Important note: Information in this article was accurate in April 2001. The state of the art may have changed since the publication date. | The online version of HEPP News displays the main article only, to view the entire newsletter download the following PDF:
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Treatment of Hepatitis C (HCV) is emerging as the most controversial subject in correctional health care. Much of the controversy around HCV testing and treatment in corrections is related to delayed recognition of the important role incarcerated individuals play in the transmission of hepatitis in the communities after they are released. State and Federal public health officials have been slow to recognize the potential benefits of screening, educating, and where possible, vaccinating incarcerated persons to prevent morbidity and mortality associated with viral hepatitis.
The Centers for Disease Control (CDC) took action this Spring, convening a meeting on Hepatitis in correctional settings that was attended by more than 100 federal and state correctional healthcare professionals.1 Representatives of correctional organizations (ACA, NCCHC) and representatives from federal agencies such as the OSHA and NIOSH also attended the meeting. CDC speakers discussed the need to expand HBV and HCV interventions, including screening, education, vaccination, and treatment of chronic hepatitis in correctional settings. Guidelines for HCV and HBV management incorporating some of the discussion points will be issued by the CDC as a supplement to the MMWR in the Fall. While sources of funding for increased hepatitis interventions in corrections were not specifically addressed at this meeting, promoting correctional settings as outposts for public health activities may ultimately lead to increased financial support from federal and state sources for correctional treatment initiatives.
In keeping with this new national focus on hepatitis in corrections, HEPP News is dedicating two of the next three issues to updates on hepatitis management. This issue addresses HCV in corrections and summarizes discussions at the CDC meeting. The second article, scheduled for June 2001, will take up the topic of Hepatitis B and Hepatitis A immunizations in correctional settings.
HCV and HBV outstrip HIV in terms of sheer numbers of inmates living with these two infections (Figure 1, Table 1). In the US, there are an estimated 4.5 million individuals living with chronic HCV infection, and 1.2 million with chronic HBV infection. 79% of current injection drug users have HCV infection.3
Inmates At Risk
Non hispanic blacks and hispanics have higher rates of HCV and HBV infection and chronic disease than whites; most cases of HCV and HBV infections are found among persons who are male, members of minority populations, and 30 to 49 years of age.6 These race and class-related risk factors for hepatitis infection probably contribute to the current concentration of HCV and HBV-infected persons in prisons and jails.
According to a recent analysis by Ted Hammett for the NIJ and the NCCHC's report to Congress,7 between 1.0 to 1.25 million individuals harboring chronic HCV infection were released from prisons and jails in the U.S. in 1996, or approximately 30% (29 to 32%) of the total population living with HCV in the U.S. The prevalence of HCV infection among U.S. prisoners is at least 10 fold higher than the estimated 2% prevalence in the general population.8
This ratio is based on estimates that 17% of state inmates are infected with HCV.9 HCV infection rates have ranged from 28% (Texas) to 67% of a higher risk subpopulation of inmates (those with abnormal liver function tests or who are known to have HIV infection) in New Jersey. Reflecting their higher rate of participation in HIV and HCV risk behaviors, incarcerated women exhibit about a third higher HCV co-infection rate than incarcerated men.10(Figure 2).
Approximately 50% of persons with hepatitis are unaware of their hepatitis infection.22 Testing for infection informs the patient and physician about the potential for and possible existence of liver damage. It should serve as an important prompt for a discussion about risky behaviors and transmission to others.23 The CDC lists correctional institutions, HIV counseling and testing sites, and drug and STD treatment programs as sites where hepatitis screening and interventions should take place. (See Table 2 for recommendations.)
Reducing the cost of screening
If the cost of screening an incarcerated population for HCV appears to be prohibitive, targeted screening can reduce the cost of screening and still identify most HCV at-risk individuals. For example, in a Wisconsin study of HCV screening in a local prison, 60.5% of HCV infections were identified by screening those who had history of IDU. By including any individuals who also had an ALT > 51, the facility identified 79.6% of HCV infections. Adding a history of liver disease to the criteria for testing allowed the identification of 83.6% of HCV-infected individuals. When individuals who were HBV+ were also screened, the correctional facility identified 90.8% of the HCV infections. The cost of testing was reduced by two thirds (compared to mass screening) using their criteria, and was very effective.25
For those who are to be treated, initial treatment of chronic HCV with ribavirin/interferon alfa is now the standard of care in community settings. Many correctional facilities are in the process of developing protocols for deciding which patients will be eligible for treatment (see the Correctional Medical Services triage form HEPPigram Part I on page 6 for an example).
Treatment selection criteria
Criteria for HCV treatment may vary slightly from one correctional system to another. In general, eligible patients (1) have evidence of persistent HCV infection and inflammation based on liver function test abnormalities and detectable virus in the blood stream; (2) have enough time left in their sentence to allow for completion of treatment (from six to 12 months) (3) are committed to a life free from substance and alcohol abuse; and (4) are educated about potential HCV treatment side effects and willing to adhere to an arduous course of treatment. (See HEPPigram on page 6 for guidance on selecting patients for HCV treatment.)
Standard therapy is to provide daily treatment with Ribavirin (usually five to six pills divided into two doses) and thrice-weekly alfa-interferon injections. (See HCV 101 on page 8 for dosing and side effects of treatment regimens). Pegylated interferon, a new form of interferon that permits once-weekly dosing, is available as PEG-Intron (peginterferon alpha-2b), and Pegasys is expected to be approved by the FDA later this Spring. Monotherapy is currently only used if the patient cannot take Ribavirin due to toxicities or side-effects.
Duration of treatment
Current recommendations on the duration of treatment are as follows:
A 24-week (six month) course of combination therapy yields results equivalent to those of a 48-week (12 month) course.
A 48-week (12 month) course yields a significantly better sustained response rate than does six months of treatment.
Duration of Interferon monotherapy: 48-weeks, regardless of genotype.
Expected Response: Combination Therapy versus Monotherapy
Combination therapy consistently yields higher rates of sustained response than monotherapy. (A sustained response implies that HCV RNA remains undetectable for six months or more after therapy stops.) With combination therapy, 40% of treatment-naïve patients respond. Patients with genotype-1 have sustained response rates of 25 to 30% (slightly better response rates are seen with lower baseline HCV viral loads). Non-genotype-1 patients achieve response rates of 60 to 65%.26,27 Other factors that increase the likelihood of a response to therapy include age <45, female gender, and mild (rather than advanced) chronic inflammation on liver biopsy. Histologic improvement occurs in 86% of patients who achieve a sustained response (SVR) and 39% of patients who relapse after initial response to combination therapy.28 Just as with HIV therapy, adherence is critical to obtain maximal response. Adherence to therapy has also been shown to increase the likelihood of a response to therapy. The SVR increases from 40% to 48% when patients receive at least 80% of both their interferon dose and their ribavirin dose for > 80% of the recommended duration.29
Pegylated delivery: Another Step Forward in Hepatitis C Therapy
Pegylated forms of interferon allow once weekly dosing, improving adherence to therapy and possibly improving response to therapy. A phase III study demonstrated that the combination of peginterferon alfa-2b (1.5 mcg/kg once weekly) plus ribavirin was significantly more effective than the combination of standard interferon alfa-2b plus ribavirin, particularly in patients with genotype 1 virus.30,31 SVR rates in this study were dependent on the actual dose received. Overall, patients who received >10.6 mg/kg/daily of ribavirin plus 1.5 mcg/kg/QW of peginterferon alfa-2b achieved a SVR of 61%. The SVR in genotype 1 patients was 48% and the SVR in non-genotype 1 patients was 88%.32
This study also demonstrated that these response rates could be further increased if patients were able to maintain adherence. Regardless of genotype, patients who received the recommended combination regimen and received >80% of their treatment had a higher sustained response than those who received < 80% of their treatment (72% vs. 46%). Genotype 1 patients who received the optimal weight-based dose of peginterferon alfa-2b plus ribavirin and adhered to at least 80% of their regimen achieved a SVR of 63%. Similar patients with genotype 2 or 3 infection achieved a SVR of 94%.33,34
Liver Biopsy
The need for confirming the extent of damage to the liver by HCV and chronic HBV infection is another area of debate, since obtaining liver biopsies can be both costly and logistically complicated in correctional settings. Liver function tests can be normal in patients with rather advanced cirrhotic features. Likewise, liver function tests may be consistently elevated in Hepatitis C patients with normal histology. Some state correctional systems do not routinely perform liver biopsies prior to initiating treatment, because of cost and logistical difficulties. Other states (e.g. FL) feel biopsies are the only real way to measure disease progression over time and therefore have made arrangement to do them on site at very reduced costs ($200 per biopsy). Depending on the cost of obtaining a liver biopsy, electing to treat all incarcerated individuals who meet the criteria for treatment may be more cost-effective, for society as a whole, than management by biopsy.35
Lowest cost intervention: Education
The lowest cost intervention for the prevention of hepatitis infection is education. Given the risk of acquiring HCV (not to mention HIV), all bloodborne pathogen screening events should lead to careful discussion of the risks of acquiring HBV and HCV infection (for those patients who have negative hepatitis serologies). The risk of transmitting hepatitis should also be made very clear (see Resources on page 9 for educational materials).
The impact of continued drug use should also be made very clear to patients, especially those who are not yet HCV infected. Young injection drug users (IDUs) acquire HCV infection at rates four times higher than the rate of acquisition of HIV; after 5 years of injection drug use, 90% of IDUs are HCV infected. For those inmates already infected with HCV, education should be provided on the impact of alcohol abuse on HCV progression (four fold increase in risk of progression, risk of liver damage directly correlated with alcohol intake) and the risk of transmission to uninfected sexual partners. Inmates who have HCV infection should, at the very least, be educated about options for treatment even if they are not eligible for treatment while incarcerated (see Resources on page 9 for expanded access programs).
Additional considerations
Another lower (but not no-cost) intervention is vaccination. For HCV infected patients, vaccination against HBV and HAV is routinely recommended, as these relatively inexpensive vaccines may reduce the risk of fulminant liver failure and the need for liver transplantation for HCV-infected patients. A new schedule of HBV vaccination (three shots at 0, 1, and 4 months) has received approval. The first shot provides up to 50% protection, and the series does have efficacy even if prolonged over several years, so the new CDC guidelines are expected to encourage HBV vaccination even in jail settings.
Should patients be ineligible for treatment due to lack of time to complete the treatment, they should be provided with the hotline numbers to access free HCV treatments, if eligible, after release. Contact the companies for more information on their expanded access programs (see Newsflashes page 9).
With the high prevalence of HCV infection among incarcerated individuals, there is a concern that treatment could overwhelm some systems' healthcare budgets. Medical decision analyst J. Wong calculated that six months of combination therapy resulted in net savings in the range of $400 to $3500 over the lifetime of each HCV infected patient.36 Dr. Wong's analysis ranked combination therapy for HCV in the same range of cost effectiveness as stool guiac testing, pneumococcal vaccination, coronary bypass surgery, and mammography. It must be noted however that the cost savings that may accrue from treatment of prisoners are primarily to society as a whole. While treatment of incarcerated individuals for hepatitis and HIV is the right thing to do and can tremendously benefit the public health, it is not realistic to expect correctional systems to shoulder this financial burden without assistance.
Management
Since the incidence of side effects to HCV combination therapy can be relatively high, and it can be difficult for incarcerated patients to quickly access their clinician to report side effects, it is important to:
One suggestion for reducing the cost of managing chronically HCV infected individuals in corrections is to make use of existing "chronic disease" clinic infrastructure and expertise existing on site - since HIV and HCV are fellow travelers, and correctional medical units might insist that the ID (HIV) expert acquire expertise in HCV and HBV management. Some clinics have set up flow sheets to reduce repetitive, unnecessary testing.
Without a good support system, a high percentage of patients will fail to complete therapy. Because of the high cost of treatment, time spent preparing patients and supporting them while on treatment is likely to be cost effective.
Cellular immune response (T helper cells or CD4 T cells and Cytotoxic T lymphocytes or CD8 T cells) is involved in mounting an immune defense against the virus. Clearly, HCV infected individuals who also have advanced HIV infection may be less able to respond to HCV infection due to their compromised cellular immune response.
Analyses of the effect of HCV and HIV co-infection on progression of either disease are often confounded by concurrent risk factors for progression. However, available data seems to indicate that HIV infection accelerates HCV liver disease. Persons who are co-infected (HIV / HCV) appear to have a 12 to 300 fold higher risk of developing hepatocellular carcinoma than non-carriers.37 Furthermore, antiretroviral agents can contribute to liver inflammation, and this may be more frequent in those who have underlying chronic hepatitis due to HCV or HBV. Ritonavir appears to be one of the ART medications that is most commonly associated with liver inflammation in HCV/HIV co- infected patients.38
The impact of HCV infection on HIV infection is less clear. In some studies, HCV infection does not appear to have an effect on the progression of HIV.39 Other studies have reported an association between more rapid progression to AIDS or death in HIV-infected patients; particularly among those who were co-infected with HCV genotypes 1a and 1b.40,41 However, a report by Sulkowski at CROI contraindicated these findings, suggesting that risk of progression was more linked to lack of access to medical care (for HIV) in his cohort of African American patients who had HIV and HCV co-infection (CROI abstract 34).
Response to HCV therapy in individuals who also have HIV infection appears to be equivalent to that of non-HIV infected individuals.42 A recent study in the Journal of the American Medical Association by Sulkowski et al indicates that 88% of co-infected patients tolerate concurrent HCV treatment and HAART.43 Following successful HCV treatment, co-infected patients are not more likely to relapse after HCV treatment than are patients who do not have concurrent HIV infection.
Currently, when exclusionary criteria are not present (see Table 2), treatment of hepatitis C is recommended for patients when CD4 and viral load values reflect good response to antiretroviral treatment. Although some controversy remains in regard to the definition of a good response to HAART, a stable CD4 T cell count greater than 200 with a stable viral load less than 400 is generally accepted.44
In summary, the high prevalence of hepatitis infections among incarcerated individuals and the availability of treatments with less than 100% efficacy forces difficult decision making in correctional health facilities. Combination IFN/ribavirin therapy is now the standard of care. National guidelines and standards for selecting patients who are to be treated, while providing access to care for HCV infected individuals regardless of incarceration status, are forthcoming from the CDC. The cost of HCV treatment is expected to be a major barrier to wide implementation of the guidelines in prisons and jails. Correctional physicians eagerly anticipate further guidance from state and federal health officials on supplemental sources of funding for HCV treatment initiatives in correctional settings.
* Consultant & Speaker’s Bureau: Agouron Pharmaceuticals, Dupont, Merck, Roche, Boehringer-Ingelheim/Roxane Laboratories
1. CDC consultants' meeting, Recommendations for Prevention and Control of Viral Hepatitis in Correctional Settings. March 5-7th 2001, Crowne Plaza Ravinia Hotel, Atlanta GA).
2. Hammett TM, Harmon P, and Rhodes W. The Burden of Infectious Disease Among Inmates and Releasees from Correctional Facilities. Prepared for National Commission on Correctional Health Care- National Institute of Justice "Health of Soon-to-be-Released Inmates" Project, June 14-15, 1999, Chicago IL. 25.
3. "Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease", MMWR October 16, 1998 / 47(RR19);1-39.
4. Harold Margolis, Hepatitis Branch NCID, CDC. Prevention and Control of Viral Hepatitis in the Community. CDC Consultants' Meeting, 2001.
5. Hammett et al., Supra, Note 2.
6. "Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease", MMWR October 16, 1998 / 47(RR19);1-39.
7. Hammett et al., Supra, Note 2.
8. Hepatitis Control Report, Winter 1999-2000; 4(4), 1.
9. Hammett et al., Supra, Note 2.
10. Reindollar RW. "Hepatitis C and the correctional population", Am J Med 1999 Dec 27;107(6B):100S-103S.
11. Ruiz JD, Molitor F, Sun RK, et al., "Prevalence and correlates of hepatitis C virus infection among inmates entering the California correctional system", West J Med 1999 Mar;170(3):156-60.
12. Fennie KP, Selwyn PA, Stephens PC, et al., "Hepatitis C Prevalence and Incidence in a Cohort of HIV+ and HIV- Female Prisoners", XIth International Conference on AIDS, Vancouver, 7-11 July 1996. Abstract Tu.C.2655.
13. Spaulding A, Greene C, Davidson K, et al., "Hepatitis C in state correctional facilities", Prev Med 1999 Jan;28(1):92-100.
14. Vlahov D, Nelson KE, Quinn TC, et al., "Prevalence and incidence of hepatitis C virus infection among male prison inmates in Maryland", Eur J Epidemiol 1993 Sep;9(5):566-9.
15. Conklin T, et al. Draft presented at Recommendations for Prevention and Control of Viral Hepatitis in Correctional Settings; CDC Consultants' Meeting, Atlanta GA, March 5-7, 2001.
16. Hepatitis C control in prison remains an elusive goal. Hepatitis Control Report, Winter 1999-2000; 4(4), 1.
17. Frank Green, "Hepatitis hits prisons: Scope of problem in state called terrifying", Richmond-Time Dispatch Online - May 3, 1999, Page: A-1; Section: Area/State.
18. Schueler L. Presentation at Symposium on Current Strategies for the Treatment and Prevention of HIV in Corrections, Sponsored by Brown University AIDS Program and Yale University HIV in Prisons Porgram, New York City, October 24, 1998.
19. Pfister JR. Recommendations for Prevention and Control of Viral Hepatitis in Correctional Settings; CDC Consultants' Meeting, Atlanta GA, March 5-7, 2001.
20. Maue, F. Recommendations for Prevention and Control of Viral Hepatitis in Correctional Settings; CDC Consultants' Meeting, Atlanta GA, March 5-7, 2001.
21. Gerard Chamberlin, MPH, Arizona Department of Corrections Health Services 2005 N Central # 700 Phoenix, AZ 85004 (602) 255-4222. Personal communication, 4/01.
22. Hammett et al., Supra, Note 2.
23. See the CDC Serostatus Approach to Fighting the Epidemic, SAFE, March 2001 issue of HEPP News, p8.
24. Modified from "Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease", MMWR October 16, 1998 / 47(RR19);1-39.
25. Pflister JR, et al., Supra, Note 19.
26. Poynard T, Marcellin P, Lee SS, et al., "Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)", Lancet 1998 Oct 31;352(9138):1426-32.
27. Serfaty L, Aumaitre H, Chazouilleres O, et al. "Determinants of outcome of compensated hepatitis C virus-related cirrhosis", Hepatology 1998 May;27(5):1435-40.
28. Ibid.
29. McHutchison JG, et al. Hepatology. 2000;32:223A.).
30. Schiff ER, Maddrey WC, et al. Tx Reporter. Jan 2001; 7-9.
31. Mans MP, McHutchinson JG, Gordon S, et al.
32. Manns MP, McHutchison JG, Gordon S, et al. [abstract 552]. Hepatology 2000;32:297A.
33. Schiff ER, Maddrey WC, et al. Tx Reporter. Jan 2001; 7-9.
34. Manns MP, McHutchison JG, Gordon S, et al. [abstract 552]. Hepatology 2000;32:297A.
35. Wong JB, Davis GL, Pauker SG. "Cost effectiveness of ribavirin/interferon alfa-2b after interferon relapse in chronic hepatitis C", Am J Med 2000 Apr 1;108(5):366-73.
36. Ibid.
37. National Institutes of Health, Office of the Director, NIH Consensus Statement: "Management of Hepatitis C", NIH Consensus Statement, Volume 15, Number 3, March 24-26, 1997.
38. Sulkowski MS, Thomas DL, Chaisson RE, et al., "Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection", JAMA 2000 Jan 5;283(1):74-80.
39. Staples CT Jr, Rimland D, Dudas D. "Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival", Clin Infect Dis 1999 Jul;29(1):150-4.
40. Sabin CA, Telfer P, Phillips AN, et al., "The association between hepatitis C virus genotype and human immunodeficiency virus disease progression in a cohort of hemophilic men", J Infect Dis 1997 Jan;175(1):164-8.
41. Soriano V, Rodriguez-Rosado R, Garcia-Samaniego J. "Management of chronic hepatitis C in HIV-infected patients", AIDS 1999 Apr 1;13(5):539-46.
42. Soriano V, Garcia-Samaniego J, Bravo R, et al. "Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group", Clin Infect Dis 1996 Sep;23(3):585-91.
43. Sulkowski MS, Thomas DL, Chaisson RE, et al, "Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection", JAMA 2000 Jan 5;283(1):74-80.
44. Carpenter CC, Cooper DA, Fischl MA, et al., "Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel", JAMA 2000 Jan 19;283(3):381-90.
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