NOTES

NOTES
HEPADNAVIRIDAE

MICROBE OVERVIEW
▪ Hepadnaviridae: family of DNA viruses, ▪ Icosahedral capsid
causes liver disease ▪ Partially double stranded, partially single
▪ Produces DNA polymerase with reverse stranded circular DNA
transcriptase, RNAse activity

Replication/multiplication COMPLICATIONS
▪ Reverse transcription (RNA intermediate) ▪ Chronic hepatitis, acute liver failure
(fulminant hepatitis), liver cirrhosis,
Structure hepatocellular carcinoma (HCC)
▪ Enveloped

HEPATITIS B VIRUS
osms.it/hepatitis-b-virus
Transmission
PATHOLOGY & CAUSES ▪ Perinatal (childbirth), parenteral (e.g. IV
drug use, blood transfusions), sexual
▪ Hepatitis B virus (HBV)
▪ HBV survives ≥ seven days in environment
▫ DNA virus: can cause acute/chronic liver
disease Highest prevalence
▫ Member of Hepadnaviridae family (only ▪ Parts of sub-Saharan Africa, mainly due to
human pathogenic species) perinatal transmission
▪ Target: hepatocytes, zone I (periportal area) ▪ Lower prevalence areas have greater
▪ Incubation period: six weeks to six months association with parenteral, sexual
transmission
Antigens
▪ Hepatitis B surface antigen (HBsAg/
Australia antigen)
TYPES
▫ Key infection marker Acute hepatitis
▪ Hepatitis B core antigen (HBcAg) ▪ Liver inflammation for < six months)
▫ Not detectable in serum; found in liver ▪ HBV penetrates hepatocytes → CD8+
with acute/chronic hepatitis B T-lymphocyte activation → cytotoxic killing
▪ Hepatitis B e antigen (HBeAg) → hepatocyte apoptosis → liver damage,
▫ Secreted by infected cells; indicates inflammation
active infection, replication ▪ Phases
▫ Early, window (antigens undetectable),
recovery

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 ▪ Acute liver failure progression: < 1% COMPLICATIONS
▪ Chronic hepatitis progression (in adults): ▪ HCC, fulminant hepatitis, liver cirrhosis
< 5%
Hepatic encephalopathy
▪ Acute liver failure
▪ Excessive nitrogen load, electrolyte
▫ Acute liver injury (severe hepatocyte
disturbances → altered neurologic
necrosis), hepatic encephalopathy,
functions in individuals with severe liver
coagulopathy
disease
▫ Excessive immune response → massive
hepatocyte lysis Hepatorenal syndrome
▫ Preexisting liver disease absence ▪ Portal hypertension → splanchnic
▫ Associated with HBV genotype D vasodilation → ↓ effective circulatory
volume → ↑ renin-angiotensin-aldosterone
Chronic hepatitis system → renal vasoconstriction →
▪ HBsAg persistent for > six months hepatorenal syndrome (liver dysfunction →
▪ Pathogenesis kidney failure)
▫ HBV penetrates hepatocytes →
Bleeding diathesis
insufficient CD8+ T-lymphocyte
activation → “immune tolerance” → ▪ Hypocoagulability → ↑ hemorrhage risk
HBV persistence
▪ Progression to HCC
SIGNS & SYMPTOMS
▫ HBV integrates to host DNA →
oncogene activation → oncogenesis Acute hepatitis
▪ Chronicity depends highly on age at time of ▪ Can be anicteric (not accompanied by
infection jaundice) with non-specific symptoms (e.g.
▫ Younger age, ↑ chronicity risk fever, malaise, nausea, vomiting)
▫ Immunosuppressed, elderly people also ▪ Some progress to icteric hepatitis with
more susceptible hepatomegaly, right upper-quadrant pain,
▪ Phases jaundice (30%), dark-colored urine (due to
▫ Immune tolerant: no liver inflammation/ conjugated hyperbilirubinemia), pale stool
fibrosis
Chronic hepatitis
▫ Immune active: liver damage,
inflammation, possible fibrosis ▪ Mostly asymptomatic/non-specific
symptoms until late disease stages
▫ Immune inactive: ↓ inflammation
▪ Exacerbations may present as acute
▫ Reactivation: liver damage,
hepatitis
inflammation, possible fibrosis
▪ Jaundice, ascites, splenomegaly,
▫ “Recovery”: occult HBV, HBsAg
encephalopathy (e.g. personality changes,
negative; still infected, disease inactive
↓ level of consciousness, intellectual
(best prognosis)
impairment, asterixis) may present
▪ Extrahepatic manifestations (occasionally)
RISK FACTORS ▫ Fever, rash, arthralgia, arthritis,
▪ IV drug use glomerulonephritis
▪ Healthcare workers
▫ Frequent contact with blades, needles,
body fluids DIAGNOSIS
▪ High-risk sexual behavior
LAB RESULTS
▪ Anal intercourse
▪ HBV DNA detection
▪ Previous HIV/hepatitis C infection
▫ Polymerase chain reaction (PCR), in-situ
hybridization, Southern hybridization

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Laboratory testing ▪ IgM antibodies against hepatitis B core

▪ ↑ alanine aminotransferase (ALT), aspartate antigen (IgM anti-HBc)
aminotransferase (AST) ▫ Acute infection/chronic hepatitis
▫ ALT > AST reactivation phase
▫ Usually ALT in acute hepatitis > 1000 ▪ IgG antibodies against hepatitis B core
U/L (may be ↓ in chronic hepatitis) antigen (IgG anti-HBc)
▫ ALT levels take longer than AST to ▫ Non-specific antibody; may be ↑ during
return to normal acute, resolved, chronic hepatitis
▪ ↑ ALT for > six months indicates chronicity ▪ Hepatitis B e antigen
▪ ↑ alpha-fetoprotein (AFP) in HCC ▫ Active replication, high infectivity
▪ Liver fibrosis ▪ Hepatitis B e antibodies
▫ ↓ leukocytes, platelets ▫ Low replication, infectivity
▫ AST/ALT > 1 (normal ≈ 0,8) Liver biopsy
▫ ↑ total bilirubin ▪ Acute hepatitis
▫ ↓ serum albumin ▫ Mononuclear infiltrate
▫ Delayed prothrombin time, ↑ ▫ Pericentral inflammation, necrosis
international normalized ratio (INR)
▫ Eosinophilic hepatocytes
Serologic marker detection through en- ▪ Chronic hepatitis
zyme immunoassay ▫ Fibrosis
▪ Hepatitis B surface antigen (HBsAg) ▫ Nodule formation
▫ Indicates infection (acute/chronic) ▫ Mononuclear portal infiltrate
▪ Hepatitis B surface antibodies (Anti-HBs) ▫ Some hepatocytes have uniformly dull
▫ Provides HBV infection immunity cytoplasm due to endoplasmic reticulum
appears after vaccination/resolved acute swelling (“ground glass” hepatocytes)
hepatitis

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 Prevention
▪ HBV vaccine
▪ Recombinant type most commonly used
▫ HBsAg inserted in yeast cells
▪ HBsAg → development of anti-HBsAg →
HBV infection immunity
▪ Intramuscular administration
▪ Three doses for coverage (very effective)
▪ Administration regime: 0, 1–2 months,
6–12 months
▫ Infant immunization: first dose at birth
▫ Does not require booster dose (long-
term protection)
Figure 78.1 Ground glass hepatocytes seen
in the liver of an individual with hepatitis B
infection. SURGERY
▪ Acute liver failure
▫ Consider liver transplantation
TREATMENT
OTHER INTERVENTIONS
MEDICATIONS ▪ Acute liver failure
▪ Antiviral monotherapy ▫ Fluid resuscitation, early nutritional
▫ Severe acute hepatitis, pre-existing support, antiviral therapy (nucleoside/
liver disease, concomitant hepatitis C/D nucleotide analogues)
infection, immunocompromised, elderly
Acute hepatitis
Acute hepatitis ▪ Supportive treatment (e.g. fluid therapy,
▪ Post-exposure prophylaxis nutrition)
▫ HBV vaccine and immunoglobulin

Chronic hepatitis
▪ Combination therapy (e.g. lamivudine,
interferon)

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HEPATITIS D VIRUS
osms.it/hepatitis-d-virus

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

▪ Hepatitis D virus (HDV/delta virus): Coinfection
incomplete RNA virus; contributes to ▪ Biphasic course with acute hepatitis
acute liver failure development, chronic symptoms
hepatitis exacerbation in people coinfected/
previously infected with HBV Acute liver failure
▪ HDV not member of Hepadnaviridae family ▪ Systemic symptoms
▪ HDV infection inhibits HBV replication ▫ E.g. fever, malaise, nausea, vomiting)
due to HBV, HDAg interaction during viral ▫ Hepatomegaly, right upper quadrant
replication pain; sometimes jaundice, dark colored
▫ Coinfected individuals: HDV urine, pale stool
predominant ▪ Hepatic encephalopathy
▫ ↑ inflammatory response (compared to ▫ Personality changes, ↓ level of
HBV alone) consciousness, intellectual impairment,
▫ Poor response to existing HBV asterixis
treatment
▪ Incubation period
▫ 6–24 weeks
DIAGNOSIS
Structure LAB RESULTS
▪ Outer envelope made of HBsAg, inner HDV ▪ Serologic marker detection
RNA, delta antigen (HDAg) ▫ IgM/IgG anti-HDV
▪ PCR assays
Transmission
▫ HDV RNA detection
▪ Parenteral, sexual, perinatal (very rare)

Satellite virus
▪ Can only infect if host also infected with
TREATMENT
HBV
MEDICATIONS
▫ Coinfection: simultaneous infection
▪ Pegylated interferon alpha
▫ Superinfection: HDV infection after
▪ Prevention
established HBV infection; more severe
▫ HBV vaccine

RISK FACTORS
▪ IV drug use, high-risk sexual behavior, HBV
SURGERY
presence ▪ Consider liver transplantation for chronic
hepatitis D, acute liver failure

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