Hepatitis B and hepatocellular carcinoma

Hepatitis B and hepatocellular carcinoma

Hepatitis B and hepatocellular carcinoma

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Hepatitis B Virus - The Cancer Culprit

  • Primary Mechanism: Chronic inflammation from persistent HBV infection is the main driver of hepatocellular carcinoma (HCC).
  • Viral Integration: HBV DNA integrates into the host genome, leading to genomic instability and activation of proto-oncogenes (e.g., MYC) or inactivation of tumor suppressors (e.g., p53).
  • Key Viral Protein: HBx protein is a major contributor. It disrupts cell cycle control, inhibits apoptosis, and modulates signaling pathways.

HBV and HCC Pathogenesis

High-Yield: The HBx protein is a transcriptional coactivator that interferes with the p53 tumor suppressor protein, crippling the cell's primary defense against malignant transformation.

Pathogenesis - From Hepatitis to Cancer

  • Chronic inflammation from persistent HBV infection is the primary driver, leading to continuous liver regeneration and cirrhosis, a major risk factor.
  • HBV DNA Integration:
    • Viral DNA integrates into the host genome, causing genomic instability.
    • Leads to insertional mutagenesis, activating proto-oncogenes or inactivating tumor suppressor genes like p53.
  • Role of Viral Proteins:
    • The HBx protein is the main oncogenic factor.
    • It disrupts cell cycle regulation, inhibits apoptosis, and activates pro-growth signaling pathways (e.g., Wnt, NF-κB).
  • Oxidative Stress:
    • Chronic inflammation and HBx activity generate reactive oxygen species (ROS), causing DNA damage.

⭐ Unlike Hepatitis C, HBV can cause hepatocellular carcinoma even in the absence of cirrhosis, primarily due to its direct oncogenic effects via DNA integration and HBx protein.

Clinical & Serology - Spotting the Enemy

  • Presentation: Often asymptomatic for decades. Late signs mirror cirrhosis or liver failure: jaundice, ascites, hepatomegaly, RUQ pain.
  • Progression Risk: ↑ with chronic infection, co-infection (HCV, HIV), alcohol, aflatoxin B1 exposure.

HBV and HCC Development Pathways

MarkerInterpretation
HBsAgActive Infection (Acute/Chronic)
Anti-HBsImmunity (Vaccination or Recovery)
Anti-HBc IgMAcute Infection (Window Period)
Anti-HBc IgGPast or Chronic Infection
HBeAgHigh Infectivity & Replication
Anti-HBeLow Infectivity

Prevention & Management - Guarding the Liver

  • Primary Prevention: Universal HBV vaccination series is key. Screen pregnant women & blood products.
  • Chronic HBV Management: Antiviral therapy (e.g., Tenofovir, Entecavir) to suppress HBV DNA replication & reduce liver inflammation.
  • HCC Surveillance: For patients with cirrhosis or high-risk features, perform liver ultrasound (US) every 6 months, with or without alpha-fetoprotein (AFP).

⭐ Antiviral therapy significantly ↓ HCC risk, but does not eliminate it. Surveillance must continue even in patients with undetectable HBV DNA.

High‑Yield Points - ⚡ Biggest Takeaways

  • Hepatitis B (HBV), a DNA hepadnavirus, is a major cause of hepatocellular carcinoma (HCC) worldwide.
  • Primary mechanism: Integration of viral DNA into the host genome, leading to genomic instability.
  • The viral HBx protein is a key oncoprotein that disrupts cell cycle regulation by inhibiting p53.
  • Chronic inflammation from persistent infection is a major driver of carcinogenesis, typically through cirrhosis.
  • Prevention with the HBV vaccine is the most effective measure against HBV-induced HCC.

Practice Questions: Hepatitis B and hepatocellular carcinoma

Test your understanding with these related questions

A 29-year-old man comes to the physician for a routine health maintenance examination. He feels well. He works as a nurse at a local hospital in the city. Three days ago, he had a needlestick injury from a patient whose serology is positive for hepatitis B. He completed the 3-dose regimen of the hepatitis B vaccine 2 years ago. His other immunizations are up-to-date. He appears healthy. Physical examination shows no abnormalities. He is concerned about his risk of being infected with hepatitis B following his needlestick injury. Serum studies show negative results for hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis C antibody. Which of the following is the most appropriate next step in management?

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Flashcards: Hepatitis B and hepatocellular carcinoma

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Where is EBV latent?_____

TAP TO REVEAL ANSWER

Where is EBV latent?_____

B cells

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