L10 Viral Hepatitis

Objectives

1. Understand viral hepatitis and the different types

2. Know the prevalence and risk factors

3. Understand the pathophysiology and transmission pathways of different hepatitis viruses

4. Know the clinical course and manifestations of Hep A, B, C

5. Distinguish vaccine candidates based on risk factors and serology results

Hep A = HAV

Hep B = HBV

Hep C = HCV

Notes

1. What is Viral Hepatitis

   • system pathogens that target the liver → hepatic infection and inflammation → Hep A-E (mainly A-C)

2. Hep B and C are major contributors to what

   • End Stage Liver Disease (ESLD)

3. What are the different, varying factors of Viral Hepatitis?

   • Transmission

   • Incubation

   • Hepatotoxicity

   • Prevention and Treatment

4. What are the criteria of ACUTE viral hepatitis

   • Discrete onset date

   • typically < 6 months

   • Jaundice

   • AST/ALT liver enzymes > 2.5 x ULN

5. What are the criteria of CHRONIC viral hepatitis

   • Inflammatory condition → Biologic/Virologic/Histologic changes

   • > 6 months

   • HBV, HCV, HDV risk factors

6. Distinguish main route of transmissions between Hep A-C

   • Fecal-Oral

     • A

   • Blood to Blood and Bodily Fluids

     • B and C

7. What type(s) of viral hepatitis have vaccines available for treatment

   • A and B

8. T/F: Those infected with Hep A will not experience reinfection

   • True, obtain life long immunity

9. What type does not have a cure?

   • B, can be self-limiting and have life-long immunity but some may result in a chronic infection and require life-long treatment

10. What treatment/cure is used for Hep C?

    • no vaccine/immunoglobulin, antiviral treatment for 6-12 weeks

11. Which types are able to result in chronic infection

    • B and C

12. Which of the following viral infections has the highest prevalence in the US?

    • C

13. Which viral infection carries the highest risk for occupational transmission to healthcare workers?

    • B

14. T/F: Hep A has only been seen in humans

    • True

15. What type of virus is HAV

    • RNA virus

16. Explain the duration of infected stool of a person with Hep A

    • 2-3 weeks prior to symptoms’ onset and 1 week after

17. What are the risk factors of Hep A

    • household or sexual contact

    • endemic regions

    • daycares

    • homelessness — no clean water

    • IV drug users (Parenteral)

    • Men who have sex with men (MSM)

    • HBV/HCV infection

18. Explain the pathophysiology of Hep A (HAV)

    1. Virus ingestion, absorption, and uptake by liver

    2. Viral replication in hepatocytes

    3. New viral particles → bloodstream (viremia) → infect other hepatocytes or fecal excretion

    4. Viremia (infected blood) within 1-2 weeks of exposure → viral shedding in feces

    5. Asymptomatic but highly transmissible

    6. Incubation period ~28 days but range 15-50

    7. Immune response → Hepatocellular injury, Signs and Symptoms occur ~ 2 months

    8. Viral Clearance

19. T/F: Hep A is generally a self limiting disease and rarely has complications/fatalities

    • True

20. What are the 2 different phases in Hep A Clinical Presentation

    • Prodromal and Icteric Phases

21. What is the Prodromal Phase

    • Non-specific viral syndrome with abrupt onset

    • ~ days to > 1 week

    • Sx: fever, fatigue, anorexia, nausea weakness, headache, +/- abdominal pain

22. What is the Icteric Phase

    • begins 10-14 days after Prodromal Phase

    • 1-4 weeks

    • Hepatitis specific Sx

      • Jaundice, Scleral Icterus, Dark Urine

23. T/F: Liver biopsy is the main diagnostic test for HAV

    • False, self limiting and doesn’t result in a chronic disease

24. Why is Serology testing the main diagnostic test for HAV

    • the body forms abs against HAV (IgM and IgG)

      • IgM specifically is used for diagnosing Active/Acute

      

25. Explain the lifespan of IgM in HAV

    • occurs early in symptomatic phase

    • declines over the months

26. Explain the lifespan of IgG in HAV

    • occurs late in disease

    • persists for life

27. What is IgG presence able to indicate?

    • Evidence of past exposure and current protection

      • ex. seen in vaccinated individuals to indicate protection

28. T/F: HAV Vaccines are only given to adults who have not been vaccinated to travel to endemic countries

    • False, vaccine preventable disease that is recommended for children between 1-2 years old

29. T/F: HAV has Prophylaxis (action taken to prevent disease)

    • True

    • Pre-Exposure Prophylaxis (PrEP)

      • primarily vaccine for international travelers

    • Post-Exposure Prophylaxis (PEP)

      • Immunoglobulin for unvaccinated or immune compromised that were exposed to HAV

30. Why is Heb B still a worldwide health problem?

    • Outside the US, they do not have access to the vaccine treatment

31. 2% of HBV infections → Acute and can lead to what?

    • Fulminant Hepatitis

      • rare but severe form of liver failure that rapidly progresses (60-90% mortality)

      

32. 5-10% of HBV will develop into what?

    • Chronic Hep B (CHB)

      

33. HBV Nomenclature

    

    • surface abs = HbsAb

    • core abs = HBcAb

34. HBV Serology results

    

35. When is Chronic Hep B (CHB) most commonly occurs?

    • Perinatal (around birth)

      • Infections in older children become chronic only around 30% of the time

36. T/F: CHB cannot be cleared

    • False, 90-95% will spontaneously clear the infection and develop lifelong immunity

37. Where geographically is found to account for 75% of CHB?

    • Southeast Asia

38. What type of virus is HBV

    • DNA Virus

39. List HBV Risk Factors

    • Parenteral (IV Drug — needles/syringes)

    • Birth from an infected mother

    • Multi-transfused patient before 1972

    • Needle sticks/sharp instrument exposures for healthcare workers

    • MSM

    • Contact with blood or open sores of infection

    • Sharing razors/toothbrushes/etc

40. T/F: HBV is Cytopathic (infection directly kills cells)

    • False, damage from immune system’s inability to clear the virus

      • Poor cytotoxic T-cell response to viral antigens → persistent inflammation → CHB, Cirrhosis, Hepatocellular Carcinoma

41. Why does HBV persists in the body

    1. Slow liver blood supply → T-cells’ overexposure to HBV antigens → Desensitization → HBV persistence

    2. Long-term (decades) HBV infection weakens T-cell antiviral potential

42. What treatments can be used for HBV

    • Therapeutic Vaccines, Prophylaxis, and Immunomodulators

      • more effective in younger patients with less impacted T-cell functions

43. HBV Lifecycle (don’t memorize ?)

    1. HBV → Hepatocytes

    2. HBV DNA Polymerase → covalently closed circular DNA (cccDNA) in Nucleus

    3. Host provides RNA template → viral DNA production

    4. Viral proteins synthesis (HBsAg, HbcAg, HbeAg)

    5. Viral replication → Matured Virions → Blood

44. What is the Clinical Presentation for Acute HBV

    • Asymptomatic but can have non-specific viral syndrome

    • Fever, fatigue, weakness, anorexia, nausea, myalgias +/- abdominal pain and hepatomegaly

45. What is Immune Tolerance

    • Virus present but the body is not reacting

      • associated with Remission phase where symptoms lessened or not present

46. What is the Immune Active Phase

    • When the body is attack the infection

47. What is the Clinical Presentation of Chronic HBV

    • Periods of remission followed by recurring flares of hepatitis, often still asymptomatic

      • immune cells responding to HBV replication and destroying hepatocytes

48. What is happening during flares even though the patient may be asymptomatic

    • progressive liver damage → scarring, fibrosis → Cirrhosis

49. How long can it take for Chronic HBV symptoms to appear

    • 30 years → similar to acute sympt and advanced liver disease

50. T/F: HBV is more prevalent in the US then HVC

    • False

51. What is HCV a leading cause and indicator (respectively) for?

    • Chronic Liver Disease and Liver Transplant

52. What type of virus is HCV

    • Single stranded RNA

      • 6 major genotypes

53. Why does HCV have frequent viral mutations

    • Lacks proofreading polymerase

54. Why does HCV persist in the body

    • inadequate humoral and cellular response

55. What is a result of HCV having a serum half-life of 2-3 hours

    • fast viral replication

56. What are the Risk Factors of HCV

    • Parenteral

    • sex with infected partner

    • perinatal

    • sharps (healthcare workers, unsterile tattoos)

    • blood/open sores

57. What are the clinical presentation of Acute HCV

    • asymptomatic

    • non-specific

      • flu-like, weight loss

58. What are the clinical presentations of Chronic HCV

    • remission periods but less than HBV

    • viral RNA > 6 months

    • chronic liver inflammation

    • asymp

    • Cirrhosis ~ 30 yrs

59. 15-25% of acute HCV result in what

    • HVC RNA Clearance

60. 75-85% of Acute HCV result in what

    • Chronic infection

      • 50-75% → Extrahepatic Diseases

      • 10-20% → Cirrhosis over 20 years → Hepatocellular carcinoma (14%) or Decompensated Cirrhosis (50% 5 year survival rate)

    

61. Chronic HCV persists for decades in who

    • untreated patients

62. HC V Life Cycle (don’t memorize)

    • Virus enters cell → RNA release → ER → Translate and Produce Polyprotein → protein cleavage via Protease Enzymes → RNA Replication via Polymerase → Viral Assembly, Budding, and Release

63. What are used from serologies/tests for diagnosing HCV

    • IgG

      • detectable within 2 months

      • past/current exposure

      • persists for years

    • HCV RNA

      • detectable within 2 weeks of infection

64. Review

65. What population has the highest risk for HCV

    • IV drug users