10/20- Fatty Liver Disease and Lab Evaluation of Liver Disease Flashcards

1
Q

What are the main etiologies of steatosis?

A

(Recall, steatosis = fat in liver)

  • Obesity
  • Diabetes mellitus
  • Alcohol
  • Drugs, e.g., corticosteroids
  • Hepatitis C
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2
Q

Describe alcoholic liver disease: prevalence/epidemiology

A
  • Alcoholic liver disease is the 3rd largest health problem in the US (1. heart disease, 2. cancer)
  • Alcoholism is the 8th leading cause of death globally
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3
Q

What are liver biopsy findings in alcoholic liver disease?

A

In decreasing order:

  • Steatosis
  • Normal
  • Increased iron in hepatocytes
  • Fibrosis
  • Alcoholic steatohepatitis
  • Cirrhosis
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4
Q

Describe the process of steatosis in liver disease

A
  • Initially Zone 3 or centrilobular
  • Entire lobule involved in severe cases
  • Hepatomegaly with soft yellow greasy liver
  • Steatosis reversible if abstain from alcohol
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5
Q

What is Nonalcoholic fatty liver disease (NAFLD)?

  • Prevalence
  • Spectrum
A
  • Potentially progressive liver disease
  • Global problem (1 billion worldwide)
  • Most common cause of chronic liver function test elevation in US
  • Spectrum ranges from steatosis to steatohepatitis, fibrosis, and cirrhosis
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6
Q

What is steatohepatitis?

  • What causes it
  • Prognosis
A
  • Classic form associated with alcohol abuse - alcoholic hepatitis
  • Nonalcoholic steatohepatitis (NASH) develops in 10-20% of those with nonalcoholic fatty liver disease
  • NASH tends to be more clinically indolent and less florid histologically than alcoholic hepatitis
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7
Q

What is nonalcoholic steatohepatitis (NASH)?

A
  • Obesity, especially morbid obesity, in adults and children
  • Diabetes mellitus
  • Metabolic syndrome
  • Develops in 10-20% of those with nonalcoholic fatty liver disease: steatohepatitis
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8
Q

What are the diagnostic criteria for metabolic syndrome?

A

At least two of these:

  • Central obesity or BMI > 30
  • Hypertension, BP > 140/90 mmHg
  • Dyslipidemia: hypertriglyceridemia and low HDL cholesterol
  • Microalbuminuria

Plus one of these:

  • Type 2 diabetes mellitus
  • Insulin resistance
  • Impaired glucose tolerance
  • Impaired fasting glucose
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9
Q

What can cause Nonalcoholic steatohepatitis?

A

Not all patients are obese…

  • Jejunoileal bypass surgery
  • Intestinal resection
  • Total parenteral nutrition (TPN)
  • Drugs:
  • Steroids
  • Tamoxifen
  • Estrogen
  • Methotrexate
  • Idiopathic
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10
Q

What is the natural history of NAFLD (Non Alcoholic Fatty Liver Disease)

A
  • Simple steatosis usually not progressive
  • 10-20% with NAFLD develop NASH
  • Up to 50% with NASH develop fibrosis
  • Fibrosis may be stable, progress or regress
  • About 20% with NASH develop cirrhosis
  • 35-50% of patients with alcoholic hepatitis who continue to drink develop cirrhosis
  • Most cryptogenic cirrhosis now thought to represent “burned-out” NAFLD
  • Patients with NASH who develop cirrhosis at increased risk for HCC
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11
Q

What are histological features of steatohepatitis?

A
  • Steatosis
  • Ballooning degeneration
  • Mallory-Denk bodies (Mallory hyaline)
  • Lobular neutrophils
  • Nonspecific portal and lobular inflammation
  • Fibrosis around terminal hepatic veins and perisinusoidal fibrosis, “chicken wire” pattern
  • Very characteristic of steatohepatitis, not seen with Hep B/C
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12
Q

What lab tests are used for evaluation of liver disease?

A
  • Measure liver excretion
  • Measure synthetic function
  • Assess hepatocellular damage
  • Assess biliary obstruction
  • Measure ability to detoxify
  • Tumor markers
  • Biopsies are done in minority
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13
Q

What are lab tests that measure liver excretion?

A
  • Serum bilirubin
  • Urine bilirubin
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14
Q

Describe serum bilirubin

  • What does the test evaluate
  • Suggests what conditions
  • What is measured
A
  • Specific test of hepatobiliary dysfunction
  • Except… Also elevated with hemolysis

Uses

  • Not sensitive for liver damage
  • Functional reserve of liver is over 2-3x daily pigment load

Measures:

  • Total bili = unconjugated + conjugated
  • When you order “serum bilirubin” you get total; could order direct as well if total is elevated or if jaundiced
  • Direct = conjugated + small fraction unconjugated*
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15
Q

T/F: There is no conjugated bilirubin in normal serum

A

True

  • BUT small amount is reported because of test methodology
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16
Q

Describe urine bilirubin

  • Source
  • Normal values
  • Suggests what conditions
A
  • From conjugated bilirubin
  • Not normally present on urine dipstick

Suggests:

  • Presence confirms clinically suspected jaundice
  • Absence with jaundice suggests unconjugated hyperbilirubinemia (unconjugated bilirubin not water-soluble)
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17
Q

What are lab tests of liver synthetic capability?

A
  • Protein
  • Albumin
  • PT/INR
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18
Q

Liver is the site of synthesis of most proteins. How is it assessed in lab?

A

Measure globulins by serum protein electrophoresis

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19
Q

What do low levels of albumin mean?

A

Low albumin levels correlate with severity of hepatocellular dysfunction

20
Q

What do PT/INR depend on?

  • What is INR?
A

Coagulation factors (proteins) synthesized in the liver

  • Factors I, II, V, VII, and X, as well as Vitamin K (1, 2, 5, 7, 10) INR used because PT varies depending on what reagents are used in the assay
  • INR is the ratio of pts PT to normal control raised to the sensitivity index of the tissue factor used in the assay
  • INR is a standard unit can be compared regardless of reagent used
21
Q

When are INR/PT elevated?

  • Usefulness?
A
  • Severe acute and advanced liver disease
  • Prognostic value
  • Assess safety of medical procedures
22
Q

What are lab tests to assess hepatocellular damage?

  • Describe what each is measuring/function of that substance
  • Where is each found (macro and micro)
  • Which is best marker
A

Transaminases- transform alpha-ketoacids into amino acids

  • Aspartate aminotransferase (AST)
  • Serum glutamic oxaloacetic (SGOT)
  • Found in liver, heart, skeletal muscle, brain, pancreas, lung, RBCs
  • > 80% in mitochondria and ER
  • Alanine aminotransferase (ALT)
  • Serum glutamate pyruvate transaminase (SGPT)
  • Mainly in liver
  • Low in kidney, heart, skeletal muscle
  • Mainly cytoplasmic
  • Usually better index of liver injury than AST
23
Q

Serum transaminases are sensitive indicators of ________

A

Serum transaminases are sensitive indicators of liver cell damage

  • Also a measure of continued hepatocyte damage in chronic hepatitis
24
Q

What is the best early index of acute viral hepatitis and recurrent activation?

A

Serum transaminases

25
Q

In acute hepatitis, which comes first, symptoms are serum transaminases?

A

Serum transaminases rise before clinical symptoms in acute hepatitis

  • Typ > 1000 U/L
  • ALT > AST
26
Q

What conditions have:

  • Lower transaminases than acute hepatitis
  • AST > ALT
A
  • Cirrhosis
  • Alcoholic liver disease
  • NASH
  • Metastases
  • Granulomas
  • Congestive heart failure

Recall: AST is in cytosol and mitochondria while ALT is mainly in cytosol; alcoholic hepatitis involves mainly mitochondrial damage and thus AST > ALT

27
Q

How can serum transaminase levels help in DDx of obstructive vs. parenchymal liver disease?

A
  • Transaminases > 400 U/L: usually parenchymal disease
  • Transaminases < 300 U/L: not as helpful in differential diagnosis
  • High alkaline phosphatase and bilirubin: obstruction
28
Q

What are tests to assess biliary obstruction or infiltrative disease?

A
  • Alkaline phosphatase
  • Direct bilirubin
29
Q

Describe alkaline phosphatase as a lab value

  • What diseases
  • Function of enzyme
  • Source
  • Location
A
  • Not specific
  • Sensitive indicator of:
  • Intrahepatic cholestasis
  • Extrahepatic cholestasis
  • Function: catalyzes hydrolysis of phosphate esters
  • Derived from: bone, liver, placenta
  • Physiological significance unclear
  • Present on bile duct epithelium and canalicular membrane of hepatocytes
  • Association with membranes -> physiological theories of plasma membrane importance
30
Q

How does liver respond to biliary obstruction?

A

Synthesizing more alkaline phosphatase

  • Released into circulation because of detergent action of retained bile salts on hepatocyte membranes
31
Q

With jaundice, what is indicated by:

  • High alkaline phosphatase levels
  • Low alkaline phosphatase levels
A
  • High: obstruction
  • Low: hepatocellular injury
32
Q

Does rise in alkaline phosphatase precede, accompany, or follow jaundice?

A
  • May rise before onset of jaundice
  • May persist after jaundice
33
Q

When may alkaline phosphatase be elevated without jaundice?

A

Infiltrative diseases:

  • Carcinoma
  • Abscess
  • Granuloma
34
Q

T/F: Alkaline phosphatase rises in cholestasis and to a lesser extent, when liver cells are injured

A

True

35
Q

What causes the highest increase in alkaline phosphatase?

A

Large duct obstruction

36
Q

What should be considered if alkaline phosphatase is increased out of proportion to bilirubin?

  • Bilirubin under 1 mg/dL
  • Alkaline phosphatase > 1000 U/L
A
  • Granulomatous disease
  • Infiltrative disease (with large duct obstruction , bilirubin usually also rises)
37
Q

What is gamma-glutamyl transferase (GGT)?

  • Indicates what
  • Location
A
  • Sensitive but nonspecific screen for liver disease; elevated in many liver diseases
  • Present in kidney, liver, pancreas, and small amounts other organs
  • Most of enzyme in blood from hepatobiliary system
38
Q

Describe the levels of GGT in various liver disease conditions… when:

  • Highest
  • Milder
  • Elevated
A
  • Highest in intra- and posthepatic biliary obstruction
  • More sensitive than alkaline phosphatase
  • Milder elevations in hepatitis
  • Elevated with primary and metastatic neoplasms
  • Elevated with alcohol abuse
39
Q

When is GGT useful?

A

In children who have higher alkaline phosphatase (from bone) due to active growth

40
Q

In adults, if high alkaline phosphatase and normal GGT, what should be considered?

A

Bone as a source of high alkaline phosphatase

41
Q

What does blood ammonia evaluate?

  • When elevated
A

Test for ability to detoxify

Elevated when:

  • Diffuse hepatocellular injury or portal blood bypasses liver
  • Hepatic encephalopathy

May be elevated in pts without hepatic encephalopathy

42
Q

What is serum alpha fetoprotein (AFP)?

  • Normal levels
  • Cause of elevation What is suggested by:
  • AFP > 1000 mg/L - AFP > 3000 mg/L
A
  • Only small amounts present in normal individuals
  • Increased levels seen with regeneration, almost never > 500 mg/L

Causes:

  • AFP > 1000 mg/L suggestive of hepatocellular carcinoma or germ cell neoplasm
  • AFP > 3000 mg/L very suggestive
  • Rarely made by other tumors, and if so, usually < 1000 mg/l
43
Q

Describe techniques/types of liver biopsy

A
  • Percutaneous “blind” core needle biopsy
  • Radiographically - guided core needle biopsy or fine needle aspiration (FNA)
  • Transjugular liver biopsy
  • Endoscopic ultrasound-guided FNA or core needle biopsy
  • Laparoscopic needle core or wedge biopsy
  • Open surgical needle core or wedge biopsy
44
Q

What are indications for liver biopsy?

A
  • Evaluate mass lesions
  • Diagnosis when clinical and lab studies equivocal
  • Assess cause of hepatomegaly
  • Evaluate asymptomatic patients with persistently abnormal LFTs
  • Distinguish whether jaundice secondary to hepatitis, obstruction
  • Grading and staging of chronic hepatitis
  • Monitor course of disease and response to treatment
  • Assess degree of injury; e.g., with toxin exposure
  • Evaluate for adverse effects of therapy, e.g., methotrexate
  • Evaluate for alcoholic liver disease and nonalcoholic fatty liver disease
  • Assess for steatohepatitis and fibrosis
  • Determine if liver involvement in systemic disease, e.g., sarcoidosis, lymphoma, etc
45
Q

What are indications for liver biopsy in liver transplant patients?

A
  • Evaluate for acute or chronic allograft rejection
  • Assess whether abnormal LFTs due to rejection, recurrent disease (esp. HCV), CMV infection, other infection, biliary obstruction, post-transplant lymphoproliferative disorder, other
  • Assess grade, stage of recurrent hepatitis
  • Evaluate response to anti-rejection or antiviral therapy