Important note: Information in this article was accurate in July 1999. The state of the art may have changed since the publication date.
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"Hepatitis C is found rife among inmates," trumpeted a recent New York Times article, 1 a "discovery" that comes as no surprise to correctional providers, since we're well aware of the relationship between drug use, incarceration, and hepatitis C (HCV) infection. Approximately 80% of persons incarcerated in the US admit to a history of using illegal drugs and about 1 in 4 have used parenteral drugs 2. Furthermore, about 4 million non-incarcerated individuals are infected with HCV. Due to the linkages between drug use, HCV, and incarceration, an estimated 1.4 million persons affected by HCV, or 30% of the total HCV cases in the U.S. are believed to pass through correctional facilities each year 3.
The number of incarcerated individuals affected by HCV is high, regardless of the region of the country. For example, Texas reported that 42,000 inmates were infected with HCV (28.6% of the incarcerated population)1. Other states also report high infection rates among inmates: Connecticut (32%) 4, Virginia (30-40%)5, Maryland (38%) 6, and California (41%)7. In New Jersey, 929 inmates were tested for HCV in response to evidence of hepatic transaminase elevations, or co-infection with hepatitis B or HIV. 67.3% of these inmates tested positive for HCV antibody 8. Many states do not formally test for HCV infection in their populations unless medically indicated (for reasons such as elevated liver function tests), therefore, current estimates of the prevalence of HCV infection in some correctional settings may be artificially low.
The prevalence of HCV infection in correctional facilities raises a number of diagnostic and management dilemmas. Unlike HIV infection, which currently requires lifelong treatment after the initiation of therapy, treatment for HCV usually requires intervention for a limited period of time. In addition, many of our patients are incarcerated for relatively brief (and sometimes hard to predict) periods of time. Therefore, it can be difficult to determine whether an individual patient will be able to complete the course of therapy, if it were to be initiated in the correctional setting.
Debate about the timing and location of the treatment course and which budget should bear the cost of treatment (correctional or community), further complicates HCV treatment decisions. And now that patients with HIV are living longer, consideration must be given to treating chronic conditions like HCV that were considered irrelevant to HIV management in the pre-HAART era. Many correctional providers would probably consider the management of HCV and HCV/HIV co-infection in the correctional setting to be their biggest challenge.
Hepatitis C virus is a member of the flaviviridae family. Infection is blood borne, and therefore can be associated with injection drug use, tattooing, and needle stick injuries 9. Infection was formerly associated with blood transfusion, until screening for HCV was initiated (1989) and new methods for detecting HCV reduced the risk of HCV transmission by blood products to 1 in 100,000 units.
About 15% of HCV exposed patients resolve their infection without sequellae, while approximately 85% of cases eventually develop chronic hepatitis and persistent although occasionally intermittent, viremia(10). Infection results in the development of closely related yet heterogeneous populations of viral genomes (quasi species). Probably as a result of this genetic diversity, HCV evades the host immune response, leading to a high rate of chronic infection. Persons with chronic HCV are often asymptomatic but have the capacity to infect others. HCV can lead to cirrhosis and liver failure (20% of chronic HCV infections). In people who are co-infected, HIV may cause HCV to advance more quickly; they have a 12 to 300 fold higher risk of developing hepatocellular carcinoma than non-carriers (10). HCV is responsible for approximately 40% of the 25,000 annual deaths from chronic liver disease in the U.S. (9).
Tests that detect antibody against the virus include the enzyme immunoassay (EIA) and the recombinant immunoblot assays (RIBA). The EIA test is suitable for screening for HCV infection. RIBA is used to confirm an EIA result in a low risk population if a positive result is suspected to be a false positive; it probably has little use in a correctional setting. The polymerase chain reaction assay for HCV (RT-PCR) enables direct quantification of the virus in the blood (similar to the HIV viral load assay). A positive RT-PCR is definitive proof of HCV infection. RT-PCR can be used to quantify virus in the course of infection; however, there is variability between laboratories, so clinicians should use the same laboratory to evaluate a patient at sequential time points. Liver biopsy can demonstrate the extent of liver injury. Many gastroenterologists are now questioning the need for routine biopsy in all HCV patients before treatment.
In 1997, the National Institutes of Health Consensus Committee recommended treatment of HCV infection with 3 million units of interferon (aIFN) subcutaneously three times a week for 12 months. The 1997 consensus statement, which includes extensive discussions of the natural history of HCV, diagnosis, and treatment, can be found at the following internet website: http://odp.od.nih.gov/consensus/statements/cdc/105/105_stmt.html/
Recent studies indicate important considerations when using interferon. Neutralizing anti-interferon antibodies have been shown to develop in some patients with chronic HCV receiving treatment with interferon. The presence of these antibodies suggests an association with a decrease in responsiveness to interferon (11).
Interferon monotherapy remained the standard treatment for HCV until last year, when the combination of interferon and oral ribavirin won FDA approval because of its improved efficacy. While ribavirin has no lasting effect when taken alone, combining 600 milligrams of ribavirin by mouth twice a day with interferon at 3 million units subcutaneously three times a week leads to a doubling of HCV RNA clearance (10). Most clinicians now initiate treatment with this form of combination therapy, rather than using interferon alone.
Interferon effectively cures between 15 to 20% of patients who are given a one-year course of therapy (9). Combination therapy with interferon and ribavirin has demonstrated 30 to 50% response rates (12, 13, 14). Response to combination therapy may even be observed in patients with advanced HCV infection and cirrhosis (15). The ideal duration of therapy-6 months versus a year-is still being determined. Non-responders to interferon monotherapy can be identified early by assessing the serum ALT level and the presence of serum HCV RNA after 3 months of therapy. If the ALT level remains abnormal, and the serum HCV RNA remains detectable, interferon therapy should be stopped, because further treatment is unlikely to produce a response. If the virus is undetectable, continuation of treatment depends on the HCV genotype (which can be checked before starting therapy). If the virus is genotype 1 (which represents >70% of the HCV in the U.S.), the therapy should be continued for another 6 months. Infection with other genotypes may only required in the initial 6 months of treatment. Detectable response may take 4 or 5 months to achieve but those who fail to respond at 6 months are unlikely ever to respond.
The following features are the most common independent factors predictable of sustained response to interferon therapy:
Other interventions that are thought to be helpful for the management of HCV include Hepatitis A (HAV) vaccination (16). Superinfection with HAV may be associated with fulminant liver failure in HCV patients.
Interferon side-effects commonly include flu-like symptoms, irritability, and depression. Hematological abnormalities such as anemia are common. Severe adverse effects include severe depression, seizures, and generalized bacterial infections (<2% of patients receiving interferon) (11). Decreasing the dosage of interferon may be helpful; severe side-effects result in the discontinuation of treatment in 5 to 10% of patients. Paradoxical worsening of hepatitis may also occur, and is thought to be due to an autoimmune response. Treatment should be discontinued in patients who have rising serum ALT levels to greater than twice the baseline. Ribavirin can produce hemolytic anemia, which can be life threatening in patients with heart disease and cerebral vascular disease. Ribavirin is teratogenic, and therefore contraindicated in women who are considering becoming pregnant and their male partners. Sexually active women and men should use reliable birth control during treatment and for at least 6 months after completion of a ribavirin regime. A male prisoner leaving prison less than 6 months after treatment ends needs warning not to impregnate a female partner until risk of teratogenicity has passed.
Co-infection with HIV further complicates HCV treatment decisions. Now that HAART has improved the overall prognosis of HIV, viral hepatitis is destined to become an increasing cause of morbidity and mortality for many of our HIV and HCV co-infected patients.
While co-infected patients can tolerate interferon therapy (17), few may respond and those who do may relapse (18, 19), although some practitioners believe the response rate for HIV and non-HIV infected patients may not differ (20). In some co-infected patients, CD4 T cell counts have been observed to plummet on interferon (21). In addition, previously asymptomatic patients with high CD4 counts who are started on interferon have developed opportunistic infections such as Pneumocystis carinnii pneumonia.
Interactions with anti-retroviral medications should be carefully considered prior to initiation of therapy. Ribavirin may block the action of zidovudine (AZT) and stavudine by inhibiting the phosphorylation of the antiretroviral drug. It does not seem to antagonize didanosine (ddI) and ribavirin/ddI combinations may even be synergistic (22). The interaction of ribavirin with all anti-retroviral drugs needs to be better defined, as few have had experience with combining these therapies.
Despite these caveats, there is emerging evidence that treating HCV in HIV co-infected patients may prevent liver failure. Outcomes may improve further since the recent approval of ribavirin in combination with interferon as standard initial HCV therapy. An AmFAR sponsored study of interferon with or without ribavirin therapy in HIV/HCV co-infected patients has been on-going since 1998. Anemia, which causes treatment withdrawals in some HCV-infected patients may be a significant problem when the combination is used in patients with HIV especially when HIV, is advanced or AZT is used. Thus, treatment of HCV is now being carefully considered for selected HIV-infected incarcerated patients. The challenge for the correctional physician lies in determining whether treatment is appropriate for an individual patient.
HCV cure rates (sustained virologic response) with currently available regimens remain low, ranging between 15 to 50%, depending on the treatment (12, 13, 14). The cost of the medication can be as high as $12,000 per year per patient. Low cure rates and high cost have led to delays in the initiation of HCV screening programs in correctional settings, even though screening for and treating HCV has been shown to be cost-effective in some populations. For older patients, a 6 month-long treatment was on the scale of other interventions that the American public would accept. For young patients, 6 months of treatment maybe cost saving (23). The use of ribavirin for HCV changes the picture-cost benefit analyses for combination therapy. Combination therapy is more expensive than interferon alfa alone, but because it has a higher success rate, it may be more cost-effective.
Careful selection criteria can further improve the cost-effectiveness of HCV treatment in the correctional setting. My colleagues and I have previously shown that a policy of routinely treating appropriately screened HCV patients with interferon treatment demands only 3% of correctional facility health care budgets (24). The following table shows the hepatitis treatment criteria at RI DOC with the addition of criteria that must be met before adding ribavirin to a regimen.
Many U.S. inmates may meet the criteria described above and receive treatment, however, the total number of HCV infected inmates treated using these criteria will be much lower than the total number of inmates who have HCV infection. One approach to limiting the impact of HCV screening on correctional budgets might be to screen only those inmates who would qualify for HCV treatment by clinical criteria. Appropriately screening HIV patients for treatment may reduce HCV treatment costs.
High HCV infection rates and new guidelines for treatment are forcing difficult decisions in correctional health facilities. In community settings, clinicians treat HCV infected patients who meet treatment criteria with combination interferon/ribavirin therapy. Guidelines for the selection of patients for therapy in correctional settings should be developed, with the participation of regional public health officials. Cost-sharing between correctional facilities and public health is a subject that needs to be explored, particularly if 30% of all people with HCV in the community cycle through correctional facilities. Treatment of these individuals to reduce HCV morbidity and mortality will have broad implications for general public health.
Treatment of HCV infection in HIV infected patients also bears careful consideration. As HAART therapy continues to prolong the lives of HIV infected people, providers need to place more importance on co-morbid conditions. More HIV patients may die from illnesses other than opportunistic infections. We recommend that all HIV infected patients receive screening for viral hepatitis antibodies (but screening does not need to take place during incarceration, especially if the stay is brief).
Correctional facilities with limited budgets are urged to develop guidelines for prioritizing whom will receive HCV therapy. We recommend that HCV/HIV co-infected patients who have participated in substance abuse treatment, have an expected duration of incarceration that permit completion of therapy, have stable psychiatric or medical conditions, have elevated transaminases but normal hematological parameters, be considered for treatment of hepatitis C virus.
The prevalence of chronic HBV (HbSAg positive patients) may be lower than HCV infection in correctional settings, but it is still a threat. In fact, HbSAg positivity rates (up to 47%) are considerably higher than in non-incarcerated populations (5%)(25).
Prisons are an ideal setting for HBV vaccination, although only a few facilities have adopted CDC guidelines recommending all inmates and exposed personnel receive the HBCV vaccine. The CDC has also recommended HbSAg screening for all pregnant women, and vaccination is recommended for the household and sexual contacts of HbSAg carriers (26). Correctional facilities can obtain HBV vaccine for free for inmate patients up until their 19th birthday under a federal program, Vaccines for Children. Accessibility may differ in each state but providers can check with local departments of health, which may be willing to consider cost sharing for HBV vaccination for older inmates, depending on the region’s incidence of HBV infection. HBV vaccination has been adopted in some correctional facilities due to the high rate of infection among inmates returning to correctional facilities. In Rhode Island, incidence of new HBV infection in recidivist women has been demonstrated to be high: 12 per 100 person years. This year, RI DOC began vaccinating inmates less than 19 years old (27). HBV vaccination is less effective in patients who already have HIV infection, thus boosters or higher doses may be needed (26).
Interferon at 5 million units subcutaneously for 16 weeks was the first treatment for chronic HBV infection. New agents for HBV, including lamivudine (3TC), adefovir (ADV) and famciclovir (Famvir) are in the process of being evaluated. Each patient should be evaluated for treatment and decisions about treatment should be made on an individual basis.
HIV may lessen the liver damage in the HIV/HBV infected patient and treatment could be less of an issue than with HCV/HIV co-infection. If, in the future, life expectancy for HIV increases further, even moderate liver damage in HIV/HBV co-infected patient may need to be addressed, especially if HBV treatment improves. Whether sequential or combination therapy is optimal is unclear. Any liver damage at all may be important if it will compromise tolerance of anti-retroviral therapy.
Contributors include: HEPP Staff and Rob Lyerla, PhD, epidemiologist in the Hepatitis Branch, National Center for Infectious Diseases, CDC.
1. New York Times, May 30,1999. A 12
2. Bureau of Justice Statistics home page
3. Hammett TM, Harmon P, 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 Status of Soon-to-be-Released Inmates" Project. Unpublished paper, May 1999
4. Fennie KP, Selwyn PA, Altice FL. Hepatitis C virus seroprevalence and seroincidence in a cohort of HIV+ and HIV- female inmates. Poster abstract TU.C.2655 presented at the XI International Conference on AIDS, Vancouver, July 9, 1996
5. Richmond-Time Dispatch Online 5/3/99
6. Vlahov D, Nelson KE, Quinn TC, Kendig N. "Prevalence and incidence of hepatitis C virus infection among male prison inmates in Maryland." European Journal Epidemiol 1993 Sep;9(5):566-9
7. Ruiz JD, Mikanda J. Seroprevalence of HIV, hepatitis B, hepatitis C and risk behaviors among inmates entering the California correctional system. California Department of Health Services, Office of AIDS, HIV/AIDS Epidemiology Office. March 1996.
8. Personal communication, Stanley Ostrawski, RN, MS MT. ASCP, CIC Statewide Infection Control Coordinator Correctional Medical Services Mt. Laurel, NJ.
9. "Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease", MMWR October 16, 1998; 47:RR-19
10. "National Institute of Health Consensus Development Conference Panel Statement: Management of Hepatitis C.", Hepatology 1997 Sep;26(3 Suppl 1):2S-10S
11. AIDS Drug Evaluation: Interferon-a-2a. Reprinted from BioDrugs 1998, July 10; 1, 65-89
12. McHutchison JG et al. "Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group.", N Engl J Med 1998 Nov 19;339(21):1485-92.
13. Davis GL et al. "Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group.", NEJM 1998; 339: 1493-9
14. Poynard T 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.
15. Marcellin P et al. "Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy.", Ann Intern Med 1997 Nov 15;127(10):875-81
16. Vento S, Garofano T, Renzini C, Cainelli F, Casali F, Ghironzi G, Ferraro T, Concia E. "Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.", N Engl J Med 1998 Jan 29;338(5):286-90
17. Boyer N, Marcellin P, Degott C, Degos F, Saimot AG, Erlinger S, Benhamou JP. "Recombinant interferon-alpha for chronic hepatitis C in patients positive for antibody to human immunodeficiency virus. Comite des Anti-Viraux.", J Infect Dis 1992 Apr;165(4):723-6.
18. Zylberberg H, Pol S. "Characteristics and treatment of hepatitis C virus infection in HIV-coinfected subjects.", AIDS Patient Care STDS 1998 Jan;12(1):11-9.
19. Marcellin P, Boyer N, Behamou JP, Erllinger S. "Interferon-alpha therapy for chronic hepatitis C in special patient populations.", Digestive Diseases and Sciences 1996 Dec;41(12 Suppl):126S-130S
20. Soriano V, Garcia-Samaniego J, Bravo R, Gonzalez J, Castro A, Castilla J, 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
21. Vento S, Di Perri G, Cruciani M, Garofano T, Concia E, Bassetti D. "Rapid decline of CD4+ cells after IFN alpha treatment in HIV-1 infection.", Lancet 1993 Apr 10;341(8850):958-9.
22. Soriano V, Garcia-Samaniego J, Bravo R et al. "Efficacy and safety of alpha-interferon treatment for chronic hepatitis C in HIV-infected patients. HIV-Hepatitis Spanish Study Group.", Journal of Infection 1995 Jul;31(1):9-13
23. Bennet WG, Inoue Y, Beck JR, Wong JG, Pauker SG, Davis GL. Hepatology 1998; 28 (4):591a.
24. Spaulding A, Greene C, Davidson K, Shneidermann M, Rich J. Prev Med 1999 Jan 28; 1: 92-100.
25. Personal communication, Rob Lyerla, PhD, epidemiologist in the Hepatitis Branch, National Center for Infectious Diseases, CDC
26. "Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States Through Universal Childhood Vaccination: Recommendations of the Immunization Practices Advisory Committee (ACIP) ", MMWR vol. 40 (RR-13); 1-19. 1991 Nov 22.
27. Rich J. Hepatitis in Recidivist Women. Oral presentation at the American Public Health Association Conference. Washington DC, 1998.
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