WHAT CAN CORRECTIONAL HEALTH CARE PROVIDERS DO?
The epidemiology of Hepatitis C Virus makes correctional institutions pivotal sites for US efforts to identify those who are infected with Hepatitis C Virus. News from this year's Conference on Retroviruses and Opportunistic Infections (CROI) highlights the fact that most of those infected with HIV are unaware of their disease.8 Unfortunately, according to the experts at the NIH consensus panel, this is also true of Hepatitis C Virus. Thus a simple but powerful first step is to provide ready access to HIV and Hepatitis C Virus testing. All prisoners should be evaluated for Hepatitis C Virus risk factors. Those with Hepatitis C Virus risks and any other prisoner who requests testing should be offered it.
Hepatitis C Virus is most readily diagnosed by the detection of antibody in serum. According to Jean-Michel Pawlotsky, M.D., one of the experts on the NIH consensus panel, current FDA-approved antibody tests for Hepatitis C Virus are highly sensitive and specific (99%), reproducible, and inexpensive, which makes them suitable for use in screening at-risk populations. (Contrary to what was said at the NIH Conference, the CDC still recommends a confirmatory test, and for screening purposes, i.e., not medical management purposes, a RIBA is recommended). A negative Hepatitis C Virus antibody (EIA) test is sufficient to exclude a diagnosis of chronic Hepatitis C Virus infection in most immune-competent patients. Rarely, those who are on hemodialysis or who are otherwise immune-deficient may have a false negative EIA. Conversely, false positive results can be obtained in those with autoimmune disorders. In these individuals, assays for Hepatitis C Virus RNA are useful adjuncts.9
Once individuals know their Hepatitis C Virus status, education about Hepatitis C Virus enables them to understand their illness, better care for themselves, and prevent transmission to others. Patients should be advised that continued alcohol use by those with Hepatitis C Virus infection can hasten the progression of liver disease. Providers should also discuss drug and alcohol addiction treatment and anti-Hepatitis C Virus treatment options. Inmate-led peer education programs can be invaluable in fostering better understanding of Hepatitis C Virus and HIV. Hepatitis C Virus- infected patients who are not already immune should be vaccinated against hepatitis A and, if indicated because of other risk factors, hepatitis B.10
Prevent further transmission
The use of a harm reduction model helps patients prevent further transmission of Hepatitis C Virus. The risk for transmission of blood borne pathogens is dramatically increased among IDUs who are not utilizing harm reduction techniques, making drug treatment and the availability of clean needles key components of prevention.1
Evaluate for treatment: Who are the best candidates?
Those patients who are the best candidates for treatment are those with chronic Hepatitis C Virus who lack significant contraindications (see Table 1) and are at the greatest risk for progression to cirrhosis (measurable Hepatitis C Virus RNA, a liver biopsy with portal or bridging fibrosis and at least moderate inflammation and necrosis, and elevated ALT values). More data has accumulated demonstrating that those with HIV infection can be effectively treated for Hepatitis C Virus. As a result, the NIH consensus panel recommended that HIV-infected people be considered for Hepatitis C Virus treatment.
The 2002 panel also reversed the 1997 recommendations that excluded treatment for all active substance abusers. As reported at the meeting, recent experience has demonstrated the feasibility and effectiveness of treating Hepatitis C Virus in some people who use injection drugs.12 Since IDUs comprise one of the largest groups of Hepatitis C Virus patients, successful treatment may lead to reduced transmission. Linking IDUs to drug-treatment programs enhances the management of Hepatitis C Virus-infected IDUs. In some settings, Hepatitis C Virus therapy has been successful even when the patients have not been completely abstinent from continued drug use or are on daily methadone.13
Patients with mild mental health problems may also be eligible for treatment, but should be closely monitored throughout the process as interferon (IFN) can exacerbate depression.13
Measure Viral Load
VL measurements can be used to confirm active infection, assess response to therapy, and evaluate end of treatment and sustained responses. Unlike HIV infection, Hepatitis C Virus Viral load does not correlate with the severity of Hepatitis C Virus infection. Viral load does correlate with the likelihood of a response to antiviral therapy. Rates of response to a course of IFN and ribavirin (RBV) are higher in patients with low levels of Hepatitis C Virus RNA (usually defined as below 2 million copies per milliliter).
Monitoring Hepatitis C Virus RNA levels during the early phases of treatment may provide information on the likelihood of a response. A viral load reduction of 2 log or more at week 12 indicates a positive response to therapy, and treatment should be continued (see HEPPigram, page 6). If viral load has not been reduced by 2 log (90%) or more at week 12, there is a low likelihood that a patient will achieve a sustained viral response, and discontinuation of therapy may be considered.14 Some patients, particularly those with HIV, may take longer to achieve a 2 log response. Furthermore, if a patient has advanced Hepatitis C Virus, continuing therapy may be useful despite less than a 2 log reduction because a course of treatment that does not result in eradication of Hepatitis C Virus may slow Hepatitis C Virus disease progression.15
There are six known Hepatitis C Virus genotypes. Patients with genotype 2 or 3 are two to three times more likely to achieve a sustained viral response to treatment than those with genotype 1. The duration of combination therapy with pegylated IFN who are not co-infected and do not have genotype 1 is usually 24 weeks, while co-infected patients and those with genotype 1 are usually treated for at least 48 weeks (See HEPPigram, page 6).
THE ROLE OF LIVER BIOPSY
The NIH consensus panel emphasized the role of liver biopsy in the management of Hepatitis C Virus. Biopsies grade the severity of disease and stage the degree of fibrosis and permanent architectural damage in a patient. Radiological testing such as ultrasound cannot indicate the stage of disease except in the setting of advanced cirrhosis. Measuring ALT also does not reliably assess the stage of liver disease, particularly in HIV-infected patients. While the majority of Hepatitis C Virus patients with consistently normal ALT have early Hepatitis C Virus disease, 22% may have more advanced disease.16 Because patients with genotypes 2 and 3 respond so well to treatment, there was some debate about the need for biopsy prior to treatment in those patients (See HEPPigram, page 6). In addition, among HIV-infected patients, a higher percentage of patients with normal ALT may have moderate or more severe liver disease. Therefore, some experts suggest that patients with consistently normal ALT be treated no differently than patients with consistently abnormal ALTs.16
In addition to more accurate staging of disease, biopsies also confirm the Hepatitis C Virus diagnosis, exclude alternative diagnoses, predict responsiveness to treatment, and provide a baseline for future comparison.17 The biopsy can provide extremely useful information, but lack of access to liver biopsy should not exclude appropriately selected patients from having access to Hepatitis C Virus treatment.
Combination therapy leads to rapid improvements in serum ALT levels and disappearance of detectable Hepatitis C Virus RNA (end of treatment response) in up to 70% of monoinfected patients. For patients with genotype 2 or 3, response rates in studies are 75-90%. For patients with genotype 1, response rates are 30-46%. Preliminary data from ongoing studies suggest that HIV-coinfected patients will have lower response rates. Success depends on several factors including genotype, viral load, and stage of disease. For patients who maintain negative Hepatitis C Virus RNA for 24 weeks after stopping Hepatitis C Virus therapy, results from several studies show 98% remain Hepatitis C Virus RNA negative (sustained response). Small studies following patients for up to 11 years show well over 90% of those who achieve a sustained response remain Hepatitis C Virus RNA negative. In some patients who were Hepatitis C Virus RNA negative, Hepatitis C Virus could no longer be found in the liver. Unlike the situation with HIV, the Hepatitis C Virus virus cannot integrate into the host genome, and therefore eradication of the virus is possible. At the NIH consensus panel, Dr. Jay H. Hoofnagle pronounced Hepatitis C Virus "curable".18 Indeed, since the last consensus panel on Hepatitis C Virus convened in 1997, the availability of highly effective combination therapy that can eradicate Hepatitis C Virus infection has lead many experts to consider treatment where previously they might not have treated. In order to evaluate the clinical outcomes and survival, however, studies of long-term follow-up for these patients and coinfected patients is necessary.
SPECIAL CONSIDERATIONS FOR HIV/Hepatitis C Virus CO-INFECTION
All HIV-infected persons should be screened for Hepatitis C Virus. The 2002 NIH consensus panelists recommended that studies are needed to determine the best strategies for treating Hepatitis C Virus and HIV co-infected patients. Co-infected patients may have an accelerated course of Hepatitis C Virus disease. As a result, some clinicians believe that early treatment of Hepatitis C Virus is indicated in those who are HIV infected. Thus far, studies of co-infected individuals have enrolled mainly patients with "stable" (usually defined as CD4 counts >300 and HIV viral loads <5000) HIV infection and well-compensated liver disease. Preliminary studies suggest that combination (IFN/RBV) therapy is more efficacious than IFN monotherapy in those who are co-infected.19
Small studies done several years ago reported that Hepatitis C Virus and HIV-co-infected patients responded to therapy just as well as mono-infected patients.20 More recently, better designed studies suggest the response rate in co-infected patients is likely to be lower than in those who are not HIV-infected. This reduced response may be attributed to the impairment HIV causes to the immune system and/or higher therapy discontinuation rates due to drug side effects and toxicities. Although it has not yet been well researched, patients co-infected with HIV may require 48 weeks therapy or longer regardless of whether they have genotype 1 or 2. Speaking at the NIH Consensus Conference, Dr. David Thomas of Hopkins suggested that the "balance has shifted" in favor of treatment of HIV-infected patients, even though larger studies will be needed to determine the rate of progression of Hepatitis C Virus in these patients, the duration of therapy that may be required and their overall response to treatment (See Figure 3). When asked by a Consensus Conference audience member what CD4 cutoff should be used to exclude patients from treatment, Dr. Thomas could not define one. He went on to say that good control of HIV infection was essential if Hepatitis C Virus were to be treated, but otherwise he could see no contraindication to treatment of HIV-infected patients.21
An additional concern is that co-infected patients may experience more side effects and adverse events, such as anemia and leukopenia. These side effects can make adherence to therapy more challenging.
A high percentage of co-infected patients are African-Americans and greater than 90% have genotype 1. Patients with genotype 1 have a lower rate of response to therapy. One study showed that African-Americans with genotype 1 experienced lower response rates than Caucasians with genotype 1, suggesting that factors other than genotype may also be responsible.23 These factors have not been well defined, and merit further research.
Side effects of therapy can include fatigue, irritability, emotional distress, weight loss, and depression. Adverse laboratory events can include anemia, leukopenia, and thrombocytopenia. More uncommonly, therapy can cause autoimmune disease (particularly thyroid disease), and suicidal ideation or attempts. For these reasons, close follow-up of patients on therapy is essential. Ideally, patients should be seen weekly for the first four weeks after initiation of therapy. After the first month, patients who are doing well can be seen less often i.e. every four weeks. It is important for prisoners to be able to inform the clinician of all side effects they experience so that effective interventions can be initiated. Support services are needed to guide patients through the process of starting and maintaining therapy.
OUTCOMES OF THERAPY
For those without cirrhosis, achieving a sustained response to therapy should prevent progression to decompensated liver disease or cancer. Experts believe that a sustained response to therapy among people with cirrhosis should also prevent progression, but studies are still inconclusive.15 Several studies previously conducted provide evidence that IFN use in patients with cirrhosis and non-responders can slow or reverse disease progression.24 These results indicate that patients with cirrhosis who achieve a sustained viral response have a good chance of stopping and perhaps reversing disease progression. Further study, however, is necessary.
Inmates at risk
The most comprehensive analysis of Hepatitis C Virus in the correctional system was compiled by Ted Hammet of Abt Associates in the context of a report for the NIJ and the NCCHC's report to Congress.5 In this report, the researchers estimated that approximately 30% of the total US population living with chronic Hepatitis C Virus was released from prisons and jails in the US in 1996 (1.0 to 1.25 million people). The overall prevalence of Hepatitis C Virus infection among inmates is estimated to be about 17% nationally, almost 10 times higher than the estimated 1.8% prevalence in the general US population.6 In certain sub-populations of inmates (ie those who are HIV-positive or who have abnormal liver function tests) the Hepatitis C Virus prevalence can be even higher. Furthermore, the Hepatitis C Virus/HIV co-infection rate is about a third higher in incarcerated women than incarcerated men, which reflects womens' participation in Hepatitis C Virus and HIV risk behaviors.4
HEPP News recently performed a survey to assess the current practices regarding Hepatitis C Virus management in state correctional facilities.7 Based on preliminary data from this study, the prevalence of Hepatitis C Virus in inmate populations ranges between 9% and 39% by state (Figure 2).
Approximately 50% of persons with chronic Hepatitis C Virus are unaware of their infection.5 Only about 2/3 of chronically infected individuals develop symptoms of infection, and these symptoms are often non-specific malaise and fatigue.8 The CDC states that "[t]esting persons in settings with potentially high proportions of injecting-drug users (e.g., correctional institutions, HIV counseling and testing sites, or drug and STD treatment programs) might be particularly efficient for identifying Hepatitis C Virus-positive persons."9
Cost associated with Hepatitis C Virus screening can be reduced by focusing on certain sub-populations that have particularly high prevalence of Hepatitis C Virus infection (see HEPP News April 2001 p2).10 There are a variety of tests available for diagnosing Hepatitis C Virus. Enzyme immunoassay (EIA) is the most cost-effective screening test; recombinant immunoblot assay (RIA) helps confirm positive EIA results, while polymerase chain reaction (PCR) is the "gold standard" for confirming active Hepatitis C Virus infection with viral replication. In rare cases, the Hepatitis C Virus antibody tests can give false negatives. Repeat antibody or viral load testing may be necessary when there is a significant suspicion of Hepatitis C Virus infection in HIV infected patients, as low CD4 T cell counts have also been associated with false negative Hepatitis C Virus antibody and PCR tests.8, 11, 12
Testing for hepatitis infection informs the patient and physician about the potential for and possible existence of liver damage, and it should serve as an important prompt for a discussion about risky behaviors (particularly if the patient is not yet Hepatitis C Virus infected), of factors associated with more rapid progression of Hepatitis C Virus disease (such as alcohol abuse) and about the potential for transmission to others.13
Who should get treated?
A number of correctional facilities have developed protocols for deciding which patients should consider initiating treatment while incarcerated (HEPP News, April 2001).I HHS recommends antiviral treatment for "patients with chronic hepatitis C who are at greatest risk for progression to cirrhosis. These persons include anti-Hepatitis C Virus-positive patients with persistently elevated ALT levels, detectable Hepatitis C Virus RNA, and a liver biopsy that indicates either portal or bridging fibrosis or at least moderate degrees of inflammation and necrosis."30
I. See protocol developed by Lou Tripoli and colleagues for CMS in HEPP News, April 2001, p.6 for example