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AUGUST 2006
Spotlight:
Spotlight - Hepatitis C Virus Management in Correctional Settings: Discussion Bethany Weaver, DO MPH Infectious Disease Consultant
Armor Correctional Health Services Disclosures: Consultant: Merck & Co. Speaker's Bureau: Merck & Co., Gilead Sciences, Inc. Advisory Board: Merck & Co. Stockholder: Pfizer Inc Case 1: A 36 year-old man presents to your clinic five days after his arrest for driving with a suspended license. He reports that he has a 10-year history of hepatitis C virus (HCV) infection and was diagnosed with AIDS after developing Pneumocystis jiroveci pneumonia (formerly known as Pneumocystis carinii pneumonia). He has a prior history of injection drug and alcohol use but has not used alcohol or injected drugs for five years. He has a history of depression without psychosis but one previous suicide attempt seven years ago. Four years ago he was prescribed a selective serotonin reuptake inhibitor (SSRI) for depression and he continues on this antidepressant without symptoms of major depression. At the time of his arrest he was in HIV care at a local community clinic. He is receiving didanosine (Videx-EC), lamivudine, and efavirenz (Sustiva) and his most recent laboratories obtained 2 months ago revealed a CD4 cell count of 250/mm3 and undetectable HIV-1 viral load. He has never received treatment for HCV. You ask him what the status of his liver disease is (i.e. liver biopsy results, HCV genotype, HCV quantitative viral load) and he tells you he has "no idea" and that he has never had a biopsy. Question: Assuming he will only be at the jail for a short time (i.e. 3 months or less) thereby making HCV treatment at your jail facility an unrealistic option, what information could you offer this inmate so that his chances of survival are improved after release? Discussion: Given the time constraint, counseling needs to focus on providing the patient with the information that will enable him to make informed choices regarding his HCV care once he returns to the community. That HCV and subsequent cirrhosis is now a leading cause of death among those with HIV infection is important for this inmate to appreciate. The inmate should be informed that there are many potential benefits of HCV treatment with pegylated interferon (peg-IFN) plus ribavirin. These include the possibility of achieving HCV eradication (i.e. sustained virologic response, SVR). The odds of such eradication depend on several factors including the genotype of the infecting virus and the degree of liver damage. If he has genotype 1 HCV - the most common in the US - he would have an approximately 15-40% chance of HCV eradication as someone co-infected with HIV. Large trials demonstrate that additional factors associated with SVR include lower baseline HCV RNA level (less than 800,000 IU/ml), absence of cirrhosis, lower body weight (< 75 kg), younger age, tolerance of a higher ribavirin dose (at least 10.6 mg/kg per day in those with genotype 1), and adherence to treatment. Beyond cure, there are other potential benefits of HCV therapy including reduced risk of liver failure and complications related to HCV, such as cryoglobulinemia and hepatocellular carcinoma, and possible reversal of early cirrhosis. HCV treatment may also retard or reverse disease progression for individuals with hepatic fibrosis who are at greatest immediate risk for end stage liver disease and death. However, this inmate should also be cautioned regarding the demands and risks of HCV therapy. The patient should understand that treatment does require injected and orally administered medications and can lead to an array of predictable side effects such as worsening depression and fatigue. Most of these adverse effects are reversible with discontinuation of HCV pharmacotherapy, although a minority may be permanent. Many patients and providers remain unaware that approximately 15% of individuals with HCV antibodies do not have detectable levels of HCV in the blood and have probably cleared the virus on their own. Thus all patients who are seropositive for HCV should have a plasma HCV RNA level checked. Importantly, all persons with HCV infection and a history of substance and alcohol dependency must be informed that many providers will not offer HCV treatment unless the patient has been "clean" from alcohol and/or illicit drugs for six months or more, despite a paucity of supporting data. This incarceration is a good opportunity to discuss prevention of HCV transmission including shared needles, sexual behaviors involving blood such as fisting, and others (perinatal, occupational, hemodialysis, household exposure to contaminated blood). Referral to a clinic or center where HCV therapy is available should be made prior to release. Case 2: Now assume the same inmate is seen by you in prison after being sentenced to three years. Questions: If HCV treatment is an option at your facility, what would be the most appropriate work-up for this patient before beginning a discussion of treatment with him and why? If you establish that he is a good candidate for HCV treatment, what other tests might you order before treatment? What toxicities associated with peg-IFN and ribavirin should you be aware of and counsel your patient about? Would you continue didanosine, lamivudine, and efavirenz during the HCV treatment? Discussion: Conduct a thorough physical examination looking for signs of decompensated liver disease (e.g. ascites) and evidence of an untreated opportunistic infection. Decompensated liver disease and/or untreated opportunistic infection represent contraindications to HCV treatment. HCV treatment could be revisited as a potential option only if the opportunistic infection is treated and the patient stabilizes on treatment; once decompensation occurs, it is too late for peg-IFN - refer for liver transplant. In individuals with decompensated liver disease/cirrhosis, an ultrasound and alpha-fetoprotein level every six months to screen for hepatocellular carcinoma should be performed. You might consider performing a liver biopsy to rule out other correctable causes contributing to the liver failure (e.g. hepatic steatosis secondary to antiretroviral therapy, iron overload) if non-invasive evaluations (e.g. serum alpha 1 antitrypsin, iron studies) are inconclusive, or to determine the degree of fibrosis. Experts currently recommend treating those with advanced HIV/AIDS (absolute CD4 cell count less than 200/mm3) with antiretroviral medications first, in an effort to achieve a CD4 cell count that is above 200/mm3 prior to HCV treatment, though some patients may not achieve this goal despite having a fully suppressed HIV viral load and would still be candidates for HCV treatment. As far as laboratory studies, as described above, HCV genotype and RNA quantitative viral load should be ordered as should a complete metabolic panel (chemistries, transaminases, total bilirubin, albumin) ,a complete blood count with platelets, and a CD4 cell count. If the HCV RNA viral load is undetectable and remains undetectable at subsequent visits, no HCV treatment is necessary since there is no evidence of chronic HCV infection. In addition, knowing the HCV genotype allows you to give the patient a projected prognosis with treatment, as not all genotypes respond the same to treatment (see figure 1 - "Response to pegylated interferon alfa-2a/ribavirin in HCV patients by genotype"). A subsequent evaluation for HIV/HCV co-infected patients who have evidence of viremia and no evidence of decompensated liver disease should include a prothrombin time-international ratio, ferritin, alpha 1 antitrypsin level, and ceruloplasmin to screen for other causes of hepatic fibrosis, hepatitis A and B serologies to screen for those eligible for immunization, a pregnancy test for women, a rapid plasmin reagent (RPR) to screen for syphilis, TSH, diabetes and depression screen, antinuclear antibody to screen for autoimmune hepatitis, a retinal exam, especially for those with pre-existing retinopathies of other causes (e.g. diabetes mellitus, cytomegalovirus, hypertension), and a liver biopsy, particularly those with HCV genotype 1. A baseline eye exam is recommended because the use of interferon has been associated with retinal vascular occlusion and hemorrhages, cotton-wool spots, and optic neuropathy. A creatinine clearance less than 50 mL/min contraindicates the use of ribavirin, which is a component of the standard HCV treatment regimen. However, peg-IFN may still be used alone in patients with significant renal impairment. Other contraindications to HCV treatment with ribavirin and peg-IFN include autoimmune disease, coronary artery disease, pancreatitis, pregnancy, and current major depression - especially if untreated/unstable from a mental health perspective. Ongoing injecting drug or alcohol use is not necessarily a contraindication to HCV treatment and should be evaluated on a case-by-case basis. HCV treatment may be deferred in those with only mild histologic changes, in which case a liver biopsy could be repeated in 2-3 years to assess for disease progression. If abnormalities such as renal impairment, anemia, thyroid disease, depression, diabetes, retinopathy, iron deficiency or overload are detected, they should be addressed and controlled before considering HCV treatment. When co-administered with peg-IFN and ribavirin, the use of several antiretroviral agents have been associated with higher risk of liver toxicity, such as hepatic steatosis and failure. For example, didanosine is absolutely contraindicated with HCV therapy given the increased risk of hepatic steatosis and lactic acidosis. In this case, didanosine must be discontinued if the patient is to receive HCV therapy. Alternatives include tenofovir and abacavir. Anemia secondary to the co-administration of zidovudine (Retrovir) and ribavirin can occur and be particularly severe requiring the use of other costly measures, such as erythropoietin and reduction of the dose of ribavirin - decreasing the likelihood of achieving SVR. Therefore, appropriate alternatives to zidovudine should be sought during HCV therapy. There is a potential inhibitory effect of ribavirin on zidovudine, and stavudine (Zerit) observed in vitro, but this has not been reported as a clinically significant affect in vivo. Neuropathy, a common side effect among those taking stavudine, didanosine, or zidovudine, may be exacerbated in patients also receiving peg-IFN. Please refer to Tables 1 and 2 for rules for discontinuation and dosing of peg-IFN and ribavirin in HIV/HCV co-infected patients. References:
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