Diagnosis, Management, and

Treatment of Hepatitis C

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.

Testing

• The optimal methods of detecting HCV infection are to screen populations for history of risk

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

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

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

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

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

Laboratory Testing

– Qualitative 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

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

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

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

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

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

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

• biopsy is not mandatory in order to initiate therapy

• A liver biopsy may be obtained to provide information on prognosis

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

treatment

• early virologic response (EVR).– 2-log drop or loss of HCV RNA 12 weeks into

therapy

treatment

• Interferon– alfa-2a 3 mU SQ t.i.w.– alfa-2b 3 mU SQ t.i.w.

• 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

treatment

• 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

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

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

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

Diagnosis and Treatment of HCV-Infected Children

• A review of the use of interferon as monotherapy in children demonstrates a SVR of 33-45 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

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

Diagnosis and Treatment of HCV-Infected Children

• Side effects were surprisingly uncommon. – There may be an adverse on weight.

– 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

• A liquid formulation of ribavirin has recently been approved for children.

• Capsules should never be opened in order to access their contents

• 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.

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.

Adverse Events

• Ribavirin– hemolytic anemia– Fatigue– Itching– Rash– Sinusitis– Birth defects– gout

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

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

Prevention

• breastfeeding.

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.

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.

• sexual transmission

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

Thank you