IMPACT OF CHRONIC VIRAL HEPATITIS ON PT D/C OF TX FOR LATENT TB-STUDY 26A (HIV)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The primary objective is to evaluate the association between chronic viral hepatits and permanent discontinuation of treatment for latent TB infection (LTBI) due to hepatotoxicity. Secondary objectives are: to describe the association between chronic viral hepatitis and temporary discontinuation of treatment for LTBI due to hepatotoxicity; to describe the association of HIV infection with hepatotoxicity requiring treatment discontinuation during treatment for LTBI (among the subset of patients with known HIV serostatus); to describe the synergism between HIV and HCV infection associated with hepatotoxicity requiring treatment discontinuation during treatment for LTBI; and to compare the time to onset of hepatotoxicity requiring treatment discontinuation during treatment for LTBI that is associated with alcohol abuse, chronic viral hepatitis, and/or HIV infection. RESEARCH PLAN: Cases, within four weeks of the time they fulfill the study definition of a case, will undergo the informed consent process and counseling regarding chronic viral hepatitis, answer a brief questionnaire regarding alcohol and concomitant medication intake, and have blood drawn for screening for acute and chronic viral hepatitis. This will require 5 to 10 cc of blood to be collected in one standard red top tube or separator tube, for storage and shipping to CDC. This tube is in addition to any testing the local clinician is conducting. Controls who agree to participate in the sub-study will undergo the informed consent process no later than the Week 8 study visit. At the Week 8 routine study visit, they will undergo counseling regarding chronic viral hepatitis, answer a brief questionnaire regarding alcohol and concomitant medication intake, and have blood drawn for screening for acute and chronic viral hepatitis. METHODS: The study design is a case-cohort study within enrollees in Study 26, which compares the efficacy of two treatment regimens for latent TB infection. A case is a clinical trial participant in either treatment arm who has study drug(s) held for any length of time associated with: (1) AST greater than or equal to 3 the upper limit of normal (ULN) and symptoms or signs of hepatitis; or (2) AST greater than 5 ULN with or without symptoms or signs of hepatitis, and who consents to be in this sub-study. Five and one-half percnt of patients enrolling in Study 26 will be randomly selected as potential controls for the sub-study at the time of enrollment in the parent study. CLINICAL RELEVANCE: Preliminary data suggst that persons with chronic viral hepatitis, with or without HIV co-infection, experience more hepatotoxicity during treatment with anti-tuberculosis drugs than do those without chronic viral hepatitis. The current U.S. TB control emphasis on expanding targeted tuberculin tesing and treatment of latent TB infection will expose populations with chronic viral hepatitis to this potential risk.