Hepatitis & Cirrhosis Flashcards
Liver Function Tests
Aminotransferases (ALT/AST) Alkaline phosphatase (AP) Gamma glutamyl transpeptidase (GGT) Albumin Prothrombin time (PT) BIlirubin
Types of Autoimmune Hepatitis
Type 1 (Classic) Type 2 (ALK-1)
Who does type 1 autoimmune hepatitis affect?
Women of all ages
Who does type 2 autoimmune hepatitis affect?
Girls & young women
Clinical Manifestations of Autoimmune Hepatitis
Mostly asymptomatic
Advanced cirrhosis
Fulminant hepatitis
Labs for Autoimmune Hepatitis
Serological markers present
Aminotransferases more elevated than bilirubin & AP
Extrahepatic Manifestations of Autoimmune Hepatitis
Hemolytic anemia Thyroiditis Celiac sprue ITP Type I DM UC
Treatment of Autoimmune Hepatitis
Corticosteroids
Azathioprine (2nd line)
Acute Complications of Steroid Therapy
HGN Hyperglycemia Insomnia Psychosis Gastric Irritaiton
Chronic Complications of Steroid Therapy
Osteoporosis PUD Glaucoma Cataracts Immunosuppresion
Define Hemochromatotosis
Gene defect resulting in increased iron absorption in the intestinal tract from the diet
What does hemochromatosis eventually lead to?
Cirrhosis
Cardiomyopathy
DB
Hypogonadism
When do symptoms of hemochromatosis usually occur?
Around age 40
Iron stores reach 15-40 g
Females delayed due to menstruation & breast feeding
Clinical Manifestations of Hemochromatosis are Influenced by What
Age Sex Alcohol use Dietary iron Menstruation & breast feeding
What factors accelerate the process of hemochromatosis?
Alcohol abuse
Hepatitis C
Classic Presentation of Hemochromatosis
Cutaneous hyperpigmentation
DM
Cirrhosis
Reversible Cardiovascular Manifestations of Hemochromatosis
Cardiomyopathy
Vibrio vulnificus
Conduction disturbances
Listeria monocytogenes
Reversible Liver Manifestations of Hemochromatosis
Pastcuerlla psudotubercullosis
Abdominal pain
Elevated LFTs
Hepatomegaly
Reversible Skin Manifestations fo Hemochromatosis
Bronzing
Grayness
Irreversible Liver Manifestations of Hemochromatosis
Cirrhosis
Hepatocellular CA
Irreversible Anterior Pituitary Gland Manifestations of Hemochromatosis
Gonadotropin insufficiency
Irreversible Pancreas Manifestations of Hemochromatosis
DM
Irreversible Thyroid Manifestations of Hemochromatosis
Hypothyroidism
Irreversible Genitalia Manifestations of Hemochromatosis
Primary hypogonadism
Irreversible Joint Manifestations of Hemochromatosis
Psuedogout
Diagnosis of Hemochromatosis
Clinical +
Elevated transferrin
Pathologic
Liver biopsy (gold-standard)
Treatment of Hemochromatosis
Avoid red meat/ iron supplements Avoid ETOH Avoid raw seafood Hepatitis A&B vaccinations Phlebotomy: take off blood
Define Phlebotomy
Removal of 500 mL of blood
Goal of Phlebotomy
Hgb = 10-12 gm/dL
Ferritin
Maintenance Phlebotomy
Every 2-4 months
Define Wilson’s Disease
Organ damage due to copper build up in the liver & brain
Pathogenesis of Wilson’s Disease
Affects the carrier protein of copper
Impairs excretion of copper via bile
Clinical Manifestations of Wilson’s Disease
Varies & non-specific
Liver disease (young children)
Neurologic symptoms
Psychiatric symptoms
Diagnosis of Wilson’s Disease
Ceruoplasmin level
24 hour urine
Kayser-Fleischer rings in eyes
Treatment of Wilson’s Disease
Chelation therapy with D-penicillamine
Three Stages of Alcoholic Liver Disease
Fatty liver (statosis)
Alcoholic hepatitis
Alcoholic fibrosis & cirrhosis
Fatty Liver
Occur within hours of alcohol binge
Tender hepatomegaly
Transaminases mildly elevated
Can occur in obese individuals & pregnancy
Clinical Manifestations of Alcoholic Hepatitis
Anorexia N/V Weight loss Abdominal pain Poor nutritional status Jaundice Fever
Physical Exam Findings in Alcoholic Hepatitis
Spider angiomas Palmar erythema Gynecomastia Parotid enlargement Testicular atrophy Ascites Encephalopathy
Lab Findings in Alcoholic Hepatitis
Leukocytosis Anemia Transaminases elevated Increased alkaline phosphatase Hyperbilirubinemia Hypoalbunemia (severe disease) Coagulopathy (severe disease) Elevated ammonia level (severe disease)
Complications of Alcoholic Liver Disease
Alcoholic fatty liver is reversible Alcoholic hepatitis usually reversible Cirrhosis GI bleed Esophageal varices Gastritis/PUD
Treatment of Alcoholic Liver Disease
Cessation of alcohol
Nutrition
Vitamin B12 & folate supplements
Fluids
R/O other causes for fever, liver disease
Glucocorticosteroids for severe hepatitis
Liver transplant
Factors Influencing Toxicity in Toxic Hepatitis
Excessive intake Excessive cytochrome P450 activity Decrease metabolism pathways to liver Depletion of glutathione stores Concomitant use of ETOH or other drugs Comorbid illness Advancing age Nutritional status
Epidemiology of Drug-Induced Liver Injury (DILI)
Most common cause of liver failure in the US
Level of Injury in DILI
Elevations in liver enzymes Acute hepatitis Cholestasis Cytotoxic or mixed Steatosis Discontinuation of agent
Most common drugs implicated in DILI in the US
Acetaminophen
Antibiotics
Treatment of Acetaminophen Overdose
Acetaminophen level
Activated charcoal
N-acetylcysteine
Greater Risk of Developing Hepatotoxicity in Acetaminophen Intoxication
Ingestion of >7.5-10 g/day
Ingestions of
N-acetylcysteine recommended for
Patients with liver tenderness +
Elevated aminotransferasis +
Acetaminophen concentration >10 mcg/mL
Acetaminophen concentrations toxic by nomogram
Types of Hepatitis
HAV HBV HCV HDV HEV HGV GBV-C
General Presentation of HAV, HBV, HCV, & HEV
Malaise Fatigue Anorexia N/V Myalgias Pale stools Dark urine Jaundice
Physical Exam Findings for Hepatitis
Jaundice
RUQ pain
+/- hepatomegaly
Labs for Hepatitis Diagnosis
Elevated transaminases Hyperbilirubinemia Birirubinuria Alkaline phosphatase mildly elevated WBC normal to low Prolonged PT
Viral Hepatitis Management
Supportive care
Manage symptoms
No acetaminophen,
ETOH, & avoid other hepatitis viruses
Epidemiology of HAV
Worldwide
US decreased due to vaccination
No chronic infection
HAV Routes of Transmission
Fecal-oral route
Close personal contact
Contaminated food/water
Blood exposure
SE of Hepatitis A Vaccination
Fever
Injection site reactions
Rash
Headache
CBC Recommendations for Obtaining Hepatitis A Vaccination
Clotting factor disorders Chronic liver disease Men having sex with men Users of illicit drugs Traveling to endemic countries Anyone wishing to obtain immunity
Postexposure Prophylaxis HAV
Hepatitis A vaccine
IG
Situations for Postexposure Prophylaxis HAV
Close personal contact Sexual contact Sharing IV needles Child care centers Food handler cases Schools, hospitals, other work settings
HBV Modes of Transmission
Sexual contact Perinatal Horizontal Percutaneous Organ transplantation Transfusions
What is the major mode of HBV transmission in developed countries?
Sexual contact
What is the major mode of HBV transmission in underdeveloped countries?
Perinatal
Methods for HBV Transmission via Percutaneous Route
IVDU
Body piercing
Nosocomial
HBV Prevention
Hepatitis B vaccine
Post-exposure Prophylaxis
First dose of vaccine
Administer HBIG
Chronic HBV Infection
Nonspecific symptoms
Exacerbations similar to acute infection
Cirrhosis
Hapatocellular CA
Extrahepatic Manifestations in HBV Infection
Fever Rash Arthralgias, arthritis Polyarteritis nodosa Glomerular disease
Types of HBV Serology
HbsAg HbcAg: Anti-HbsAg HbeAg HBV DNA assays
Hepatitis B Surface Antigen (HbsAg)
Prior to onset of symptoms
Present
Hepatitis B Core Antigen (HbcAg)
Intracellular antigen in affected hepatocytes
Acute infections
Anti-HbsAg
Persists for life
Carriers of HBV
Present after disappearance of HbsAg
Only anti-HbsAg = immunization
Hepatitis B E Antigen (HbeAg)
Secretory protein
HBV replication & infectivity
HBV DNA Assays
Assess HBV replication
Recovery from HBV associated with disappearance of HBV DNA
Monitor chronic HBV
Treatment for Chronic HBV
Interferon
Peginterferon
Define Peginterferon
Modification of interferon so they don’t have to have it as often
Indications for Treatment of HBV
HBeAG +
High serum HBV DNA
Active liver disease
Contraindications for Interferon/Peginterferon
Decompensated cirrhosis
Carriers for HBV
SE of Peginterferon
Flu-like symptoms Immunosuppression Abdominal pain N/V Dry mouth hair loss Blurred vision Depression Anemia
Other Medications for Treating Hepatitis B
Lamivudine (Epivir)
Adefovir (Hepsera)
Entecavir (Baraclude)
Telbivudine (Tyzeka)
Epidemiology of HCV
Most common chronic liver disease
Decreasing in numbers in US
Majority of liver transplants in US
Transmission of HCV
IVDU/sex with IVDU Jail 3+ days Religious scarification Blood transfusion Struck/cut with bloody object Pierced body parts Immunoglobulin injection Perinatal transmission Solid organ transplant
Who should be screened for HCV?
Ever IVDU Clotting factors before 1987 Blood/organs before July 1992 On chronic hemodialysis Evidence of liver disease Infected with HIV Healthcare workers after exposure to HCV + blood/mucus Children born to HCV + mothers
Symptoms of Chronic HCV Infection
Fatigue
Diagnosis fo HCV
HCV rises within 8 days to 8 weeks
Anti-HCV + within 12 weeks
Difficult to distinguish acute vs. chronic
Management of HCV
Assess severity of disease ETOH cessation no Tylenol No jail Vaccinate against Hep A & B
Evaluation for Treatment of HCV
Liver biopsy
Test for HIV
Evaluate for other liver disease
Continued IVDU/ETOH abuse
Treatment for Chronic HCV
Peginterferon
Ribavirin
Protease inhibitors
How to assess for treatment response to HCV
HCV RNA -
Sustained RNA - 6 months after treatment
SE of Peginterferon or Ribavirin
Bone marrow suppression Myalgias Headaches Low grade fever Neuropsychiatric symptoms Non-productive cough/dyspnea Ischemic retinopathy Retinal hemmorrhage Thyroid dysfunction Rash, hair loss, hearing loss, insomnia
Protease Inhibitors
Showing promise
Very spend
Many SE
Liver Transplantation for HCV Patients
New liver can be infected with HCV
Treatment with peg interferon + ribavirin may prolong survival
Younger liver that is already HCV + seems to help
HDV
Requires HBV to replicated (HBsAG coat)
HDV Genotypes & Locations
Genotype 1: western world
Genotype 2: eastern world
Genotype 3: Venezuela, Columbia, Brazil, Peruvian, & Amazon bases
5 others known
Genotype 1 HDV
Increased risk for fulminant course
Progression to cirrhosis rapid
Transmission of HDV
Parenteral
Close personal contact
Multiple transfusions
Contaminated dialysis equipment
Clinical Features of HDV
Co-infection with HBV
Super-infection on top of chronic HBV
Prevention & Treatment of HDV
Hepatitis B vaccine
IVIG for Hep B
Chronic HDV: pegintereron
Epidemiology of HEV
Waterborne virus
No chronic form
HEV Transmission
Fecally contaminated water
Blood transfusion in endemic areas
Mother to newborn
Epidemiology of GBV-C
High incidence in US
Flavivirus
Doesn’t cause hepatitis in humans
Protective effect with co-infections with HIV
Acute Hepatitis Complications
Cholestatis hepatitis
Raging fulminant hepatitis
Chronic hepatitis (Hep B, C, D)
Typical Progression of Chronic Hepatitis
Chronic inflammation in portal areas
Necrosis/inflammation
Fibrosis
Cirrhosis
Define Cirrhosis
Development of fibrosis of liver with formation of regenerative nodules
Results in impairment of synthetic, metabolic, & hemodynamic functions of liver
Diagnostics of Cirrhosis
US
CT
MRI
Biopsy: gold standard
How to determine etiology of cirrhosis?
History
labs
Etiologies of Cirrhosis
Alcohol hepatitis Chronic HCV Cryptogenic Primary biliary cirrhosis (PBC) Chronic HBV Wilson's disease Hemochromatosis Non-alcoholic steatohepatitis
Lab Abnormalities in Cirrhosis
Elevated AST/ALT Slightly elevated alkaline phosphatase Bilirubin elevated Albumin falls PT increases Hyponatremia High levels of ADH Pancytopenia
Why Anemia in Cirrhosis?
Acute/chronic GI bleed Folate deficiency Hypersplenism Bone marrow suppression Anemia of chronic disease
Define Portal HTN
Increased blood pressure in the portal vein due to increased resistance to the blood passing through the vessels in the liver
Portal HTN Results in
Esophageal varices Caput medusa Hemorrhoids Splenomegaly Ascites Palmar Erythema
Management of Portal HTN
Remove ascitic fluid
Portal shunts
Treat liver disease
Liver transplant
Reversible Neuropsychiatric Abnormalities in Hepatitis Encephalopathy
Cognitive abilities
Psychiatric state
Motor impairment
Precipitating Causes of Hepatic Encephalopathy
Cirrhosis Hypovolemia GI bleed Hypokalemia/metabolic alkalosis Hypoxia Sedatives or tranquilizers Hypoglycemia Infection Hepatoma/ vascular occlusion
West Haven Criteria for HE Stage 0
Consciousness: normal
Intellect & behavior: normal
Neurologic: normal
West Haven Criteria for HE Stage 1
Consciousness: mild lack of awareness
Intellect & behavior: shortened attention span
Neurologic: mild asterixis/tumor
West Haven Criteria HE Stage 2
Consciousness: lethargic
Intellect & behavior: disoriented, inappropriate behavior
Neurologic: obvious asterixis, slurred speech
West Haven Criteria HE Stage 3
Consciousness: somnolent but arousable
Intellect & behavior: gross disorientation, bizarre behavior
Neurologic: muscular rigidity, clonus, hyper-reflexia
West Haven Criteria HE Stage 4
Consciousness: coma
Intellect & behavior: coma
Neurologic: decerebrate posturing
Diagnosis of HE
Neurotoxins: ammonia & manganese
CT
MRI
Treatment of HE
Lactulose Correct hypokalemia Determine stage Exclude non-hepatic causes of altered mental function Low protein Rifampin Intubation
SE of Lactulose
Abdominal cramping Bloating Flatulence Severe diarrhea or electrolyte abnormalities Ileus Hypovolemia