9. Viral hepatitis_pharmacotherapy .pptx

pharmacotherapy

1. Viral hepatitis 1

2. Out line 2 Learning objectives Definition Epidemiology Types Clinical presentation treatment

3. Learning objectives 3 At the end of the class you will able to: Describe the epidemiology of viral hepatitis Describe the clinical presentation of viral hepatitis Treatment options of hepatitis B and C viruses Prevention of hepatitis A

4. Definition 4 Viral hepatitis refers to the clinically important hepatotropic viruses responsible for: Hepatitis A (HAV) Hepatitis B (HBV) Delta hepatitis Hepatitis C (HCV) And hepatitis E .

5. Definitions of Acute and Chronic Hepatitis 5 Acute hepatitis: Defined as an illness with a discrete date of onset with jaundice or increased serum aminotransferase concentrations > 2.5 times the ULN is a systemic process and lasts as long as, but not exceeding, 6 months Chronic hepatitis: is an inflammatory condition of the liver that involves ongoing hepatocellular necrosis for 6 months or more beyond the onset of acute illness.

6. Hepatitis A 6 HAV infection primarily occurs through transmission by: the fecal–oral route person-to-person or by ingestion of contaminated food or water. The incidence of HAV correlates directly with: low socioeconomic status poor sanitary conditions and overcrowding . HAV infection usually produces a self-limited disease and acute viral infection with a low case-fatality rate, and confers lifelong immunity .

7. Hepatitis A 7 The disease exhibits three phases: Incubation (averaging 28 days, with a range of 15 to 50 days) Acute hepatitis (generally lasting 2 months) Convalescence . Most patients have full clinical and biochemical recovery within 12 weeks. Nearly all individuals will have clinical resolution within 6 month s of the infection. HAV does not lead to chronic infections .

8. Clinical Presentation of Acute Hepatitis A 8 Signs and symptoms • The preicteric phase brings nonspecific influenza-like symptoms consisting of anorexia, nausea, fatigue, and malaise. • Abrupt onset of anorexia, nausea, vomiting, malaise, fever, headache, and right upper quadrant abdominal pain with acute illness. • Icteric hepatitis is generally accompanied by dark urine, acholic (light-colored) stools, and worsening of systemic symptoms. • Pruritus is often a major complaint of icteric patients.

9. Clinical presentation 9 Physical examination • Icteric sclera, skin, and secretions • Mild weight loss of 2–5 kg • Hepatomegaly Laboratory tests •Positive serum immunoglobulin M anti-hepatitis A virus. •Mild elevations of serum bilirubin, γ -globulin, and hepatic transaminas ( alanine transaminase and aspartate transaminase ) values to about twice normal in acute anicteric disease. •Elevations of alkaline phosphatase, γ - glutamyl transferase , and total bilirubin in patients with cholestatic illness.

10. Hepatitis A 10 The diagnosis of acute HAV infection is: Based on clinical criteria of acute onset of Fatigue Abdominal pain Loss of appetite Intermittent nausea and vomiting Jaundice or elevated serum aminotransferase levels And serologic testing for immunoglobulin (Ig) G anti-HAV.

11. Treatment : AVH 11 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 Chloral hydrate Steroid use is not recommended

12. Prevention 12 The spread of HAV can be best controlled by avoiding exposure . The most important measures to avoid exposure include good hand-washing techniques and good personal hygiene practices . Two inactivated virus vaccines are currently licensed in the United States, Havrix and Vaqta . IG is used when pre- or postexposure prophylaxis against HAV infection is needed.

13. Prevention 13 For people recently exposed to HAV and not previously vaccinated, IG is indicated for: Those in close contact with an hav -infected person All staff and attendees of daycare centers when HAV is documented If involved in a common source exposure (such as a food-borne outbreak) Classroom contacts of an index case patient , and schools , hospitals , and work settings where close personal contact occurred with the case patient. • Common vaccine side effects include soreness and warmth at the injection site , headache , malaise , and pain .

14. Recommendations for HAV 14 All children at 1 year of age In areas without existing hepatitis A vaccination programs, catch-up vaccination of children ages 2–18 years can be considered. Persons traveling to or working in countries that have high or intermediate endemicity of infection . A Men who have sex with men. Illegal-drug users. Persons who have occupational risk for infection (e.g., persons who work with HAV-infected primates or HAV in a research laboratory setting). Persons who have clotting-factor disorders . Persons who have chronic liver disease (e.g., persons with chronic liver disease caused by hepatitis B or C and persons awaiting liver transplants).

15. 15 Hepatitis B

16. Hepatitis B 16 HBV is a leading cause of chronic hepatitis , cirrhosis , and hepatocellular carcinoma . Transmission of HBV occurs sexually, parenterally , and perinatally . Approximately 20% of patients with chronic HBV infection develop complications of decompensated cirrhosis, including hepatic insufficiency and portal hypertension .

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18. 18 Hepatitis B—Serology Hepatitis B Surface Antigen HBsAg Serologic indication of infection Circulates in bloodstream Hepatitis B Surface Antibody Anti-HBs; HBsAb Indicates long-term immunity (e.g. vaccine) or patient recovery Hepatitis B Core Antibody Anti-HBc; HBcAb Antibody against viral core DNA IgM = acute infection IgG = prior infection Hepatitis B E Antigen HBeAg Secretory viral protein Indicates active viral replication, high infectivity Hepatitis B E Antibody Anti-HBe; HBeAb USUALLY indicates low infectivity, recovery, non-replicating state HBV DNA Viral load

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20. Hepatitis B 20 There are three phases of HBV infection. The incubation period for HBV is 4 to 10 weeks during which patients are highly infective. This is followed by a symptomatic phase with intermittent flares of hepatitis and marked increases in aminotransferase serum levels . The final phase is seroconversion to anti-hepatitis B core antigen (anti- HbcAg ).

21. Hepatitis B 21 Patients who continue to have detectable hepatitis B surface antigen ( HbsAg ) and HBcAg and a high serum titer of HBV DNA for more than 6 months have chronic HBV. Clinical manifestations of acute HBV infection are age dependent. Infants infected with HBV are generally asymptomatic, while about 85% to 95% of children aged 1 to 5 years are asymptomatic.

22. Prevention 22 Prophylaxis of HBV can be achieved by vaccination or by passive immunity in post-exposure cases with hepatitis B immunoglobulin . • Two products are available for prevention of hepatitis B infection: Hepatitis B vaccine, which provides active immunity And hepatitis B immuneglobulin ( hbig ), which provides temporary passive immunity . • The goals of immunization against viral hepatitis include prevention of the short-term viremia that can lead to Transmission of infection Clinical disease And chronic HBV infection .

23. Prevention 23 Side effects of the vaccines are soreness at the injection site , headache , fatigue , irritability , and fever .

24. Hepatitis B Immune Globulin 24 HBIg is used only for: Postexposure prophylaxis for HBV for perinatal exposure of infants of HBv -carrier mothers Sexual exposure to HBsAg -positive persons Percutaneous or permucosal exposure to HBsAg -positive blood And exposure of an infant to a caregiver who has acute hepatitis B. •The recommended dose is 0.06 mL/kg administered intramuscularly.

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26. Treatment 26 The key goals of therapy are: To increase the likelihood of immunoclearance of the virus Prevent disease progression to cirrhosis or hepatocellular carcinoma And to minimize further liver injury . Successful therapy is associated with loss of HBcAg status and seroconversion to anti- HBcAg . No specific therapy is available for the management of acute HBV infection. Some patients with chronic HBV infection should be treated.

27. Treatment 27 All chronic HBV infection patients should avoid alcohol and be immunized against HAV . Drug therapy is used to suppress viral replication by immune mediating or antiviral effects. Interferon α 2b (IFN- α 2b ), lamivudine, telbivudine , adefovir , entecavir , Tenofovir and pegylated IFN- α 2a (PEG-IFN) are approved in the United States for first-line treatment of chronic HBV.

28. Treatment 28 Treatment for a minimum of 12 months is associated with greater sustained virologic response rates than treatment for 4 to 6 months. Lamivudine (100 mg daily given orally) may be used alone or in combination with PEG-IFN for chronic HBV.

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31. 31 Hepatitis C

32. Hepatitis C 32 HCV is the most common blood-borne pathogen. Screening for HCV infection is recommended in selected groups who are at high risk for infection. HCV is most often acquired through IV drug use; sexual contact Hemodialysis Household Occupational perinatal exposure.

33. Hepatitis C 33 In the vast majority of patients (up to 85%) acute HCV infection leads to chronic infection defined by persistently detectable HCV RNA for 6 months or more. Patients with acute HCV are often asymptomatic and undiagnosed . One third of adults will experience some mild and nonspecific symptoms, including fatigue, anorexia, weakness, jaundice, abdominal pain, or dark urine.

34. Hepatitis C 34 The most common symptom of chronic HCV infection is persistent fatigue. An estimated 20% of patients with chronic HCV infection will develop cirrhosis and half of those patients will progress to decompensated cirrhosis or hepatocellular carcinoma. The diagnosis of HCV infection is confirmed with a reactive enzyme immunoassay for anti-HCV. Serum transaminase values are elevated within 4 to 12 weeks after exposure.

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39. Treatment 39 Contraindications to treatment include: Autoimmune hepatitis Decompensated liver disease Women who are pregnant or patients whose female partners are pregnant Hemoglobinopathies Creatinine clearance <50 ml/ min Hemodialysis Or ischemic cardiovascular or cerebrovascular disease.

40. Treatment 40 Treatment response is best in patients with HCV genotype 1 and those who take at least 80% of their medications for at least 80% of the treatment time. All patients with chronic HCV infection should be vaccinated for hepatitis A and B. Patients should be advised to maintain good overall health , stop smoking , and avoid alcohol and illicit drugs .

41. Treatment 41 The of treatment for chronic HCV infection is a combination of once-weekly PEG-IFN and a daily oral dose of ribavirin. Sustained virologic response rates are 54% to 56% . Therapy is optimized based on genotype, patient weight, and response to therapy . Common side effects of ribavirin are fatigue, flu-like symptoms, neutropenia, thrombocytopenia, and anemia.

42. Common Side Effects Associated with Peginterferon Therapy (Experienced by >20% of Patients) 42 Fatigue Arthralgia Fever Musculoskeletal pain Headache Insomnia Nausea Depression Anorexia Anxiety/emotional lability Rigors Alopecia Myalgia Injection site reactions

43. Prevention 43 No HCV vaccine is currently available

44. Recommendations for Hepatitis C Virus (HCV) Screening 44 Current or past injection drug use Coinfection with HIV Ever on chronic hemodialysis Patients with unexplained elevated ALT levels or evidence of liver disease Health care and public safety workers after an occupational exposure Children born to HCV-positive mothers Immigrants from countries with a high prevalence of HCV infection

45. 45 Thank you