Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The project is well designed and the purposes are useful and clear

However, too many of the patients enrolled are either lost or poor of clinical or follow up information

This does not make the paper without value but the authors should spend some time in suggesting strategies to overcome this problem

Author Response

Comments 1: The project is well designed and the purposes are useful and clear.
However, too many of the patients enrolled are either lost or poor of clinical or follow up information.
This does not make the paper without value but the authors should spend some time in suggesting strategies to overcome this problem

Response 1: We thank the reviewer for this valuable comment. We have added a paragraph in the Discussion addressing potential strategies to overcome this issue as follows. “Future programmes should consider the involvement of a dedicated staff to improve patient monitoring and prevent loss to follow-up across the care cascade. In addition, the adoption of HCV reflex testing could substantially reduce drop-out between diagnostic steps”.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript entitled “Hepatitis free hospital: retrospective results of an in-hospital project of hepatitis C virus microelimination” by Cerini et al. is an interesting study describing the outcomes of a hospital-based hepatitis C virus (HCV) screening program conducted at San Giuseppe Hospital in Milan between 2021 and 2024. The study evaluates a screening strategy based on systematic anti-HCV testing for all hospital admissions, followed by confirmatory HCV-RNA testing when indicated, and subsequent referral to specialist care. The main objective of the work is to assess the feasibility and potential impact of a streamlined in-hospital diagnostic and referral pathway in terms of case detection, linkage to care, and treatment initiation.

Overall, the paper is well structured and clearly written. The results and discussion are well presented, and the findings are, in my opinion, highly relevant. The manuscript provides timely evidence supporting hospital-based screening as a pragmatic micro-elimination strategy.

The study is particularly interesting because it highlights a substantial burden of undiagnosed or untreated infections among older individuals, who are frequently missed by current population-based screening initiatives. The results demonstrate that hospital settings can serve as effective platforms for identifying hidden or residual HCV infections and facilitating linkage to care, thus contributing to HCV elimination targets.

I have no major concerns, and I consider the manuscript suitable for publication in Viruses in its current form.

Author Response

Comments 1: The manuscript entitled “Hepatitis free hospital: retrospective results of an in-hospital project of hepatitis C virus microelimination” by Cerini et al. is an interesting study describing the outcomes of a hospital-based hepatitis C virus (HCV) screening program conducted at San Giuseppe Hospital in Milan between 2021 and 2024. The study evaluates a screening strategy based on systematic anti-HCV testing for all hospital admissions, followed by confirmatory HCV-RNA testing when indicated, and subsequent referral to specialist care. The main objective of the work is to assess the feasibility and potential impact of a streamlined in-hospital diagnostic and referral pathway in terms of case detection, linkage to care, and treatment initiation.

Overall, the paper is well structured and clearly written. The results and discussion are well presented, and the findings are, in my opinion, highly relevant. The manuscript provides timely evidence supporting hospital-based screening as a pragmatic micro-elimination strategy.

The study is particularly interesting because it highlights a substantial burden of undiagnosed or untreated infections among older individuals, who are frequently missed by current population-based screening initiatives. The results demonstrate that hospital settings can serve as effective platforms for identifying hidden or residual HCV infections and facilitating linkage to care, thus contributing to HCV elimination targets.

I have no major concerns, and I consider the manuscript suitable for publication in Viruses in its current form.

Response 1: We thank the Reviewer for the thorough evaluation and the encouraging comments. We are pleased that the relevance of our findings, the structure of the manuscript, and the presentation of results met the Reviewer's expectations.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript presents the results of universal hospital-based HCV screening in large hospital and its possible impact on achieving HCV elimination goals. These data clearly demonstrate the potential to identify people living with undiagnosed HCV infection who may be missed by current screening strategies. The paper is written well. There are some minor comments:

1. The current title of the manuscript (“Hepatitis free hospital”) is somewhat misleading, suggesting the elimination of intra-hospital HCV transmission. Please consider modification of the title to reflect the value of the study – universal hospital-based screening and linkage to care.
2. Introduction: “…extension of screening to the broader 1948–1988 birth cohort is required in Italy…” Please provide literature data supporting this statement – serosurvey data, age-specific incidence rates, etc.
3. Results: Anti-HCV detection rates in males vs. females, and in birth cohorts – please apply statistical analysis to assess whether observed differences were statistically significant.
4. Results: “…with a higher proportion of unknown HCV RNA status in these older cohorts…” – Please clarify whether HCV RNA status was unknown before admission to the hospital or remained unknown after hospital-based screening because they did not undergo HCV RNA testing.
5. Results: “Regarding the identified routes of infection, intravenous drug use, blood transfusions prior to the 1990s, and the use of non-disposable glass syringes for pharmacological treatments were reported.” – Please specify in Methods section how these data were collected.
6. Discussion: “…the observed age distribution of infections is consistent with established epidemiological patterns in Italy” – Reference is needed.

Author Response

Comments 1: The current title of the manuscript (“Hepatitis free hospital”) is somewhat misleading, suggesting the elimination of intra-hospital HCV transmission. Please consider modification of the title to reflect the value of the study – universal hospital-based screening and linkage to care.

Response 1: We thank the Reviewer for this insightful comment. The title “Hepatitis Free Hospital” originates from a structured project aimed at identifying HCV cases within the hospitalized population through a simplified pathway for diagnosis and linkage to care.

Within this framework, the concept of a “hepatitis-free hospital” refers to the creation of a “hepatitis-free zone”, achieved by systematically identifying and treating infected individuals during hospitalization. For this reason, we believe that the current title simply reflects the rationale and objectives of the project. However, we remain open to further suggestions from the Reviewer and the Editor.

Comments 2: Introduction: “…extension of screening to the broader 1948–1988 birth cohort is required in Italy…” Please provide literature data supporting this statement – serosurvey data, age-specific incidence rates, etc.

Response 2: We thank the reviewer for this comment. We have revised the sentence as follows: “…. extension of screening to the broader 1948–1988 birth cohort is required in Italy to meet WHO targets, as supported by Italian serosurveys and modelling studies [Rosato V et al., Viruses 2022, D'Ambrosio R et al., Liver Int 2023, Kondili LA et al., Liver Int 2020].”

Comments 3: Results: Anti-HCV detection rates in males vs. females, and in birth cohorts – please apply statistical analysis to assess whether observed differences were statistically significant.

Response 3: We thank the reviewer for this comment. We used chi-square Chi-square or the Fischer exact test to assess differences in anti-HCV detection rates between males and females, across birth cohorts, and between ward types.  The observed differences were statistically significant (p<0..001). We have revised the manuscript in the section Methods and Results.

Comments 4:Results: “…with a higher proportion of unknown HCV RNA status in these older cohorts…” – Please clarify whether HCV RNA status was unknown before admission to the hospital or remained unknown after hospital-based screening because they did not undergo HCV RNA testing.

Response 4: We thank the Reviewer for the clarification. We confirm that the unknown HCV RNA status refers to the period before hospital admission. We have revised the manuscript to make this explicit, as follows"…with a higher proportion of unknown HCV RNA status before hospital admission in these older cohorts"

Comments 5: Results: “Regarding the identified routes of infection, intravenous drug use, blood transfusions prior to the 1990s, and the use of non-disposable glass syringes for pharmacological treatments were reported.” – Please specify in Methods section how these data were collected.

Response 5: We thank the Reviewer for this comment. We confirm that information on routes of infection was collected at hospital admission through the patients’ medical history. We have added the following sentence to the Methods section: Data on potential routes of HCV transmission, including intravenous drug use, blood transfusions prior to the 1990s, and use of non-disposable glass syringes, were collected by physicians as part of the routine anamnestic interview performed at the time of clinical assessment."

Comments 6: Discussion: “…the observed ae distribution of infections is consistent with established epidemiological patterns in Italy” – Reference is needed.

Response 6: We thank the Reviewer for this comment. We have added the requested references to support this statement.