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Comprehensive Guide to Viral Hepatitis: Causes, Symptoms, Treatment

Learn about the different types of Viral Hepatitis, their causes, clinical manifestations, diagnostic studies, treatments, and control measures. Discover the importance of vaccines and immunotherapy in preventing and managing this liver inflammation.

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Comprehensive Guide to Viral Hepatitis: Causes, Symptoms, Treatment

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  1. Viral Hepatitis Therapeutics

  2. Hepatitis- Description • Inflammation of the liver • Acute viral hepatitis • Most common cause • Viral infection accounts > 1/2 cases of acute hepatitis • Types of Infectious Viral Hepatitis: • A • B • C • D • E • G

  3. Hepatitis- Description • Other possible causes • Drugs (alcohol) • Chemicals • Autoimmune liver disease • Metabolic diseases • Viruses

  4. Epidemiology of Viral Hepatitis • HAV is the most common cause of acute hepatitis • HCV is the most common cause of chronic hepatitis. • See Table 1

  5. Clinical Manifestations 1-Preicteric phase • Precedes jaundice • Lasts from 1 to 21 days • Period of maximal infectivity for hepatitis A • Anorexia • Nausea • Abdominal discomfort • Right upper quadrant

  6. Clinical Manifestations -Preicteric phase • Vomiting • Constipation • Diarrhea • Malaise • Headache • Low-grade fever • Arthralgias • Skin rashes

  7. Clinical Manifestations 2-Icteric phase • Lasts 2 to 4 weeks • Characterized by jaundice • Pruritus 3-Posticteric phase • Begins as jaundice is disappearing • Lasts weeks to months • Malaise • Easy fatigability

  8. Complications • Most patients with acute viral hepatitis recover completely with no complications • Overall mortality rate < 1% • Fulminant hepatic failure FHF • Chronic hepatitis • Cirrhosis • Hepatocellular carcinoma HCC

  9. Diagnostic Studies • Transaminases (ALT, AST) • Alkaline phosphatase • Serum proteins • Serum bilirubin • Urinary bilirubin • Prothrombin time • Biopsy • Physical assessment • Splenomegaly • Palpable liver • Serology

  10. Treatment • No specific treatment or therapy for acute viral hepatitis • Most patients can be managed at home • Drug Therapy • No specific drug therapies • Supportive therapy • antiemetics • diphenhydramine (Benadryl) • chloral hydrate

  11. Hepatitis A (HAV) • “Infectious Hepatitis” • Picornavirus family (RNA)-cytopathic • More common in developing countries • Travelers • Frequently occurs in small outbreaks

  12. Clinical Features of HAV • Fecal-oral (food, water) route of transmission • Found in feces 2 or more weeks before the onset of symptoms and up to 1 week after the onset of jaundice • Present in the blood only briefly • 2-4 weeks incubation

  13. Clinical Manifestations of HAV • Acute onset • Mild flu-like manifestations • More severe & higher mortality in adult > children • Typical cases→several weeks of malaise, anorexia, nausea, vomiting, and ↑ ALT/AST • Jaundice develops in more severe cases. • no carrier state • Fulminant hepatic failure rare (0.14% fatal) but almost exclusively in >50 y.o. age group

  14. Diagnosis of hepatitis A • Anti-HAV immunoglobulin M (IgM) • Appears in the serum as the stool becomes negative for the virus • Detection of IgM anti-HAV indicates acute hepatitis • disappears several months after the initial infection • Anti-HAV immunoglobulin G (IgG) • IgG anti-HAV is an indicator of past infection • Presence of IgG antibody provides lifelong immunity

  15. Treatment of acute of HAV Infection • Treatment is supportive • no antiviral therapy available. • Hospitalization for patients with nausea and vomiting →dehydration. • Patients with acute liver failure require close monitoring to ensure they do not develop FHF

  16. Control of Hepatitis A-Vaccine Active Immunity • Two-dose vaccine (HAVRIX or VAQTA) -adults every 6-12 months -peds=3 doses (0,1,6-12mo.) Especially For • International travelers to endemic regions. • Where endemicity rates are high (high-risk sexual activity, IV drug abusers, developmentally challenged, daycare employees, lab workers, handlers of primates, any patient with chronic liver disease)

  17. Hepatitis A Vaccine Combination vaccine-A+B (Twinex) • Typical administration involves 3 injections of 1 mL IM on a 0-, 1-, and 6-month schedule. • FDA approved for use in adults only

  18. Control of Hepatitis A- IG Passive immunotherapy with IgG 1-Pre-exposure • 0.02 mL/kg IM for individuals who anticipate spending < 3 months in an endemic region. • 0.06 mL/kg IM every 4-6 months if they are planning to spend > 3 months in a region where HAV is endemic

  19. Control of Hepatitis A- IG Passive immunotherapy with IgG 2-Post-exposure • 0.02 mL/kg, given IM as a single dose.

  20. Hepatitis B • “Serum Hepatitis” • DNA- Virus • Incubation period = 45-180 days • Higher risk of developing HCC

  21. Transmission of HBV • Perinatal • Sexual • Parenteral

  22. High Risk Groups For HBV • Adolescents. • Residents / staff of homes for devel. challenged • Hemodialysis patients • Factor conc. recipients • Household members/ sex partners of HBV carriers • Travelers (> 6 mo., endemic, close with locals) • Travelers (short-term if med. setting) • IVDA • Prisoners

  23. Clinical Manifestations • Insidious onset • Symptoms more severe • Fewer GI symptoms • the clinical illness associated with acute HBV infection may range from mild to severe (<1% FHF). • After acute hepatitis resolves • 95% of adult & 5-10% of infants develop anti-HBV antibody, clear HBsAg and HBV virions, and fully recover. • 5% of adult and 90-95% of infants develop chronic infection.

  24. Inactive Carrier State • 70-90% of HBsAg carriers → inactive carrier state • Have no symptoms, WNL LFTs, and normal or minimally abnormal liver biopsy results. • Evidence of HBV replication nonexistent or minimal,(serum HBV DNA of 0-30,000 copies/ml) • Remain infectious to others through parenteral or sexual transmission. • Ultimately develop HBsAb and clear the virus. • Some develop chronic hepatitis • Remain at low risk for HCC. • no effective antiviral therapies are available

  25. Chronic Hepatitis • 10-30% of HBsAg carriers develop chronic hepatitis. • Often symptomatic. most commonly with Fatigue • May occasionally experience acute flare of disease, similar to acute hepatitis. • May have extrahepatic manifestations, including polyarteritis nodosa, cryoglobulinemia, and glomerulonephritis. • Have abnormal LFTs, evidence for active HBV replication, and inflammatory or fibrotic activity on liver biopsy. • May be considered either HBeAg-positive or HBeAg-negative. • Approximately 20% develop cirrhosis or HCC.

  26. Diagnosis of acute HBV infection HBsAg • The 1st serum marker • Represents presence of HBV virions in the blood. • does not indicate whether the infection is acute or chronic. • may remain detectable for life • Individuals with + HBsAg → carriers of HBV • Inactive carriers • chronic hepatitis. • +HBeAg and HBV DNA →a state of active viral replication and a high level of infectivity.

  27. Diagnosis of acute HBV infection Anti-HBc (HBcAb). • The 1st antibody to appear • Initially, IgM → diagnostic for acute infection. • later, IgM disappears → IgG anti-HBc appears and indicates a patient has been infected with HBV • Remain + in patients who recover and in persistent infection

  28. Diagnosis of acute HBV infection Anti-HBs • believed to offer immunity to future exposures to HBV. • may persist for the life of the patient. HBeAg a marker of viral replication disappears when viral replication slows& anti-HBe is detected. Anti-HBe may persist for years

  29. Control of HBV -Vaccine 1-Pre-exposure Vaccination • Infants/children, at anterolateral thighs • 2-3 doses • Form 11-20 y.o. at 2,4,6 months • from Birth, at 1-2, 6-18 months • Adults, at Deltoid (3 doses) • 0,1,6 months (or 0,2,12 months) • use high dose vaccine in immunosupp., dialysis, severe liver disease • boost when level < 10mIU/mL on annual testing

  30. Markers after vaccination for HBV • > 90% of recipients develop protective anti-HBs. • Vaccine recipients are not positive for anti-HBc unless previously infected with HBV.

  31. Control of HBV -Vaccine 2-Post-Exposure HBV Prophylaxis • Risk of acquisition • 20-66% from needle-stick injury • 90% mother → child • HBV vaccine series + HBIG 0.06 ml/kg • May not need HBIG to prevent perinatal transmission (only vaccine) if mother is HBeAg –ve.

  32. Control of HBV -IG Hepatitis B Immune Globulin • Hepatitis B immune globulin (HBIG) derived from plasma. • Provides passive immunization for individuals with recent exposure to a patient infected with HBV. • Also administered following liver transplantation to persons infected with HBV to prevent HBV-induced damage to the liver allograft.

  33. Treatment of Chronic HBV • When to Treat? Candidates for antiviral therapy must have evidence of active HBV infection • HBV DNA > 105 copies/mL in patients who are positive for HBeAg • HBV DNA > 104 copies/mL in patients who are negative for HBeAg • Seropositive for HBsAg > 6mo • Increased AST/ALT

  34. Treatment of Chronic HBV • Goal of antiviral treatment inhibition of viral replication→ loss of HBeAg and HBV DNA • Secondary goals • reduce symptoms • prevent or delay the progression of chronic hepatitis to cirrhosis or HCC. • Antiviral therapy infrequently leads to viral eradication • No antiviral therapy is available for inactive carriers who do not have actively replicating virus.

  35. Treatment response criteria

  36. Predictors of Response

  37. Treatment of Chronic HBV Interferon alfa • INF have antiviral and immunomodulatory effects. • ↑ ALT is common 8-12 weeks after starting therapy → INF-induced activation of the cell-mediated immune system. • Loss of HBeAg and HBV DNA occurs in 37% of patients. • INF is most effective when • administered shortly after exposure • when it is used in patients with an ALT > 100 U/L who do not have a markedly elevated level of HBV DNA.

  38. Treatment of Chronic HBV Interferon is less effective in patients with (1) lifelong HBV infection, (2) a low ALT level (ie, <100 U/L), (3) a high HBV DNA level, (4) end-stage renal disease, (5) HIV infection, (6) a need for immunosuppressive therapy

  39. Treatment of Chronic HBV Adverse Effects of INF • Common but lead to discontinuation of the drug in only 5-10% of patients. • Flu like symptoms (fatigue, fever, headache, myalgia, arthralgia), • Neuropsychiatric symptoms (depression, irritability, somnolence), • Hematological effects (granulocytopenia, thrombocytopenia), • Miscellaneous effects (pain at injection site, dyspepsia, alopecia, thyroid function abnormalities).

  40. Treatment of Chronic HBV 1-INF Alpha- (2b) Monotherapy • Adults: 5mU qd or 10 mU 3/w x 4-8 months • Children: 6mU/sq.m. BSA 3/w x 4-8 months • Pegylated INF alfa may also be used once per week by S/c. • Don’t use if decompensated liver dis. • If doesn’t respond to course of IFN alone : • retreat,? IFN+ riba , IFN+ lami, IFN +adef, lami alone , adef alone

  41. 2-Lamivudine for Chronic HB • Lamivudine is a synthetic nucleoside analogue inhibits DNA polymerase–associated reverse transcriptase and can suppress HBV replication. • Treatment with 100 mg/d po for 1 year → loss of HBsAg in 32% of patients. • Histological improvement and a statistically significant ↓ in the rate of development of hepatic fibrosis.

  42. Treatment of Chronic HBV Advantages of Lamivudine for Chronic HB • Ease of use and low risk of ADR • Effective in non-responders to INF (high HBV DNA levels). • Successful in decompensated cirrhosis and recurrent hepatitis B after liver transplantation. Disadvantages • 24% of patients who initially responded develop resistance within 1st year of therapy. • Incidence ↑ to 69% after 5 years of therapy. • Due to development of a mutation in the HBV DNA polymerase gene. • Resistance may also lead to a reversion of improvements seen on liver biopsy specimens

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