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Additional file 5. Primary end point analyses of mean and sum scores of FSS-9 at baseline and EOT12 Legends: The table displays the mean and sum scores of FSS-9 at baseline and EOT12 among participants who were included in the intention-to-treat and per-protocol analyses, respectively. The FSS-9 sum score ranges from 9 points, no fatigue, to 63 points, worst fatigue. Each item was ranged on a Likert scale from 1 point, no fatigue, to 7 points, worst fatigue. EOT12: 12 weeks after the end of treatment; SD: Standard deviation.

Additional file 2. The US-English and the Norwegian versions of the FSS-9. Legends: FSS-9; Nine-items Fatigue Severity Scale. All items in the FSS-9 are ranged as a Likert scale from 1 to 7, where 1 indicates “strongly disagree” and 7 indicates “strongly agree”.

Additional file 1. Norwegian national HCV treatment guidelines during the study period.

Additional file 7. A linear prediction of changes in FSS-9 sum scores from baseline to EOT12. Legends: The figure displays the linear predictionincluding 95 % confidence intervals of changes in FSS-9 sum scorefrom baseline to EOT12 for integrated and standard HCV treatment groups. EOT12: 12 weeks after the end of HCV treatment; FSS-9: Nine-item fatigue severity scale; HCV: Hepatitis C virus.

Additional file 12. Linear mixed model of the association between sociodemographic factors, injecting drug use, and drug use and FSS-9 sum score. Legends: The table displays a linear mixed model analysis regression of the impact of sociodemographic factors, injecting drug use, and drug use on FSS-9 sum scores at baseline and from baseline to EOT12in the study sample. The FSS-9 sum score ranges from 9 points, no fatigue, to 63 points, worst fatigue. “Educational attainment” was defined as the highest level of education completed. “Injecting substance use” was defined as having injected any substance at least once during the 12 months leading up to the first health assessment. Drug use was categorized according to the use during the past year. Frequent drug use was defined as consuming at least one of the drugs in the five drug classes more than weekly during the year leading up to the first health assessment. Participants who did not use drugs or used them less than weekly during the year were categorized as having “no frequent use of drugs”. Missing values were identified in 1.4% of FSS-9 scores, 1.1 % of educational attainment, 2.5 % of injecting drug use and 3.3 % of drug use at baseline and 29.9% of FSS-9 score at EOT12, and all were handled as “missing at random” and replaced with estimated values using expectation- maximization algorithm. Except for the “achieving SVR” predictor, we kept all the predictor variables constant at the baseline level in predicting changes in the FSS-9 sum scores from baseline to EOT12. To explore whether predictors predicted changes in the FSS-9 score from baseline to EOT12, the interaction between these factors and timeand EOT12) were added. EOT12: 12 weeks after the end of HCV treatment; FSS-9: Nine-item fatigue severity scale; HCV: Hepatitis C virus; SVR: Sustained virological response.

Additional file 8. Pen’s parades of FSS-9 sum scores at baseline and EOT12. Legends: The figures display participants who received integrated and standard HCV treatment and were included in the per-protocol analysis. The graphs demonstrate the FSS-9 sum scores at baseline/prior to the HCV treatment and EOT12. The red line represents the FSS-9 sum scores at baseline when the participants are in sorted order by FSS-9 sum scores to highestscore). The blue spikes demonstrate the FSS-9 sum score at EOT12. The length of the spikes mark the changes in the FSS-9 sum score from baseline to EOT12. Participants without spikes did not complete FSS-9 assessment at EOT12. The dotted line demonstrates the cut-off value for severe fatigue. EOT12: 12 weeks after the end of treatment; FSS-9: Nine-item Fatigue Severity Scale.

Additional file 4. Distribution of FSS-9 sum scores for integrated HCV treatmentand standard HCV treatmentgroups at baseline. Legends: The two graphsdisplay the FSS-9 sum scores for integrated HCV treatmentand standard HCV treatmentat baseline. The red lines demonstrate the distribution of the FSS-9 sum scores with skewness –0.8and –0.5and kurtoses 2.7 and 2.3. The FSS-9 sum scores ranges from 9 points, no fatigue, to 63 points, worst fatigue.

Additional file 6. Linear mixed model of ΔFSS-9 sum score from baseline to EOT12 for integrated HCV treatment (per-protocol) (number of participants = 212, number of observations: 424). Legends: The table displays a linear mixed model analysis (Restricted Maximum Likelihood) regression of the impact of integrated HCV treatment on changes in FSS-9 sum scores (ΔFSS-9 sum scores) from baseline to EOT12 (per-protocol analysis), adjusted for acheiving SVR at EOT12. The FSS-9 sum score ranges from 9 points, no fatigue, to 63 points, worst fatigue. EOT12: 12 weeks after the end of HCV treatment; FSS-9: Nine-item fatigue severity scale.

Additional file 9. Linear mixed model of ΔFSS-9 sum scores from baseline to EOT12 for integrated HCV treatment (intention-totreat, sensitivity analysis without computed data), adjusted for SVR at EOT12 (number of participants = 189, number of observations: 378). Legends: The table displays a linear mixed model analysis (Restricted Maximum Likelihood) regression of the impact of integrated HCV treatment and SVR on changes in FSS-9 sum scores (ΔFSS-9 sum score) from baseline to EOT12 (intention-to-treat analysis without computed data by the expectation–maximization algorithm). The FSS-9 sum score ranges from 9 points, no fatigue, to 63 points, worst fatigue. EOT12: 12 weeks after the end of HCV treatment; FSS-9: Nine-item fatigue severity scale; SVR: Sustained virological response.

Additional file 3. Aspartate aminotransferase to platelet ratio index. Legends: The figure displays the equation to calculate APRI score. AST upper limit of normal range was defined as 45 IU/Land 35 IU/L.

Additional file 10. Linear mixed model of ΔFSS-9 sum scores from baseline to EOT12 for integrated HCV treatment, adjusted for SVR . Legends: The table displays a linear mixed model analysis regression of the impact of integrated HCV treatment and SVR on changes in FSS-9 sum scoresfrom baseline to EOT12. The FSS-9 sum score ranges from 9 points, no fatigue, to 63 points, worst fatigue. EOT12: 12 weeks after the end of HCV treatment; FSS-9: Nine-item fatigue severity scale; SVR: Sustained virological response.

Additional file 1.

Additional file 3. The Cronbach’s α if-item-deleted and Item-Total correlation for the FSS-3 and FSS-9, and these scales including the VAFS. FSS-9: Nine-item Fatigue Severity Scale; FSS-3: Three-item Fatigue Severity Scale; VAFS: Visual Analogue Fatigue Scale; No.: Number of patients. *Due to high internal consistency and almost equal Cronbach’s α of the remaining items, we deleted item 8 using clinical judgement. Item 8 could be difficult to answer if patients were affected by substances or were going through substance withdrawals. **We deleted item 9 using clinical judgement due to high internal consistency and almost equal Cronbach’s α in the remaining items and the fact that unemployment was frequently reported among patients with SUDs. Tables a) and c) show the Cronbach’s α if-item-deleted for the FSS-3 and FSS-9, and these scales including the VAFS using data from the first health assessment (baseline) (Table a) and the second health assessment (Table c). Tables b) and d) show the Item-Total correlation for the FSS-3 and FSS-9, and these scales including the VAFS using data from the first health assessment (baseline) (Table b) and the second health assessment (Table d). The values in bold represent the FSS-3’s Cronbach’s α if-item-deleted and Item-Total correlation.

Additional file 1. The number of months from baseline to the second or third measurements. No.: Number of patients; SD: Standard deviation; ref.: Reference. Tables display the number of patients with one, two, and three health assessments, including the Fatigue Severity Scale and the Visual Analog Fatigue Scale measurements. The table displays the time interval between the second and third health assessments and baseline.

Additional file 2. The US-English and the Norwegian versions of the nine-item Fatigue Severity Scale. FSS-9: Nine-item Fatigue Severity Scale. All items in the FSS-9 are answered with a Likert scale from 1 to 7 where 1 indicates “strongly disagree” and 7 indicates “strongly agree”.

Additional file 2 Adjusted linear mixed model for the Substance Use Severity Index (SUSI) for patients with two or more SUSI measurements (N = 170). CI: Confidence Interval; OAT: Opioid Agonist Therapy; cSUSI: Mean Change in Substance Use Severity Index; SUD: Substance Use Disorder. 1) The SUSI is a continuous variable ranging from 0 to 1, where 0 indicates no substance use and 1 indicates daily substance use for all substances (cannabis, amphetamines, cocaine, opioids, benzodiazepines, and alcohol). 2) The value shows the difference in adjusted SUSI between “going to inpatient detoxification” and “not going to inpatient detoxification” at baseline (before detoxification). 3) Interpretation: the cSUSI per year from baseline of a constant predictor and its comparator (e.g., the cSUSI of “ongoing injecting substance use” (constant predictor) and “no ongoing inject substance use” (constant comparator) per year from baseline). 4) Interpretation: the cSUSI of a time-varying predictor and its time-varying comparator per year from baseline (e.g., the cSUSI per year of “going to inpatient detoxification” and “not going to inpatient detoxification” from baseline). The table displays a linear mixed model analysis (Restricted Maximum Likelihood regression) evaluating the impact of inpatient intoxication, injecting substance use, age, and gender on the SUSI at baseline and from baseline (over time) among patients undergoing outpatient SUD treatment with two or more substance use measurements.

Additional file 5. Mean (SD) item scores for single items on the FSS-9 at baseline and follow-up. Legend: FSS-9: Nine-item Fatigue Severity Scale; I: Item; OAT: Opioid agonist therapy; SD: Standard Deviation. Follow-up: The FSS-9 score on the last health assessment during the study period among patients with two or more annual health assessments. Mean (SD) item scores for single items on the FSS-9 for patients using methadone or buprenorphine as OAT opioid.

Additional file 3. Aspartate aminotransferase to platelet ratio index (APRI). Description: APRI: Aspartate aminotransferase to platelet ratio index. The figure displays the APRI score equation. The AST upper limit of normal range was defined as 45 IU/L (male) and 35 IU/L (female).

Additional file 4. Potential correlations between sociodemographic and clinical factors and fatigue. The figure shows that potential sociodemographic and clinical comorbidities may affect fatigue among patients with substance use disorders.

Additional file 6. Linear mixed model of fatigue (FSS-9) adjusted for sociodemographic and clinical factors among patients receiving methadone as an OAT opioid at baseline (N = 209). Legends: APRI: Aspartate transaminase to platelet ratio index; CI: Confidence interval; CRP: C-reactive protein; FSS-9: Nine-item Fatigue Severity Scale; eGFR: estimated glomerular filtration rate; HIV: Human Immunodeficiency virus; kPa: Kilopascal; OAT: Opioid Agonist Therapy. 1) Age per 10 years was centred according to mean age (43 years) in the study sample at baseline. 2) Includes amphetamine or cocaine use. The OAT opioid ratio: a ratio between the received dose of OAT opioids per day divided by the expected mean dose of OAT opioids (buprenorphine 18 mg, buprenorphine-naloxone 18/4.5 mg or methadone 90 mg). The educational level: highest level of education was coded 0–4 with 4 as the highest educational level. Unstable housing situation: living on the street, homeless shelter, or with family and friends at any time in the past 30 days prior to the health assessment. Debt difficulties: struggling with repaying current illegal and legal debt. Injecting substance use: Having injected a substance in the past 12 months prior to the health assessment. Frequent use of substances: at least weekly during the past 12 months prior to the health assessment. Viral load of HCV: From − 0.5 to 0.5, where the range ≥ − 0.5 to 0 identifies the high viral load (HCV PCR ≥ 800,000 IE/ml). Zero (0) defined patients without HCV infection. When using the Bonferroni corrected p-values (αaltered = 0.05 / 43 = 0.0012), the predictors did not affect the FSS-9 sum score significantly. The table displays a linear mixed model analysis (Restricted Maximum Likelihood regression) evaluating sociodemographic and clinical factors’ (predictors) changes in the FSS-9 sum score at baseline and their influence on changes in the FSS-9 sum score (time trend) per year from baseline among patients receiving methadone as an OAT opioid. The predictors’ effect estimates and time trends estimate adjusted mean differences in the FSS-9 sum score.

Additional file 2. The US-English and the Norwegian versions of FSS-9. Description: Legends: FSS-9; Nine-item Fatigue Severity Scale. All items in the FSS-9 are ranged as a Likert scale from 1 to 7, where 1 indicates “strongly disagree” and 7 “strongly agree”.

Additional file 3. Opioid agonist therapy and hepatitis C treatment in Norway and Sweden

Additional file 1. The number of months from baseline to the second or third health assessment. No.: Number of patients; SD: Standard deviation; ref.: Reference. The table displays the number of patients with one, two, and three health assessments, including a nine-item Fatigue Severity Scale score. The table displays the time between baseline and the second and third health assessments.

Additional file 7. Linear mixed model of fatigue (FSS-9) adjusted for sociodemographic and clinical factors among patients receiving buprenorphine as an OAT opioid at baseline (N = 321). Legends: APRI: Aspartate transaminase to platelet ratio index; CI: Confidence interval; CRP: C-reactive protein; FSS-9: Nine-item Fatigue Severity Scale; eGFR: estimated glomerular filtration rate; HIV: Human Immunodeficiency virus; kPa: Kilopascal; OAT: Opioid Agonist Therapy. 1) Age per 10 years was centred according to mean age (43 years) in the study sample at baseline. 2) Includes amphetamine or cocaine use. The OAT opioid ratio: a ratio between the received dose of OAT opioids per day divided by the expected mean dose of OAT opioids (buprenorphine 18 mg, buprenorphine-naloxone 18/4.5 mg or methadone 90 mg). The educational level: highest level of education was coded 0–4 with 4 as the highest educational level. Unstable housing situation: living on the street, homeless shelter, or with family and friends at any time during the past 30 days prior to the health assessment. Debt difficulties: struggling with repaying current illegal and legal debt. Injecting substance use: Having injected a substance during the past 12 months prior to the health assessment. Frequent use of substances: at least weekly during the past 12 months prior to the health assessment. Viral load of HCV: From − 0.5 to 0.5, where the range ≥ − 0.5 to 0 identifies the high viral load (HCV PCR ≥ 800,000 IE/ml). Zero (0) defined patients without HCV infection. When using the Bonferroni corrected p-values (αaltered = 0.05 / 43 = 0.0012), the predictors did not affect the FSS-9 sum score significantly. The table displays a linear mixed model analysis (Restricted Maximum Likelihood regression) evaluating sociodemographic and clinical factors’ (predictors) changes in the FSS-9 sum score at baseline and their influence on changes in the FSS-9 sum score (time trend) per year from baseline among patients receiving buprenorphine as an OAT opioid. The predictors’ effect estimates and time trends estimate adjusted mean differences in the FSS-9 sum score.

Additional file 1. Methodology description: estimating chronic hepatitis C (HCV) prevalence among people on opioid agonist therapy (OAT) in Norway and Sweden