1. Diagnosis, Management, and Treatment of Hepatitis C

2. Background
The hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease.
HCVis the leading cause of death from liver disease in the United States.

3. Testing
The optimal methods of detecting HCV infection are to screen populations for history of risk

4. Persons for Whom HCV Testing Is Recommended
Persons who have injected illicit drugs in the recent and remote past
Persons with conditions associated with a high prevalence of HCV infection
Persons with HIV infection
– Persons with hemophilia who received clotting factor concentrates before1987
– Persons who were ever on hemodialysis
– Persons with unexplained abnormal aminotransferase levels

5. Persons for Whom HCV Testing Is Recommended
Prior recipients of transfusions or organ transplants
Persons received blood from a donor who later tested positive for HCV infection
–transfusion of blood or blood products before July1992
–organ transplant before July 1992

6. Persons for Whom HCV Testing Is Recommended
Children born to HCV-infected mothers
Health care, emergency medical and public safety workers after a needle stick injury or mucosal exposure to HCV-positive blood
Current sexual partners of HCV-infected persons

7. Laboratory Testing anti-HCV 8 week
a negative anti-HCV does not exclude HCV infection in patients with
suspected liver disease.
acute HCV infection
immunosuppressed states.
HIV infection
chronic hemodialysis

8. Laboratory Testing HCV ribonucleic acid document viremia.
quantitative assays
The level of HCV RNA in blood helps in predicting the likelihood of response to treatment, and the change in the level of HCV RNA during treatment can be used to monitor response.
the same quantitative test should be used to avoid confusion
Not as sensitive

9. Laboratory Testing Qualitative assay recombinant immunoblot assay
Sensitive
primary test or to confirm a positive HCV antibody result
recombinant immunoblot assay
limited usefulness in clinical practice
may establish the cause of a positive anti-HCV immunoassay in a person with undetectable HCV RNA

10. Laboratory Testing
A positive immunoblot result followed by two or more instances in which HCV RNA cannot be detected using a licensed, qualitative assay suggest that HCV infection has resolved and no further HCV testing is indicated

11. Laboratory Testing HCV Genotyping There are 6 major HCV genotypes.
Genotype does not predict the outcome of infection
predict the likelihood of treatment response
determines the duration of treatment.
Current commercial tests fail to identify the genotype in a small proportion (3%) of HCV-positive persons

12. Liver Biopsy
The role of liver biopsy in the management of patients with chronic hepatitis C is currently being debated.
treatment effectiveness
potential risks of the procedure
concern of sampling error.
procedure may not be necessary as a prelude to treatment

13. Liver Biopsy degree of fibrosis
treatment is generally advised if the liver biopsy displays a Metavir score of 2 or an Ishak score of 3

14. Liver Biopsy
weighing the risks, benefits and costs of existing HCV treatments and of liver biopsy, most experienced clinicians routinely obtain a liver biopsy in patients with HCV genotype-1 infection to guide recommendations for treatment

15. Liver Biopsy
Patients infected with HCV genotypes 2 and 3 have a high likelihood of response
An interval of 4 to 5 years between biopsies may be needed to measure change

16. biopsy is not mandatory in order to initiate therapy
A liver biopsy may be obtained to provide information on prognosis

17. treatment
55% to 85% of persons who develop acute hepatitis C will remain HCV infected.
5% to 20% are reported to develop cirrhosis over periods of approximately 20 to 25 years
Infection is considered eradicated when there is a sustained virologic response (SVR)
the absence of HCV RNA in serum by a sensitive test at the end of treatment and 6 months later

18. treatment early virologic response (EVR).
2-log drop or loss of HCV RNA 12 weeks into therapy

19. treatment
Interferon
alfa-2a 3 mU SQ t.i.w.
alfa-2b 3 mU SQ t.i.w.

20. treatment
Peginterferon alfa-2a (40 kd) 180 micg SQ once weekly regardless of weight
Peginterferon alfa-2b (12 kd) 1.5 micg/kg SQ once weekly
Ribavirin 800–1200 mg PO daily (in 2 divided doses), dose depending on infection, genotype, and patient weight

22. Efficacy and Predictors of Response
SVR can be predicted
Pretreatment patient characteristics
EVR
genotype
Strongest predictor of response
Pretreatment HCV RNA levels
younger ages,
absence of bridging fibrosis and cirrhosis.
Race

28. Retreatment of Failed Previous Treatment
Retreatment with peginterferon plus ribavirin should be considered for nonresponders or relapsers who have significant fibrosis or cirrhosis and who have undergone previous regimens of treatment using nonpegylated interferon

29. Diagnosis and Treatment of HCV-Infected Children
The seroprevalence is 0.2% for children under 12 years of age and 0.4% for those 12 to 19 years of age
Children are less likely to have symptoms,
spontaneous viral clearance,
normal or near-normal aminotransferase values
they also have a slower rate of advancement to end-stage liver disease

30. Diagnosis and Treatment of HCV-Infected Children
Data show that the characteristic histological lesions of HCV occur with the same frequency in children as in adults
As in adults, the biggest challenge is identifying appropriate candidates for therapy

31. Diagnosis and Treatment of HCV-Infected Children
A review of the use of interferon as monotherapy in children demonstrates a SVR of percent.
This is significantly better than the SVR for adults.
When the data is further scrutinized, the SVR for genotype 1 is 26% and 70% for other genotypes

32. Diagnosis and Treatment of HCV-Infected Children
The higher response rate observed in children might be the result of
the earlier stage of the disease,
higher relative interferon dosage,
lack of comorbid conditions.
artifact due to small study size

33. Diagnosis and Treatment of HCV-Infected Children
Side effects were surprisingly uncommon.
There may be an adverse on weight.

34. There have been a few studies that utilized combination therapy to treat children.
In one study, children aged 5 to 11 were treated with 3 mU/m2 of standard interferon three times a week and either 8, 12, or 15mg/kg body weight of ribavirin daily.

35. A 15mg/kg dose of ribavirin was associated with the highest SVR and comparable side effects when compared with lower-dose ribavirin
Increased SVR and fewer adverse events in children as compared with adults
The FDA has approved the use of Rebetron for the treatment of hepatitis C in children 3 to 17 years old

36. A liquid formulation of ribavirin has recently been approved for children.
Capsules should never be opened in order to access their contents

37. The use of pegylated interferon therapy in children has not been published.
Preliminary studies in children suggest safety and efficacy in a recently completed phase 1 trial.

38. A randomized controlled trial of combination therapy of pegylated interferon with and without ribavirin is funded by the NIH (Peds- C Clinical Trial) and is currently in progress.

39. Adverse Events interferon alfa Neutropenia hrombocytopenia, Depression
Hypothyroidism and hyperthyroidism
Irritability
Concentration and memory disturbances
visual disturbances
fatigue, muscle aches
Headaches
nausea and vomiting,
skin irritation, low-grade fever, weight loss, insomnia,hearing loss, tinnitus, interstitial fibrosis and hair thinning.

40. Adverse Events Ribavirin hemolytic anemia Fatigue Itching Rash
Sinusitis
Birth defects
gout

41. superimposition of hepatitis A virus infection in persons with chronic liver disease, particularly those with hepatitis C, has been associated with fulminant hepatitis

42. Prevention reducing transmission to the newborn
the risk of HCV transmission at the time of delivery is 1% to 5%
the prevalence of HCV infection among women of childbearing age is 1.2%
No fetal scalp monitors
delivery within 6 hours of rupture of membranes
c/s delivery
Post-exposure immune globulin does not prevent infection

43. Prevention
breastfeeding.

44. Prevention horizontal transmission of HCV from child to child is rare
The American Academy of Pediatrics does not recommend restricting school attendance or participation in routine activities, including contact sports.

45. Prevention
● HCV-infected persons should be counseled to avoid sharing toothbrushes and dental or shaving equipment and be cautioned to cover any bleeding wound in order to keep their blood away from others
● Persons should be counseled to stop using illicit drugs.

46. sexual transmission
● HCV-infected persons should be advised to not donate blood, body organs, other tissues, or semen

49. Thank you