Important note: Information in this article was accurate in June 2000. 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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The hepatitis C virus (HCV) is responsible for 60-70% of chronic hepatitis and 30% of cirrhosis, end stage liver disease, and liver cancer in the United States. Approximately 1.8% or close to 4.5 million Americans are infected with HCV, and HCV causes an estimated 8,000-10,000 deaths each year in this country. 75-85% of those infected with HCV develop chronic liver disease1. Chronic infection varies in severity and clinical course. Many of those infected will have normal liver enzymes and no clinical symptoms. Approximately 50% of these individuals are unaware of their HCV infection.2. Of those who develop chronic liver disease, perhaps 20% will eventually progress to cirrhosis and several percent will develop liver carcinoma1.
During the 1980's an average of 230,000 new HCV infections occurred each year in the US.3 The number of new infections declined after the introduction of improved methods for the detection of HCV in the blood supply.
Currently, most HCV transmission is associated with injection drug use (IDU). 79% of current IDUs have HCV infection.3 Young IDUs acquire HCV infection at rates four times higher than they acquire HIV; after five years of injection drug use, 90% of users are HCV infected. Non-Hispanic blacks and African Americans have higher rates of HCV infection and chronic disease than whites; most cases of HCV infection are found among persons who are male, members of minority populations, and 30 to 49 years of age.3
Given the linkages between HCV infection and drug use, gender, age, and minority populations, it is not surprising that almost one third (1.4 million) of the 4 million individuals in the United States who are believed to be infected with HCV pass through correctional facilities each year.2 The prevalence of HCV infection among U.S. prisoners is at least 10- fold higher than the estimated prevalence of 2% in the general population (4, 2). Where surveys have been carefully performed, HCV infection rates among inmates have ranged between 30 and 40%5. Estimates of HCV infection in state correctional facilities range from 28% (Texas) to 54% among women in California (see Figure 2). HIV-infected incarcerated women exhibit a slightly higher HCV co-infection rate than HIV-infected incarcerated men (see Figure 2).
The CDC specifically recommends testing persons in settings with potentially high proportions of injection drug users (see Table 1). For instance, the CDC lists correctional institutions, HIV counseling and testing sites, or drug and STD treatment programs as potential settings.3 It should be noted that sexual transmission and maternal-infant transmission is uncommon. Testing should be accompanied by appropriate counseling and medical follow-up. Even if treatment is not to be initiated, persons who test positive for HCV should be given information about risk and prevention of disease and risk of transmission to others. Co-infection with HIV has been said to reduce HCV antibody test accuracy, however a recent study by Thio et al. suggested that third-generation antibody based assays are sufficiently accurate for diagnosis.13
There are two basic approaches to the treatment of HCV: monotherapy with interferon alpha, or combination therapy with interferon alpha and ribavirin. Combination therapy is more expensive and has a higher incidence of side effects, but is significantly more effective. When interferon is used alone, approximately 30-35 % of patients will become HCV RNA negative after treatment, but only 15-20% will have a sustained response once therapy is stopped.3 With combination therapy, the initial response rate increases to 50-55% and the sustained response after treatment is completed is 35-45%.3 In general, combination therapy should be used unless there are contraindications to the use of ribavirin.(See HIV 101 on page 8.)
Interferon alpha 2-a and alpha 2-b are given subcutaneously three times a week in a dose of 3 million units. Consensus interferon is administered in a dose of 9 µm thrice weekly. A new formulation, pegylated interferon, will be dosed once a week and leads to sustained levels of interferon, which may increase efficacy. Ribavirin is administered orally in a dose of 1000 mg daily for those who weigh less than 75 kg and 1200 mg daily for those > 75 kg. Treatment with ribavirin may reduce fibrosis of the liver, which slows advancement of liver disease.14 (See HEPPigram on page 6 for an HCV treatment algorithm.)
IFN side effects commonly include fatigue, myalgias, headache, nausea, vomiting, fever, irriability, and depression. Hematological abnormalities, such as anemia, are common. Severe adverse effects include major depression, seizures, and generalized bacterial infections3 Dosing IFN in the evening and pre-medicating with ibuprofen is often used to reduce myalgias. Decreasing the dosage of IFN 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 inpatients who have heart disease and cerebral ascular disease. Close monitoring of the patient and blood counts are imperative. Ribavirin can also cause fatigue, pruritus, rash, and nasal stuffiness. Furthermore, ribavirin is teratogenic, and therefore contraindicated in women patients who are considering becoming pregnant and their male partners. Sexually active women and men should use birth control during treatment and for at least six months after completion of a ribavirin regime. A male prisoner leaving prison fewer than six months after cessation of treatment needs to be warned to avoid having unprotected sex, leading to pregnancy with a female partner, until risk of teratogenicity has passed.
The incidence and severity of side effects can be very high. Since it can be difficult for incarcerated patients to quickly access their clincian, it is important to: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 then while on treatment is likely to be cost effective.
Other interventions that are thought to be helpful for the management of HCV include hepatitis A (HAV) vaccination.8 Superinfection with HAV may be associated with fulminant liver failure in HCV patients. For similar reasons, HBV vaccination is also recommended if the patient is not previously immune (see HEPPigram, page 6).
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 may worsen HCV liver disease. Persons who are co-infected (HIV and HCV) appear to have a 12 to 300 fold higher risk of developing hepatocellular carcinoma than non-carriers.15 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.1
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.16 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 (17, 18).
HCV treatment in those who also have HIV infection can be as successful as in non-HIV infected individuals.19 In contrast, treatment of HIV infection may be more difficult to manage in patients who have HCV co-infection, as hepatotoxicity to anti-HIV therapy appears to be more common among these individuals. Therefore, patients who are co-infected with HCV and HIV might benefit from sequential treatment of their infections.20 In many cases, it is better to control HIV infection and restore the immune system first. Following successful HCV treatment, co-infected patients are not more likely to relapse after HCV treatment than patients who do not have concurrent HIV infection (19, 21).
Currently, treatment of hepatitis C, where exclusionary criteria are not present, 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 400 with an undetectable viral load is generally accepted.
With the high prevalence of HCV infection among incarcerated individuals, there is a concern that treatment of HCV could overwhelm some system's healthcare budgets. Some cost benefit analyses, however, have provided data in favor of treatment of those with HCV. A recent decision analysis performed by Wong demonstrated that six months of therapy with interferon alpha resulted in a net savings in the range of $400 to $3,500 over the lifetime of each patient.22 Dr. Wong's analysis ranked interferon treatment in the same range of cost effectiveness as stool guiac testing, pneumococcal vaccination, coronary bypass surgery, and mammography.
The analysis did not include cost data for combination therapy with interferon and ribavirin, a more effective intervention for HCV, which might yield even more favorable savings estimates. More recently, Wong suggested using the three month outcome of treatment as a test for response This approach may be less expensive and easier to implement in correctional settings, and he found (in a non-correctional model), to do so would reduce the cost of managing patients with chronic HCV, without any detrimental impact on patient outcomes.23
As with many other chronic medical conditions, much of the morbidity and mortality attributable to HCV does not manifest itself until well after many infected inmates have paroled. Correctional systems are faced with the dilemma of how to prioritize treatment for HCV compared to treatments for other expensive medical conditions for which there are more effective treatments and oftentimes more imminent sequelae. These concerns and the limited efficacy of currently available treatments for HCV have influenced some correctional systems to adopt highly restrictive inclusion and exclusion criteria for HCV treatment (8, 10). While criteria based on medical outcomes are clearly required, correctional physicians need to weigh other exclusion criteria more carefully, keeping in mind that a year 2000 dollar spent on treatment may reduce the eventual cost (to society) of caring for patients who may require liver transplants in 20 to 30 years (10).
Treatment of HCV infection in HIV infected patients also bears careful consideration. It is currently standard HIV care practice to screen all HIV infected patients for viral hepatitis antibodies. Screening does not need to take place during incarceration if prior records are obtained or if the stay is brief.
In summary, the high prevalence of HCV infection and the availability of expensive treatments with limited efficacy force difficult decision making in correctional health facilities. In community settings, most clinicians now treat HCV infected patients who meet treatment criteria with combination IFN/ribavirin therapy. Guidelines for the selection of patients who are candidates for therapy in correctional settings have been developed but not widely adapted. Correctional facilities are urged to adopt guidelines for prioritizing whom will receive HCV therapy. 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.
*Consultant: Agouron Pharmaceuticals, Bristol-Myers Squibb Speaker’s Bureau: Agouron Pharmaceuticals, Bristol-Myers Squibb, Glaxo Wellcome
**Consultant: Agouron Pharmaceuticals, Bristol-Myers Squibb Speaker’s Bureau: Agouron Pharmaceuticals, Bristol-Myers Squibb
1. Consensus Development Conference Panel Statement: Management of Hepatitis C. Hepatology 1997; 26(Suppl 1): 2s-10s.
2. Hammett TM, Harmon P, Rhodes W. Oral Abstract #571. Presented at the National HIV Precention Conference, Atlanta, GA. August 31, 1999.
3. MMWR Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease, MMWR: October 16, 1998 / Vol. 47 / No. RR-19.
4. Hepatitis C control in prison remains an elusive goal. Hepatitis Control Report, Winter 1999-2000; 4(4), 1.
5. Reindollar RW. Hepatitis C and the correctional population, Am J Med 1999 Dec 27;107(6B):100S-103S.
6. 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.
7. Fennie KP, Selwyn PA, Altice FL. Abstract TuC2655 presented at the XI International Conference on AIDS, Vancouver, July 9, 1996.
8. Spaulding A, Green C, Davidson K et al. Hepatitis C in state correctional facilities, Prev Med 1999 Jan;28(1):92-100.
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10.. Spaulding AC, Lally M, Rich JD, Dieterich D. AIDS Reader 1999, May 5; 9(7):481-491.
11.. Green, F. Hepatitis hits prisons; Scope of problem in state called terrifying, Richmond-Time Dispatch, Section: State, Pg. A-1 (5/3/99).
12.. 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 Program, New York City, October 24, 1998.
13.. Thio CL, Nolk KR, Astemborski, J, Vlahov, D, Nelson KE, Thomas DL. Screening for hepatitis C virus in human immunodeficiency virus-infected individuals., J Clin Microbiol 2000 Feb;38(2):575-7.
14.. Shiffman ML, Hofmann CM, Contos MJ et al. A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia, Gastroenterology 1999 Nov;117(5):1164-72.
15.. 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.
16.. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. 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.
17.. Staples CT, 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.
18.. Sabin, CA, Telfer P, Phillips AN, Bhagani S., Lee CA. 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.
19.. Soriano V, Rodriguez-Rosaldo R, Garcia-Samaniego J. Management of chronic hepatitis C in HIV-infected patients, AIDS 1999 Apr 1;13(5):539-46.
20.. 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.
21.. Soriano V, Bravo R, Garcia-Samaniego J, et al. Relapses of chronic hepatitis C in HIV-infected patients who responded to interferon therapy. Hepatitis/HIV Spanish Study Group AIDS 1997 Mar;11(3):400-1.
22.. Wong JB. Cost-effectiveness of treatments for chronic hepatitis C, Am J Med 1999 Dec 27;107(6B):74S-78S.
23.. Wong JB, Bennett GB, Koff RS, Pauker SG. Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs, JAMA 1998 Dec 23-30;280(24):2088-93.
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