Review for 10.1186/s12876-023-02750-2 (2023)

Title: The care cascade for hepatitis C virus and prognosis of chronic hepatitis C patients treated
with antiviral agents in a tertiary hospital
Version: 1 Date: 18 Apr 2022
Reviewer's report:
Ref: Submission ID d454ef7e-2839-4d6e-9f18-c174c5d720ca
Overall
The authors present an analysis of data from patients from one hospital in South Korea and
present a diagnosis and care cascade and assess cumulative incidence of HCC over 15 years.
The manuscript is well-organised and well-written. The relevant (Introduction) and Discussion
are not really in my scope, therefore I have focussed on the Results and Methods. With some
clarification n the methods, this provides interesting ‘real-world’ data over a long period on
HCV diagnosis and outcomes in a select, but relevant group of people.
Methods
Study design
1. It is somewhat unclear to me what the overall study design is. The authors describe it as
“retrospective cohort study” however describe study procedures which sound like a prospective
cohort such as “HCV antibody examination was performed at baseline visits as part of the study
enrollment process.” Further, patients have accumulated follow-up time for HCC incidence,
therefore must have had prospective follow-up. However, consent was waived, so perhaps this
is the construction of a cohort based on chart review, or it is secondary analysis of a previous
prospective cohort, but I am unsure. This confusion makes it difficult to then understand things
like the sampling (comment below), how data was collected and stored, and who collected the
data and when. Suggest revising to have a clearer description of what the study design is.
Study population
2. Please add further clarification as to how the study sample was selected, including:
2.1 Further details of inclusion criteria if there were any beyond being a patient and being anti-
HCV positive.
2.2 If there was a sampling frame, such as all patients and what this N was.
2.3 How patients eligible for the study were identified and included.
2.4 The authors described the study as retrospective, and “Patients who were anti-HCV positive
and visited a single tertiary academic institution (Gangnam Severance Hospital) during the study
period were included. It is not clear to me if it is all admitted patients, all emergency patients,
all patients to a particular department. Further, is it consecutive patients, or some other way of
selecting patients.
2.5 Please clarify if patients could only contribute once to the dataset or more than once.
It is important for assessing any selection bias, and the generalisability of the sample to make
the sample frame and then the sampling strategy clear to the reader. Often studies find including
a patient flow chart answers these questions efficiently for readers.
Baseline work up
3. Suggest the authors clarify how patients were offered or received HCV RNA because
the statement in the methods contradicts the results, that is, in Figure 1 ~ 36% of patients
received CHV RNA tests, so it cannot be all patients that were anti-HCV positive, as suggested
by the following sentence: “Next, those who were anti-HCV positive underwent HCV RNA
quantification to confirm HCV infection and HCV genotyping.”
4. Like above, not all patients that were HCV RNA positive received treatment. The language
in the methods implies that all patients were treated (“Patients who were confirmed to be HCV
RNA positive were started on hepatitis C treatment.”) and I suggest these needs revising to
clarify that treatment must have been not offered to all and/or not taken up by all.
Statistical analysis
5. Please clarify what the comparators are that are being tested in the following tests, that is,
what are the groups. “Student’s t-test was used to compare continuous variables, while Fisher’s
exact tests or chi-squared test were used to compare categorical variables”
6. The construction of the cascade of diagnosis and care is a helpful result, but should be
described in the methods. As, in how patients got assessed as being in each step, what were the
denominators at each step.
7. The description of the cumulative incidence is not entirely clear to me: “The cumulative
incidence rates of HCC and liver cirrhosis were investigated using the Kaplan–Meier method
and compared by the log-rank test.” As I understand it, Kaplan-Meir constructs the survivor
function, and in the absence of competing risks, 1-S(t) or 1-the KM can be used to construct
the cumulative incidence. The log rank test can compare differences in the survivor function
between groups. I think these methods could be revised to be slightly more accurate of what the
analyses are, that is, it is cumulative incidence risk over 15 years. Further, it is helpful to specify
what parameter the log-rank is using in the test.
8. Suggest clarify which groups were selected for comparison of cumulative incidence and the
rationale, it was not clear to why in Figure 3 and 4 these groups were important enough to have
compare between.
9. I cannot see any results in text, tables or figures of a Cox model: “Multivariate Cox
proportional hazard analysis was used to identify independent predictors of HCC or liver
cirrhosis development.” The methods do not describe what I would consider detail needed for
a time-to-event analysis (mainly date of HCC), and total person-years for calculation of an
incidence rate, to then proceed to a Cox PH model, so perhaps including this text was in error.
10. Please describe how missing data were treated.
Results
11. An overall Table 1 I think is always helpful, and suggest it is added. It is not clear to me
why the Table 1 only includes the patients treated.
Limitations
12. Related to comment above on methods, I suggest that further relevant additions be made to
the limitations as they are made to the methods, for example, a comment on any selection bias,
and any missing data.