Hepatitis B
Epidemiology
Etiology
Pathophysiology
Replication cycle of HBV
HBV carries a DNA polymerase with both DNA and RNA-dependent functions, also known as reverse transcriptase (RT).
- After entering the host cell's nucleus, reverse transcriptase completes the positive strand of the virus's partially double-stranded relaxed circular DNA (rcDNA).
- The rcDNA is converted to covalently closed circular DNA (cccDNA) primarily by host enzymes in a process that is not entirely understood.
- The cccDNA is then transcribed into viral mRNA by host RNA polymerase.
- The viral mRNA leaves the nucleus and is translated into HBV core proteins and new reverse transcriptase in the cytoplasm.
- Viral mRNA and reverse transcriptase are packaged into a capsid, where viral mRNA is then reverse-transcribed into viral rcDNA.
- New viral DNA genomes are enveloped and leave the cell as progeny virions.
Clinical features
Outcomes
- Acute hepatitis with complete resolution
- Most common, > 95% in infected adults
- Chronic hepatitis (with or without cirrhosis and the attendant increased risk of hepatocellular carcinoma)
- Fulminant hepatitis with massive liver necrosis.
Diagnostics
- HBsAg: infection or not
- Anti-HBc: acute (IgM) or chronic (IgG); current & history infection vs immunized
- Anti-HBs: window or recovery
- Chronic infection (inactive): HBsAg (+), Anti-HBc (+, IgG), Anti-HBe (+)
- Recovery: conversion from HBsAg (+) to Anti-Hbs (+) in chronic infection, also HBV DNA needs to be undetectable
During the window period, anti-HBc IgM and anti-HBe may be positive. But they don't give a clear picture of current infectiousness because they may indicate previous infection.
Pathology
Active viral hepatitis
Most cases are marked by significant panlobular lymphocytic inflammation (ie, involving the entire lobule), which develops in response to the viral antigens. To control the infection, cytotoxic T cells trigger apoptosis of infected hepatocytes by binding death receptors (eg, Fas) on the plasma membrane and by secreting cytotoxic mediators (eg, perforins, granzymes). As a result, a cascade of caspase enzymes breaks down hepatocyte proteins and DNA, leading to cell shrinkage, chromatin condensation and fragmentation, and budding apoptotic bodies (ie, membrane-bound cellular fragments).
- Eosinophilic single-cell necrosis (Councilman bodies)
- An eosinophilic remnant of apoptotic hepatocytes seen on liver biopsy. Associated with yellow fever and viral hepatitis.
- An eosinophilic remnant of apoptotic hepatocytes seen on liver biopsy. Associated with yellow fever and viral hepatitis.
- Bridging necrosis
Chronic viral hepatitis
- Interface hepatitis (piecemeal necrosis)
- Periportal liver cell necrosis with lymphocytic infiltration
- The cause of interface hepatitis is a CD8 T-cell‑induced hepatocyte apoptosis.
- Indicates chronic active hepatitis and poor prognosis
- Periportal liver cell necrosis with lymphocytic infiltration
- Fibrous septa
- Ground glass hepatocytes (Characteristic for HBV)
- Accumulation of hepatitis B surface antigen within infected hepatocytes. This results in the appearance of a finely granular, homogeneous, pale eosinophilic cytoplasm (ground-glass hepatocytes).
- Pathognomonic for hepatitis B
- Accumulation of hepatitis B surface antigen within infected hepatocytes. This results in the appearance of a finely granular, homogeneous, pale eosinophilic cytoplasm (ground-glass hepatocytes).
Treatment
Prevention
Perinatal Hep B
- Breastfeeding may be started immediately if there are no contraindications (e.g., cracked or bleeding nipples), regardless of whether individuals:
- Have HBsAg positive or unknown status
- Are receiving antiviral therapy
- Infants with HBV infection
- Infants usually immune-tolerant (normal or mildly elevated liver enzymes, no symptoms)
- Because HBV is not cytopathic itself and newborns lack mature cytotoxic T-cells that mediate damage infected hepatocytes, the degree of hepatic tissue damage will be very limited.
- High risk for chronic infection
- High viral load & HBeAg positive
- Infants usually immune-tolerant (normal or mildly elevated liver enzymes, no symptoms)
Hepatitis D
- Pathogen: hepatitis D virus (HDV)
- Comprises an outer lipoprotein envelope made of the hepatitis B surface antigen (HBsAg) for entry into host cells and an inner ribonucleoprotein structure in which the HDV genome resides
- Epidemiology: 5% of all patients with chronic HBV infection carry HDV.