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The Correctional Doctor's Dilemma: Hepatitis C Treatment
Anne S. De Groot, M.D.*
Joseph Bick, M.D.**
Editors HEPP News

The hepatitis C virus (Hepatitis C Virus) 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 Hepatitis C Virus, and Hepatitis C Virus causes an estimated 8,000-10,000 deaths each year in this country.  75-85% of those infected with Hepatitis C Virus develop chronic liver disease (1). 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 Hepatitis C Virus infection (2). Of those who develop chronic liver disease, perhaps 20% will eventually progress to cirrhosis and several percent will develop liver carcinoma (1).

Hepatitis C Virus Epidemiology in Corrections
During the 1980's an average of 230,000 new Hepatitis C Virus infections occurred each year in the US (3). The number of new infections declined after the introduction of improved methods for the detection of Hepatitis C Virus in the blood supply. 

Currently, most Hepatitis C Virus transmission is associated with injection drug use (IDU). 79% of current IDUs have Hepatitis C Virus infection (3). Young IDUs acquire Hepatitis C Virus infection at rates four times higher than they acquire HIV; after five years of injection drug use, 90% of users are Hepatitis C Virus infected. Non-Hispanic blacks and African Americans have higher rates of Hepatitis C Virus infection and chronic disease than whites; most cases of Hepatitis C Virus infection are found among persons who are male, members of minority populations, and 30 to 49 years of age (3). 

Given the linkages between Hepatitis C Virus 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 Hepatitis C Virus pass through correctional facilities each year (2). The prevalence of Hepatitis C Virus 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, Hepatitis C Virus infection rates among inmates have ranged between 30 and 40% (5). Estimates of Hepatitis C Virus 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 Hepatitis C Virus co-infection rate than HIV-infected incarcerated men (see Figure 2).

Who should get tested for Hepatitis C Virus?
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 Hepatitis C Virus 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 Hepatitis C Virus antibody test accuracy, however a recent study by Thio et al. suggested that third-generation antibody based assays are sufficiently accurate for diagnosis (13).

Treatment Options 
There are two basic approaches to the treatment of Hepatitis C Virus: 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 Hepatitis C Virus 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 Hepatitis C Virus treatment algorithm.)

HIV and Hepatitis C Virus Co-infection
Analyses of the effect of Hepatitis C Virus 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 Hepatitis C Virus liver disease. Persons who are co-infected (HIV and Hepatitis C Virus) 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 Hepatitis C Virus or HBV (1).

The impact of Hepatitis C Virus infection on HIV infection is less clear. In some studies, Hepatitis C Virus 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 Hepatitis C Virus genotypes 1a and 1b (17, 18).

Hepatitis C Virus 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 Hepatitis C Virus co-infection, as hepatotoxicity to anti-HIV therapy appears to be more common among these individuals. Therefore, patients who are co-infected with Hepatitis C Virus 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 Hepatitis C Virus treatment, co-infected patients are not more likely to relapse after Hepatitis C Virus 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.

Cost Benefit Analyses
With the high prevalence of Hepatitis C Virus infection among incarcerated individuals, there is a concern that treatment of Hepatitis C Virus could overwhelm some system's healthcare budgets.  Some cost benefit analyses, however, have provided data in favor of treatment of those with Hepatitis C Virus. 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 Hepatitis C Virus, 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

Conclusion
As with many other chronic medical conditions, much of the morbidity and mortality attributable to Hepatitis C Virus 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 Hepatitis C Virus 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 Hepatitis C Virus have influenced some correctional systems to adopt highly restrictive inclusion and exclusion criteria for Hepatitis C Virus 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 Hepatitis C Virus 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 Hepatitis C Virus 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 Hepatitis C Virus 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 Hepatitis C Virus therapy. Cost-sharing between correctional facilities and public health is a subject that needs to be explored, particularly if 30% of all people with Hepatitis C Virus in the community cycle through correctional facilities. Treatment of these individuals to reduce Hepatitis C Virus morbidity and mortality will have broad implications for general public health.