Infections

• Acute viral hepatitis


  Lasts less than 6 months
• Chronic viral hepatitis


  Lasts more than 6 months
• Acute viral hepatitis typically presents with

  fatigue,

  malaise,

  nausea,

  vomiting,

  anorexia,

  low-grade fever,

  jaundice,

  dark urine,

  and RUQ tenderness
• Chronic viral hepatitis can be asymptomatic or present with non-specific symptoms like malaise and fatigue
• Histopathology of viral hepatitis


  • Hepatocyte injury and ballooning degeneration
  • Hepatocyte death and necrosis with replacement by scar tissue (bridging necrosis)
  • Pan-lobular mononuclear infiltration
• Laboratory findings in viral hepatitis

  Increased serum AST and ALT, with ALT higher than AST

  Exception: In advanced fibrosis/cirrhosis, AST becomes higher than ALT
• Hepatitis E virus (HEV)


  RNA virus, transmitted by fecal-oral route

  Acute, self-limiting disease, can cause fulminant hepatitis in pregnancy

  HEV antigen/RNA early, anti-HEV IgM during symptoms, anti-HEV IgG late
• HBV transmission routes


  • Parenteral (blood, needlesticks, dialysis, transfusions)

  Sexual

  Perinatal
• HBV serological markers


  HBsAg: Active infection

  Anti-HBs: Recovery or immunity

  HBeAg: Active viral replication, high infectivity

  Anti-HBe: Low infectivity

  Anti-HBc IgM: Recent infection

  Anti-HBc IgG: Past/chronic infection
• Interferon alpha is used to treat chronic hepatitis B infection
• Histopathology of chronic hepatitis B


  • Ground glass appearance of hepatocytes due to HBV proteins
• Liver damage in chronic hepatitis B is mediated by cytotoxic T cells, not the virus itself
• Extrahepatic manifestations of HBV

  • Hematologic (aplastic anemia)
  • Renal (membranous, MPGN)
  • Vascular (polyarteritis nodosa)
• Hepatitis B vaccine is a subunit vaccine containing HBsAg
• Hepatitis B infection phases

  1. Incubation period

  2. Appearance of HBsAg

  3. Appearance of HBeAg and viral DNA

  4. Appearance of IgM anti-HBc

  5. Disappearance of HBeAg

  6. Appearance of anti-HBe

  7. Disappearance of HBsAg

  8. Appearance of anti-HBs
• Window period


  Period of infection without detectable HBsAg and anti-HBs
• During acute hepatitis B, liver enzymes especially ALT are elevated
• If HBsAg persists after 6 months, it indicates chronic hepatitis B infection
• Serological markers in different hepatitis B infection stages

  • Acute infection: HBsAg, IgM anti-HBc
  • Window period: Anti-HBe, IgM anti-HBc
  • Chronic infectious: HBsAg, HBeAg, IgG anti-HBc
  • Chronic non-infectious: HBsAg, IgG anti-HBc
  • Recovery: Anti-HBs, Anti-HBe, IgG anti-HBc
• Hepatitis D virus 


  Single-stranded RNA virus that requires HBsAg to infect hepatocytes
• HDV infection


  • Can occur as co-infection with HBV or super-infection in chronic HBV carrier
  • Associated with worse prognosis and increased risk of cirrhosis
• Vaccination against hepatitis B also protects against hepatitis D
• Hepatitis C virus (HCV)


  Enveloped, single-stranded RNA virus that lacks 3'-5' exonuclease activity, leading to high genetic variability
• HCV has 6 or more genotypes and multiple sub-genotypes due to genetic mutations
• HCV transmission


  • Mainly parenteral, also sexually and perinatally
  • Long incubation period of 2 weeks to 6 months
• Acute HCV infection type


  Can be asymptomatic or mild hepatitis, but more commonly causes chronic infection
• Extrahepatic manifestations of HCV

  • Hematologic (cryoglobulinemia, ITP, autoimmune hemolytic anemia, NHL)
  • Renal (MPGN, membranous GN)
  • Vascular (leukocytoclastic vasculitis)
  • Dermatologic (porphyria cutanea tarda, lichen planus)
  • Endocrine (diabetes, autoimmune hypothyroidism)
• HCV screening


  Anti-HCV antibody test is the best screening test, HCV RNA is the gold standard
• Chronic HCV infection


  Anti-HCV positive, HCV RNA positive, persistently elevated liver enzymes
• Histopathology of HCV


  Lymphoid aggregates, focal macrovesicular steatosis
• HCV treatment medications


  • NS5A inhibitors (ledipasvir, daclatasvir)
  • NS5B inhibitors (sofosbuvir, dasabuvir)
  • NS3/4A inhibitors (simeprevir, grazoprevir)
  • Ribavirin
• HCV treatment

  • No monotherapy approved, combination therapy required
  • Interferon alpha can also be used
• Viral hepatitis is inflammation of the liver parenchyma, most commonly caused by hepatitis viruses A, B, C, D, and E
• Routes of transmission for hepatitis viruses

  • Fecal-oral: HAV, HEV
  • Parenteral, sexual, perinatal: HBV, HCV, HDV
• Hepatitis A virus (HAV)

  RNA picornavirus with short incubation period, causes acute hepatitis with good prognosis
• Hepatitis B virus (incubation T + common presentations)

  DNA hepadnavirus with long incubation period (1-6 months), can cause acute hepatitis, chronic hepatitis, cirrhosis, or fulminant hepatitis
• Hepatitis C virus (HCV) {Taxonomy + Incubation}


  RNA flavivirus with long incubation period, commonly causes chronic hepatitis that can progress to cirrhosis or HCC
• Hepatitis D virus 


  RNA delta virus that requires HBsAg to infect, can cause co-infection or super-infection in chronic HBV, associated with worse prognosis
• Hepatitis E virus {Class + Incubation T + complications (2)}


  RNA hepeviridae with short incubation period, causes self-limiting acute hepatitis, but can cause fulminant hepatitis in pregnant women
• Measles (Who is affected?)


  One of the most contagious infectious diseases and remains a leading cause of death particularly among young children especially in areas with low rates of vaccination