Hepatitis B

(Hepatology 2007;45:507-39. Clin Gastroenterol Hepatol. 2006;4:936-62; Hepatology. 2004;39:1-5)

DEFINITION:

A hepatotrophic virus; the liver is the primary site of infection, replication and cellular damage
Chronic hepatitis: presence of clinical, biochemical, and serologic abnormalities for up to 6 months

EPIDEMIOLOGY:

350 million cases worldwide; 1.25 million in US; most cases in Asia and Africa; causes 30% of acute and 15% of chronic hepatitis in the US
10th leading cause of death in the world, 5th leading infectious disease cause of death in the world
Chronicity of HBV acquired during infancy: 90%; acquired during adulthood: 5%
- In general, when a patient gets acute HBV: 95% recovery, 5% chronically infected, Fulminant hepatic failure (very rare)

ETIOLOGIES:

Transmission: sexual (most common), percutaneous, perinatal
- Household/intimate contacts need to be vaccinated since they are at most risk
Incubation: 1-6 months
Pregnant women/Vertical Transmission/Breastfeeding: Lamivudine for treatment; prophylaxis is available; See also Liver- Pregnancy Pearls (Chapter 4.25)
- Hep B: Transmission 1st Trimester (10%), 3rd Trimester (90%); All women tested in 3rd trimester
  - Test mother for HBsAg, if +, Protect baby after delivery with HBIG (0.5 ml) and Vaccine (0.5 ml at birth and 1 & 6 months)
  - Test mother for HBsAg, If −, Baby should only get full dose of Hep B Vaccine (not HBIG) at delivery
  - Hep B Vaccine is safe in pregnant patients

PATHOPHYSIOLOGY:

Virus: DNA, circular gene shape, envelope, 42 nm in size; Replicates at 10¹¹ virions/day
8 genotypes identified: A-H; The future may tell us that certain genotypes are better treated with either Nucleosides analogues or PEG-INF
Spilled blood contaminated with HBV can be infectious for up to one week (i.e. DNA viruses resist degradation)

CLINICAL MANIFESTATIONS/PHYSICAL EXAM:

Natural History: anorexia, nausea, vomiting, fatigue, abdominal pain, mild fever, jaundice, dark urine, light colored stools
- Acute: 70% subclinical, 30% jaundice, <1% fulminant hepatitis (100 cases/year)
- Chronic: <5% (adult-acquired), >90% (perinatally-acquired); females are more likely to be chronic carriers
Extra-hepatic: Polyarteritis Nodosa (<1%), Membranoproliferative Glomerulonephritis

LABORATORY STUDIES:

Transaminitis (↑ ALT/AST); See also Liver- LFTs (Chapter 4.20)
Serologic & Virologic:

Surface: “Far & Away” (i.e. Ag & Ab separated by window)
- -HBsAg: appears before symptoms; used to screen blood donor; Neg = viral clearance
- -anti-HBs: indicates resolution of acute disease & immunity (sole marker after vaccination)
Core: “In the middle” (i.e. Ab in the window)
- -HBcAg not found in blood tests
- -IgM anti-HBc: first Ab to appear; indicates acute infection
  
  Window Period = HBsAg become −, anti-HBs not yet +, anti-HBc only clue to infection
  
  Therefore, workup for suspected acute symptomatic HBV is HBsAg & IgM anti-HBc
- -IgG anti-HBc: indicates previous (HBsAg−) or chronic (HBsAg+) HBV infection ‘Total core tests’ are both IgM and IgG and most labs use this as a screening; be careful!
Reprinted with permission from Sabatine S: Pocket Medicine 2nd ed. Baltimore: Lippincott Williams & Wilkins, 2004:3-16.

E Particles: “Together” (i.e. Ag & Ab overlap)
- -HBeAg: by product (evidence) of viral replication and defines ↑ infectivity/acute infection
  
  Precore Variant: eAg not generated with +DNA, but anti-HBe can develop due to cross-reactivity with cAg
  
  If HBeAg +, then HBV DNA must be +; If HBeAg −, then either Precore Variant (VL >100K), or Inactive Carrier (VL <100K)
- -anti-HBe: indicates waning viral replication, ↓ infectivity/replication
DNA:
- HBV DNA: presence in serum correlates with active viral replication in liver; Use hybridization, not PCR (too sensitive)

DIAGNOSTIC STUDIES:

Biopsy: degree of inflammation (grade) & amount of fibrosis (stage); no other test makes this determination accurately
- Stages (Fibrosis): 1. portal fibrosis, 2. periportal fibrosis, 3. septal fibrosis, 4. cirrhosis
- Grade (Inflammation): 1. minimal lobular, 2. mild portal, 3. moderate piecemeal necrosis, 4. severe portal with piecemeal necrosis

	Surface:		Core:	E Particles:
	HBsAg	anti-HBs	anti-HBc	HBeAg	anti-HBe	DNA/ALT/Course of Action:
-Acute hepatitis:	+	−	IgM	+	−	+ DNA, Observe, resolution likely 90% to 95% of adults
-Window period:	−	−	IgM	±	±	+DNA
-Recovery (prior exposure):	−	^a	IgG	−	±	−DNA (protected from further infection)
-Immunization:	−	^a	−	−	−	−DNA (protected from further infection)
-Chronic (Replicative EAg+):	+	−	IgG	+	−	+ DNA, ↑ ALT: EAg+/Wild Type, Initiate tx w/goal » Inactive Carrier
Chronic (Immune Tolerant):	+	−	IgG	+	−	+ DNA, nl ALT: Immune Tolerant, <5% respond to IFN, better with NA
Chronic (Non-Replicative):	+	−	IgG	−	+	− or ↓ DNA, nl ALT: Chronic Inactive Carrier, Observe
Chronic (Precore Variant):	+	−	IgG	−	±	+ DNA, ↑ ALT: EAg-/Precore Variant, Initiate tx (likely lifelong)
-Isolated Core:	−	−	IgG	−	+	No significance, unless transplant patient^*
^aNotice only options with + anti-HBs ^*Represents past infection with immunity, but loss anti-HBs; if transplanted, 50/50 chance the recipient will get HBV