Approach to abnormal LFT

Question 1

List the components of a liver function test (LFT)

Answer 1

1) ALT/AST –> hepatitic enzymes
2) ALP/GGT –> cholestatic enzymes
3) Bilirubin
4) LDH

Question 2

Define significant alcohol consumption

Answer 2

Men >210g alcohol/week
Women >140g alcohol/week

14g alcohol is equivalent to

1. Beer 360mL (12oz)
2. Wine 150mL (5oz)
3. Spirits 45mL (1.5oz)

Question 3

Outline the risk factors for viral hepatitis

Answer 3

1) IV drug use (HBV/HCV)
2) Blood transfusion before 1992 (HCV)
3) Shellfish (HAV/HEV)

HBV/HCV –> parenteral usually blood borne
HAV/HEV –> fecal oral

Question 4

List the types of LFT abnormalities

Answer 4

1) Hepatitic = elevated ALT/AST possibly bilirubin
2) Cholestatic = elevated ALP possibly bilirubin
3) Isoalted hyperbilirubinemia = only elevated bilirubin

Question 5

List the tests of liver synthetic function

Answer 5

1) Albumin –> hypoalbuinemia suggest chronic process
2) Prothrombin time –> 3 possibilities
1. significant hepatocellular dysfunction
2. vitamin K malabsorption
3. vitamin K deficiency due to prolonged jaundice

Prothrombin time should correct w/parenteral K administration; if not there is hepatocellular injury

Question 6

Outline the clinical significance of the AST to ALT ratio

Answer 6

AST to ALT ratio >2 suggests alcoholic liver disease

- further supported if GGT is elevated

Question 7

Outline the difference in magnitude of AST or ALT elevation in specific liver conditions

Answer 7

AST/ALT >2x = chronic HBV/HCV reactivation
AST/ALT >10x = acute HBV flare/exacerbation

AST/ALT >4x = nonalcoholic fatty liver disease (NAFLD)
AST>8x/ALT>5x = alcoholic fatty liver disease (AFLD)
AST/ALT >25x = acute viral/toxin related hepatitis
AST/ALT>50x = ischemic hepatopathy

Question 8

List causes of hepatitic jaundice i.e. elevated AST/ALT

Answer 8

Common causes

1) Infectious (HBV, HCV, HAV, HEV, EBV, CMV)
2) Alcohol
3) Drugs (paracetamol, etc…)
4) Autoimmune hepatitis

Other hepatic causes

5) Wilson disease
6) Hemochromatosis
7) Congestive hepatopathy (e.g. right heart failure)
8) Ischemic hepatopathy (e.g. Budd-Chiari syndrome)
9) Sinusoidal obstruction syndrome (e.g. veno-occlusive disease)

Extrahepatic causes

10) HELLP syndrome (hemolysis, elevated liver enzymes, low platelets
11) Muscle disorders (e.g. polymyositis, long distance running)
12) Thyroid disorder
13) Alpha-1 antitrypsin deficiency
14) Adrenal insufficiency
15) Celiac disease

Question 9

Outline the diagnosis of acute liver failure

Answer 9

1) Anorexia, malaise, nausea, vomiting
2) Jaundice, RUQ pain, mental status changes
3) Hepatic encephalopathy
4) Hepatitic picture w/LFTs >10x normal
5) Prolonged PT/INR (INR ≥1.5)

Question 10

List investigations for hepatitic jaundice

Answer 10

Blood tests

1) LFT for AST:ALT (>2 alcoholic; 45% for hemochromatosis
10) Creatinine kinase for muscle disorders
11) TFT for thyroid disorders

Imaging
1) Transabsominal USG w/Doppler for vascular occlusion to rule out Budd-Chiari syndrome

If all of the above are non-diagnostic and patient is worsening go for liver biopsy

Question 11

Outline the indications for liver biopsy

Answer 11

1) Investigations all negative but >6m AST/ALT elevation

2) Development of acute liver failure (hepatic encephalopathy + INR ≥1.5 + hepatitic picture LFT >10x normal)

Question 12

When is expectant management for elevated AST/ALT acceptable? What interval would monitoring be done?

Answer 12

1) AST/ALT elevation less than 5x normal
2) Asymptomatic

Monitor LFT every 3-6m

Question 13

Outline the approach to elevated ALP

Answer 13

1) Rule out physiologic causes
1. Pregnancy
2. Postprandial >1.5-2x normal repeat fasting sample
2) Blood for GGT or 5’-nucleotidase

Normal GGT or 5’-nucleotidase = ALP likely from bone so evaluate for bone disorders

Elevated GGT or 5’-nucleotidase =ALP likely hepatobiliary so do RUQ USG for dilated bile ducts

Dilated bile ducts = extrahepatic cholestasis –> MRCP/ERCP
No dilated bile ducts = intrahepatic cholestasis –> check antimitochondrial antibodies (AMA)

AMA+ve + USG normal –> liver biopsy
AMA-ve + USG abnormal –> liver biopsy

AMA-ve + USG normal –> assess ALP elevation magnitude
≥50% normal = MRCP/ERCP/liver biopsy
less than 50% normal = observe

Question 14

List causes for extrahepatic biliary obstruction

Answer 14

1) Choledocholithiasis (most common) ± complications e.g. acute cholangitis, biliary pancreatitis
2) Periamupllary carcinoma obstruction (cholangiocarcinoma, pancreatic head, ampullary tumour, duodenal carcinoma)
3) Biliary strictures
1. Primary sclerosing cholangitis w/extrahepatic stricture
2. Complication post invasive procedure
3. Chronic pancreatitis w/stricturing of distal bile duct
4. Biliary anastomotic stricture post liver transplant
4) Infections
1. Clonorchis sinensis
2. Ascaris lumbricoides
3. AIDS cholangiopathy

Question 15

List causes for intrahepatic biliary obstruction

Answer 15

1) Drugs (most common!!!) [stop offending drug)
2) Primary biliary cirrhosis (PBC) [check AMA]
3) Primary sclerosing cholangitis (PSC) [check ANCA]
4) Viral hepatitis (HBV, HCV, HAV, HEV, EBV, CMV)
5) Liver metastasis
6) Alcoholic hepatitis
7) Infiltrative [by biopsy]
8) Bengin postoperative cholestasis
9) Cholestasis of pregnancy
10) Total parenteral nutrition

Question 16

List infiltrative diseases causing cholestatic jaundice

Answer 16

1) Tuberculosis
2) Lymphoma
3) Amyloidosis
4) Sarcoidosis
5) Hepatic abscess

Question 17

List causes of elevated GGT

Answer 17

1) Alcoholism
2) Barbiturates
3) Phenytoin
4) Myocardial infarction
5) COPD
6) Diabetes mellitus
7) Chronic kidney disease

Question 18

List mechanisms of unconjugated indirect hyperbilirubinemia

Answer 18

1) Bilirubin overproduction
2) Impaired bilirubin uptake
3) Impaired bilirubin conjugation

Question 19

List mechanisms of conjugated direct hyperbilirubinemia

Answer 19

1) Reduced excretion into bile ductules

2) Bilirubin leakage into blood from hepatocytes

Question 20

List the causes of unconjugated indirect hyperbilirubinemia

Answer 20

1) Bilirubin overproduction
1. Extravascular hemolysis
2. Intravascular hemolysis
3. Ineffective erythropoiesis
2) Impaired bilirubin uptake
1. Heart failure
2. Portosystemic shunts
3. Drugs e.g. rifampicin, probencid
4. Gilbert syndrome
3) Impaired bilirubin conjugation
1. Hyperthyroidism
2. Ethynylestradiol (in oral contraceptive pills)
3. Liver disease (e.g. hepatitis, cirrhosis, Wilson disease)
4. Crigler-Najjar syndrome Type 1 and 2
5. Gilbert syndrome

Question 21

List the causes of conjugated direct hyperbilirubinemia

Answer 21

Essentially the same as causes of cholestasis; divide into intrahepatic and extrahepatic

Write causes later…refer to previous flashcards

Question 22

List the common drugs causing intrahepatic choelstasis

Answer 22

A EAST MAN

Azoles
Erythromycin
Amphotericin
Steroids
Thionamides
Methotrexate
Anticonvulsants
NSAIDs

Question 23

In investigating elevated ALP…

what is the 1st step

Answer 23

Rule out physiologic causes

1) Pregnancy
2) Postprandial ALP elevation (repeat fasting sample)

Question 24

In investigating elevated ALP…

after ruling out physiologic causes of ALP elevation what is the next step

Answer 24

Check origin of ALP –> check GGT + 5’-nucleotidase

1) Bone = normal GGT or 5’-nucleotidase
2) Hepatic = elevated GGT or 5’-nucleotidase

Question 25

In investigating elevated ALP…

if GGT or 5’-nucleotidase is elevated what is the next step

Answer 25

Check RUQ USG for dilated bile ducts

1) Dilated bile ducts present = extrahepatic cholestasis
2) Dilated bile ducts absent = intrahepatic cholestasis

Question 26

In investigating elevated ALP…

if dilated bile ducts are present suggestive of extrahepatic cholestasis what is the next step

Answer 26

Confirm by MRCP/ERCP

Question 27

In investigating elevated ALP…

if dilated bile ducts are absent suggestive of intrahepatic cholestasis what is the next step

Answer 27

Check antimitochondrial antibody (AMA)

1) AMA +ve –> liver biopsy
2) AMA -ve –> look at magnitude of ALP elevation

Question 28

In investigating elevated ALP…

if patients have normal RUQ USG with no dilated bile ducts and are AMA-ve what is the next step

Answer 28

Assess magnitude of ALP elevation
1) ≥50% normal = MRCP/ERCP or liver biopsy
2)

Question 29

In investigating elevated ALP…

when is liver biopsy indicated

Answer 29

1) AMA +ve

2) ALP elevation ≥50% normal