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Hepatitis C Dr. Alipour
Chronic 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 infection
Despite the overall decline in HCV, infection rates among young adults may be increasing between 2002 and 2009 among age 15 to 24 years .
Illicit 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 1987 hemodialysis pts and those with unexplained abnormal
aminotransferase levels
Screening and diagnosis
Prior recipients of transfusions or organ transplants before July 1992
Children born to HCV-infected mothers Healthcare, emergency and public safety
workers after a needle stick injury or mucosal exposure to HCV-positive blood
Current 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 patients Dialysis patients Organ transplantation In those with unexplained liver disease
whose anti-HCV test is negative
HCV RNA for screening?
HCV RNA assays:Qualitative TMA method lower limit 10 IU/ml Amplicor 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 intermittent HCV 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 abstinence NSAIDs should be avoided in 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 vaccine HBV vaccine
Before antiviral therapy is started: LFT CBC TSH 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 of ribavirin.
In addition, the genotype is an important predictor of the likelihood of obtaining a SVR.
HCV genotype testing
A 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 fibrosis compensated liver dis Acceptable hematologic and biochemical
indices Willing to be treated and conform to
treatment requirements No contraindications to treatment
Who should be treated?
Total serum bili <1.5 g/dL INR <1.5 Albumin >3.4 g/dL Platelet count >75,000 cells/mm3 No evidence of hepatic encephalopathy or ascites Acceptable hematological and biochemical indices Hemoglobin >13 g/dL for men and >12 g/dL for
women Neutrophil count >1500 cells/mm3 Creatinine <1.5 mg/dL
Compensated liver disease?
Pts who failed prior treatment Current users of illicit drugs or alcohol who
are willing to participate in a substance abuse program
Liver bx without fibrosis or mild fibrosis Acute hepatitis C
PTS who may be candidate for Rx
Coinfection with HIV Less than 18 years of age Chronic kidney disease either requiring or
not requiring hemodialysis Decompensated cirrhosis Recipient of a liver transplant
Treatment contraindication
Major, uncontrolled depressive illness hypersensitivity to drugs A kidney, heart, or lung transplant Autoimmune hepatitis Untreated thyroid disease
Treatment contraindications
Severe concurrent dis. such as severe HTN, heart failure, significant CAD, poor controlled diabetes, COPD
Less than two years of age
Pregnant, contemplating pregnancy (including men), or unwilling to assure contraception
Treatment contraindication
Withhold treatment if: HCV acquisition before the age of 35 years Female sex Alcohol abstinence No or minimal fibrosis on liver biopsy Treat if: Initial biopsies show moderate activity or
some degree of fibrosis
Persistently normal serum ALT treat or not?
HCV genotype (genotypes 2 and 3 are more responsive to treatment than genotypes 1 and 4)
Baseline viral load (≤600,000 to 800,000 IU/mL) Race (whites have higher response rates than
African Americans and Latino whites) Host genetic factors (eg, IL28B polymorphisms) Use of combination therapy with peginterferon
and ribavirin Treatment adherence
PREDICTORS OF A TREATMENT RESPONSE
RVR: HCV RNA negativity after 4wks of treatment; if the HCV RNA remains negative at 12 wks it is known as an extended rapid virologic response (eRVR)
EVR: at least a 2 log reduction in HCV RNA (a partial EVR) or HCV RNA negativity (a complete EVR) by wk 12 of treatment
Delayed virologic response: HCV RNA negativity at week 24 in pts who fail to achieve a complete EVR (such patients are also known as "slow responders")
End of treatment response (EOT): HCV RNA negativity at the end of treatment
SVR: absence of HCV RNA by PCR six months after stopping treatment
ASSESSING A TREATMENT RESPONSE
peginterferon alfa-2a(Pegasys), the dose is 180 micrograms SQ/wk
peginterferon alfa-2b(Peg-Intron), the dose is 1.5 microgram/kg SQ/wk
DOSES OF PEGINTERFERON
Peginterferon + ribavirin Ribavirin is not weight-based All pts receive 800 mg in daily divided
doses (typically 400 mg twice daily) Duration:24 wks Better response to peg+ ribavirin than
genotype 1 or 4
Genotype 2 or 3
Ribavirin is weight-based Peg alfa-2a+ ribavirin 1000 mg if
weight=< 75 kg 1200 mg if weight >75 kg Peg alfa-2b+ ribavirin 800 mg if wt<65 kg 1000 mg if wt 65 to 85 kg 1200 mg if wt >85 to 105 kg 1400 mg if wt>105 kg Duration: 48wks
Genotype 4
Pts 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 treatment
Most 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 treatment
Dual therapy: peg+ ribavirin
Triple therapy: peg+ ribavirin+ PI
Protease inhibitors should never be used as monotherapy due to the development of resistance
Treatment-naïve: 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 log drop 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 log drop 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 (not low-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 effects The most serious side effects are anemia
and teratogenic effects.
Ribavirin side effects
Hemolytic 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.
THE END