HCV

Hepatitis C Dr. AlipourChronic hepatitis C virus (HCV) infection is one of the most common chronic liver disease and accounts for 8000 to 13,000 deaths each year.

The majority of liver transplants performed in the United States are for chronic HCV. The CDC estimates that the number of new cases of acute HCV infection in the United States was 230,000 per year in the 1980s to its current level of about 19,000 cases per year

The overall incidence in 2006 was estimated to be 0.3 per 100,000 The decline relates primarily to reduced infections in injection drug users Transfusion-associated hepatitis has had little impact on the recent change in the incidence of HCV infectionDespite the overall decline in HCV, infection rates among young adults may be increasing between 2002 and 2009 among age 15 to 24 years .Intravenous drug useBlood transfusion Sex with an intravenous drug user Having been in jail more than three daysReligious scarificationHaving been struck or cut with a bloody objectPierced ears or body partsImmunoglobulin injection

Transmission routesIllicit drug use Blood transfusion Hospitalization Organ transplantation Sexual or household contact Perinatal transmission Hemodialysis Other Transmission routes

Natural history of HCV WHO SHOULD BE TESTED(AASLD)

IVDA in the recent and remote past, including those who injected only once Those with conditions associated with a high prevalence of HCV including: patients with HIV infection hemophilia who received clotting factor concentrates before 1987hemodialysis ptsand those with unexplained abnormal aminotransferase levels

Screening and diagnosis Prior recipients of transfusions or organ transplants before July 1992Children born to HCV-infected mothersHealthcare, emergency and public safety workers after a needle stick injury or mucosal exposure to HCV-positive bloodCurrent sexual partners of HCV-infected persons

Screening assays designed to detect antibody anti-HCV with high sensitivity(EIA)

Supplemental assays designed to help identify false positive screening test(RIBA and HCV RNA)

EIA

HCV RNA RIBA

HIV patientsDialysis patientsOrgan transplantationIn those with unexplained liver disease whose anti-HCV test is negative

HCV RNA for screening?HCV RNA assays:QualitativeTMA method lower limit 10 IU/mlAmplicor method lower limit 50 IU/mlQuantitative

Quantitative assays are used before treatment to measure baseline HCV viral load and during treatment to assess on-treatment response. Pts with a low pretest probability of infection:

Pts without risk factors for HCV who have a positive EIA-2 (such as blood donors) require confirmatory testing, particularly if they have no biochemical evidence of chronic liver disease (HCV RNA Qualitative or RIBA)Pts with a high pretest probability of infection: Over 90% of pts with biochemical or clinical evidence of chronic liver dis. and a positive EIA-2 particularly if they have risk factors for HCV infection such as a Hx of transfusion, injection drug use, nasal cocaine use, or other percutaneous exposures should undergo quantitative HCV RNA determination Spontaneous clearance of virus Technical reasons Passively acquired from blood transfusions Maternal anti-HCV antibodies in babies Viremia may be intermittentHCV RNA may be below the limit of detection

Anti-HCV in the absence of HCV RNA Patients who are HCV RNA negative and EIA positive should be retested in several months since some will be false negatives Pts diagnosed with HCV should also be tested for HIV and hepatitis B due to the common modes of transmission Alcohol abstinenceNSAIDs should beavoidedin pts with advanced liver dis.Acetaminophen not exceed 2 g per 24 hours

Treatment Screening for esophageal varices and HCC in cirrhotic pts

Vaccination including:HAV vaccineHBV vaccine

Before antiviral therapy is started: LFTCBCTSH level A pregnancy test is required in women The HCV genotype and serum HCV RNA level

HCV genotyping is essential before treatment, since the genotype defines the duration of therapy and dose ofribavirin.

In addition, the genotype is an important predictor of the likelihood of obtaining a SVR.

HCV genotype testingA 2009 guideline of AASLD recommends:

liver bx be considered in pts with chronic HCV if the pt and provider wish information regarding fibrosis stage for prognostic purposes or to make a decision regarding Rx.

Establish the presence of concomitant diseases

The guideline also notes that the noninvasive tests are useful for defining the presence or absence of advanced fibrosis Liver bx 18 years of age or older HCV RNA detectable in the serum Liver bx with chronic hepatitis and significant fibrosiscompensated liver disAcceptable hematologic and biochemical indicesWilling to be treated and conform to treatment requirementsNo contraindications to treatment

Who should be treated?Total serum bili 75,000 cells/mm3 No evidence of hepatic encephalopathy or ascitesAcceptable hematological and biochemical indicesHemoglobin >13 g/dL for men and >12 g/dL for womenNeutrophil count >1500 cells/mm3 Creatinine 75 kgPeg alfa-2b+ ribavirin 800 mg if wt85 to 105 kg 1400 mg if wt>105 kgDuration: 48wks

Genotype 4Pts who achieve an SVR who do not have cirrhosis do not require any specific follow-up for their HCV But some will check an HCV viral load one year after the completion of treatment to confirm that the pt has SVR

Pts who fail to achieve an SVR should be followed for signs of progression of their liver dis. F/U after treatmentMost pts should receive therapy with peginterferon, weight-based ribavirin, and a protease inhibitor( boceprevir or telaprevir).

The addition of a PI to regimens increases SVR rates from 40-50% to 70-80%

Genotype 1 treatmentDual therapy: peg+ ribavirin

Triple therapy: peg+ ribavirin+ PI

Protease inhibitors shouldneverbe used as monotherapy due to the development of resistance

Treatment-nave: have never received any treatment for HCV

Prior relapsers: Patients who had an undetectable viral load at the end of treatment but who did not achieve a SVR

Partial responders: who achieved a 2 logdrop in HCV RNA by week 12 of treatment but who did not achieve an end of treatment response

Null responders: who did not achieve a 2 logdrop in HCV RNA by week 12 of treatment

Telaprevir is only used for the treatment of pts with genotype 1

Telaprevir is given as 750 mg (two 375 mg tab.) 3 times per day with food (notlow-fat) Telaprevir based TT

Boceprevir is given as 800 mg (four 200 mg capsules) 3 times/day starting at week four of treatment

Boceprevir should be given with food.

Boceprevir-based TT

The most frequent side effects of interferon:

Flulike symptoms (in>90% of pts) Alopecia (in 10% to 30%)Depression Hypothyroidism Hyperthyroidism

Anemia Cough Pharyngitis Insomnia,dyspnea, pruritus, rash, nausea, and anorexia are the most common side effectsThe most serious side effects are anemia and teratogenic effects. Ribavirin side effectsHemolytic anemia is reversible and usually resolves within the first month after therapy is stopped

If anemia is severe or slow to recover, the pt's iron stores should be assessed

Administration of hematopoietic growth factors (e.g,erythropoietin) may enable a pt to continue full-dose peginterferon+ribavirin.

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