In this study young, HCV-infected IDUs had much higher ALT levels than normal. This is the first known study to demonstrate that cessation in alcohol use is associated with decreased ALT and AST among young, HCV-infected IDUs, whereas uptake of alcohol use is associated with an increase in ALT and AST. These changes were particularly pronounced in those with presence of HCV RNA in sera, providing evidence of syngeristic effects of HCV replication and alcohol metabolism on liver damage. Although self-reported alcohol use did not differ by intervention arm, there was modest evidence of intervention efficacy based on ALT and AST. However, other factors seemed to have a greater influence on change in alcohol use behaviors including, ever receiving a diagnosis of liver disease, marijuana use, and homelessness. While there was an encouraging increase in alcohol abstinence at three and six months follow-up among all of the HCV-infected IDUs in this study, many reported fluctuating between use and abstinence, which has been observed previously among a mixed sample of non-IDU and IDU in drug treatment [23
These findings support current guidelines recommending testing of high-risk individuals for HCV and providing counseling for alcohol cessation. One of our novel findings was a dose-response effect between ALT or AST and alcohol use (i.e., reduction in ALT and AST levels with abstinence and increases in levels with uptake of alcohol consumption) among young, HCV-infected individuals. After stratifying by presence of HCV RNA in sera, this effect was observed only in those with detectable of HCV RNA. Given that these were all young IDUs who had injected drugs for a mean and median of 6 years, they were not likely have been infected with HCV for prolonged durations, suggesting that alcohol use and active HCV-infection may synergistically damage the liver over a short period, which is supported by evidence from clinical studies [9
]. These findings highlight the importance of active case identification, HCV RNA testing in HCV antibody-positive individuals, and alcohol cessation counseling for HCV-infected IDUs of all ages who are RNA positive.
Normal ALT levels are generally accepted as less than 40 IU/L [7
]. In this study, median ALT scores at baseline were 28% higher than this overall, and 38% higher among those reporting alcohol use; which is surprising given that ALT and AST in younger individuals tends to be lower [24
]. Elevated ALT is suggestive of liver fibrosis [25
] and higher HCV viral load [27
]. Very few participants (4% at baseline and follow-up) had AST/ALT ratios >2, but 22% had AST/ALT ratios > 1 which may suggest higher viral loads and active HCV damage. Participants’ young age, and relatively short period of injecting, suggests a short duration of HCV infection, implying that changes observed in AST and ALT with alcohol use may be representative of the synergistic damage in HCV RNA positive individuals.
Given the importance of alcohol cessation demonstrated in our study, it is disappointing that our intervention only showed modest associations with reduction in ALT and AST and no associations with self-reported alcohol use. However, the intervention was not primarily designed for this purpose. Given the intervention’s efficacy in reducing distributive needle sharing [17
], additional tailoring to incorporate liver function test results into intervention messages may yield greater reductions in alcohol consumption. Brief alcohol interventions may be highly effective in achieving reductions in alcohol use [28
]. In particular, short interventions incorporating motivational interviewing (MI) have been shown to reduce alcohol consumption among IDU [15
] and HCV-infected IDU in treatment [16
]. A combination of approaches may be necessary for one intervention to address both injection equipment sharing and alcohol use, as evidenced in a recent control trial comparing MI and education, which demonstrated efficacy in reducing alcohol consumption in both arms, but not receptive needle sharing [30
]. Incorporating MI into the STRIVE intervention might be effective in combining alcohol cessation with reductions in distributive needle sharing.
The differences we observed in biological and behavioral measures of alcohol consumption may be due to greater accuracy of biological measures, as compared to self-reported behaviors; participants may be reluctant to report behaviors or may not remember when they consumed alcohol. It is more likely that ALT and AST levels were more sensitive to reductions in alcohol use, which was not captured by our survey measures. These findings also suggest the need for both behavioral and biological markers in measuring alcohol consumption in interventions targeting HCV-infected individuals.
Most participants recalled having received counseling to reduce alcohol use at HCV diagnosis and those who had a previous diagnosis of liver disease transitioned to alcohol abstinence more rapidly, reinforcing the notion that medical counseling may have some impact on behavior change for young IDUs. The increase in the number of participants reporting abstaining from alcohol use in either study arm from baseline through six-month follow up is encouraging and suggests that educational messages aimed at liver wellness may influence young IDUs’ alcohol use behavior.
Not surprisingly, we found that those who were homeless transitioned to abstinence more slowly. Homelessness is related to decreased resources and increased risk behaviors among drug users [22
] and was previously associated with higher AUDIT scores in a previous analysis of the STRIVE baseline sample [32
]. It is critical to provide additional resources to homeless IDUs in order to support and encourage opportunities for drug and alcohol treatment.
Similarly, associations observed between transitioning to alcohol use and smoking marijuana were not unexpected. Simultaneous poly-substance use, or using more than one substance at once, is commonly reported with marijuana and alcohol [33
]. While this finding suggests that alcohol cessation interventions may be more effective with inclusion of marijuana cessation, other studies suggest that cessation of marijuana may result in increased alcohol use [35
]. Future studies examining the effects of marijuana use on alcohol cessation in current and former IDUs could assist in developing more effective alcohol cessation interventions among HCV-infected IDUs.
Although this study involved a randomized controlled trial, there were some limitations. Since alcohol cessation was not the primary outcome of our intervention, the study was neither powered nor designed to measure alcohol cessation as an endpoint. Dynamic changes in alcohol use observed over this six-month period suggest that this duration was too short for estimating long-term trends in alcohol use. Studies of alcohol use patterns over a longer period of time could provide more information on predictors of changes in alcohol use and durability of a behavior change intervention. Additionally, more precise measures of amount of alcohol used daily, would have been helpful in assessing reductions in use, not just cessation, and determining thresholds of dangerous amounts of alcohol use in HCV-infected IDUs. Changes in alcohol use among a mixed sample of IDU and non-IDU in drug treatment over a 4–5 year period, demonstrated similar fluctuations in alcohol use, but noted that abstainers were unlikely to become heavy users when transitioning to alcohol use [23
]. By chance, participants randomized to the intervention group reported less alcohol use at baseline than did those in the control arm. This lack of balance in randomization was also noted when examining efficacy of this intervention in reducing distributive needle sharing [17
]. However, this was unlikely to affect our analyses as there were no observed effects of the intervention on reported alcohol use, self-reported alcohol use was adjusted for in models examining the effect of the intervention on ALT and AST, and other measures of alcohol use examined changes in behavior, which would have been detected regardless of baseline use.
Since HCV RNA was only measured at six-month follow-up, data was missing for some participants, and we were unable to measure changes in HCV RNA positivity from baseline to follow-up. However, it is unlikely that HCV RNA status changed over the relatively short study period. Additionally, AST and ALT were measured at only two time points, and natural fluctuation may occur; however, it is unlikely that fluctuation in AST and ALT would follow the patterns observed by changes in alcohol use and would be less extreme among those not changing alcohol use patterns. In addition, some factors known to affect AST and ALT (e.g., obesity, coffee, etc ) [24
] were not measured in this study. In light of the young age of the sample, it is reasonable to assume that AST and ALT should be relatively low [24
], and given the relationship between alcohol use and increased ALT and AST specific to HCV RNA-positive IDUs, it is unlikely that the associations observed could be explained by these unmeasured factors. Follow-up data were only available on 85% of the originally randomized sample; however, no significant differences were observed between those who were followed up and those who were not. All self-reported outcome measures may suffer from socially desirable response bias; however, this was likely to be minimized by the use of A-CASI [19
This study provides further critical evidence that alcohol cessation is an important goal for chronically HCV-infected individuals of any age, providing an important justification for screening high-risk populations. Our data suggest that alcohol cessation can have profound effects on reducing ALT and AST among young IDUs with active HCV infection. Some young, HCV-infected IDUs are motivated to reduce their alcohol use, but may require more intensive alcohol cessation interventions to realize meaningful, long-term reductions. Interventions aimed at reducing alcohol consumption in this population may be particularly successful if they are integrated into clinical care and monitoring of HCV infection.