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

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Flashcards in 10/20- Fatty Liver Disease and Lab Evaluation of Liver Disease Deck (45)

What are the main etiologies of steatosis?

(Recall, steatosis = fat in liver)

- Obesity

- Diabetes mellitus

- Alcohol

- Drugs, e.g., corticosteroids

- Hepatitis C


Describe alcoholic liver disease: prevalence/epidemiology

- 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


What are liver biopsy findings in alcoholic liver disease?

In decreasing order:

- Steatosis

- Normal

- Increased iron in hepatocytes

- Fibrosis

- Alcoholic steatohepatitis

- Cirrhosis


Describe the process of steatosis in liver disease

- Initially Zone 3 or centrilobular

- Entire lobule involved in severe cases

- Hepatomegaly with soft yellow greasy liver

- Steatosis reversible if abstain from alcohol 


What is Nonalcoholic fatty liver disease (NAFLD)?

- Prevalence

- Spectrum

- 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


What is steatohepatitis?

- What causes it

- Prognosis

- 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


What is nonalcoholic steatohepatitis (NASH)?

- Obesity, especially morbid obesity, in adults and children

- Diabetes mellitus

- Metabolic syndrome

- Develops in 10-20% of those with nonalcoholic fatty liver disease: steatohepatitis


What are the diagnostic criteria for metabolic syndrome?

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


What can cause Nonalcoholic steatohepatitis?

Not all patients are obese...

- Jejunoileal bypass surgery

- Intestinal resection

- Total parenteral nutrition (TPN)

- Drugs:

  • Steroids
  • Tamoxifen
  • Estrogen
  • Methotrexate

- Idiopathic


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

- 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


What are histological features of steatohepatitis?

- 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 


What lab tests are used for evaluation of liver disease?

- Measure liver excretion

- Measure synthetic function

- Assess hepatocellular damage

- Assess biliary obstruction

- Measure ability to detoxify

- Tumor markers

- Biopsies are done in minority


What are lab tests that measure liver excretion?

- Serum bilirubin

- Urine bilirubin


Describe serum bilirubin

- What does the test evaluate

- Suggests what conditions

- What is measured

- Specific test of hepatobiliary dysfunction

  • Except... Also elevated with hemolysis


- Not sensitive for liver damage

  • Functional reserve of liver is over 2-3x daily pigment load


- 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*


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


- BUT small amount is reported because of test methodology


Describe urine bilirubin

- Source

- Normal values

- Suggests what conditions

- From conjugated bilirubin

- Not normally present on urine dipstick


- Presence confirms clinically suspected jaundice

- Absence with jaundice suggests unconjugated hyperbilirubinemia (unconjugated bilirubin not water-soluble)


What are lab tests of liver synthetic capability?

- Protein

- Albumin



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

Measure globulins by serum protein electrophoresis


What do low levels of albumin mean?

Low albumin levels correlate with severity of hepatocellular dysfunction


What do PT/INR depend on?

- What is INR?

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


When are INR/PT elevated?

- Usefulness?

- Severe acute and advanced liver disease

- Prognostic value

- Assess safety of medical procedures


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

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


Serum transaminases are sensitive indicators of ________

Serum transaminases are sensitive indicators of liver cell damage

- Also a measure of continued hepatocyte damage in chronic hepatitis


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

Serum transaminases


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

Serum transaminases rise before clinical symptoms in acute hepatitis

- Typ > 1000 U/L



What conditions have:

- Lower transaminases than acute hepatitis


- Cirrhosis

- Alcoholic liver disease


- 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


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

- Transaminases > 400 U/L: usually parenchymal disease

- Transaminases < 300 U/L: not as helpful in differential diagnosis

- High alkaline phosphatase and bilirubin: obstruction


What are tests to assess biliary obstruction or infiltrative disease?

- Alkaline phosphatase

- Direct bilirubin


Describe alkaline phosphatase as a lab value

- What diseases

- Function of enzyme

- Source

- Location

- 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


How does liver respond to biliary obstruction?

Synthesizing more alkaline phosphatase

- Released into circulation because of detergent action of retained bile salts on hepatocyte membranes


With jaundice, what is indicated by:

- High alkaline phosphatase levels

- Low alkaline phosphatase levels

- High: obstruction

- Low: hepatocellular injury


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

- May rise before onset of jaundice

- May persist after jaundice


When may alkaline phosphatase be elevated without jaundice?

Infiltrative diseases:

- Carcinoma

- Abscess

- Granuloma


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



What causes the highest increase in alkaline phosphatase?

Large duct obstruction


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

- Bilirubin under 1 mg/dL

- Alkaline phosphatase > 1000 U/L

- Granulomatous disease

- Infiltrative disease (with large duct obstruction , bilirubin usually also rises)


What is gamma-glutamyl transferase (GGT)?

- Indicates what

- Location

- 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


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

- Highest

- Milder

- Elevated

- 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


When is GGT useful?

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


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

Bone as a source of high alkaline phosphatase


What does blood ammonia evaluate?

- When elevated

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


What is serum alpha fetoprotein (AFP)?

- Normal levels

- Cause of elevation What is suggested by:

- AFP > 1000 mg/L - AFP > 3000 mg/L

- Only small amounts present in normal individuals

- Increased levels seen with regeneration, almost never > 500 mg/L


- 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 mg/l


Describe techniques/types of liver biopsy

- 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


What are indications for liver biopsy?

- 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


What are indications for liver biopsy in liver transplant patients?

- 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