Hepatitis & Cirrhosis Flashcards
Liver Function tests
Enzyme tests? 3
Synthetic Function? 2
Other? 1
Enzyme tests:
- Aminotransferases—ALT & AST
- Alkaline phosphatase—AP
- Gamma glutamyl transpeptidase—GGT
Synthetic function:
- Serum albumin
- PT—prothrombin time
Other
- Bilirubin
History, History, History
for Liver problems?
8
- Exposure to chemicals, meds, herbs
- Accompanying symptoms
- Parenteral exposure
- IV and intranasal drug use
- Tattoos and piercings
- Sexual activity
- Travel and exposure history
- Alcohol history
Physical Exam
for liver problems?
6
- Cachexia suggests malnutrishment - drinking or drug use
- Stigmata of longstanding liver disease
- Signs of alcoholic liver disease
- Enlarged left supraclavicular node- Cancer
- JVP suggests RHF secondary to portal HTN
- Right pleural effusion in the absence of advanced ascites can be seen in cirrhosis
Autoimmune Hepatitis
- Two types?
- Characterized by what? 2
1.
- Type 1 (Classic): occurs in women of all age groups
- Type 2 (ALKM-1): occurs in girls and young women
2. Characterized by - circulating autoantibodies (not thought to be part of the pathophysiology)
- High levels of serum globulin concentrations
Histopathology Autoimmune Hepatitis
Clinical Manifestations of Autoimmune Hepititis? 3
Labs? 2
Clinical Manifestations
- Asymptomatic
- Subclinical and those presenting w/ advanced cirrhosis
- Fulminant hepatitis
Labs:
- Presence of serological markers
- Generally aminotransferases more elevated than bilirubin and AP
Extrahepatic Manifestations of autoimmune anemia?
6
- Hemolytic anemia
- Thyroiditis
- Celiac sprue
- ITP
- Type I DM
- Ulcerative colitis
ALL of these tend to be AUTOIMMUNE
- Treatment of Autoimmune Hepatitis?
- Acute risks and complications with steriods? 5
- Long term risks? 6
- 2nd line?
- Corticosteriods for sympatomatic disease
2.
- HTN
- high blood sugar,
- psychosis,
- insomnia
- gastric irritation
2.
- Clouding of the lens in one or both eyes (cataracts)
- High blood sugar, which can trigger or worsen diabetes
- Increased risk of infections
- Thinning bones (osteoporosis) and fractures
- Suppressed adrenal gland hormone production
- Thin skin, bruising and slower wound healing
3. Azathioprine a 2nd line agent
- Hemachromatosis is what?
- What gene?
- Genetic disease due to autosomal recessive
- Identified gene HFE
Most common single gene disorder:
10% Caucasians heterotozygous
0.5% Caucasians homozygous
Very rare in other populations
Hemochromatosis–Pathophysiology
- Gene defect results in what?
- What does this cause?
- Eventual fibrosis & organ failure leads to what? 4
- Gene defect results in increased iron absorption in the intestinal tract from the diet
- Iron overload in the body
3.
- Cirrhosis
- Cardiomyopathy
- Diabetes
- Hypogonadism
Iron Overload
- Normal iron content in the body?
- Normally iron storage is controlled so there is no what?
- Accumulation of _______ mg/yr. of iron occurs in hemochromatosis
- Symptoms usually occur when? 2
- Females have delayed symptoms because of what? 2
- 3-4 mg /day
- no excess accumulation
- 500-1000 mg/yr.
4.
- around age 40
- when iron stores reach 15-40 g!
5.
- menstruation
- breast feeding
Hemochromatosis Clinicical Manifestations are influenced by?
6
- Age
- Sex
- Alcohol use
- Dietary iron
- Menstruation & breast feeding
- Unknown factors
- Hemochromatosis is accelerated by what? 2
- Classic presentation?
1.
- Alcohol abuse &
- hepatitis C accelerate the process
2. Classic presentation: - cutaneous hyperpigmentation w/ diabetes & cirrhosis
Reversible Manifestations of hemachromatosis?
- CV? 2
- Liver? 3
- Skin? 2
- Infections? 3
- CV:
- Cardiomyopathy
- conduction disturbances - Liver:
- abdominal pain
- elevated LFTs
- hepatomegaly - Skin:
- bronzing (melanin deposition)
- grayness (iron deposition) - Infections:
- Vibrio vulnificus
- Listeria monocytogenes
- Pastcuerlla pseudotubercullosis
Irreversible Manifestations of Hemacromatosis
- Liver? 2
- Anterior pituitary gland?
- Pancreas?
- Thyroid?
- Genitalia?
- Joints?
- Liver: : cirrhosis, hepatocellular CA **
- Anterior pituitary gland: gonadotropin insufficiency leading?
- Pancreas: diabetes mellitus (30-60%)
- Thyroid: hypothyroidism
- Genitalia: primary hypogonadism
- Joints: pseudogout
Diagnosis of Hemochromatosis
Combination of?
3
- Clinical
- Laboratory
- Pathologic
Diagnosis of Hemochromatosis
- Laboratory? 2
- Gold Standard?
1.
- Elevated serum transferrin saturation > 45%**
- Elevated serum ferritin
2. -Confirmation = ‘Gold Standard’ = liver biopsy (also defines extent of disease)
Treatment of Hemacromatosis
- Education for evidence of iron overload/complications? 4
- Mainstay of treatment?
- Education for evidence of iron overload/complications:
- Avoid red meat, iron supplements
- Avoid alcohol
- Avoid handling or eating raw seafood (increased risk of infections)
- Receive vaccinations for hepatitis A & B - Mainstay of treatment–Phlebotomy
Hemacromatosis Phlebotomy
- Removal of 500 ml of blood removes ______mg Iron
- Do weekly until iron depletion:
Hgb = ?
Ferritan ?
Transferritin saturation ?
- Maintenance: ?
- 250
- Do weekly until iron depletion:
Hgb = 10 – 12 gm/dL
Ferritan < 50
Transferritin saturation < 50%
- Maintenance: phlebotomy every 2-4 months
Hemacromatosis Genetic Testing
- Screen who?
- Likely to uncover who?
- Screening test cost: ?
- Screen 1st degree relatives unless under 18 YO
- Likely to uncover homozygotes who are asymptomatic
- Screening test cost: $200; done on whole blood sample
Wilson’s Disease
- aka?
- Inheritated how?
- Affects what kind of metabolism?
- Organ damage due to what?
- Easily treated if what?
- a.k.a. “hepatolenticular degeneration”
- Autosomal recessive
- Affects copper metabolism
- Organ damage due to copper build up in the liver and brain
- Easily treated if diagnosed early
- Difficult to diagnose!!!
Pathogenesis of
Wilson’s Disease
2
Pathogenesis:
- The abnormal gene ATP7B affects the carrier protein of copper which is primarily in hepatocytes
- It also impairs the excretion of copper via bile
Wilson’s Disease Clinical manifesations?
- Presents when?
- What kind of symptoms? 3
Presentation varies widely and is often non-specific
- Generally presents between the 1st and 3rd decade:
2.
- Liver disease (usually presenting sx in young children)
- Neurologic symptoms
- Psychiatric symptoms
Wilson’s disease
Dx? 3
Tx? 1
Prognosis?
DIAGNOSIS:
- Ceruoplasmin level
- 24-hour urine for copper excretion
- Look for Kayser-Fleischer rings in eyes
Tx:
- Once diagnosed chelation therapy w/ D-penicillamine is the treatment of choice (lifelong)
PROGNOSIS:
Universally fatal if untreated
Alcoholic liver dz: three stages?
Three stages:
- Fatty liver (steatosis)
- Alcoholic hepatitis
- Alcoholic fibrosis and cirrhosis
Fatty Liver
- Most patients present how?
- Can occur how soon after a large alcohol binge & if continues to drink can progress?
- May have tender what?
- What is mildly elevated?
- Can also occur in what other populations? 2
- Most patients asymptomatic
- Can occur within hours of a large alcohol binge & if continues to drink can progress
- May have tender hepatomegaly
- Transaminases mildly elevated
- Can also occur in obese individuals and pregnancy
Alcoholic Hepatitis
- Range of presentation?
- Symptoms? 8
- Asymptomatic to extremely ill
2.
- Anorexia,
- N/V,
- weight loss,
- abdominal pain,
- poor nutritional status
- HSM
- Jaundice
- Fever is common
Physical Exam for alcoholic hepatitis?
7
- Spider angiomas
- Palmar erythema
- Gynecomastia
- Parotid enlargement
- Testicular atrophy
- Ascites
- Encephalopathy
Lab findings for alcoholic hepatitis?
8
- Leukocytosis w/ left shift (in severe disease)
- Anemia (Macrocytic- B12*** or GI blood loss/microcytic)
- Transaminases elevated: AST: ALT ratio usually greater than 2:0 (ratio rarely seen in other forms of liver disease)
4 Increased AP (> 3x normal)
- Hyperbilirubinemia (60-90%)
- Hypoalbunemia (severe disease)
- Coagulopathy (severe disease)
- Elevated ammonia level (severe disease)
Complications of Alcoholic LD
6
- Alcoholic fatty liver is reversible
- Alcoholic hepatitis—usually is reversible, but may run a fulminant course progressing to fibrosis and death
- Long standing alcoholic liver disease can lead to cirrhosis
Others:
- GI bleeds
- esophageal varices
- gastritis/PUD
What are these?
Mallory Bodies
- Treatment of Alcoholic LD? 2
- Supportive therapy? 5
1.
- CESSATION of ALCOHOL!
- Liver transplant in appropriate patients
2. Supportive treatment: - Nutrition
- Folic Acid
& Vitamin B12
- Fluids
- R/O other causes for fever, liver disease such as Hep C, Hemochromatosis, neoplasm
- Glucocorticosteroids for severe hepatitis
Toxic Hepatitis: Factors influencing toxicity?
8
- Excessive intake
- Excessive cytochrome P450 activity
- Decrease metabolism pathways in liver
- Depletion of glutathione stores
- Concomitant us of alcohol or other drugs
- Comorbid illness
- Advancing age
- Nutritional status
What is the most common cause of liver failure in the US?
Toxic Heptitis
Drug-induced liver injury (DILI):
DILI: What kind of liver injury could it cause?
3
Least likely to cause?
May be
- cholestasis,
- cytotoxic or
- mixed,
less likely steatosis
Toxic Hepatitis: Most common drugs implicated in DILI in U.S.? 2
Acetaminophen
Antibiotics
Treatment for acetaminophen overdose: 3
- Acetaminophen level
- Activated charcoal if ingested within 2-3 hours
- N-acetylcysteine for severe overdose
Chronic Acetaminophen Intoxication
- Signs and symptoms are nonspecific and often confused with what?
- Patients who are at greater risk for developing hepatotoxicity:? 4
- Signs and Sx are nonspecific: confused w/ viral diagnosis
2.
- Ingestion of > 7.5 to 10 g over 24 hours
- Ingestion of less than 4g w/ increased susceptibility
- Liver tenderness, jaundice or ill-appearing
- Supratherapeutic acetaminophen concentrations (> 20 mcg/mL)
Treatment Chronic Acetaminophen Toxicity: Treatment w/ NAC recommended for?
4
- All patients w/ liver tenderness &
- Elevated aminotransferases &
- Serum acetaminophen concentrations >10 mcg/mL
- If serum acetaminophen concentrations are potentially toxic by the nomogram
Viral Hepatitis’s
What are the types?6
A, B, C, D, E, & G
Hepatitis A (HAV)
Hepatitis B (HBV)
Hepatitis C (HCV)
Hepatitis D (HDV)
Hepatitis E (HEV)
Hepatitis G (HGV)
GB virus type C (GBV-C)
General Presentation
Primarily seen w/ HAV, HBV, HCV, HEV: Many cases can be asymptomatic especially in children
- Usually prodrome after exposure: this consists of what? 5
- Malaise and fatigue
- Anorexia, N/V
- Myalgia’s
- Pale stools, dark urine (urobiligen- direct being excreted in the urine and not in the stool like usual)
- Jaundice
General Signs on Exam of viral hep?
3
- Jaundice
- RUQ pain
- +/- Hepatomegaly
Labs for viral hep?6
- Transaminases elevated, usually in thousands w/ ALT > AST
- Hyperbilirubinemia
- Bilrubinuria
- Alkaline phosphatase mildly elevated
- WBC normal to low
- May have prolonged PT
Acute Viral Hepatitis Management
5
- Supportive care***
- Manage symptoms
No other liver toxins:
- Acetaminophen
- Alcohol
- Avoid exposure to other hepatitis viruses