Liver (Washington) Flashcards
Define steatosis
Fatty infiltration of the liver (TGs and other fats inside hepatocytes)
Define steatohepatitis
When inflammation is a/w fatty infiltration of the liver
Define cirrhosis
- Chronic degenerative disease
- Hepatocytes are damaged and replaced by scar tissue
- Results in decreased function of the liver
What is AST? What does it test for?
- Aspartate Aminotransferase
- Enzyme normally found in RBCs, liver, heart, muscle, pancreas, kidneys
- Tests for liver damage (along with ALT)
- Formerly called SGOT
What are normal AST levels (generally)?
Low
How is the amount of AST in the blood related to tissue damage?
Directly - more AST in blood means more tissue damage
What does the ratio of AST to ALT tell us?
Whether liver or another organ has been damaged
Which liver lab test component is mainly found in liver tissue?
ALT
AST is less specific
Which is more specific to the liver - ALT or AST?
ALT
What is ALT? What does it test for?
- Alanine Aminotransferase
- Enzyme found mainly in liver
- Tests for liver damage/disease
- Formerly called SGPT
What are normal values of ALT (generally)?
Low
What is ALP? What does it test for?
- Alkaline Phosphatase
- Enzyme made mostly in liver and bone (some in intestines, kidneys, placenta)
- Non specific
The liver makes more ____ (ALT, AST, ALP) than other organs or bones
ALP
Abnormally elevated levels of ALP could be from:
- Rapid bone growth (puberty)
- HyperPTH
- Vit D deficiency
- Liver damage
What is GGT?
- Gamma glutamyl transpeptidase
- Enzyme in blood that functions as a transport molecule to help liver metabolize drugs/toxins
- Found in many places but NOT bone
- Can help you determine if high ALP is prob due to bone disease
What does a high ALP with a high GGT indicate?
Liver or bile ducts damage
high GGT rules out bone as a cause!
What does a high ALP with a normal GGT indicate?
Bone disease
Define total bilirubin
Amount of bilirubin in a blood sample
How does bilirubin circulate in the blood?
In 2 forms:
- Direct (conjugated)
- Indirect (unconjugated)
Features of indirect bilirubin
- Unconjugated
- Insoluble
- Conjugated in the liver
- Not measured directly form the blood (need total and direct values)
Which type of bilirubin cannot be measured straight from the blood?
Indirect
need total and direct to calculate
Elevated levels of indirect bilirubin indicates:
- Hemolysis
- Failure of liver uptake
Features of direct bilirubin
- Conjugated
- Soluble
- Measured directly in blood
Elevated levels of direct bilirubin indicates:
Impaired secretion of liver
Define albumin, its functions, and what it evaluates
- Protein made by the liver
- Helps move bilirubin, Ca, hormones and meds through blood
- Keeps fluid in blood from leaking out into tissues
- Used to assess liver and kidney disease
Decreased levels of albumin occurs when?
- When body does not get or absorb enough nutrients
- Crohn’s, after wt loss surgery, low protein diets, Celiac
Increased levels of albumin occurs when?
- Dehydration
- High protein diet
Define alcoholic liver disease
-Acute or chronic inflammation
-Parenchymal necrosis of liver
induced by alcohol
What is the MC precursor of cirrhosis in the US?
Alcoholic liver disease
Is alcoholic liver disease reversible or irreversible?
Reversible in early stages
3 major stages of ALD
- Fatty liver
- Alcoholic hepatitis
- Cirrhosis
Features of fatty liver stage of ALD
- Present in 90+% of binge and chronic alcoholics
- Asymptomatic
- Reversible w/cessation of alcohol
Features of alcoholic hepatitis stage of ALD
- 10-20% of alcoholics
- Asymp - symptomatic
- Reversible w/cessation
- Precursor to cirrhosis
What stage of ALD is the precursor to cirrhosis?
Alcoholic hepatitis
What is the first histologic response to any hepatotoxic stimuli (e.g. ETOH)?
Fat accumulation
Where does fat accumulation in the liver occur?
At the location of alcohol dehydrogenase (leading to a deficiency of this enzyme)
What is the hallmark of alcoholic hepatitis?
Hepatocyte injury (degeneration, necrosis, PMN infiltration, fibrosis)
What is the most important risk factor of ALD?
Quantity AND duration of alcohol intake
Who is more susceptible to ALD?
-Females (lower levels of alcohol dehydrogenase to begin with) -Concurrent HCV -Genetics -Fatty liver from obesity
How does ALD occur in pts w/concurrent HCV?
- Develop at a younger age
- Worse survival
What is the amount of alcohol per day threshold for males vs. females in developing ALD?
- Males: 80+ g/d
- Females: 30-40+ g/d
- 1 drink is approx. 12 g
If symptoms are present in early ALD (fatty liver), what would it be?
- Hepatomegaly
- RUQ tenderness (occasionally)
- Nausea
- Jaundice (very rare)
How does advanced (alcoholic hepatitis) ALD present?
- SOME are asymp
- Fever
- Spider nevi
- Jaundice
- Abdominal tenderness
- Encephalopathy
- Portal HTN (ascites, esophageal varices)
What lab abnormalities may be found in early (fatty liver) ALD?
- Modest increase in GGT, AST, ALT
- High TGs
- High cholesterol
- High bilirubin (occasionally)
What lab abnormalities may be found in advanced (alcoholic hepatitis) ALD?
- Severe increase in GGT, AST, ALT, AST:ALT
- High bilirubin (common)
- High ALP
- Low albumin
- Coagulopathy (increased PT)
What imaging is used to evaluate alcoholic liver disease? What does it detect?
Ultrasound:
- Fatty infiltration
- Size of liver
- Biliary obstruction
- Ascites
- CANNOT detect fibrosis or inflammation
Liver ultrasound cannot detect:
Fibrosis and inflammation
What is needed for definitive diagnosis of ALD?
Liver biopsy
U/S cannot detect fibrosis and inflammation
Describe liver biopsy’s role in ALD:
- Needed for definitive diagnosis
- Guides therapy
What does early ALD show on liver biopsy?
Macrovesicular fat
What does advanced ALD show on liver biopsy?
PMN infiltration w/hepatic necrosis, Mallory bodies, and fibrosis
*Findings are non-specific and identical to those of NASH (non-alcoholic steatohepatitis)
General treatment of ALD
- Abstinence from alcohol
- Proper nutrition (including potentially folic acid, thiamine, zinc supplements)
- Psych counseling
Pharmacologic treatment of ALD
- Methylprednisolone with taper MAY reduce short term mortality in alcoholic hepatitis
- Pentoxifylline (TNF-inhibitor) reduces 1 month mortality rates in alcoholic hepatitis
- NO benefit to use both
Surgical treatment of ALD
Liver transplant for end stage cirrhosis
When is Methylprednisolone used in ALD?
- For alcoholic hepatitis
- Given for 1 month w/a taper
- MAY reduce short term mortality
What is Pentoxifylline and when is it used in ALD?
- TNF inhibitor
- Given for 1 month
- Reduces 1 month mortality rate in alcoholic hepatitis
- Decreases hepatorenal syndrome
- Used when corticosteroids are contraindicated, no benefit to use both
What is the most important prognostic factor of ALD?
Continued excessive ETOH use
What is the MC chronic liver disease in US?
Nonalcoholic Fatty Liver Disease (NAFLD)
Why is NAFLD increasing in children?
Increasing childhood obesity in the US
What is the MC cause of NAFLD?
Obesity
What meds can cause NAFLD?
- Corticosteroids
- Amiodarone
- Diltiazem
- Tamoxifen
What conditions can cause NAFLD?
- DM
- High TGs
- Cushing’s
- PCOS
- OSA
- Metabolic syndrome
What is the pathology of NAFLD?
Macrovesicular steatosis
What are the biggest risk factors for progression of NAFLD to advanced hepatic fibrosis and cirrhosis?
- Older age
- Obesity
- DM
How does NAFLD present?
- Most are asymp
- Mild RUQ discomfort
- Hepatomegaly (up to 75% of pts)
What is the MC presenting sign of NAFLD?
Hepatomegaly
Is progression of NAFLD to chronic liver disease common or uncommon?
Uncommon
What abnormal lab findings could present in NAFLD?
- Mildly elevated AST, ALT, or ALP
- Ratio of ALT:AST is almost always greater than 1
How is imaging used in evaluating NAFLD?
Macrovascular steatosis may be seen on US/CT/MRI, but it will NOT distinguish b/w steatosis or steatohepatitis
What is the diagnostic test of choice for NAFLD?
Liver biopsy
What does liver biopsy assess for NAFLD?
Degree of fibrosis and inflammation
Who should NOT have liver biopsy performed if NAFLD suspected?
Asymp pts w/normal LFTs
What must be ruled out in diagnosing NAFLD?
- Hazardous levels of ETOH use
- Hepatotoxic meds
General treatment of NAFLD
- Wt loss
- Dietary fat restriction
- Exercise
Pharmacologic treatment of NAFLD
-Thiazolidinediones
-Vit E
-Metformin
-Pentoxifylline
(all currently being studied)
Surgical tx of NAFLD
Gastric bypass
When is gastric bypass indicated in NAFLD?
BMI 35+
What is the prognosis of NAFLD?
- Benign and reversible
- Do have increased mortality compared to those without NAFLD
- CAN progress to NASH
Cirrhosis develops in how many NAFLD pts?
1-3%
If cirrhosis develops in NAFLD, what is the pt at increased risk for?
Liver cancer
*New studies showing an increased risk even in NAFLD pts who don’t develop cirrhosis
Risk factors for NASH
- Overweight/obese
- DM
- NAFLD (25% get NASH)
How does the histology of NASH present?
Exactly like alcoholic hepatitis
How does NASH present in patients?
- Asymp early in disease
- As disease progresses, fatigue, wt loss and weakness
What is the definitive diagnostic test of NASH?
Liver biopsy
since all imaging cannot distinguish steatosis from steatohepatitis
Treatment of NASH
- Lifestyle (wt loss, low fat diet, physical activity)
- Avoid hepatotoxins
Does NASH progress to advanced disease?
- May be a/w fibrosis (40% pts)
- Cirrhosis develops in 9-25%
- Hepatocellular carcinoma considered a complication in those who develop cirrhosis
What is considered a complication of NASH pts who develop cirrhosis?
Hepatocellular carcinoma
Is cirrhosis reversible or irreversible?
- May be reversible if cause is removed early in the disease
- Irreversible in advanced stages
How do s/s of cirrhosis correlate to severity of disease?
Regardless of cause of cirrhosis, s/s present the same and indicate severity of disease
What are the 2 MC causes of cirrhosis in the US?
- Alcohol
- HCV
Pathology of cirrhosis
- Fibrosis leads to physical changes of liver
- Formation of regenerative nodules
- Decreased function and an alteration of blood flow
Stages of cirrhosis
- Compensated (no complications, liver can still compensate and manage)
- Compensated (w/varices)
- Decompensated (w/complications)
How do labs present in cirrhosis?
- Macrocytic anemia
- WBC low OR high
- Thrombocytopenia
- Prolonged PT
- Elevated AST, ALT, ALP
- Elevated bilirubin
- Low albumin
How is Doppler US used in evaluating possible cirrhosis?
- Liver size
- Presence of nodules, ascites
- Patency of blood vessels
How is CT/MRI used in evaluating possible cirrhosis?
Assess suspicious nodules for malignancy
How is esophagogastroduodenoscopy used in evaluating possible cirrhosis?
Confirms presence of varices and can detect causes of bleeding
What is the gold standard for diagnosis of cirrhosis?
Liver biopsy
How is liver biopsy used in evaluating cirrhosis?
- 80-100% sensitivity depending on method and size/number of specimens obtained
- Can sometimes suggest actual cause of cirrhosis
When is liver biopsy not necessary in evaluating possible cirrhosis?
If clinical, lab, radiologic data strongly suggest presence of cirrhosis
General treatment of cirrhosis
- Tx underlying cause if known
- ETOH cessation
- Proper diet
- Psych
- Vaccines (HAV, HBV, pneumococcal, annual influenza)
Pharmacologic treatment of cirrhosis
NO meds currently available to halt progression or reverse cirrhosis
What is the MC complication of cirrhosis?
Ascites and edema
Why does ascites/edema occur with cirrhosis?
Portal HTN
How do you treat ascites?
- Na restriction
- Diuresis (Spironolactone first THEN add a loop)
- Paracentesis
- Transjugular hepatic portosystemic shunt (TIPS)
What does the onset of ascites with cirrhosis indicate?
Poor prognosis
less than 50% survival in 2 yrs
When treating ascites, what is the 1st line diuretic?
Spironolactone
*then Loop diuretic
When is paracentesis performed in cirrhosis pts?
Pts with:
- Massive ascites
- Respiratory compromise
- Not responding to diuretics
What is spontaneous bacterial peritonitis?
- Complication of cirrhosis
- Infection of pre-existing ascitic fluid W/O evidence of a secondary source
- MC organism is E. coli
What is the MC organism of spontaneous bacterial peritonitis?
E. coli
d/t bacterial translocation of GI flora through lymph system causing bacteremia which then gets into ascitic fluid
How does spontaneous bacterial peritonitis present?
Fever, abdominal pain, tenderness, altered mental status
How is spontaneous bacterial peritonitis diagnosed?
Paracentesis showing:
-Positive ascitic fluid culture and/or elevated PMN count
What is the treatment of spontaneous bacterial peritonitis?
2nd generation Cephalosporin (MC cefotaxime)
*These pts are on proph abx for live to prevent recurrent infection
What is the most life threatening complication of cirrhosis?
Variceal hemorrhage
How to treat variceal hemorrhage?
- Vasoconstricting agents
- Balloon tamponade
- Endoscopic therapy w/sclerotherapy
- TIPS
What is the primary prophylaxis treatment of esophageal varices?
Routine endoscopy screening for all pts with cirrhosis (every 6-12 months)
What should pts with cirrhosis be screened for and how often?
Routine endoscopy screening for esophageal varices every 6-12 months
What is hepatorenal syndrome?
- Complication of cirrhosis
- Renal failure in pts w/advanced liver disease
- Functional renal failure w/o renal pathology
- POOR prognosis unless liver transplanted
What is hepatic encephalopathy?
- Complication of cirrhosis
- Change in mental status
- Gut derived neurotoxins are not removed by the liver and get to the brain (causing encephalopathy)
How is hepatic encephalopathy diagnosed and treated?
- Clinical diagnosis
- Hydration w/IV fluids
- Lactulose
- Mannitol
- Rifaximin or Metronidazole + Neomycin (if pt does not tolerate Lactulose)
- Zinc supplement
How does lactulose help treat hepatic encephalopathy?
- Removes GI nitrogenous products
- Goal is 2-3 BM/day
How does mannitol help treat hepatic encephalopathy?
Decreases brain swelling
If a pt does not tolerate lactulose, what can be given for tx of hepatic encephalopathy?
Rifaximin OR Metronidazole with Neomycin
What is hepatopulmonary syndrome and how does it present?
- Complication of cirrhosis
- Intrapulmonary vascular dilatations OR AV communications/fistulas (R-L shunt)
- Dyspnea, drop in O2 sat (worse in upright position)
What is portopulmonary hypertension and how is it diagnosed?
- Complication of cirrhosis
- Pulmonary HTN in pts w/portal HTN
- Rare
- Diagnose by echo and cardiac cath
What is coagulopathy?
- Universal complication of cirrhosis
- Decreased synthesis of clotting factors and impaired clearance of anticoagulants
How to treat coagulopathy in cirrhosis pts?
Vit K supplementation
*If synthesis/production of clotting factors is diminished then Vit K will NOT help - need FFP (fresh frozen plasma) if active bleeding or before a required procedure only
What is the ultimate treatment of decompensated cirrhosis?
Liver transplant
5 yr survival is as high as 80%
What is hemochromatosis?
- Inherited disorder of iron metabolism
- Progressive increase in hepatic iron deposition which can lead to cirrhosis
- Increased risk of hepatocellular carcinoma
How can hemochromatosis be diagnosed and how is it treated?
- Elevated fasting transferrin saturation and ferritin level
- Genetic testing
- Liver biopsy
- Tx = regular phlebotomy
What is Wilson’s disease and who does it affect?
- Rare autosomal recessive disorder of copper (failure to excrete excess copper leading to liver damage)
- Young adults and adolescents
How is Wilson’s disease diagnosed?
- Low serum cerulosplasmin concentration
- Increased hepatic copper on liver biopsy
Treatment of Wilson’s disease?
Copper-chelating agents indefinitely
MC presenting sign of Wilson’s disease?
Kayser-Fleischner ring (around iris of eye)
What is alpha-1 antitrypsin deficiency?
- Autosomal recessive disorder that causes abnormal folding of the protein
- Failure of secretion from liver leads to liver disease
How is alpha-1 antitrypsin deficiency diagnosed?
Phenotype testing and alpha-1 antitrypsin levels
Treatment of alpha-1 antitrypsin deficiency
Liver transplant is curative
Inherited metabolic liver diseases:
- Hemochromatosis
- Wilson’s disease
- Alpha-1 antitrypsin deficiency
