Reaching the Unreachable: Hepatitis C virus (HCV) Microelimination in Prisons and Addiction Centers

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

1. The periods of data collection are quite different (prison: 2017–2025, addiction centers: 2024–2025). Why was the time window so different?
2. Please provide confidence intervals for SVR rate.
3. Among addiction center population, why do only 46 of 83 RNA-positive individuals return for treatment?
4. The study mentions the use of FibroScan in both settings, but only 7 of 43 patients in addiction centers underwent assessment. This limitation needs to be discussed with reasons for the low uptake.
5. Figures 1 and 2 are informative, but the authors should add percentages alongside absolute values which will allow readers quickly grasp the proportion of positive HCV RNA cases relative to those screened or positive antibody.
6. Please provide the number of individuals screened, the number of HCV RNA positive, and SVR rates across the three addiction centers.
7. Please provide HBV screening results (e.g., HBsAg, anti-HBc) for the addiction center cohort, as these are mentioned as routine tests, but no data are presented.
8. The manuscript reports that 98 of 497 HCV antibody-positive inmates were co-infected with HIV and were excluded from the HCV mono-infection analysis. However, it is unclear whether these co-infected individuals were offered treatment for HCV, please clarify this point.
9. The manuscript mentioned that all patients were routinely tested for HIV testing, but HIV test results are not reported for the addition center cohort.

Author Response

Porto, 23rd December, 2025

 

 

Dear Editor,

 

We kindly thank you for the opportunity to submit a revised version of the manuscript "Reaching the unreachable: HCV microelimination in prisons and addiction centers" - (Gastroent-4052636)

 

We found your comments very helpful to improve our manuscript and we have addressed all of the points raised.

We hope that you consider the current manuscript acceptable for publication.

 

On behalf of all the co-authors, we are looking forward to hearing from you.

 

Yours sincerely,

 

Rui Gaspar

 

 

Reviewers' Comments to Author:

 

1. The periods of data collection are quite different (prison: 2017–2025, addiction centers: 2024–2025). Why was the time window so different?

We thank the Reviewer for this comment.

We first start the prison’s project in 2017 and was successful that was expanded through the whole country. In 2023 we decided to amplify our treatment net and start a new project in the addiction centers.

 

1. Please provide confidence intervals for SVR rate.

We thank the Reviewer for this comment.

As this is an absolute value, based on the patients that respond to treatment, it does not have a confidence interval.

 

 

1. Among addiction center population, why do only 46 of 83 RNA-positive individuals return for treatment?

We thank the Reviewer for this comment.

This finding is particularly interesting, as it reflects genuine differences between the two settings. In the prison setting, all inmates reside within the facility and can therefore easily access the outpatient clinic. In contrast, many patients attending addiction centers present only once and may not return for subsequent visits, which explains the high rate of loss to follow-up.

 

1. The study mentions the use of FibroScan in both settings, but only 7 of 43 patients in addiction centers underwent assessment. This limitation needs to be discussed with reasons for the low uptake.

We thank the Reviewer for this comment. The reason is the same as that described in previous point. Although some patients underwent treatment, the FibroScan examination had to be scheduled at a specific time, and a large number of patients did not attend their appointments. We add this information to the text.

 

1. Figures 1 and 2 are informative, but the authors should add percentages alongside absolute values which will allow readers quickly grasp the proportion of positive HCV RNA cases relative to those screened or positive antibody.

We thank the Reviewer for the comment. We add this information to the figures.

 

1. Please provide the number of individuals screened, the number of HCV RNA positive, and SVR rates across the three addiction centers.

We thank the Reviewer for this comment. We do not have the exact number of the individuals screened as we did not receive that information. Among the 83 individuals with detectable HCV-RNA, 56% were from Cedofeita, 22% from the West Porto and 22% from the East Porto. Of the 43 patients, 22 were from the Cedofeita center, 9 from the West center and 12 from the East center. Only one patient did not present SVR 12, and this was from the East center. We add this information to the text.

 

 

1. Please provide HBV screening results (e.g., HBsAg, anti-HBc) for the addiction center cohort, as these are mentioned as routine tests, but no data are presented.

We thank the Reviewer for the comment. No patients tested positive for HBs antigen; however, 53.5% were positive for HBc antibody.

 

1. The manuscript reports that 98 of 497 HCV antibody-positive inmates were co-infected with HIV and were excluded from the HCV mono-infection analysis. However, it is unclear whether these co-infected individuals were offered treatment for HCV, please clarify this point.
2. We thank the Reviewer for the comment. All patients were offered treatment under the same criteria; however treatment was managed by the Infectious Disease Department.
3. The manuscript mentioned that all patients were routinely tested for HIV testing, but HIV test results are not reported for the addition center cohort.

We thank the Reviewer for highlighting this point. All patients were tested for HIV; however, the results were communicated exclusively to the Infectious Disease Department, which was responsible for the management of patients with positive results. We add this information to the text.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors presented the use of IFN-free DAAs for treating incarcerated individuals and patients in addiction centers with chronic HCV infection (with or without HIV) in Portugal. Compared with the general population, the effectiveness and tolerability of DAAs were similarly excellent, supporting the objective of achieving HCV microelimination in this special population.

1. Abstract (line 15): Please correct the SVR rate from 96% to 95% to ensure consistency with the Introduction (line 38).
2. Although no HBV coinfection was identified in this cohort, the authors should describe the referral pathway and clinical management plan that would be used if HBsAg-positive patients were encountered.
3. Testing for HCV genotype should be listed among the laboratory assessments. In addition, the manuscript does not specify which assays were used for HCV RNA quantification and HCV genotyping. Please provide the product name, manufacturer, city/country, and the lower limit of detection (LLOD) for each test.
4. The Methods section should describe how adherence to DAA therapy was ensured, as this was highlighted in the Results.
5. Statistical analysis: No comparative analyses are presented in the manuscript. Therefore, tests for variance comparison are unnecessary unless the authors intend to compare characteristics between incarcerated and addiction-treatment populations. If so, Mann–Whitney U tests and chi-square tests could be used to compare medians and proportions between these two independent cohorts.
6. Figures 1 and 2 can be merged into a single figure.
7. Table 1: Baseline characteristics should be clearly presented and compared between patients in correctional facilities and those in addiction centers. Variables should include age, sex, race, HCV RNA level, HCV genotype, fibrosis stage, ALT, DAA regimen, source of infection, and other relevant parameters. Please present these as median (range) and number (percentage), as appropriate.
8. Please also report platelet count, AST, FIB-4 index, eGFR, albumin, total bilirubin, AFP, and comorbidities such as type 2 diabetes, hypertension, and dyslipidemia, if available.
9. Please clarify whether any imaging studies were performed prior to antiviral treatment to assess portal hypertension (particularly ascites) or hepatocellular carcinoma.
10. Lines 251–252 are redundant and should be removed.
11. Line 281 should read 74.4%.

Author Response

Porto, 23rd December, 2025

 

 

Dear Editor,

 

We kindly thank you for the opportunity to submit a revised version of the manuscript "Reaching the unreachable: HCV microelimination in prisons and addiction centers" - (Gastroent-4052636)

 

We found your comments very helpful to improve our manuscript and we have addressed all of the points raised.

We hope that you consider the current manuscript acceptable for publication.

 

On behalf of all the co-authors, we are looking forward to hearing from you.

 

Yours sincerely,

 

Rui Gaspar

 

 

Reviewers' Comments to Author:

The authors presented the use of IFN-free DAAs for treating incarcerated individuals and patients in addiction centers with chronic HCV infection (with or without HIV) in Portugal. Compared with the general population, the effectiveness and tolerability of DAAs were similarly excellent, supporting the objective of achieving HCV microelimination in this special population.

1. Abstract (line 15): Please correct the SVR rate from 96% to 95% to ensure consistency with the Introduction (line 38).

We thank the Reviewer for the comment. We add this information to the text

 

1. Although no HBV coinfection was identified in this cohort, the authors should describe the referral pathway and clinical management plan that would be used if HBsAg-positive patients were encountered.

We thank the Reviewer for this comment. In cases of HBsAg-positive patients, individuals were referred to the Department of Hepatology for treatment and follow-up. We add this information to the text

 

1. Testing for HCV genotype should be listed among the laboratory assessments. In addition, the manuscript does not specify which assays were used for HCV RNA quantification and HCV genotyping. Please provide the product name, manufacturer, city/country, and the lower limit of detection (LLOD) for each test.

We thank the Reviewer for this comment. For HCV RNA quantification it was used the Roche COBAS TaqMan HCV quantitative test, from Germany with a lower limit of detection of 15 IU/mL. For HCV genotyping it was used the Toche Amplicor HCV test. We add this information to the text.

 

1. The Methods section should describe how adherence to DAA therapy was ensured, as this was highlighted in the Results.

 

We thank the Reviewer for this comment. In the prison setting it was alreadt described: “Treatment was initiated either the same day or the following day. Prison healthcare staff were informed of the treatment schedule and were daily supervised administration of DAAs, as they were already trained in delivering opioid substitution therapy”. In the addiction centers we add this information.

 

1. Statistical analysis: No comparative analyses are presented in the manuscript. Therefore, tests for variance comparison are unnecessary unless the authors intend to compare characteristics between incarcerated and addiction-treatment populations. If so, Mann–Whitney U tests and chi-square tests could be used to compare medians and proportions between these two independent cohorts.

We thank the Reviewer for this comment. We agree with the reviewer and removed that information.

 

1. Figures 1 and 2 can be merged into a single figure.

We thank the Reviewer for this comment. We attemped to merge the two images; however, the final became unclear. If acceptable, we propose to retain the two figures as originally presented.

 

1. Table 1: Baseline characteristics should be clearly presented and compared between patients in correctional facilities and those in addiction centers. Variables should include age, sex, race, HCV RNA level, HCV genotype, fibrosis stage, ALT, DAA regimen, source of infection, and other relevant parameters. Please present these as median (range) and number (percentage), as appropriate.

We thank the Reviewer for the comment. We changed table 1 and 2 and put all the information available together.

 

1. Please also report platelet count, AST, FIB-4 index, eGFR, albumin, total bilirubin, AFP, and comorbidities such as type 2 diabetes, hypertension, and dyslipidemia, if available.

We thank the Reviewer for the comment. We changed table 1 and 2 and put all the information available together.

 

1. Please clarify whether any imaging studies were performed prior to antiviral treatment to assess portal hypertension (particularly ascites) or hepatocellular carcinoma.

We thank the Reviewer for this comment. We did not performed imaging studies prior to antiviral treatment as they are only indicated in cases of cirrhosis. If ascites was not detectable at physical exam, imaging studies were only performed in case of cirrhosis.

 

 

1. Lines 251–252 are redundant and should be removed.

We thank the Reviewer for the comment. We changed this information in the text

 

1. Line 281 should read 74.4%.

We thank the Reviewer for the comment. We changed this information in the text

 

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Line 116: a typo for "Roche".