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)

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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.