Hepatology Flashcards
1. Understanding Liver Function Tests
4 categories of liver tests
- Tests for Hepatocellular damage (2)
- Tests for Cholestasis (2)
- Tests for Biliary Excretion (2)
- Tests for Liver synthetic function (2)
- Tests for Hepatocellular damage (AST, ALT)
- Tests for Cholestasis (alk phos, ggt)
- Tests for Biliary Excretion (tbili, dBili)
- Tests for Liver synthetic function (albumin, PT/INR)
- ALT = direct damage to hepatocytes*
- Need to order a hepatic panel to get GGT*
- Unconjugated bilirubin = not bound*
Liver Function Tests
- (1): amino alanine transferase (mainly from cytosol of _____)
- (1): aspartate amino transferase measure cellular _____
- (1) reflect the liver’s synthetic capacity
- (3) measure hepatic excretory function
- ALT: amino alanine transferase (mainly from cytosol of hepatocytes)
- AST: aspartate amino transferase measure cellular integrity
- Prothrombin time and albumin reflect the liver’s synthetic capacity
- Bilirubin, gamma-glutamyl- transpeptidase (GGT), and alkaline phosphatase (ALP) measure hepatic excretory function
Other things in the body effect AST
Normal Transaminases
- Normal ranges defined by “healthy” population (e.g. blood donors) and cutoff range ____ in different clinics/hospitals
- True normal for alt may be elevated
- Uln (upper limit of normal) in a young healthy patient may be higher than they should be
- Normal ranges defined by “healthy” population (e.g. blood donors) and cutoff range differs in different clinics/hospitals
- True normal for alt may be elevated
- Uln in a young healthy patient may be higher than they should be
Evaluation of Cellular Integrity
- AST may be elevated in (2)
- An elevated GGT confirms?
- (1) highest in toxin, drug induced, viral, or ischemic hepatitis
- (1) more specific to liver damage
- AST / ALT ratio
- ALT > AST = (1)
- AST > ALT = (1), what ratio?
- AST may be elevated in myocardial infarction and musculoskeletal injury
- An elevated GGT confirms hepatic origin
- ALT highest in toxin, drug (ie statins) induced, viral, or ischemic hepatitis
- ALT more specific to liver damage
- AST / ALT ratio
- ALT > AST – hepatitis
- AST > ALT – alcohol - ratio >2:1
Examples of Typical Transaminase Elevation
Match each ratio to the cause
AST/ALT
- 160/80 =
- 120/180 =
- 46/78 =
- 400/800 =
- 19000/16000 =
- 2000/2000 =
AST/ALT
- 160/80 = Alcoholic hepatitis
- 120/180 = Autoimmune hepatitis (alt a bit higher)
- 46/78 = Chronic hep C (low grade inflammation)
- 400/800 = Acute viral hep C
- 19000/16000 = ETOH + Tylenol toxicity (severe injury)
- 2000/2000 = Acute hep A (equal values)
Alkaline Phosphatase (ALP) ↑+ GGT ↑
=
Causes (3)
Think Liver specifically biliary source
Obstruction
Infiltration
Congestion
(is the bile blocked/slow flowing?)
ALP↑ and GGT normal
(probably not (1))
- Isoenzymes (alternative form of same ALP enzyme): ____ CA, b____
- B____ disease?
- I______ (malignancy
- Endocrine: primary or secondary (1)
Probably not biliary disease
- Isoenzymes (alternative form of same ALP enzyme): liver CA, biliary
- skeletal/bone (Pagets?)
- Intestinal (malignancy
- Endocrine: primary or secondary hyperparathyroidism
Both ALP and GGT levels become elevated when you have issues with your bile ducts or have certain liver diseases, but only ALP will be elevated if you have bone disease.
Evaluation of Excretory Function
-
(1) has origin in _____ tissues
- May be normally elevated in late pr____, childhood/adolescence
- Elevation correlates with ch_____ injury
- Elevated (1): cholestasis or liver damage
- (1) is a sensitive indicator of hepatic disease, particularly caused by drugs, chemicals, or alcohol
-
ALP has origin in multiple tissues
- May be normally elevated in late pregnancy, childhood/adolescence
- Elevation correlates with cholestatic injury
- Elevated bilirubin: cholestasis or liver damage
- GGT is a sensitive indicator of hepatic disease, particularly caused by drugs, chemicals, or alcohol
ALP high in pregnancy dt high osteoblastic activity -> depositing calcium to help baby’s bones grow
Evaluation of Protein Synthesis
- Albumin synthesis can be affected by liver disease, dietary pr_____, al____, tr____, and cortico_____
- Elevated PT/INR may be due to one of these factors or due to Vitamin __ deficit
- Albumin synthesis can be affected by liver disease, dietary protein, alcohol, trauma, and corticosteroids
- Elevated PT/INR may be due to one of these factors or due to Vitamin K deficit
2. Abnormal LFTs
- Will patients always be symptomatic?
- Symptoms: an____, mal____, weight ____, pr____
-
Detailed (1) history
- PMH: hepatitis (or symptoms of), abdominal surgery, blood transfusions (before 1992)
- Social history: _____ intake
- S____ history
- Household/work exposure to ch_____
- F____ history of liver diseases
- Patient may be asymptomatic or symptomatic
- Symptoms: anorexia, malaise, weight loss, pruritis
- Detailed medication history
- PMH: hepatitis (or symptoms of), abdominal surgery, blood transfusions (before 1992)
- Social history: alcohol intake
- Sexual history
- Household/work exposure to chemicals
- Family history of liver diseases
Physical Exam
Findings present only probably with significant damage
- Sclera (1)
- Skin exam (3)
- Abdominal exam (4)
- Neuro exam (1)
- Icterus
- Spider angioma, palmar erythema, jaundice
- Ascites, RUQ tenderness, hepatomegaly, splenomegaly
- Asterixis
- Asterixis = twitching of fingers when they hold their hands in front of them - asctd with elevation of ammonia*
- Elevated ammonia -> day night reversal, memory impairment, confusion (asctd with end stage liver disease)*
Diagnostics/Labs
- _____ function panel
- This includes (2)
- C___ does not include ggt
- C__ w/diff
- Liver function panel
- This includes ggt, bilirubin
- CMP does not include ggt
- CBC w/diff
Hepatitis Panel
Hep A (1)
Hep B (3)
Hep C (1)
- Hepatitis A Ab total
- Hepatitis B s ab
- Hepatitis B s ag with reflex
- Hepatitis B core ab total
- Hepatitis C ab with reflex to HCV RNA
Hepatitis A Ab total
=
can you vaccinate?
Hepatitis A Antibody
Have they ever had hepatitis and is immune? (hep A antibody total) -> if negative some labs will automatically reflex - can vaccinate for Hep A but no vaccine for Hep C
Hepatitis B Labs
What does each value mean?
- Hepatitis B s ab =
- Hepatitis B core ab total =
- Hepatitis B s ag with reflex =
- If positive surface antibody and core antibody =
- If positive surface antibody and negative core antibody =
- Hepatitis B s ab = IMMUNITY through vaccination or past infection (we want this to be positive)
- Hepatitis B core ab total = EXPOSURE to Hep B (kind of like the IgM of
- Hepatitis B s ag with reflex = CURRENTLY REPLICATING/ACTIVE INFECTION (AG = actively growing)
- If positive surface antibody and core antibody = had a past infection that cleared and has immunity
- If positive surface antibody and negative core antibody = passive immunity from vaccine
Investigation of Abnormal LFTs
Additional tests to investigate why liver enzymes are elevated, what are we looking for?
(2) (3), (5)
Looking for autoimmune disease
Immunoglobulins
- IgG
- IgM
- IgA
Autoantibodies
- ANA (anti-nuclear)
- A-SM (anti-smooth muscle)
- A-LKM (ant-liver/kidney microsomal)
- AMA (anti-mitochondrial)
- P-ANCA (antineutrophil cytoplasmic)
Immunoglobulins + Abnormal LFTs
- IgG can indicate (1)
- IgM can indicate (1)
- IgA can indicate (1)
- IgG = Autoimmune hepatitis
- IgM = Primary biliary cirrhosis (PBC)
- IgA can indicate = alcohol
Auto-Antibodies + Abnormal LFTs
- ANA (anti nuclear) (3)
- A-SM (anti-smooth muscle) (2)
- A-LKM (anti-liver/kidney microsomal) (1)
- AMA (anti mitochondrial) (1)
- P-ANCA (antineutrophil cytoplasmic) (1)
- ANA (anti nuclear)-AIH, primary sclerosing cholangitis (PSC), PBC - bc ANA is non-specific
- A-SM (anti-smooth muscle)-AIH, PSC
- A-LKM (anti-liver/kidney microsomal) – AIH
- AMA (anti mitochondrial) – PBC
- P-ANCA (antineutrophil cytoplasmic)- PSC
P-ANCA also asctd with chron’s and colitis
Hemochromatosis
=
Labs to check
- Iron labs (1)
- Consider human (1) genotype
Genetic condition where you have iron overload and iron gets deposited in liver and causes inflammation and damage
- Ferritin, Transferrin saturation
- HFE (human homeostatic iron regulator protein)
- hemochromatosis + statin example of a synergistic combo -> 1+1 = 4*
- Tx for hemochromatosis = blood removal/transfusion*
Hemachromatosis Labs
- Normal Ferritin levels
- < ___ ugm/l for males and
- < ___ ugm/l for females
- Fe sat = fe/tibc x 100 (normal < ___%)
- Investigate when saturation > __-__%
- Fasting fe > ____ ugm/dl suggests true abnormality
- Normal Ferritin levels
- < 300 ugm/l for males and
- < 200 ugm/l for females
- Fe sat = fe/tibc x 100 (normal < 33%)
- Investigate when saturation > 50-_55%
- Fasting fe > 175 ugm/dl suggests true abnormality
Hemachromatosis Genetic Predisposition
(2) genetic defects
1 or both gene mutations is present in 85-95% of pts with genetic hemochromatosis and 5% without
_____ zygotes may have some degree of iron overload
C282y and h63d genetic defects
1 or both gene mutations is present in 85-95% of pts with genetic hemochromatosis and 5% without
heterozygotes may have some degree of iron overload
Wilson’s Disease
=
What lab value do we check if we are suspecting this disease? What does it do?
Genetic autosomal recessive condition that leads to impairment of cellular copper transport resulting in copper accumulation in liver, brain, cornea
Low Ceruloplasmin
Ceruloplasmin is the major carrier of copper in the blood and an important enzyme with ferroxidase activity. Ceruloplasmin is synthesized by hepatocytes and secreted in the blood
Wilson’s Disease S/S
(1)*
- Over time liver damaged, becomes _____
- Majority of patients diagnosed between ages __-__
- H____, n_____ and ps_____ clinical manifestations
- Hemo____ common finding
- Imaging (1)
Kayser-Fleischer rings
(visible in 50% patients), dark (brown) rings that appear to encircle the iris of the eye
- Over time liver damaged, becomes cirrhotic
- Majority of patients diagnosed between ages 5-35
- Hepatic, neurologic and psychiatric clinical manifestations
- Hemolysis common finding
- Imaging- US
(suspect in young patients with headaches, behavioral issue (that doesn’t rly match ADHD)
Alpha 1 Anti-Trypsin Deficiency
=
Results from _____ within the hepatocyte of un secreted variant (1)
(1) lab value to check
Inherited disorder affecting lungs, liver (and rarely skin)
Results from accumulation within the hepatocyte of un secreted variant AAT protein
Alpha 1 Anti-Trypsin level
- Autosomal co dominant transmission (complicated genetic profile-over 150 allelic variants)
- “Toxic gain of function”
Approach to Elevated Liver Function Tests
Radiology
(5)
Abdominal Ultrasound
HIDA (Hepatobiliary Iminodiacetic Acid Scan)
CT
Magnetic Resonance Cholangiopanreatography (MRCP)
Endoscopic retrograde cholangiopancreatography (ERCP)
Abdominal ultrasound: may detect obstruction, not fully reliable-may have contracted gallbladder but the presence of common bile duct stones
ERCP can remove stones or place a stent
Caveats
- Abnormal LFTs do not always ______ liver disease……
- Normal LFTs do not always ______ liver disease…….
- (1) virus – 1 out of 6 patients with persistently normal ALT will have significant pathology on liver biopsy
- Clear link between (1) elevation and liver mortality, even for values within the normal range
- In a community setting >70% with abnormal imaging (fibrosis on US) had _____ LFTs
- Abnormal LFTs do not always indicate liver disease……
- Normal LFTs do not always exclude liver disease…….
- HCV – 1 out of 6 patients with persistently normal ALT will have significant pathology on liver biopsy
- Clear link between ALT elevation and liver mortality, even for values within the normal range
- In a community setting >70% with abnormal imaging (fibrosis on US) had normal LFTs (End stage cirrhosis will show normal LFTs bc their hepatocytes are NOT working)
Differential Diagnosis
-
Elevated ALT and AST
- al____ or v____ hepatitis; cyto____ drugs, NASH = /NAFLD =
-
Elevated Alkaline Phosphatase
- ob_____ of (1) system
- intrahepatic: med____ or inf_____
- extrahepatic: gall_____
-
Elevated Bilirubin
- may be elevated in hep____
-
Elevated ALT and AST
- alcoholic or viral hepatitis; cytotoxic drugs, NASH/ NAFLD (non-alcoholic steatohepatitis-fatty liver disease)
-
Elevated Alkaline Phosphatase
- obstruction of biliary system
- intrahepatic: medications or infiltrative
- extrahepatic: gallstones
-
Elevated Bilirubin
- may be elevated in hepatitis
Plan
- First step is d______ testing
- If no underlying cause is found and patient is asymptomatic, ______ ~_-_ months for progressive symptoms and liver dysfunction
- Do further lab testing with (1) panel and consider (1) imaging; if abnormal-consult with a (1)
- First step is diagnostic testing
- If no underlying cause is found and patient is asymptomatic, observe ~1-3 months for progressive symptoms and liver dysfunction
- Do further lab testing with hepatitis panel and consider ultrasound; if abnormal-consult with a specialist
- hepatitis panel + US (if pt is large may need CT/MRI)*
- still no findings, specialist will probably want to get a liver biopsy*
Therapeutic Recommendations
- Eating recommendation =
- Prohibit use of (2)
- Avoid sed_____
- Monitor P__, serum al_____, and b_____
- Daily (1); regular hem_____ testing
- Check for signs of (1) CNS at each visit
- Check abdomen for signs of (1)
- Maintain normal caloric intake
- Prohibit use of alcohol or hepatotoxic agents (ie tylenol)
- Avoid sedatives
- Monitor PT, serum albumin, and bilirubin
- Daily weights; regular hemoccult testing
- Check for signs of encephalopathy at each visit
- Check abdomen for signs of ascites
- Chronic Liver Disease
Causes of Chronic Liver Disease
- Al_____
- V_____
- Non-alcoholic ____ liver disease
- Immunological (3)
- Genetic / Metabolic (3)
- Alcohol
- Viral
- Non-alcoholic fatty liver disease (NAFLD or NASH)
- Immunological
- Autoimmune hepatitis
- Primary sclerosing cholangitis
- Primary biliary cirrhosis
- Genetic / Metabolic
- Hereditary hemochromatosis
- Wilson’s disease
- Alpha 1- antitrypsin deficiency
Liver Disease Severity
- Biochemical (3) labs
- Clinical presentation (3)
- Biochemical
- Albumin
- PT
- Bilirubin
- Clinical
- Ascites
- Hepatic encephalopathy
- Nutritional status
Jaundice or Icterus
- Pre-hepatic Causes =
- Hepatic Causes =
- Post-hepatic Causes =
- Pre-hepatic Causes = Disorders that cause hemolysis and lead to excessive bilirubin levels
- Hepatic Causes = Hepatic injury
- Post-hepatic Causes = Obstructions of bile ducts
History: Jaundice
- Abdominal (1): obstruction
- Skin (1): indicates biliary obstruction
- Easy (1) on skin: due to splenomegaly secondary to portal (1) or alcohol secondary to dietary insufficiency- inadequate vitamin (1)
- Alcoholism, exposure to hepatitis (A, B, C, D, E), flu-like prodrome, hepatocellular disease risk factors
- (1) urine, (1) stools: conjugated bilirubinemia
- Hx gall____, sur___, f____: obstruction
- Meds causing cholestasis: est______, pheno____
- Abdominal pain: obstruction
- Pruritis: indicates biliary obstruction
- Easy bruising: due to splenomegaly secondary to portal hypertension or alcohol secondary to dietary insufficiency- inadequate vitamin K
- Alcoholism, exposure to hepatitis (A, B, C, D, E), flu-like prodrome, hepatocellular disease risk factors
- Dark urine, pale stools: conjugated bilirubinemia
- Hx gallstones, surgery, fever: obstruction
- Meds causing cholestasis: estrogens, phenothiazides
Physical Exam
- Focus on signs of liver disease other than jaundice, including
- Skin (3)
- Chest (1)
- Testes (1)
- Abdomen (1)
- Liver exam
- S___, f____ness, t_____ of surface, p___
- _____ liver indicates advanced hepatocellular disease
- Portal hypertension: (1)megaly, prominent abdominal v_____pattern, as____
- (1) enlarged-inflamed/ obstructed
- Splenomegaly
* may be hemo____ disease
- Focus on signs of liver disease other than jaundice, including
- Skin = brusing, spider angiomas, palmar erythema
- Chest = gynecomastia
- Testes = testicular atrophy
- Abdomen = presence or absence of ascites also should be noted
- Liver exam
- Size, firmness, texture of surface, pain
- Small liver indicates advanced hepatocellular disease
- Portal hypertension: splenomegaly, prominent abdominal venous pattern, ascites
- Gallbladder enlarged-inflamed/ obstructed
- Splenomegaly may be hemolytic disease
Diagnostics for Chronic Liver Disease
- L____
- (1) with diff and platelets
- Coags (2)
- H_____ profile
- C____
- Iron panel (3)
- LFTs
- CBC with diff and platelets
- PT/PTT (pt/inr ratio included)
- Hepatitis profile
- CMP
- Serum iron, ferritin, transferrin saturation
Additional Diagnostics to Consider in Chronic Liver Disease
- Serum cer______
- Anti_____ antibodies (AMA)
- Anti-______ antibodies (ANA)
- Anti-___ _____ Antibodies (ASMA)
- Anti-l____ k____ microsomal (Anti-LKM)
- ___ anti_____activity
- (1) disease screening included
- Serum ceruloplasmin
- Antimitochondrial antibodies (AMA)
- Anti-nuclear antibodies (ANA)
- Anti-Smooth Muscle Antibodies (ASMA)
- Anti-liver kidney microsomal (Anti-LKM)
- α 1 antitrypsin activity
- (HIV screening included)
Chronic Liver Disease Imaging
- U______
- C___ scan
- E_ _ _
- M _ _ _
- En_____ ultrasonography
- Liver b_____
- Ultrasound
- CT scan
- Endoscopic retrograde cholangiopancreatograpy
- Magnetic resonance cholangiopancreatography
- Endoscopic ultrasonography
- Liver biopsy
- Jaundice Management
- Treatment of (1) disease process
- Liver (1) if LFTs fail to return to normal after 6 months
- Cholangitis
- Anti_____, (1) with di____
- Diet
- ____ protein (vegetable proteins), ____ sodium, ___ alcohol
- Supplements
- MVI = , (1) acid
- Treatment of underlying disease process
- Liver biopsy if LFTs fail to return to normal after 6 months
- Cholangitis (inflammation of biliary system, most commonly caused by bacterial infection)
- Antibiotics, ERCP with dilation
- Diet
- High protein (vegetable proteins), low sodium, no alcohol
- Supplements
- MVI = multivitamin infusion, folic acid
Jaundice Management Continued
- Avoid barb_____ and sed____
- (1) Rx- to reduce blood ammonia levels- 20-30G TID-QID
- (1) Rx if encephalopathy worsening on lactulose
- Pruritis
- (1) sequesterants- cholestyramine TID
- Anti-h______
- Mild s____
- Em_____
- Liver t______
- Avoid barbiturates and sedatives
- Lactulose- to reduce blood ammonia levels- 20-30G TID-QID
- Rifaximan if encephalopathy worsening on lactulose
- Pruritis
- Bile acid sequesterants- cholestyramine TID
- Anti-hystamines
- Mild soaps
- Emollients
- Liver transplant
bile acid sequestrants -be careful bc can cause constipation - want them to stool to excrete the ammonia
5. Hepatitis
=
Causes (3), (2) diseases
Inflammation of the liver
Alcohol
Viruses
Medications
Autoimmune diseases
Metabolic diseases
Medication Induced Hepatitis
Common medications that cause hepatitis
- Ac______
- All_______
- High dose as___
- Capto____
- Carb_______
- Iso______
- Keta______
- Methyl____
- NS_____
- Pro______
- Sulf______
- Acetaminophen
- Allopurinol
- High dose aspirin
- Captopril
- Carbamazepine
- Isoniazid
- Ketaconazole
- Methyldopa
- NSAIDs
- Procainamide
- Sulfonamides
Viral Hepatitis Stages
I
II
III (3) Sx
IV
I Incubation
II Prodromal – anorexia, nausea/vomiting, malaise, upper respiratory infection symptoms, myalgia, arthralgia, fatigue, abdominal pain
III Icteric – jaundice, dark urine, pale stools
IV Convalescent – improved well-being
Prevention of Hepatitis
Vaccines available for which hepatitis viruses?
- Hep A vaccine should be given to which children, which adults?
- Can you give the Hep A vaccine if you have Hep B or C?
- If a pregnant woman has chronic hepatitis B, the infant should receive (2)
- Which hepatitis do we not have a vaccine for?
Hepatitis A and B.
- Hep A vaccine
- Children 12 to 23 months of age
- Adults who travel or work in locations with a higher prevalence of hepatitis A infection.
- Vaccination for hepatitis A also should be given to people with hepatitis B and C.
- Infant should receive the hepatitis B vaccine as well as hepatitis B immune globulin to prevent the development of chronic hepatitis B.
- There is no vaccine for hepatitis C