissue
What is the “rule of 3s” for identifying the cause of CLD?
Big 3: HBV, HCV, alcohol
AI 3: AIH, PBC, PSC
Metabolic 3: haemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency
Other 3: fatty liver disease (NASH), Budd-Chiari (hepatic vein thrombosis), chronic biliary obstruction (e.g. tumour, CF)
What are 4 main functions of the liver and how are these related to staging of CLD?
Make proteins include clotting factors: low levels of albumin/clotting factors results in coagulopathy, bleeding, ascites and oedema
Processes bilirubin: failure to excrete results in jaundice
Metabolises drugs and toxic waste (e.g. ammonia): build up of waste products leads to encephalopathy
First port for blood from intestines: portal HTN results in ascites, splenomegaly and varices (+/- bleeding)
List 3 other problems which may result from CLD
Hepatorenal syndrome (renal failure due to CLD)
HCC (aka hepatoma but NOT benign)
Metabolic failure
What kinds of liver disease is HCC associated with?
Cirrhosis from any cause
HBV in the absence of cirrhosis
What is the presentation of metabolic failure related to CLD?
Hypoglycaemia (late)
Feminisation/masculinisation
What does “decompensation” in the context of CLD refer to?
Any of the following: jaundice, ascites/oedema, coagulopathy, variceal bleeding, hepatorenal syndrome
What does “hepatic failure” refer to?
Presence of porto-systemic encephalopathy (PSE)
What Ix should be performed before a TOE in a patient with CLD
Gastroscopy to screen for oesophageal varices
Describe the Child-Pugh system for classification of CLD
Encephalopathy: none = 1, I-II/suppressed = 2, III-IV = 3
Ascites: none = 1, mild = 2, severe = 3
INR: under 1.7 = 1, 1.7-2.2 = 2, >2.2 = 3
Albumin: >35 = 1, 28-35 = 2, under 28 = 3
Bilirubin: under 34 = 1, 35-50 = 2, 50 = 3
Class A: 5-6 points
Class B: 7-9 points
Class C: 10-15 points
What is the 1 and 2 year survival rate for classes A, B and C in the Child-Pugh scoring system?
A: 1 year survival 100%, 2 year 85%
B: 1 year survival 81%, 2 year 57%
C: 1 year survival 45%, 2 year 35%
What is MELD and when is it used?
Model for End-stage Liver Disease
9.6 logE (creatinine (umol/L)/8) + 3.8 logE (bilirubin (umol/L)/17.1) + 11.2 logE (INR) + 6.4
Gives score between 6 and 40; lower scores under 20
Used for transplant listing
What are some of the advantages and limitations of MELD?
Continuous, objective variables
BUT can’t calculate at bedside and subject to lab variability
CLD patient undergoes mitral valve repair and later develops exertional dyspnoea
O/E: dullness to percussion and reduced breath sounds on R
CXR: fluid on R side of chest, echo shows good cardiac function
Dx?
Mx?
Dx: CLD with hepatic hydrothorax (ascites which tracks into pleural space)
Mx: increased diuretics with spironolactone and frusemide, occasional drainage via U/S and replacement of fluid with IV concentrated albumin
Why do we try and avoid using normal saline in patients with decompensated liver disease?
Ascites
List 9 complications of CLD
Jaundice Bleeding varices Ascites (and SBP) Encephalopathy Hepatorenal syndrome HCC Nutrition OP Infection (CLD patients should be vaccinated)
How should CLD be managed?
Treating the cause
Managing and preventing complications
How should alcoholism be treated?
Encourage abstinence
?inpatient detox/withdrawal
Support/counselling
Pharmacological interventions (anti-craving medications)
How is HBV treated?
Oral nucleos(t)ide analogues Peg-IFN
How is HCV treated? When do you not treat?
Peg-IFN + ribavirin +/- new agents
Not if decompensated CLD
How should haemochromatosis as an underlying cause of CLD be treated?
Venesection
How is AIH treated?
Prednisolone +/- azathioprine/mercaptopurine
How is PBC treated?
Urso-deoxycholic acid
How is PSC treated?
ERCP +/- stent or balloon dilatation occasionally
What possible causes of jaundice should be considered in a CLD patient?
Portal vein thrombosis
Biliary obstruction (tumour, gallstone)
Infection (esp SBP)
What forms of fluid retention may be seen in CLD patients?
Ascites
Oedema
Pleural effusions
What is the mechanism of fluid retention in CLD?
Renal Na+ and H2O retention via activation of RAAS
How is fluid retention in CLD managed?
Salt and fluid restriction
Large volume paracentesis (ascitic tap)
Diuretics (spironolactone/amiloride, frusemide)
What are the possible locations of varices in CLD?
Oesophageal
Gastric
Rarely duodenal
Describe 2 methods of primary prophylaxis for bleeding varices in CLD
Variceal band ligation (banding)
Non-selective B-blockers (propanolol)
List 5 secondary treatments for bleeding varices in CLD
Octreotide or terlipressin Abx (reduces bacterial translocation) Endoscopic banding (or sclerotherapy) Senstaken-Blakemore (SB) tube TIPSS
TIPSS
Transjugular intrahepatic portosystemic stent/shunt
What is an SB tube?
Medical device inserted through the nose or mouth and used occasionally in the management of upper GI haemorrhage due to oesophageal varices
Octreotide
GH, glucagon and insulin inhibitor (somatostatin analogue)
Terlipressin
Vasopressin analogue
What is encephalopathy and how does it present?
Reversible impaired brain function
Spectrum of symptoms from mild slowing to coma, or stroke-like syndromes
Describe the mechanism of encephalopathy in CLD
Ammonia build-up
Oxidative stress
Impaired neurotransmission (e.g. GABA-benzodiazepine neurotransmitters)
PSE
Portosystemic encephalopathy
List 5 causes of encephalopathy
Drugs Increased ammonia Dehydration Portal vein thrombosis or primary HCC TIPSS
What drugs can cause encephalopathy?
Benzodiazepines
Alcohol
Narcotics
What are some causes of increased ammonia which may lead to encephalopathy?
GI bleeding, constipation
Infection
Electrolyte imbalance, alkalosis, hypoxia
What is hepatorenal syndrome? What different types exist?
Worsening renal function in the setting of CLD
Type I = acute (
Mechanism of hepatorenal syndrome
More blood flowing in portal system
Less blood flowing to kidneys
What changes are seen on UEC in hepatorenal syndrome?
Creatinine rises and urinary volume and urinary Na+ fall
How does cirrhosis cause OP?
Combination of cholestasis, vit D deficiency, physical inactivity, alcohol excess and hypogonadism
What treatment options exist if medical therapy fails?
Consider liver transplant; we have no truly effective hepatic support systems
Transplant will cure many disorders but in HCV reinfection occurs 100% of the time
How long can a liver graft survive?
> 20 years
List 4 reasons for deferral from liver transplant waiting list
Too early (liver function too good, MELD too low e.g. MELD
Name 3 factors which limit rates of liver transplantation
Donor organ supply
Size
Blood group
How are recipients on the liver transplant waiting list ranked?
By MELD score
Which CLD patients should be referred for transplantation?
Anyone with decompensated CLD (ascites, variceal bleeding, encephalopathy, hepatorenal syndrome, HCC)
Mr PH, 54 year old man, born in Hong Kong to Chinese parents and lived in Hong Kong, Korea and Singapore
Routine screening for blood donation at age 16 revealed chronic hepatitis B infection
LFTs normal, seen by GP and told no further Ix required
FHx: mother has HTN and renal failure (HBV status unknown), father died of lung cancer aged 63, brother diagnosed with HCC (HBV positive), other siblings HBV positive
Pt requested scan from GP which revealed 9 cm x 7.8 cm HCC in segments 5/6
Referred to liver clinic
Ix: ALT 58/Bilirubin 19/ALP 98/GGT 307, HBV viral load log 6, platelets 220/INR 1.0/albumin 40, HBsAg positive, HBeAg positive, AFP 6
Mx?
Started on entecavir
?R hemi hepatectomy (residual L lobe must be at least 0.6% body weight)
?transplantation
Describe the Mazzaferro (Milan) criteria for liver transplantation
Single lesion 5 cm or less
Up to 3 separate lesions,
Describe the UCSF criteria for liver transplantation
Single HCC 6.5 cm or less
Up to 3 lesions, largest of which is
When and how is downstaging performed?
For patients currently outside transplant criteria
Loco-regional therapy provides “bridging” to prevent tumour progression: TACE, radio-embolisation with beads (SIR-Spheres/SIRTEX), RFA
TACE
Transarterial chemoembolisation
RFA
Radiofrequency ablation
What % of patients can be successfully downstaged?
~30-60%
What is the difference in survival rates between patients who require downstaging to meet transplant criteria vs patients who do not need downstaging?
5-year survival rates are comparable
SIR-Spheres/SIRTEX
Selective Internal Radiation Therapy (SIRT)
What are some possible complications of liver transplantation and how can these be managed?
Humoral rejection: plasmapheresis
Infection: e.g. CMV, treated with IV ganciclovir
Anastomotic stricture: ERCP
Describe the epidemiology of HCC in Australia
9th most common cause of cancer death in Australia
Fastest increasing cause of cancer deaths
18% survival 5 years after diagnosis
Majority associated with chronic viral hepatitis
Describe the epidemiology of HCC in Australia
9th most common cause of cancer death in Australia
Fastest increasing cause of cancer deaths
18% survival 5 years after diagnosis
Majority associated with chronic viral hepatitis
Give some reasons why HCC may be increasing
Underdiagnosed: 45% of Australians with HBV are unaware of their status, screening and monitoring not routine, stigma, language barriers, confusion about “carrier status”, Medicare auditing
Undertreated: only ~1/5 of those who could benefit receive antiviral therapy (
What are the top countries of birth for chronic HBV in Australia?
China
Vietnam
Philippines
Italy
What are the top countries of birth for chronic HBV in Australia?
China
Vietnam
Philippines
Italy
Who should be screened for HBV?
Individuals from countries of high or intermediate prevalence: Aboriginals, Asia, Africa, South Pacific Islands, Middle East (except Cyprus and Israel), European, Mediterranean (Malta and Spain), South and Central America, Eastern Europe (except Hungary), Caribbean Household contacts Sexual contacts IVDU Multiple sexual partners MSM Prisoners Those with HCV or HIV Dialysis patients All pregnant women All who receive immunosuppressive therapy
What qualifies as a high vs intermediate prevalence area?
High: HBsAg 8%
Intermediate: HBsAg 2-7%
How is HBV screened for and what actions are indicated for a positive result?
HBsAg, HBsAb, HBcAb
If HBsAg positive, refer to specialty clinic
If HBcAb positive, risk of reactivation with immunosuppression
Recommend serology testing of household, close and intimate contacts
Vaccinate non-immune individuals
Describe the natural Hx of HBV and the changing clinical indications throughout
Immune tolerance: high HBV DNA, normal LFTs, HBeAg, monitor every 6-12 months
Immune clearance: high HBV DNA, abnormal LFTs, HBeAg positive, at risk of progression to cirrhosis and HCC therefore should be referred for consideration of treatment
Immune control: low HBV DNA, normal LFTs, HBeAg negative, anti-HBe positive, monitor every 6-12 months
Immune escape: high HBV DNA, abnormal LFTs, HBeAg negative, anti-HBe positive, at risk of progression to cirrhosis and HCC therefore should be referred for consideration of treatment
What is the effect of timely screening and Mx on the natural Hx of HBV?
Treatments are effective and well tolerated
Rates of cirrhosis decrease by 52%
Rates of HCC decrease by 47%
25% mortality transforms to 97% surviva
What is the effect of timely screening and Mx on the natural Hx of HBV?
Treatments are effective and well tolerated
Rates of cirrhosis decrease by 52%
Rates of HCC decrease by 47%
25% mortality transforms to 97% surviva
7 issues facing GPs in the Mx of HBV
Lack of community awareness Stigma, language and cultural diversity Time and inadequate financial support Unclear referral pathways Limited feedback from specialists Lack of prescribing opportunities Fear of Medicare auditing
What are the key domains in the HBV strategy?
Increase community awareness, education and decrease stigma in a culturally appropriate way
Increase access to testing and vaccination
Increase clinical Mx and treatment rates
Support research to guide action
What is cultural competency and how can it effect medical Mx?
Based on shared social experience, cultural characteristics and ancestry
Effects on patient/provider knowledge, attitudes and access
“Cultural competency” aims to improve accessibility and effectiveness of healthcare from cultural and linguistically diverse populations
What is cultural competency and how can it effect medical Mx?
Based on shared social experience, cultural characteristics and ancestry
Effects on patient/provider knowledge, attitudes and access
“Cultural competency” aims to improve accessibility and effectiveness of healthcare from cultural and linguistically diverse populations
What is medical negligence?
Medical negligence may involve a patient who receives care below a reasonable standard that results in an injury (or disease) or causes an existing injury to become worse
