In this study, we assessed the ability of the KMSK scale, when self-administered, to assess the prevalence of lifetime drug use and dependence in a large number of patients with viral hepatitis. The use of a standardized questionnaire identified prior or current drug use in a significantly higher percentage of our patients than that recorded by health care professionals in the medical record. We found that approximately two-thirds of patients reported prior alcohol and tobacco use. The finding that one-third of individuals reported lifetime dependence to heroin or cocaine and that one-sixth were co-dependent on both substances, is quite important because of the adverse effect that drug use has on adherence to anti-HCV medication. The finding that approximately one-fifth of patients reported prior alcohol dependence is also significant because alcohol has been shown to synergize with HCV as a promoter of fibrogenesis, to reduce the sensitivity to interferon, and to decrease adherence to anti-viral therapy [20
]. The finding of such a high level of dependence in a hepatology clinic is a surprise; heretofore, addiction has not been identified to this extent as a concomitant disease, which is often deserving of treatment. These results argue for active screening for addiction among patients with viral hepatitis.
Integration of HCV and HIV treatment with addiction management is important as each can reinforce compliance with the other. As approximately three-fourths of our patients had advanced hepatic fibrosis, HCV treatment was strongly indicated in the majority of our study subjects. Active screening for addiction among HCV-infected patients under therapy should be pursued as active drug use may compromise compliance with the therapeutic regimen, and treatment of addiction might increase the efficacy of antiviral agents. Opiate replacement therapy, methadone or buprenorphine, has been shown to prevent “relapse” in rodent models [26
] and humans [28
]. Furthermore, it has been shown to normalize the hypothalamus-pituitary-adrenal axis in humans [29
]. Although effective pharmacologic therapy does not presently exist for cocaine addiction, abstinence-based programs are recommended [30
]. When the addicted patient is stabilized, HCV treatment efficacy has been shown to be equivalent to that of a nonaddicted population [31
]. In contrast, those who relapse to active drug use demonstrate significantly lower levels of adherence [33
], which potentially could compromise treatment efficacy [34
Assessment of illicit drug use conventionally relies on direct patient questioning during a medical evaluation, a process that may be inaccurate because health care providers may be reluctant to inquire about drug use and because patients may be hesitant to discuss this topic. Alternatively, drug use assessment via a standardized questionnaire, such as the KMSK scale, has several advantages. As we illustrate, the scale can detect drug use in significantly more individuals than were detected through the medical record. The scale could be completed by patients while awaiting their clinic appointment and subsequently scanned into the electronic medical record. The medical record provides a permanent repository that permits instantaneous information retrieval and restricts access to maintain patient confidentiality.
Self-administration of the KMSK scale has several limitations and advantages. As the scale was originally designed and validated to be administered during an interview, the validity and reproducibility of patients’ responses and cutoff scores for a diagnosis of dependence when the instrument is self-administered have not been determined. Additional limitations include the availability of the KMSK scale in other languages, i.e., only Hebrew and Spanish, failure to distribute or to collect the scale by the clinic staff, or incomplete or partial responses to individual items. While the majority of our sample (53%) completed all four sections of the KMSK scale, a significant minority (10%) did not complete any section. The completion rate for each KMSK section may also reflect the degree of stigma attached to the use of a particular substance. As we observed, for example, the completion rate for alcohol and tobacco was markedly higher than for the illicit drugs, cocaine and heroin. This suggests that part of the explanation for the incomplete KMSK scales that we received might result from an individual’s fear of stigmatization because of the prior use of illicit substances. Advantages of self-administration include potential distribution to large numbers of patients in diverse venues, such as community-based clinics or sexually transmitted diseases clinics, where the scale could be utilized as a surveillance instrument to identify those at high-risk for HCV infection.
While we used the shorter, validated lifetime version of the KMSK scale in this study, other forms of the scale have been developed, and their clinical relevance should be assessed in future studies. In addition to lifetime use, subsequent iterations of the scale assess heroin, cocaine, alcohol and tobacco use and dependence in the past 30 days, and sections covering illicit benzodiazepene, amphetamine, and marijuana use and dependence have been added. Separate sections of the scale can be administered individually tailored to a specific purpose. For example, assessment of alcohol dependence in a hepatology clinic may afford an opportunity to discuss the detrimental effects of alcohol on hepatic fibrogenesis. Although assessment of tobacco use may be more frequently assessed in a drug treatment facility than in a hepatology practice, counseling by any health care provider about the dangers of tobacco use may augment cessation [35
]. Selecting the sections of the KMSK scale most relevant to the clinical venue and the disease under evaluation will streamline its administration while maximizing the utility of the information gathered for the clinician or the researcher.
We also investigated the relationship between the use of specific drugs and demographic, virologic, and patient-derived variables. We found significant associations between cocaine use and HIV/HCV co-infection, alcohol use and elevated HCV RNA levels, heroin use and increased CD4+ cell counts, and heroin use and higher stages of hepatic fibrosis.
Investigation of the epidemiology of drug use-related infectious diseases may identify high-risk populations that could benefit from targeted screening. The association we observed between cocaine dependence and HIV/HCV co-infection suggests that noninjection drug use may be an important route of HIV transmission [25
] and that cocaine users should be screened for these infections. Although injection drug use has conventionally been the more important route of HCV transmission [3
], a higher percentage of HCV-infected patients reported cocaine use, suggesting that this route of self-administration could be important for HCV transmission. These drugs can also have pleiotropic effects on the immune system that may underlie the associations described in the present work. Since the early days of the AIDS epidemic, heroin use in the absence of HIV-1 infection has been known to be associated with increased number of T-cells, including CD4+
cell counts [36
], along with reduced numbers and function of natural killer cells. Additionally, the immunosuppressive effect of alcohol may lead to diminished immune control of viral replication resulting in significantly higher HCV RNA levels as we observed in this study [37
In summary, we have demonstrated that a standardized scale identifies a high percentage of patients with a prior history of cocaine and heroin use attending a hepatology clinic. Furthermore, the KMSK scale identified an unexpectedly high percentage of patients with dependence to cocaine or heroin and co-dependence to both substances. Given the high prevalence of use and dependence to licit and illicit drugs, routine screening for addiction should be integrated into the clinical management of patients with viral hepatitis.