Updated: 4/2/2020

Hepatitis B Virus

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  • A 35-year-old presents to the emergency department due to abdominal pain and malaise. He also reports "yellow-ing" of his skin. Medical history is noncontributory. Social history is notable for intravenous drug use and having multiple sexual partners. Physical examination is remarkable for right upper quadrant tenderness, generalized jaundice, and scleral icterus. Laboratory studies demonstrate the presence of HBsAg and significantly elevated IgM anti-HBc, and HBeAg.
  • Classification
    • a Hepadnavirus in the Hepadnaviridae family
      • circular, partially double-stranded DNA virus 
  • Epidemiology
    • risk factors
      • not receiving hepatitis B virus (HBV) vaccine
      • sexual contact with a person with HBV
      • illicit drug use
      • having HIV and hepatitis C virus
  • Transmission 
    • perinatal transmission
    • blood transfusion
    • transplant
    • sexual contact
    • blood exposure
  • Pathogenesis
    • once the HBV is in the bloodstream, it makes its way to the liver, where it replicates within hepatocytes, causing immune-mediated hepatitis via CD8+ T-cells and natural killer cells
    • when HBV is inside the hepatocyte, the viral genome enters the hepatocyte nucleus
      • the positive strand of the HBV DNA is synthesized and is converted to covalently closed, circular DNA (cccDNA) 
        • the HBV genome undergoes reverse transcription, creating a pre-genomic RNA, which becomes encapsidated
          • a new negative and subsequent positive strand of the HBV DNA is eventually synthesized
            • the partially double-stranded HBV DNA nucleocapsid can enter more hepatocytes to produce more cccDNA
  • Prognosis
    • most immunocompetent adult patients spontaneously recover 
    • most neonates progress to chronic infection
    • worse prognosis with coinfection with hepatitis D or hepatitis C infection
  • Symptoms
    • acute hepatitis
      • anorexia
      • nausea
      • right upper quadrant pain
    • chronic hepatitis
      • many are asymptomatic
      • fatigue
  • Physical exam
    • acute hepatitis
      • jaundice and scleral icterus
        • typically resolves in 1-3 months
    • chronic hepatitis
      • normal
      • may have stigmata of chronic liver disease
        • e.g., spider angiomata, ascites, and asterixis
      • extrahepatic manifestations
        • polyarteritis nodosa
        • membranous nephropathy (leading to nephrotic range proteinuria)
          • and less commonly, membranoproliferative glomerulonephropathy
        • aplastic anemia
  • Serologic studies 
    • HBsAg
      • indicates that there is an HBV infection
    • anti-HBs
      • indicates immunity to HBV infection via
        • prior infection
        • vaccination
    • HBcAg
      • an antigen associated with the core of the HBV
    • anti-HBc
      • IgM antibodies against HBc suggests an acute or recent infection
      • IgG antibodies against HBc suggest a previous exposure or chronic infection
      • during the window period, may be the only positive serologic test suggesting infection
    • HBeAg 
      • infected hepatocytes secrete this antigen, suggesting active replication, thus having high transmissibility 
    • anti-HBe
      • suggest low transmissibility
  • Hepatitis A infection
    • differentiating factor
      • presence of anti-hepatitis A antibodies in serological testing
  • Hepatitis C infection
    • differentiating factor
      • presence of anti-hepatitis C antibodies in serological testing
  • Medical
    • vaccination
      • indication
        • as a preventative measure against HBV infection 
          • all neonates
          • all unvaccinated infants, children, and adolescents
          • all unvaccinated adults with an increased risk of contracting the infection
            • healthcare personnel
            • a sexually-active person with multiple sexual partners
            • end-stage renal disease
            • HIV infection
            • chronic liver disease
    • tenofovir or entecavir
      • indication
        • monotherapy for acute HBV infection in patients with fulminant infection or severe acute hepatitis (e.g., increased INR)
        • monotherapy for chronic HBV infection with immune-active chronic hepatitis
          • HBeAg-positive
          • HBeAg-negative with elevated viral DNA levels and a transaminitis
        • patients with hepatocellular carcinoma
      • comments
        • acute HBV infection is usually symptomatically treated as most cases self-resolve
  • Superinfection with hepatitis D virus
  • Acute fulminant hepatic failure
  • Cirrhosis
  • Hepatocellular carcinoma

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Questions (6)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2

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Topic COMMENTS (21)
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