67 terms

Liver Disease 1 & 2 12-12

OM3 - Johnson - 2hrs

Terms in this set (...)

Describe the multiple functions of the hepatocyte
-Synthesis of serum proteins (albumin, coagulation factors, hormones, growth factors)
-Synthesis of bile and carriers (cholesterol, bile acids, lecithin, phospholipids)
-Regulation of nutrients (glucose, glycogen, lipids, cholesterol, amino acids...)
-Metabolism and conjugation of lipophilic compounds (bilirubin, anions, cations, drugs)
-Production of urea
Recognize history and physical exam findings consistent with liver disease
Review of Systems—fatigue, nausea, decreased appetite, itching, abdominal pain, bloating, "tea-colored" urine, "clay colored" stool, malaise...
Social history—IV drug use, alcohol use, tattoos, unsafe sexual practices, sick contacts, travel history...
Family history of hepatic disease
Medication use—OTC's, herbals, recent changes
History of blood transfusions
Occupation- exposures to hepatotoxins: PVC, CCl4...
Surgery—recent cholecystectomy

Scleral icterus/jaundice
Hepatic tenderness
Palmar erythema
Spider angiomata
Testicular atrophy
Confusion, stupor, coma
Dilated abdominal veins (Caput medusa)
Kayser-Fleisher rings (Wilson's disease)
Hyperpigmentation/slate-gray pigmentation
Muscle wasting/cachexia
Know what labs make up "Liver Function" tests and how to interpret them
Indicators of liver cell injury
Amount of elevation does not indicate prognosis
ALT>AST in most cases
In alcoholic liver disease, AST:ALT is at least 2:1
Best measure of liver function in the acute setting
Made by hepatocytes
May be low in chronic hepatic disease
Total and Direct Bilirubin
Indirect = Total - Direct
Breakdown product of the porphyrin ring of heme
Alkaline Phosphatase- elevated in cholestasis, growing children (bone turnover), pregnant women (placenta) and others
Hepatitis serology
Anti-mitochondrial Antibody (AMA) - screens for primary biliary cirrhosis
Ammonia - may make you think of hepatic encephalopathy in a pt with impaired mental status
Platelet count
Recognize and diagnose Gilbert's syndrome and make treatment recommendations
higher incidence in Males
Usually diagnosed after puberty
-> Stress, fatigue, alcohol, fasting and illness may cause an increase in bilirubin level and jaundice—it is transient
*Caused by a reduction of UGT1A1 activity

Phenobarbitol reduces bilirubin level
Recognize a case of Primary biliary cirrhosis (PBC)
Females > males
Incidence: middle age (30-65 years)
Associated w/Sjogren's, Scleroderma, CREST, RA, autoimmune thyroiditis

presents as Obstructive jaundice, cirrhosis:
Fatigue, pruritis

Elevated alkaline phosphatase
Elevated anti-mitochondrial antibodies (AMA)
Elevated GGT.
Elevated conjugated (direct) bilirubin

Tx = Ursodeoxycholic acid (Ursodiol)
Liver transplant

-> Chronic inflammation and fibrous obliteration of intrahepatic bile ductules
Recognize a case of Primary Sclerosing cholangitis (PSC)
Etiology unknown
Males > females
Incidence 20-40 yr
Associated with ulcerative colitis

Presentation similar to PBC (fatigue, pruritis)

can lead to:
Biliary cirrhosis

"string-of-beads" appearance on imaging

Tx = Liver transplant

-> Inflammation of biliary tree
Recognize and diagnose acute viral hepatitis and make treatment recommendations
Some individuals may have no symptoms and normal aminotransferase levels

Phase 1: incubation
Phase 2: Preicteric (prodrome) phase: malaise, anorexia, nausea, flu-like symptoms, better in AM—most contagious

Phase 3: Symptomatic icteric phase: dark urine, icterus/jaundice, clay colored stool, RUQ pain, worsening fatigue and worsening nausea, weight loss

Phase 4: convalescence: return of appetite, ↓bilirubin, ↓AST, ↓ALT

10-20% develop a serum sickness-like syndrome during the preicteric phase
Rash, hives, arthralgias, fever

look for needle tracks or tattoos
liver may be palpable

Histology: parenchymal inflammation, spotty necrosis

serology used to Dx

uncommonly can manifest w/Severe HA, encephalitis, aseptic meningitis, seizure, acute ascending flaccid paralysis, nephritic syndrome, seronegative arthritis
Interpret the serology for hepatitis A
elevated transaminases and positive anti-HAC IgM
-> IgM anti-HAV during acute illness
Interpret the serology for hepatitis B
Hepatitis B surface Ag (HBsAg) = infection

Hepatitis B surface Ab(Anti-HBs) = immunity

Total Hepatitis B core Ab(Anti-HBc) = previous or ongoing infection

IgM Ab to Hep B core Ag (IgM anti-HBc) = acute infection

Hep B e antigen (HBeAg) = active viral replication and infectivity, associated with a worse prognosis

Hepatitis B e Ab (HBeAb or anti-HBe) = indicates seroconversion (full recovery)

HBV DNA = more sensitive test for Hep B
Interpret the serology for hepatitis C
active infection = HCV RNA, HCV Ab reactive
Recognize a case of hepatitis A and be able to make management and prevention recommendations
Incubation: mean 28 days
Transmission: fecal-oral
- International travel
- Sexual contact/household members
- Ingestion of contaminated food/water
High risk:
Daycare centers and their contacts
Male-male sexual contact

Diagnosed by elevated transaminases and positive anti-HAC IgM

Adults: fever, fatigue, nausea, arthralgia, jaundice
Children: characteristically asymptomatic (< 6 yr of age)
Can lead to fulminant hepatic failure (< 1%) or relapse
NEVER becomes chronic
What labs should you order prior to vaccinating a person for hepatitis A?
check the total anti-HAV (remains indefinitely after infection & confers immunity)
Recognize and diagnose acute and chronic hepatitis B and make management and prevention recommendations
DNA virus with a core antigen (HBcAg) and a surface antigen (HBsAg)
Incubation: mean 90 days
Transmitted by blood and body fluids
High risk groups include medical personnel

Insidious onset
**May become chronic leading to increased risk of cirrhosis and hepatocellular carcinoma

jaundice, fatigue, arthralgias
Recognize and diagnose acute and chronic hepatitis C and make management and prevention recommendations
Single stranded RNA virus
Incubation: mean 45 d

Predominantly spread via contact with infected blood
- parenteral drug use, blood transfusion, needle stick accidents , unknown in 10%
- Sexual transmission occurs but is not common
- Maternal-fetal spread in about 5% of cases
- Intranasal cocaine use, tattoos and body piercing increase risk of infection
30-50% of HIV infected people also have hep C
Prior to 1992 was the most common cause of hepatitis d/t blood transfusion

Common cause of chronic liver disease and transplantation in the U.S.

75-85% of newly infected people develop chronic disease
60-70% w/chronic infection develop chronic liver disease

Can lead to cirrhosis and hepatocellular carcinoma
- Many are asymptomatic and have normal AST/ALT
-> AST/ALT and HCV RNA fluctuates
Diagnosis: anti-HCV, HCV-RIBA, HCV RNA

Extrahepatic manifestations: skin rashes, urticaria, joint/muscle aches, kidney ds, neuropathy, glomerulonephritis, seronegative arthritis, Sjogren's synd, non-Hodgkin's type, B-cell lymphoma, lichen planus.

Prevention: avoid high-risk behavior, use universal precautions
what are the long term sequelae of chronic hepatitis B?
fulminant hepatic failure, chronic disease, cirrhosis, hepatocellular carcinoma, vasculitis, glomerulonephritis
what are the long term sequelae of chronic hepatitis C
hepatocellular carcinoma
Recognize a case of hepatitis D and understand the consequences of HDV
Incomplete RNA virus, requires presence of HBV

HDV is more severe than HBV alone
May be acquired at same time as acute HBV (co-infection)

May occur spontaneously in a known HBV carrier (superinfection)

- Both forms may be associated with a severe or fulminant type of hepatitis
Superinfection may accelerate the progression of chronic HBV to cirrhosis
If patient with known HBV suddenly worsens, or if the patient presents with symptoms worse than expected for acute HBV, check for HDV

To treat HDV treat the HBV
Recognize a case of fulminant hepatic failure and make management recommendations
Hepatic encephalopathy :
Stage 1: subtle changes in affect, insomnia, difficulty concentrating
Stage 2: drowsiness, disorientation, confusion
Stage 3: marked somnolence, incoherence
Stage 4: coma

Cerebral edema
INR elevated, low grade DIC
GI bleeding
Multi-organ failure
Severe acid-base and electrolyte abnormalities
+/- jaundice
Complicating infections and ARDS

d/t massive hepatic necrosis, altho pathogenesis is often unclear

many etiologies

Consider need for emergent liver transplantation
- high Mortality
Recognize, diagnose and make management recommendations for alcoholic liver disease
Elicit risk factors based on H&P
Evaluate lifetime ETOH consumption
Exposure to other drugs
Any h/o other liver problems
Check for signs of chronic liver disease

AST usually < 300, If >400 suspect an additional cause
GGT usually >600+, but is nonspecific
Bilirubin may be elevated along with alk phos
25% may be jaundiced
-> Hyperglycemia, dyslipidemia common
Hypoalbuminemia and coagulopathy common in advanced disease
Ultrasound most common imaging test for screening
Liver biopsy is gold standard

Stop Drinking!
Supportive care
For severe alcoholic hepatitis:
MVI w/o iron
Folate, thiamin
Vit K
Improve diet—restrict protein if encephalopathic
-> Not a candidate for transplant until sober
Recognize, diagnose and make management recommendations for nonalcoholic fatty liver disease (NAFLD)
often no symptoms other than hepatomegaly

2 -4-fold ↑ ALT and AST
AST/ALT ratio < 1 in most
Serum ALP sl ↑ in 1/3
Normal bilirubin, albumin and protime
↑ serum ferritin level

Vague RUQ pain
Spider angiomata
Palmar erythema
Low-titer (< 1:320) ANA
↑ transferrin saturation
HFE gene mutation (C282Y)

Weight loss (Exercise and diet)
Control of Metabolic Syndrome
-> Antidiabetic/Insulin-sensitizing agents
-> Lipid-lowering agents
Bariatric surgery for morbid obesity
Avoidance of toxins
Describe the basic pathogenesis of NAFLD
d/t hepatic fat accumulation and hepatic oxidative stress. The oxidative stress acts upon the accumulated hepatic lipids, resulting in lipid peroxidation and the release of lipid peroxides -> produces reactive oxygen species
List the most common causes of cirrhosis of the liver
Autoimmune hepatitis
Alcohol-induced LR injury
Drug or toxin induced LR injury
Viral hepatitis B, C, D
Metabolic diseases
Nonalcoholic steatohepatitis
Malnutrition and postjejunoileal bypass surgery
Cryptogenic disease
Vascular derangements
Biliary disorders
Describe the clinical progression of cirrhosis
Often silent
Most remain asymptomatic until decompensation occurs
80-90% of LR parenchyma must be destroyed before LR failure manifests clinically

Early, well-compensated cirrhosis may manifest as:
Anorexia, wt loss, weakness, fatigue, easy bruising, osteoporosis

Later manifestations may include:
jaundice, gynecomastia, testicular atrophy, GI varices

Decompensated disease can result in complications:
Ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, portal hypertension, variceal bleeding

Most common causes of death from cirrhosis:
hepatic failure, GI hemorrhage, hepatocellular CA, infections and renal failure
what are the consequences of cirrhosis?
portal HTN, hepatorenal syndrome, hepatic encephalopathy, malnutrition, coagulopathies, hepatocellular carcinoma
what are the clinical sequelae of portal hypertension?
varices, ascites, spontaneous bacterial peritonitis
how do you screen for hepatocellular carcinoma?
who is at most risk for developing hepatocellular carcinoma?
pt's with cirrhosis, chronic hepatitis B & C, primary biliary cirrhosis
Recognize a case of Wilson's disease
autosomal recessive—occurs in adolescence and early adulthood

Results in psychiatric changes (emotional labiality, psychosis), extrapyramidal symptoms (resembling Parkinson's) and hepatitis, which can lead to hepatic decompensation

Kayser-Fleisher rings—may be seen in the eye on slit lamp exam
May cause hemolytic anemia

d/t deficiency of ceruloplasmin -> copper accumulation in liver & brain (basal ganglia)
Recognize a case of Hemochromatosis
Males > Females
Primary form is hereditary
Secondary form caused by anemia, alcoholism, multiple transfusions and other disorders

causes the body to absorb and store too much iron
-> micronodular cirrhosis and hepatocellular CA, DM, "bronzing" of the skin, CHF, cardiac arrhythmias, hypogonadism

Dx: ↑ serum iron and ferritin, ↑ tissue iron
Tx: Phlebotomy
what are the clinical consequences of Wilson's disease and make treatment recommendations
Results in psychiatric changes (emotional labiality, psychosis), extrapyramidal symptoms (resembling Parkinson's) and hepatitis, which can lead to hepatic decompensation
Kayser-Fleisher rings—may be seen in the eye on slit lamp exam
May cause hemolytic anemia

liver biopsy is gold standard
Tx = penicillamine, zinc, liver transplantation
which liver function tests detect injury to hepatocytes?
Aminotranferases (AST/ALT)
which liver function tests detect the liver's capacity to transport organic anions & metabolize drugs?
Bilirubin, bile acids
which liver function tests detect the liver's biosynthetic capacity?
Serum albumin, PT/INR, lipoproteins, ceruloplasmin, ferritin, alpha-1-antitrypsin
which liver function tests detect chronic inflammation of the liver, altered immunoregulation or viral hepatitis?
Immunoglobulin, hepatitis serology, specific autoantibodies
Describe the category of liver disease by predominant serum enzyme abnormality:
1. hepatocellular
2. cholestatic
3. infiltrative
1. AST, ALT > AP
2. AP > AST, ALT or elevated AP w/nearly normal AST, ALT
3. elevation of AP w/near normal AST, ALT
what imaging can be done to evaluate the liver?
Ultrasound—detects dilated bile ducts if obstructed—is cheap and 95% sensitive

CT—may help in determining cause of obstruction

ERCP (endoscopic retrograde cholangiopancreatography)—useful when obstruction is not seen on US, but still strongly suspected
MRCP (magnetic resonance cholangiopancreatography)
what causes jaundice?
increased bilirubin levels when it is overproduced, uptake is impaired, defective conjugation or excretion is impaired.
what is bilirubin?
major product formed when Hgb breaks down.
Bilirubin (unconjugated) is insoluble in water.
To be transported in blood bilirubin must be solubilized (conjugated).
Unconjugated bilirubin is bound to albumin and sent to the liver for conjugation with glucuronic acid by glucuronyl transferase and excretion into the small intestine via the biliary system.
generally describe unconjugated bilirubin
measured as indirect bilirubin
never present in urine
generally describe conjugated bilirubin
unbound in serum
measured as direct bilirubin
present in urine when > 3-4 mg/dL
what are some causes of unconjugated (indirect) bilirubinemia
increased RBC turnover (hemolytic anemia)
physiologic (newborn babies)
hereditary (Gilbert & crigler-najjar syndromes)
what are some causes of conjugated (direct) bilirubinemia
biliary tract obstruction
Biliary tract disease (Primary biliary cirrhosis [PBC], Primary sclerosing cholangitis [PSC])
Hereditary (Dubin-Johnson and Rotor syndromes)
Liver diseases (cirrhosis and hepatitis)

Gallstones, pancreatic CA, cholangiocarcinoma, cholangitis
Alcohol: cirrhosis
Toxins: acetaminophen, halothane, INH, steroids, carbon tetrachloride, PO4, mushrooms (amanita)
Infection: viral hepatitis
Post operative
what is the treatment for acute viral hepatitis?
Sensible nutrition
Avoid alcohol until convalescence
Limit sexual contacts until partners receive prophylaxis
Watch for complications, e.g. fulminant hepatic failure
Follow up to resolution
All cases of acute hepatitis should be reported to local or state health dept
what is hepatitis E?
RNA virus
Incubation: mean: 40 days
Prevalent in developing countries with a hot climate, inadequate water supply, poor sanitation

Transmission: fecal-oral, contaminated water or food supplies, possibly zoonotic—swine, rats, deer

Usually self-limited, but has a 10-20% mortality rate in pregnant women.
No known cases of progression to chronic disease in developing countries
In developed countries: reports of chronic disease in those on immunosuppressives for solid organ transplant
what is the consequence of being infected w/HBV at birth?
90% of those infected become chronic
-Testing mandatory in 1st trimester of pregnancy
-HBV immune globulin and Hep B vaccine given to baby within 12 hr of birth if mom has HBV
how do you diagnose acute HBV?
HBsAg, IgM anti-HBc
what is the treatment for hepatitis B?
no Rx for acute hep B

Chronic HBV:
HBsAg+ and anti-HBc+ on 2 separate samples 6 months apart,
Or: HBsAg+, anti-HBc+ and IgM anti-HBc neg on a single sample
whats the recommended testing sequence for ID'ing current HCV infection?
1. test for HCV antibody
2. test for HCV RNA (if previous step is +)

- if both are (+) = current infection
what is the treatment for chronic hepatitis C?
Peginterferon and ribavirin (Pegasys):
Gentotype 1: 48 wk
Genotype 2 and 3: 24 wk
Direct acting antivirals (DAA's):

-> side effects include: Flu-like symptoms, hemolytic anemia, depression, irritability
When you suspect acute viral hepatitis you should obtain what serologic tests?
IgM anti-HAV
IgM anti-HBc
If patient wants HAV vaccine and immunity unknown what should you do first?
check the Total anti-HAV first—if positive they are immune
how do you check for immunity after receiving the HBV vaccine?
obtain anti-HBs 1-2 months after the last injection—it should be > 100* mlU/mL
what are risk factors for non-alcoholic fatty liver Dz?
Diabetes mellitus
Polycystic ovarian ds.
Genetic—inborn errors of metabolism
Environmental: occupational exposures (monomeric vinyl chloride), dietary influences (excess fructose, hi fat, TPN), medications (estrogens, amiodarone, diltiazem, glucocorticoids, tamoxifen, etc.)
Surgery—bariatric, extensive sm bowel resection
Strongly linked to insulin resistance
what are the major goals of treatment of cirrhosis?
Slowing/reversing the progression of disease
Preventing superimposed insults to the liver
Preventing and treating complications
Determining the appropriateness and optimal timing for liver transplantation
how do you diagnose cirrhosis?
US and CT can delineate the characteristic features of a cirrhotic liver, and the presence of portal HTN, but are not diagnostic
No specific blood tests for cirrhosis

Lab abnormalities may include:
Anemia, ↑ bilirubin, ↑ alk phos, AST:ALT>2, ↑PT, ↓albumin, ↑ ammonia, resp alkalosis, ↓Mg, ↓phos, hyponatremia, hypokalemia, ↑aldosterone
Liver biopsy is the "gold standard"
what is portal hypertension?
Increased intrahepatic resistance to the passage of blood flow thru the LR d/t cirrhosis and regenerative nodules

Increased splanchnic blood flow secondary to vasodilatation within the splanchnic vascular bed
what are some of the clinical features of portal hypertension?
Gastroesophageal varices with hemorrhage
Portal-systemic hepatic encephalopathy
Thrombocytopenia and leukopenia

Hyperdynamic circulation
-> Increased cardiac output, expanded blood volume, decreased systemic vascular resistance w/relative hypotension
how do you diagnose portal hypertension?
Constellation of signs—varices, ascites, encephalopathy
-> caput medusa, parotid enlargement, spider angiomata, esophageal varices

Portal-systemic vascular channels form gastroesophageal varices, caput medusa, hemorrhoids
Endoscopy shows varices

Mesenteric and hepatic angiography done to evaluate for portal-systemic shunt surgery
Describe a variceal hemorrhage
Painless, massive hematemesis with or without melena
-> Commonly results in hypovolemia and shock
Mortality high
Surviving patients at increased risk for rebleed by 50-75% in the first 2 yr

EGD—procedure of choice, to ligate the varicosities and evaluate for other causes of hematemesis
describe the clinical features of ascites
Increasing abdominal girth
Peripheral edema

Shifting dullness, fluid wave
US or CT
what is the treatment for ascites?
Protein conc<1 g/dL
Salt restriction, < 2 g/day
Fluid restriction if hyponatremic
Diuretics: spironolactone, furosemide
Large volume paracentesis + albumin
Consider TIPS procedure
Consider liver transplant
Describe spontaneous bacterial peritonitis
Present with fever, chills, abdominal pain, altered mental status, elevated WBC, or no symptoms
=> seen in pt's w/ascites

Need to have a high clinical suspicion
Dx by paracentesis: >300 PMNs/μL is diagnostic

Generally d/t single organism, e.g. E. coli, strep or enterococcus.
Responds to 3d generation cephalosporin's, but may need broader coverage w/piperacillin/tazobactam

High rate of reoccurrence—up to 70% in 1 yr. Prophylactic antibiotics may be warranted
what is hepatorenal syndrome?
Form of functional renal failure w/o renal pathology

Mechanism poorly understood

Characterized by worsening azotemia with avid sodium retention and oliguria
Azotemia, hyponatremia, oliguria, hypotension
Serum Cr>1.5 g/dL, low urine Na d/t Na retention

Exclude other causes of renal failure (e.g. dehydration, contrast dye, meds)
Often seen in those with refractory ascites

Precipitated by GI bleed, sepsis, paracentesis, aggressive diuresis
Treatment is difficult, prognosis is poor
Best therapy is liver transplantation
what causes hyperammonemia
Loss of muscle and portal-systemic shunting contribute to the elevated ammonia levels

Ammonia is produced by the intestinal bacteria when protein is digested.
The liver converts it to urea and it is excreted by the kidneys.
Muscle converts ammonia to glutamine by combining it with glutamic acid
Describe Hepatic encephalopathy
Neuropsychiatric syndrome
presents as:
Alteration in behavior and consciousness
Asterixis "liver flap"
Fluctuating neurologic signs
Distinct EEG changes
Sleep disturbances
Cerebral edema

may be d/t ammonia, but multifactorial
?Intra/extrahepatic shunting of blood to systemic circulation bypassing the liver, toxic substances then not detoxified by the LR and effect the CNS

Numerous precipitating events: includes electrolyte imbalances, infection, increased dietary protein, GI bleed, medication reaction
Treatment: multifactorial and difficult
Eliminate precipitating factors
Lower blood ammonia and other toxins
Neomycin, rifaximin
Low dietary protein
describe malnutrition with advanced liver disease
Due to liver principally involved in regulation of protein and energy metabolism
Once cirrhotic, patients are more catabolic and muscle protein is metabolized
Other factors multiple: poor dietary intake, alterations in gut nutrient absorption, alterations in protein metabolism
Dietary supplements helpful and may help prevent catabolic state
Osteoporosis common d/t malabsorption of vit D and calcium
what protein is elevated in ~1/2 of people w/hepatocellular carcinoma?
alpha fetoprotein