10/20- Fatty Liver Disease and Lab Evaluation of Liver Disease Flashcards
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
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*
T/F: There is no conjugated bilirubin in normal serum
True
- 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
Suggests:
- 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
- PT/INR
Liver is the site of synthesis of most proteins. How is it assessed in lab?
Measure globulins by serum protein electrophoresis