Trial Outcomes & Findings for HCV and Co-morbid Alcohol Use Disorders: A Translational Investigation of Antiviral Therapy Outcomes on CNS Function (NCT NCT03902366)

Of 119 assessed for eligibility, 63 met inclusion criteria (38 AUD-/HCV-, 20 AUD+/HCV-, 5 HCVc) and were enrolled in the study. 17 participants were excluded after enrollment. Due to low recruitment numbers and no significant differences between the HCV groups, individuals with a history of HCV were assigned to one group (HCVc).

HCV and Co-morbid Alcohol Use Disorders: A Translational Investigation of Antiviral Therapy Outcomes on CNS Function

The Attention Module is a marker of attentional capacity, working memory, and processing speed. T-scores are derived by converting raw scores using normative tables that account for age and education. T-scores range from 20 to 80 with a mean of 50 and standard deviation of 10. Lower T-scores (below 40) indicate below average performance and higher T-scores (above 60) indicate above-average performance. NAB Attention Module subtests include: Dots, Numbers and Letters, Driving Scenes, Digits Forward, and Digits Backward. Subtest scores were averaged to compute a total score. Change was calculated as the value at 6 months minus the value at baseline. Larger numbers represent greater improvement in attention performance, a score of 0 indicates no change in performance and negative numbers indicate a worsening of attention performance over time.

The Memory Module is a marker of learning, recall, and recognition memory. T-scores are derived by converting raw scores using normative tables that account for age and education. T-scores range from 20 to 80 with a mean of 50 and standard deviation of 10. Lower T-scores (below 40) indicate below average performance and higher T-scores (above 60) indicate above-average performance. NAB Memory Module subtests include: List Learning, Shape Learning, Story Learning, and Daily Living Memory. Subtest scores were averaged to compute a total score. Change was calculated as the value at 6 months minus the value at baseline. Larger numbers represent greater improvement in memory performance, a score of 0 indicates no change in performance and negative numbers indicate a worsening of memory performance over time.

The Executive Functions Module of the NAB is a marker of executive function, including problem-solving and mental flexibility. T-scores are derived by converting raw scores using normative tables that account for age and education. T-scores range from 20 to 80 with a mean of 50 and standard deviation of 10. Lower T-scores (below 40) indicate below average performance and higher T-scores (above 60) indicate above-average performance. NAB Executive Function Module subtests include: Mazes, Judgement, Categories, and Word Generation. Subtest scores were averaged to compute a total score. Change was calculated as the value at 6 months minus the value at baseline. Larger numbers represent greater improvement in executive function performance, a score of 0 indicates no change in performance and negative numbers indicate a worsening of executive functioning performance over time.

This outcome measure evaluates the change in the number of days of alcohol use from baseline to a 6-month follow-up, using the 30-Day Timeline Followback (TLFB) method. The TLFB is a structured, retrospective interview technique that allows participants to accurately recall their alcohol consumption patterns over the previous 30 days. For this outcome, the number of days on which alcohol was consumed will be assessed at baseline (the start of the study) and again at the 6-month follow-up assessment. A positive change would indicate an increase in the number of days of alcohol use, while a negative change would indicate a reduction in the number of days of alcohol use over the 6-month period.

The BART is a computerized measure of risk-taking behavior that concurrently measures several domains (i.e., risky decision-making, reward/negative outcome processing) during fMRI scanning. The ratio of balloon pumps made to maximum pumps allowed is a measure of risk-taking behavior. A ratio of 1 indicates that a participant inflated the balloon to its maximum allowed pumps, while a ratio closer to 0 suggests that the participant was much more conservative in their approach. Change was calculated as the value at 6 months minus the value at baseline and ranges from -1 to 1. A positive change indicates an increase in risk-taking behavior and a negative change indicates a decrease in risk-taking behavior over time.

The MID is a validated task to examine anticipatory brain responses to reward during fMRI scanning. This outcome measure evaluates the change in reaction time (RT) of participants in response to monetary reward cues during the MID. Reaction time is defined as the duration (in milliseconds) from the presentation of the cue to the participant's response (e.g., button press). The MID involves various reward conditions, including different monetary values and probabilities, allowing for an evaluation of participants' anticipatory responses to potential rewards. A positive difference indicates an increase in RT at 6-months compared to baseline, suggesting potential decreases in motivation, cognitive load, or changes in reward sensitivity. Conversely, a negative difference indicates a decrease in reaction time, which may reflect improved motivation, enhanced cognitive processing speed, or increased responsiveness to monetary incentives over time.

The Fatigue Severity Scale (FSS) is a 9-item self-report questionnaire designed to measure level of fatigue. The FSS is graded on a 7-point Likert-like scale ranging from 1 ("strongly disagree") to 7 ("strongly agree"). The score for all 9 items is summed to constitute the FSS score. The minimum FSS score is 7 and the maximum score possible is 63. A higher score represents greater fatigue severity. Change was calculated as the value at 6 months minus the value at baseline and reported here. A higher positive score indicates an increase in fatigue symptoms at 6 months compared to baseline, a lower negative score would indicate a decrease in fatigue symptoms over 6 months and a score of 0 would indicate no change in fatigue symptoms over 6 months.

The Beck Depression Inventory Second Edition (BDI-II) is a 21-question multiple-choice self-report inventory that measures depression. There is a four-point scale for each item ranging from 0-3. The total score can range from 0 to 63 points. Higher scores reflect a great level of depression severity.

MRI-based diffusion tensor imaging (DTI) tractography is used to measure fractional anisotropy (FA), an indicator of CNS microstructural integrity. Increases in FA may reflect enhanced fiber organization or myelination, while decreases often indicate demyelination, axonal loss, or reduced coherence of white matter tracts. The JHU white-matter tractography atlas was used to extract FA values from 20 structures. Percent change was calculated. A positive number indicates an increase in FA after 6 months and a negative number indicates a decrease in FA from baseline to 6 months.

MRI-based diffusion tensor imaging (DTI) tractography is used to measure mean diffusivity (MD), which is the average rate of water diffusion in all directions within brain tissue. An increase in MD often indicates microstructural disruption, such as axonal loss, demyelination, or increased extracellular space due to edema or atrophy and decreases in MD can reflect cellular proliferation or restricted diffusion, as seen in certain types of gliosis or inflammatory conditions. The JHU white-matter tractography atlas was used to extract MD values from 20 structures. Percent change was calculated. A positive number indicates an increase in MD after 6 months and a negative number indicates a decrease in MD from baseline to 6 months.

Change was calculated as the value at 6 months minus the value and baseline. A positive number indicates an increase in inflammatory markers in plasma samples and a negative value indicates a decrease in inflammatory markers at 6 months.