SOAP. – Elevated Liver Enzymes – SỔ TAY LÂM SÀNG

Elevated Liver Enzymes

Kathy R. Reese and Cheryl A. Glass

Definition

Liver function tests (LFTs) used to determine the health of the liver are not direct measures of its function. The liver has excretory, metabolic, protective, detoxification, hematologic, and circulatory functions. LFTs may be abnormal even in patients with a healthy liver. Normal laboratory chemistry values may vary according to age, gender, ethnicity, blood group, and postprandial state, as well as other factors such as exercise and pregnancy. Uses for common liver chemistry tests (see Table 14.8) include the following:

A.Assessing the severity of hepatocellular injury.

B.Evaluating cholestatic problems.

C.Following the trend of hepatic disease.

D.Diagnosing for the presence of latent liver disease (i.e., differential diagnosis of ascites or hematemesis).

E.Screening for suspected cases during outbreaks of infective hepatitis.

F.Making differential diagnosis of the different types of jaundice.

G.Screening persons exposed to hepatotoxic drugs. A wide variety of drugs are associated with liver disease and require monitoring of liver function including carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, statins, sulfonamides, terbinafine, chlorpromazine, and methotrexate. In addition, drugs can cause fatty liver and steatohepatitis and vascular injury. Methotrexate treatment requires special care, to prevent dose-dependent liver fibrosis, and noninvasive markers of fibrosis should be monitored. Although statins can lead to drug-induced liver injury, this is very rare, with studies demonstrating they are safe in patients with preexisting abnormal liver enzymes.

Incidence

A.The incidence of elevated liver enzymes is undetermined. Abnormal elevations of serum liver chemistries may occur in 1% to 4% of the asymptomatic population.

Pathogenesis

A.Pathogenesis varies by diagnosis.

Predisposing Factors

A.Predisposing factors are dependent on the suspected or known medical diagnosis.

Common Complaints

A.Asymptomatic.

B.Pruritus.

C.Jaundice.

D.Ascites.

E.Fatigue.

F.Weight loss.

G.Change in the color of urine (dark) or stools (clay-colored).

H.Abdominal pain.

I.Nausea/vomiting.

Subjective Data

A complete medical history is the single most important part of the evaluation of a patient with elevated LFTs.

TABLE 14.8 Liver Chemistry Tests and Implications

Liver Chemistry Test	Clinical Implication of Abnormality
ALT	Hepatocellular damage
AST	Hepatocellular damage
ALP	Cholestasis, infiltrative disease, or biliary obstruction
Albumin	Synthetic function
Alpha-fetoprotein	Cancer marker when elevated
Bile acids: Urine bile salts, bile pigments, and urobilinogen	Cholestasis or biliary obstruction, impaired hepatic update or secretion, or portal-systemic shunting
Bilirubin: Serum total, direct and indirect bilirubin	Cholestasis, impaired conjugation, or biliary obstruction
Cholesterol, serum triglycerides	Lipoprotein production and metabolism, chronic cholestasis
Fibrinogen	Liver damage/cirrhosis, acute liver insufficiency, poisoning
GGT	Cholestasis or biliary obstruction, malignant involvement in hepatocellular disease, more sensitive than other enzymes in alcoholism
Hepatitis surface antigen, IgM, antibody, RNA, genotype, viral load	Differentiation of type of hepatitis
LDH	Hepatocellular damage not specific for hepatic disease
Total proteins, albumin globulin, (A/C ratio)	Hepatitis, advanced liver disease
PT	Synthesis function in hepatocellular disease, fulminate hepatitis
Plasma ammonia	CNS dysfunction/toxicity or end-stage liver disease
5NT	Cholestasis or biliary obstruction
Urea	End-stage liver disease

5NT, 5′-nucleotidase; ALT, alanine transaminase; ALP, alkaline phosphatase; AST, aspartate transaminase; CNS, central nervous system; GGT, gamma-glutamyl transpeptidase; IgM, immunoglobulin M; LDH, lactate dehydrogenase; PT, prothrombin time.

A.Because of polypharmacy a full review of medications, herbals, and over-the-counter (OTC) drugs should be under-taken to identify medications that should be avoided in the geriatric population, duplicate medications, and medications that are able to be to be decreased or deprescribed.

B.Determine the duration of LFT abnormalities (if known).

C.Review the presence of accompanying symptoms, including arthralgias, myalgias, rash, abdominal pain, fever, pruritus, and changes in the color of urine or stool.

D.Has the patient experienced any anorexia or weight loss? Over what period of time did weight loss occur?

E.Review parenteral exposures, including transfusions (especially if occurred prior to 1992), intravenous (IV) and intranasal drug use, tattoos, and sexual history.

F.Review the patient’s recent travel history—food, sexual history, regions of travel, purpose of travel, exposure to other sick contacts.

G.Review the patient’s exposure to people with jaundice.

H.Review the patient’s occupational and recreational history and possible exposure to hepatotoxins.

I.Review the patient’s history of alcohol consumption. Significant alcohol intake is generally considered greater than 210 g alcohol per week in a male or greater than 140 g alcohol per week in a

female occurring over at least a 2-year period. Fourteen grams of alcohol is contained in a 12-ounce beer, 5 ounces of wine, or 1.5 ounces of liquor.

J.Evaluate the gestational age of pregnancy. Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is generally presents in the mid-second trimester or third trimester of pregnancy.

Physical Examination

A.Temperature (if infection is suspected), pulse, respirations, blood pressure (BP), and height, and weight to calculate body mass index (BMI).

B.Observation:

1.Observe for temporal and proximal muscle wasting.

2.Perform eye and mouth (mucous membranes) examination for icterus.

3.Perform dermal examination for icterus, spider nevi, palmar erythema, presence of caput medusae (the presence of dilated veins seen on the abdomen; noted with cirrhosis of the liver and portal hypertension).

4.Evaluate the presence of gynecomastia.

5.Observe for the presence of jugular venous distension (JVD), a sign of right-sided heart failure (HF) that suggests hepatic congestion.

C.Auscultate heart and lungs.

D.Percuss abdomen.

E.Palpate:

1.Abdominal examination:

a.Evaluate the presence of hepatomegaly; focus on the size and consistency of the liver.

b.Evaluate the presence of splenomegaly; focus on the size of the spleen. An enlarged spleen is most easily appreciated with the patient in the right lateral decubitus position.

c.Assess for ascites: Note presence of a fluid wave or shifting dullness.

d.Assess for an abdominal mass.

2.Lymph nodes: Evaluate lymphadenopathy.

3.Conduct testicular examination for testicular atrophy (increased estrogen/reduced testosterone).

Diagnostic Tests

A.The particular LFT tests ordered are related to the suspected or identified medical diagnosis. Table 14.9 shows common serologic tests for viral hepatitis.

B.The pattern of elevated liver biochemistries suggests the underlying cause:

TABLE 14.9 Serologic Tests for Hepatitis

ABLE 14.9 Serologic Tests for Hepatitis

Virologic Test	Usual Clinical Implication of a Positive Test
Hepatitis A-IgM	Positive in acute hepatitis A
Hepatitis A-IgG	Positive in response to previous hepatitis A infection or vaccination
HBsAg	Positive during active hepatitis B infection
Hepatitis B surface antibody	Positive in response to previous hepatitis B infection or vaccination
Hepatitis B core antibody-IgM	Positive during active hepatitis B infection
Hepatitis B core antibody-IgG	Positive in response to current or prior hepatitis B infection
HBV-DNA	Positive during active hepatitis B infection
Hepatitis Be antigen	Positive test indicates replicative state of wild-type hepatitis B infection
Hepatitis Be antibody	Positive after replicative state of wild-type hepatitis B infection
HBV viral load	Assess hepatitis B virology
HCV-antibody ELISA	Positive during or after hepatitis C infection
HCV Recombinant ImmunoBlot Assay (RIBA)	Positive during or after hepatitis C infection
HCV-RNA	Positive during hepatitis C infection
HCV viral load	Assess hepatitis C virology
HCV genotype	Genotyping is used for evaluation of the length of therapy

ELISA, enzyme-linked immunosorbent assay; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; IgG, immunoglobulin G; IgM, immunoglobulin M.

TABLE 14.10 Differential Diagnosis With Elevated Liver Enzymes

Infiltrating diseases of the liver •Sarcoidosis •TB •Fungal infection •Amyloidosis •Lymphoma •Metastatic malignancy •HCC
Acute viral hepatitis (A-E, EBV, CMV, herpes)	Wilson’s disease (genetic disorder of biliary copper excretion)
Cholestasis disease	Acute bile duct obstruction
Chronic hepatitis B, C	Hemolysis
Steatosis/NASH	Rhabdomyolysis
HH	Thyroid disorders
Medication/herbal-induced	Strenuous exercise-induced changes
Alpha-1-antitrypsin deficiency	Pregnancy—HELLP syndrome
Cirrhosis	Toxin(s) exposure
Celiac disease	Acute Budd–Chiari syndrome
Alcohol-related liver injury	Anorexia nervosa

EBV, Epstein–Barr virus; CMV, cytomegalovirus; HCC, hepatocellular carcinoma; HELLP syndrome, hemolysis, elevated liver enzymes, and low platelets; HH, hereditary hemochromatosis; NASH, nonalcoholic steatohepatitis; TB, tuberculosis.

1.Elevation of aminotransferases indicates hepatocyte injury.

2.Elevation of alkaline phosphatase (ALP) indicates cholestasis.

3.Changes in albumin and/or prothrombin time (PT) indicate interruption in the synthesis process.

C.The magnitude of the elevation can indicate the underlying cause:

1.Aspartate transaminase (AST): alanine transaminase (ALT) of greater than 2:1 indicates alcohol-related disease. If the AST:ALT is greater than 3:1 the chance of alcohol-related disease is at 96%.

2.AST and ALT normal to two times upper limit normal (ULN) indicates chronic hepatitis B or C.

3.AST and ALT less than four times ULN occurs in nonalcoholic hepatic disease.

4.AST less than eight times ULN and ALT less than five times ULN indicates alcoholic hepatic disease.

5.AST and ALT greater than 25 times ULN indicates acute viral hepatitis.

6.AST and ALT greater than 50 times ULN indicates ischemic hepatitis.

Differential Diagnoses

A.Table 14.10 shows differential diagnoses with elevated liver enzymes.

Plan

A.The clinical significance of any liver chemistry test abnormality must be interpreted in the context of the clinical situation. All abnormalities should be confirmed before additional tests are added. Follow-up blood chemistries can vary according to the nature of the initial elevation:

1.An elevated ALP should be rechecked with additional testing with gamma-glutamyl transpeptidase (GGT) or fractionated ALP to determine if the elevation is related to hepatic disease or from an outside location such as bone.

2.An elevated bilirubin should be fractionated to determine if it is conjugated or unconjugated.

3.Serology for viral hepatitis, viral infections, autoimmune disease, muscular disease, Wilson’s disease, and pregnancy may also be added according to the patient’s history and exam.

4.Abdominal ultrasound should be undertaken.

5.If the source is not obvious by laboratory testing and ultrasonography, liver biopsy is recommended.

6.Lifestyle modifications, including discontinuance of medications and alcohol, weight loss, and dietary changes, can be recommended as appropriate.

B.Refer to gastroenterology or hepatology any patient with persistent elevation of aminotransferases greater than two times ULN or of ALP greater than 1.5 times ULN.

C.Patients with marked abnormalities of liver tests, or with signs and symptoms of chronic liver disease (CLD) or hepatic decompensation (i.e., ascites, encephalopathy, coagulopathy, or portal hypertension), should be evaluated and treated in a more expeditious manner than asymptomatic patients.

Follow-Up

A.Follow-up testing for elevated LFTs, including abdominal/liver ultrasonography, CT, MRI, and liver biopsy, is dependent on the risk factors for disease, symptoms and history, and physical finding of the suspected or identified medical diagnosis. A liver chemistry test that is normal does not ensure that the patient is free of liver disease. If a laboratory error is suspected, the laboratory test should be repeated.

Consultation/Referral

A.Consider a consultation or referral to a hepatologist, gastroenterologist, or infectious disease specialist.

Individual Considerations

A.Adults:

1.Pregnancy: HELLP syndrome is a severe form of pregnancy-induced hypertension (PIH or preeclampsia). It may occur anywhere from the mid-second trimester to immediate postpartum. HELLP syndrome occurs in 0.2% to 0.6% of pregnancies. The etiology is unknown. The presence of laboratory abnormalities confirms the diagnosis. Treatment of HELLP syndrome will not be covered. However, the laboratory abnormalities that are noted include the following:

a.Hemolytic anemia.

b.Proteinuria.

c.Serum AST level (>70 international unit (IU)/L).

d.Low platelet count (<10,000 cells/mL).

e.Serum lactate dehydrogenase (LDH) level (>600 IU/L).

f.Total bilirubin level (>1.2 mg/dL).

B.Geriatrics:

1.Elevated liver enzymes are common in the elderly:

a.One in six of the general population aged 75 and above has at least one elevated liver test of AST, ALP, or bilirubin.

2.Elevated liver enzymes levels (mainly ALT, GGT, and ALP but not AST) are positively associated with the prevalence of metabolic syndrome in the elderly.

3.A history of diabetes and an assessment of dementia were associated with both elevated AST and ALP, with a history of heart attack associated only with increased ALP.