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Elisabeth Volpert DNP, APRN, FNP-C
Define liver function tests.
Review laboratory test: AST/AFT, bilirubin, Alk
Phos, hepatitis panel PT/INR and GGT.
Identify patients with abnormal liver functions.
Demonstrate proper assessment of abnormal
liver functions.
LFT Assess injury to liver cells
Liver’s ability to synthesize proteins
Excretory functions of the liver
ALT- Alanine aminotransferase Amino acid metabolism, released with tissue damage
AST- Aspartate aminotransferase enzyme Derived from organs other than the liver
Protein levels and Prothrombin time Reflects the livers synthetic capacity
Albumin Lowered in depressed syntheses and may complicate
liver disease (Kwo et,al. 2017)
Bilirubin
Breakdown product of RBC after conjugation in the liver and secretion in biliary system excretion
GGT- serum bilirubin, y-glutamyltransferase
Measures hepatic excretory function
Transport of amino acids and peptides into the liver cells
Helpful in evaluating alcohol abuse
Alkaline phosphatase
Measures hepatic excretory function
Present in membranes between the liver and bile duct
Released in disorders affecting the bile duct (Kwo et,al. 2017)
(Newsome et al., 2018)
Initial investigation for potential liver disease should include: Bilirubin Albumin Alanine aminotransferase (ALT) Alkaline phosphatase (ALP) γ-glutamyltransferase (GGT)
Clinical Correlation
Elevated in 1-9% of the asymptomatic population Further diagnostic serology and biopsy is normal
in 6% of these patients (Kwo et,al. 2017)
Drug induced liver toxicity
Drug metabolism
CYP 450
“Natural” products
Idiosyncratic Reactions
Unpredictable
Reaction with a metabolite that is only produced in a person based on genetic predisposition
Cholestatic Reaction
Estradiol, antipsychotic, Chlorpromazine, Augmentin and Erythromycin
(Newsome et al., 2018)
Hepatitis
Viral and autoimmune
Alcohol Induced
Viral Infection
Fatty Liver
Portal Hypertension
Hepatocellular Carcinoma
44-year-old African-American female here for f/u on controlled DMII and HTN.
FHx: Mother CAD HTN, Father HTN
SHx: Non- smoker, occasional alcohol use, works in IT (sits majority of the day)
Vitals:
BP 130/80
HR 72
RR 16
Height 5’4
Weight 202.6 lbs
BMI 34.67kg/m2
Lab results:
HgbA1c 7.2%
AST 40 U/L
ALT 59 U/L
ALP 65 U/L
Total Bilirubin 1.1 mg/dL
Total Cholesterol 154 mg/dL
HDL 43 mg/dL
Triglycerides 210 mg/dL
LDL 83 mg/dL
Imaging results:
Hepatomegaly and echogenic liver consistent with steatosis.
Non-alcoholic Fatty Liver Disease (NAFLD)
Non-alcoholic Steatohepatitis (NASH)
AST/ALT
ALT>AST 1 to 4 times upper limit
Total bilirubin
Increased in decompensated disease
Alk Phos
Up to twice upper limit of normal
GGT
Increased level think advance disease with fibrosis
CBC
Anemia and thrombocytopenia secondary to
hypersplenism in cirrhosis or portal hypertension (Bazick et al., 2015)
Lipid
Hypertriglyceridemia
PT/INR
Elevation indicating an impaired or
decompensated liver synthetic function
Albumin
Decreased with impaired liver synthetic function
ANA
Low titer
Iron studies
Serum ferritin >1.5 times the upper limit of normal
suggestive of NASH and advanced fibrosis (Bazick et al., 2015)
Liver ultrasound Abnormal echotexture
Fibrosis Score http://gihep.com/calculators/hepatology/nafld-
fibrosis-score/
Fibroscan
Biopsy In patients who had a baseline liver biopsy that
showed NASH and who have a stable or improving physical examination and laboratory findings Repeat a liver biopsy in five to seven years Obtain a liver biopsy sooner if there is evidence of
worsening liver disease (Singal A., Bataller R, Ahn J., Kamath PS., Shah VH. 2018)
(Newsome et al., 2018)
57-year-old AA male here for f/u on chronic LBP, HTN, DMII with proteinuria.
FHx: Unknown
SHx: Current smoker 1ppd for the past 20 years, drinking 3 glasses of gin nightly, is not employed.
Vitals:
BP 122/72
HR 64
RR 16
Height 6”1
Weight 250 lbs
BMI 33.91kg/m2
Lab results:
HgbA1c 6.4%
AST 97 U/L
ALT 86 U/L
ALP 106 U/L
Total Bilirubin .6 mg/dL
GGT 600 U/L
Imaging results:
Fibroscan
Evaluation
AST/ALT ratio >2
GGT
Alk phos
Bilirubin
Albumin
PT/INR
Hepatitis panel
MDF score
Liver ultrasound
Liver biopsy
Indirect
Measurement of unconjugated bilirubin
Direct
Bilirubin conjugated in liver and excreted in bile (Stahl, Haschak, Popovic, Brown, 2018)
Causes of Impaired bilirubin conjunction Hyperthyroidism
Sepsis
Gilbert disease Affecting 3-7% of population Inherited
Decreased UDPGT leads to decreased conjugation of unconjugated bilirubin
Asymptomatic
Fasting
Stress Evaluation
Direct Bilirubin
AST/ALT
GGT
CBC (Memon, Weinberger, Hegyi, Aleksunes, 2016)
Causes of increased bilirubin production
Hemolysis
Dyserythropoiesis
Causes of impaired hepatic bilirubin uptake
Heart failure
Sepsis
Can originate from hepatic infection
Medications (Memon, Weinberger, Hegyi, Aleksunes, 2016)
Other causes
Hemolytic anemia
Premature destruction of RBCs
Hb-low
MCHC-increased
Ret count-increased
LDH-increased
Pernicious anemia
Haptoglobin-decreased
LDH-increased
Hepatitis
Obstructive Jaundice (Memon, Weinberger, Hegyi, Aleksunes, 2016)
Causes Cirrhosis
Hepatitis
Dubin-Johnson
Liver mets
Obstructive jaundice
Stones
Strictures
Pancreatic cancer
Obstruction in pancreatic head
Pregnancy
Cholestasis (Memon, Weinberger, Hegyi, Aleksunes, 2016)
71-year-old white male with history of prostate cancer here for f/u on HTN, knee pain and IBS.
He sees psych for depression and is currently on multiple medications including Nortriptline and Restoril.
FHx: HTN, Father HTN, Brother HLD and Bipolar
SHx: Non- smoker, occasional alcohol use
Vitals:
BP 112/74
HR 62
RR 16
Height 5”10
Weight 188 lbs
BMI 26.97kg/m2
Lab results:
AST 23 U/L
ALT 26 U/L
ALP 201 U/L
Total Bilirubin .6 mg/dL
Imaging results:
Liver ultrasound unremarkable
Bone scan negative for metastatic disease
Causes other than liver Bone disease
Pagets Osteomalacia Sarcoma
Rickets Metastatic disease
Bowel infarction
Cholelithiasis
Hyperparathyroidism ESRD
Hyperphosphatemia
Perforated ulcer
Pregnancy Third trimester
Medication (Ruhl & Everhart,2012)
(Kim, 2019)
38-year-old white female here for PE but also
reported having nausea and vomiting 2 days ago
lasting 3 days after eating at a restaurant.
She states symptoms have resolved.
Physical exam NL
Lab results:
AST 877 U/L
ALT 1612 U/L
ALP 284 U/L
Total Bilirubin 5.1 mg/dL
Direct Bilirubin 3.7 mg/dL
GGT 577 U/L
Anti-HAV IgM
Positive at the onset of symptoms
Remains positive for 4-6 months
Previous HAV
May have prolong presence of IgM - false positive
Anti-HAV IgG
History of
Last for decades
AST- may reach >10,000 and is typical >ALT
Bilirubin- increased about 5-10mg/dl
BUN/Cr- mild increase
PT (Koff,1992)
42-white-female here for f/u on poorly controlled
DMII and HTN.
FHx: Mother DMII, ESRD, HTN
SHx: She smokes 1/2ppd for 20 years, does not
drink alcohol and has history of illicit drug use
(non injectable)
On PE was noted to have new tattoos.
Lab results:
HgbA1C 11.4%
AST 381 U/L
ALT 517 U/L
ALP 115 U/L
Total Bilirubin .8 mg/dL
Lab results:
AST 381 U/L to 18 U/L
ALT 517 U/L to 18 U/L
ALP 115 U/L to 71 U/L
Lab Appears Disappears
HBsAg 2-10 weeks after
exposure
4-6 months of
infection
If >6 months chronic
HBsAb Several weeks after
HBsAg disappears
Immunized
Resolved infection
HBcAb IgM Weeks of acute
infection
4-8 months
Eval for acute hep B
(flares in chronic)
HBeAg Early part of acute
infection
If present for >
3months after acute
infection increase
risk for chronic
After peak ALT
HBV DNA
HBV genotype
AFP
Hepatocellular carcinoma
Liver ultrasound
Poorly defined margins
Irregular internal echoes
Liver biopsy
Necroinflammation with or without fibrosis (Singal, Bataller, Ahn, Kamath, Shah, 2018)
58-year-old white male c/o diffuse arthralgia
increased in knees and hips.
FHx: Mother CAD, Father ETOH abuse, Brother
Dementia
SHx: non-smoker, h/o alcohol abuse and illicit drug
use (quit drinking 10 years ago) works as a
carpenter
Vitals: stable
PE: unremarkable
Lab results:
AST 48 U/L
ALT 50 U/L
ALP 78 U/L
Total Bilirubin .6 mg/dL
History of illicit injection drug use or intranasal cocaine use
Those who received clotting factors made before 1987
Those who received blood/organs before July 1992
Those who have been informed that they received blood from a donor who later tested positive for HCV
Children born to HCV-infected mothers
Those with a needle stick injury or mucosal exposure to HCV-positive blood
(Wilkins, Akhtar, Gititu, Jalluri, Ramirez, 2015)
Those who are a current sexual partner of an
HCV-infected person
Those with evidence of liver disease
Those born in the United States between 1945
and 1965
Those who were ever on chronic hemodialysis
Those infected with HIV
Incarcerated individuals (Wilkins, Akhtar, Gititu, Jalluri, Ramirez, 2015)
Those undergoing combination antiviral
treatment
Measure at weeks 2 and 4
CBC
Amniotransferase
Then at 4-8 week intervals
TSH every 3-6 months
RNA
At 4, 12, 24 and 48 weeks
Stop if levels have not decreased by at least 2 log units
at 12 weeks
Stop if not below 1000 IU/mL at 4 weeks
Stop if any virus is detected at 24 weeks (Wilkins, Akhtar, Gititu, Jalluri, Ramirez, 2015)
Bazick J, Donithan M, Neuschwander-Tetri BA, et al. (2015). Clinical model for NASH and advance fibrosis in adult patients with diabetes and NAFLD: guidelines for referral in NAFLD. Diabetes Care.38 (7):1347-1355.
Ruhl, C. E., & Everhart, J. E. (2009). Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology. 136(2), 477–85.
Kim, S., (2019). Optimal evaluation of the eesults of liver function tests. Korean Journal of Medicine. 94(1):89-95.
Kwo PY, Cojen SM, Lim JK (2017). Clinical guideline: evaluation of abnormal liver chemistries. American Journal of Gastroenterology. 112 (1): 18-35.
Koff R. S. (1992). Clinical manifestations and diagnosis of hepatitis A virus infection. Vaccine, 10 Suppl 1, S15–S17.
Memon N, Weinberger BI, Hegyi T, Aleksunes LM. Inherited disorders of bilirubin clearance (2016). Pediatric Res. 79(3):378-386.
Newsome PN, Cramb R, Davison SM, et al. (2018). Guidelines on the management of abnormal liver blood tests. Gut. 67(1):6-19.
Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. (2018) ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol. 113(2):175-194.
Stahl EC, Haschak MJ, Popovic B, Brown BN (2018). Macrophages in the Aging Liver and Age-Related Liver Disease. Front Immunol, 9,2795.
Wilkins, T., Akhtar, M., Gititu, E., Jalluri, C., & Ramirez, J. (2015). Diagnosis and Management of Hepatitis C. American family physician, 91(12), 835–842.