Hepadnaviridae Notes

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Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Hepadnaviridae essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Hepadnaviridae by visiting the associated Learn Page.
NOTES NOTES HEPADNAVIRIDAE MICROBE OVERVIEW ▪ Hepadnaviridae: family of DNA viruses, causes liver disease ▪ Produces DNA polymerase with reverse transcriptase, RNAse activity Replication/multiplication ▪ Reverse transcription (RNA intermediate) Structure ▪ Enveloped ▪ Icosahedral capsid ▪ Partially double stranded, partially single stranded circular DNA COMPLICATIONS ▪ Chronic hepatitis, acute liver failure (fulminant hepatitis), liver cirrhosis, hepatocellular carcinoma (HCC) HEPATITIS B VIRUS osms.it/hepatitis-b-virus PATHOLOGY & CAUSES ▪ Hepatitis B virus (HBV) ▫ DNA virus: can cause acute/chronic liver disease ▫ Member of Hepadnaviridae family (only human pathogenic species) ▪ Target: hepatocytes, zone I (periportal area) ▪ Incubation period: six weeks to six months Antigens ▪ Hepatitis B surface antigen (HBsAg/ Australia antigen) ▫ Key infection marker ▪ Hepatitis B core antigen (HBcAg) ▫ Not detectable in serum; found in liver with acute/chronic hepatitis B ▪ Hepatitis B e antigen (HBeAg) ▫ Secreted by infected cells; indicates active infection, replication Transmission ▪ Perinatal (childbirth), parenteral (e.g. IV drug use, blood transfusions), sexual ▪ HBV survives ≥ seven days in environment Highest prevalence ▪ Parts of sub-Saharan Africa, mainly due to perinatal transmission ▪ Lower prevalence areas have greater association with parenteral, sexual transmission TYPES Acute hepatitis ▪ Liver inflammation for < six months) ▪ HBV penetrates hepatocytes → CD8+ T-lymphocyte activation → cytotoxic killing → hepatocyte apoptosis → liver damage, inflammation ▪ Phases ▫ Early, window (antigens undetectable), recovery OSMOSIS.ORG 417
▪ Acute liver failure progression: < 1% ▪ Chronic hepatitis progression (in adults): < 5% ▪ Acute liver failure ▫ Acute liver injury (severe hepatocyte necrosis), hepatic encephalopathy, coagulopathy ▫ Excessive immune response → massive hepatocyte lysis ▫ Preexisting liver disease absence ▫ Associated with HBV genotype D Chronic hepatitis ▪ HBsAg persistent for > six months ▪ Pathogenesis ▫ HBV penetrates hepatocytes → insufficient CD8+ T-lymphocyte activation → “immune tolerance” → HBV persistence ▪ Progression to HCC ▫ HBV integrates to host DNA → oncogene activation → oncogenesis ▪ Chronicity depends highly on age at time of infection ▫ Younger age, ↑ chronicity risk ▫ Immunosuppressed, elderly people also more susceptible ▪ Phases ▫ Immune tolerant: no liver inflammation/ fibrosis ▫ Immune active: liver damage, inflammation, possible fibrosis ▫ Immune inactive: ↓ inflammation ▫ Reactivation: liver damage, inflammation, possible fibrosis ▫ “Recovery”: occult HBV, HBsAg negative; still infected, disease inactive (best prognosis) RISK FACTORS ▪ IV drug use ▪ Healthcare workers ▫ Frequent contact with blades, needles, body fluids ▪ High-risk sexual behavior ▪ Anal intercourse ▪ Previous HIV/hepatitis C infection 418 OSMOSIS.ORG COMPLICATIONS ▪ HCC, fulminant hepatitis, liver cirrhosis Hepatic encephalopathy ▪ Excessive nitrogen load, electrolyte disturbances → altered neurologic functions in individuals with severe liver disease Hepatorenal syndrome ▪ Portal hypertension → splanchnic vasodilation → ↓ effective circulatory volume → ↑ renin-angiotensin-aldosterone system → renal vasoconstriction → hepatorenal syndrome (liver dysfunction → kidney failure) Bleeding diathesis ▪ Hypocoagulability → ↑ hemorrhage risk SIGNS & SYMPTOMS Acute hepatitis ▪ Can be anicteric (not accompanied by jaundice) with non-specific symptoms (e.g. fever, malaise, nausea, vomiting) ▪ Some progress to icteric hepatitis with hepatomegaly, right upper-quadrant pain, jaundice (30%), dark-colored urine (due to conjugated hyperbilirubinemia), pale stool Chronic hepatitis ▪ Mostly asymptomatic/non-specific symptoms until late disease stages ▪ Exacerbations may present as acute hepatitis ▪ Jaundice, ascites, splenomegaly, encephalopathy (e.g. personality changes, ↓ level of consciousness, intellectual impairment, asterixis) may present ▪ Extrahepatic manifestations (occasionally) ▫ Fever, rash, arthralgia, arthritis, glomerulonephritis DIAGNOSIS LAB RESULTS ▪ HBV DNA detection ▫ Polymerase chain reaction (PCR), in-situ hybridization, Southern hybridization
Chapter 78 Hepadnaviridae Laboratory testing ▪ ↑ alanine aminotransferase (ALT), aspartate aminotransferase (AST) ▫ ALT > AST ▫ Usually ALT in acute hepatitis > 1000 U/L (may be ↓ in chronic hepatitis) ▫ ALT levels take longer than AST to return to normal ▪ ↑ ALT for > six months indicates chronicity ▪ ↑ alpha-fetoprotein (AFP) in HCC ▪ Liver fibrosis ▫ ↓ leukocytes, platelets ▫ AST/ALT > 1 (normal ≈ 0,8) ▫ ↑ total bilirubin ▫ ↓ serum albumin ▫ Delayed prothrombin time, ↑ international normalized ratio (INR) Serologic marker detection through enzyme immunoassay ▪ Hepatitis B surface antigen (HBsAg) ▫ Indicates infection (acute/chronic) ▪ Hepatitis B surface antibodies (Anti-HBs) ▫ Provides HBV infection immunity appears after vaccination/resolved acute hepatitis ▪ IgM antibodies against hepatitis B core antigen (IgM anti-HBc) ▫ Acute infection/chronic hepatitis reactivation phase ▪ IgG antibodies against hepatitis B core antigen (IgG anti-HBc) ▫ Non-specific antibody; may be ↑ during acute, resolved, chronic hepatitis ▪ Hepatitis B e antigen ▫ Active replication, high infectivity ▪ Hepatitis B e antibodies ▫ Low replication, infectivity Liver biopsy ▪ Acute hepatitis ▫ Mononuclear infiltrate ▫ Pericentral inflammation, necrosis ▫ Eosinophilic hepatocytes ▪ Chronic hepatitis ▫ Fibrosis ▫ Nodule formation ▫ Mononuclear portal infiltrate ▫ Some hepatocytes have uniformly dull cytoplasm due to endoplasmic reticulum swelling (“ground glass” hepatocytes) OSMOSIS.ORG 419
Figure 78.1 Ground glass hepatocytes seen in the liver of an individual with hepatitis B infection. TREATMENT MEDICATIONS ▪ Antiviral monotherapy ▫ Severe acute hepatitis, pre-existing liver disease, concomitant hepatitis C/D infection, immunocompromised, elderly Acute hepatitis ▪ Post-exposure prophylaxis ▫ HBV vaccine and immunoglobulin Chronic hepatitis ▪ Combination therapy (e.g. lamivudine, interferon) 420 OSMOSIS.ORG 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 (longterm protection) SURGERY ▪ Acute liver failure ▫ Consider liver transplantation OTHER INTERVENTIONS ▪ Acute liver failure ▫ Fluid resuscitation, early nutritional support, antiviral therapy (nucleoside/ nucleotide analogues) Acute hepatitis ▪ Supportive treatment (e.g. fluid therapy, nutrition)
Chapter 78 Hepadnaviridae HEPATITIS D VIRUS osms.it/hepatitis-d-virus PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Hepatitis D virus (HDV/delta virus): incomplete RNA virus; contributes to acute liver failure development, chronic hepatitis exacerbation in people coinfected/ previously infected with HBV ▪ HDV not member of Hepadnaviridae family ▪ HDV infection inhibits HBV replication due to HBV, HDAg interaction during viral replication ▫ Coinfected individuals: HDV predominant ▫ ↑ inflammatory response (compared to HBV alone) ▫ Poor response to existing HBV treatment ▪ Incubation period ▫ 6–24 weeks Coinfection ▪ Biphasic course with acute hepatitis symptoms Structure ▪ Outer envelope made of HBsAg, inner HDV RNA, delta antigen (HDAg) LAB RESULTS Transmission ▪ Parenteral, sexual, perinatal (very rare) Satellite virus ▪ Can only infect if host also infected with HBV ▫ Coinfection: simultaneous infection ▫ Superinfection: HDV infection after established HBV infection; more severe RISK FACTORS ▪ IV drug use, high-risk sexual behavior, HBV presence Acute liver failure ▪ Systemic symptoms ▫ E.g. fever, malaise, nausea, vomiting) ▫ Hepatomegaly, right upper quadrant pain; sometimes jaundice, dark colored urine, pale stool ▪ Hepatic encephalopathy ▫ Personality changes, ↓ level of consciousness, intellectual impairment, asterixis DIAGNOSIS ▪ Serologic marker detection ▫ IgM/IgG anti-HDV ▪ PCR assays ▫ HDV RNA detection TREATMENT MEDICATIONS ▪ Pegylated interferon alpha ▪ Prevention ▫ HBV vaccine SURGERY ▪ Consider liver transplantation for chronic hepatitis D, acute liver failure OSMOSIS.ORG 421

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Hepadnaviridae essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Hepadnaviridae by visiting the associated Learn Page.