Madison Clinic
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Management of Hepatitis C in HIV

NEW: Hepatitis C Co-Infection Clinic

AASLD 2009 Guidelines on Hepatitis C - [pdf] [link]

  1. Epidemiology/Natural History
  2. Diagnosis of Chronic HCV
  3. Management/Treatment
  4. Monitoring Therapy and Managing Toxicity
  5. Health Maintenance
  6. Prevention
  7. References

I. Epidemiology/Natural History

  • 30% of HIV+ patients co-infected with HCV in US and Europe
  • Approximately 2,700,000 patients with chronic HCV in US (vs. 900,000 w/ HIV)
  • 80% of HIV+ patients become chronically infected (vs. 60-85% in HIV- patients)
  • Incidence of HCV in US was an estimated 19,000 new infections in 2006 though this is likely an underestimate because most new infections are asymptomatic and undiagnosed
  • Approximately 70% of IDUs infected w/ HCV
  • Other risk factors include blood transfusion before ’92, sex with infected person, high-risk sexual practices, medical care in foreign country and possibly intranasal cocaine
  • HCV progresses more rapidly in HIV+ patients
  • Within 10-15 years, 15-25% of co-infected patients developed cirrhosis (vs. 2-6% in HIV- patients)
  • Progression of HCV also increased by older age at time of infection, male gender, lower CD4, EtOH
  • HCV viral load and genotype are not associated with HCV disease progression (but are associated w/ response to therapy)
  • Effect of HCV on HIV disease progression is controversial

II. Diagnosis of Chronic HCV

  • The third generation ELISA tests for HCV have decreased number of false positive and negative results
  • Rarely, in patients with advanced HIV and chronic HCV, HCV antibodies are lost
  • In patients with advanced HIV and unexplained transaminitis, an HCV RNA should be checked to rule out a false negative antibody test
  • Only in very low risk patients (eg blood donors w/ negative viral load) does the more specific RIBA need to be checked to confirm HCV infection
  • HCV viremia can be transient so an initial negative viral load should be rechecked before assuming that the patient spontaneously cleared HCV

III. Management/Treatment

  • Serial ALTs are an insensitive way to monitor disease activity – patients with normal ALTs can still have significant fibrosis on biopsy, especially, if they are HIV-co-infected
  • Once HCV viremia is confirmed there is no benefit in monitoring HCV RNA while not on therapy
  • It is controversial whether control of HIV slows progression of HCV
  • Increased risk of hepatotoxicity with nevirapine in patients with HCV
  • Increased risk of hepatic steatosis with ddI/d4T – presence of >30% steatosis on liver biopsy has been associated with decreased rates of treatment success
  • Co-administration of didanosine and ribavirin is contraindicated (high levels of pancreatitis and mitochondrial toxicity)
  • Increased rates of anemia in patients on AZT and ribavirin
  • Concern with in vitro antagonism between ribavirin and thymidine analogues (d4T and AZT) has not led to increased virologic failure in clinical trials but decreased success rates are being reported with abacavir with possible drug interaction
  • Liver biopsy provides very useful information
  • Given poor response rates with genotypes 1+4, treatment can be deferred if fibrosis score is 0 or 1 (if treatment is deferred, re-biopsy in 5 years to assess disease progression)
  • If genotype 2+3, many would treat low fibrosis scores given better response rate
  • Treatment involves 48 weeks of pegylated interferon (pegasys 180 mcg sc q week or PEG-Intron 1.5 mcg/kg sc q week) and ribavirin.
  • The dosing of ribavirin is controversial, but many practitioners dose ribavirin based on weight for genotype 1 infections at doses as high as 15mg/kg (1000mg-1600mg/day in divided doses)
  • For treatment of genotype 2+3 infections, it appears ribavirin 400mg po bid is equivalent to higher doses
  • In 3 randomized trials on treatment of HCV in HIV infected patients, dose of ribavirin was 400-500mg po bid
  • At HMC’s Hepatitis Clinic, ribavirin 400mg po bid given to patients with non-genotype 1 virus; patient with genotype 1 get 600mg po bid if >70kg and 500mg po bid if <70kg
  • For all comers, sustained virologic response (SVR) (eg negative HCV RNA 24 weeks following treatment) rates vary from 27-47% but with genotype 1 response rates vary from 14%-38%
  • If no early virologic response at 12 weeks (defined as ≥ 2 log decrease in HCV RNA level or undetectable viral load) patient very unlikely to gain benefit, and treatment can be discontinued
  • If still with detectable HCV RNA at week 24, especially, if genotype 1, consider discontinuation
  • Rapid virologic response – undetectable HCV RNA at week 4 of therapy – is associated with 80-90% rate of sustained virologic clearance
  • Value of continuing treatment in relapsers or non-responders is unclear (may preserve liver fxn)
  • Most patients treated in studies had early or well-controlled HIV (unclear if data can be extrapolated to patients with more advanced HIV)
  • In patients w/ CD4<350, HAART should be optimized prior to starting HCV treatment
  • Treatment is contraindicated in patients with decompensated cirrhosis (Child class B or C, especially with symptoms of ascites or encephalopathy), active substance abuse, pregnancy (or inability to practice birth control), seizure disorder, severe cardiovascular disease and severe depression (especially with history of suicidality in past year)

IV. Monitoring Therapy and Managing Toxicities

  • General Monitoring
    • CBC with absolute neutrophil count at week 2, 4, and then q2-8 weeks depending on cytopenias that develop
    • TSH at baseline and q3 months
    • HCV RNA at week 4, 12, (24 if not yet undetectable), and 48 (end of treatment for genotype 1), and 6 months post-treatment
    • Pregnancy test baseline, q12 weeks if woman of childbearing potential
    • LFTs q 8-12 weeks in patients with cirrhosis.
  • Anemia

- It is believed the dose of ribavirin has major effect on rates of SVR
- On average, Hg will fall 1-3mg/dL with ribavirin
- Package insert recommends dose reducing ribavirin if Hg<10 mg/dL and stopping if Hg<8.5 mg/dL.
- In order to avoid dose reductions on ribavirin, darbepoietin 100mcg sq qweek can be given when Hct<30 or symptomatic.

  • Neutropenia

- The manufacturer recommends reducing interferon dose if ANC<750 and stopping interferon when ANC<500
- Many use filgrastim 300mcg subcutaneously once daily to treat neutropenia on interferon or peg-filgastim 6mg subcutaneously once a month

  • Thrombocytopenia

- More difficult to manage than anemia or neutropenia
- Generally hold doses of peg-interferon when platelets<20,000

  • Depression

- Follow closely for signs of depression
- Some providers place patients with a history of depression on SSRI prior to treatment

  • Myalgias

- can be managed with acetaminophen or NSAIDS

In addition to Dr. Shuhart, the hepatitis pharmacist Allison (x5526) can be helpful in managing dose adjustments of interferon and ribavirn and managing toxicities

V. Health Maintenance

  • Patients with HCV should have HAV and HBV serologies tested and be vaccinated if not immune

VI. Prevention

  • The CDC does not recommend condoms to prevent HCV transmission in long term sexual relationships (rarely transmitted in these relationships), but do recommend condom use in short term relationships
  • Sharing of needles or other drug paraphanelia should be discouraged

VII. References

Carrat, Pegylated Interferon Alfa-2b vs Standard Interferon Alfa-2b, plus ribavirin for Chronic Hepatitis C in HIV-Infected Patient, JAMA 2004;292:2839-48.

Chung, Raymond et al, Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV co-infected patients, NEJM 2004;351:451-9

Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study  of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009 Apr;49(4):1335-74.

Rockstroh, Jurgen et al, HIV and HCV co-infection, The Lancet Infectious Diseases 2004 2004; 4:437-444. Torriani, Francesca et al, Peginterferon alfa-2a plus ribavirin for chronic HCV infection in HIV-infected patients, NEJM 2004; 351:438-50

Torriani, Francesca et al, Peginterferon alfa-2a plus ribavirin for chronic HCV infection in HIV-infected patients, NEJM 2004; 351:438-50

Pol, Soriano. Management of chronic hepatitis C virus infection in HIV-infected patients. Clin Infect Dis. 2008 Jul 1;47(1):94-101

 

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