Reviewer's report
Title:Effects and Outcomes of Interferon Treatment in Japanese Hepatitis C
Patients
Version: 1Date:13 July 2012
Reviewer: Hirofumi Uto
Reviewer's report:
This study examined the long-term prognosis of HCV-positive residents in an
isolated Japanese island and investigated the effects of IFN treatment in
comparison with the HCV-negative general population. This study is interesting
because it elucidates the mortality in HCV-infected patients with IFN treatment is
similar to that of general resident groups, although the mortality in HCV-infected
patients without IFN treatment was higher than that of general resident groups.
However, several points should be considered.
Specific Comments:
1. Authors stated that this study is prospective. However, gender- and
age-matched general resident may be enrolled to this study after the follow-up
period. If so, is this study prospective? Please indicate this point clearly.
2. Authors stated that the survival rate of members of the hepatitis C group who
received IFN treatment was comparable to that of the general resident group
irrespective of the effect of IFN treatment (Page 12, line 21-). However, these
results should be due to the small number of patients. The survival rate in
patients with Non-SVR seems to be lower compared to that with SVR (Figure 5C
and D), even if there is no statistical difference. Authors should show the
difference of survival rate between SVR group and non SVR group, and discuss
this point clearly.
3. The effect of IFN treatment for improvement of survival rate though to be due
to the reduction of liver-related death (Table 3). Please indicate the mortality
associated with liver-related death in Group A1, Group A2 and Group B using the
Kaplan-Meier method; these survival curves should be different. In addition, the
other disease mortality in these Groups should be shown using Kaplan-Meier
method; those survival curves would be similar. Furthermore, it was reported that
patients with the risk factors of high age at HCV eradication and heavy alcohol
intake might be at heightened risk for the development of HCC within 5 years
after HCV eradication (J Gastroenterol. 2011; 46: 799-808). Because liver-related
death had been occurred in IFN treatment group, the authors should discuss this
point.
4. Previous reports (J Hepatol 2010; 53: 36-42) have already shown that chronic
HCV infection is associated with a higher mortality and liver-related deaths. In
addition, the percentage of cause of death in this study is similar to the previous
reports (Hepatology 2009; 50:393-9). This study used gender- and age-matched
general resident as control and this comparison is interesting. However, authors
should add the resident positive for HCV antibody and negative for HCV RNA as
a control in addition to general resident in Figure 2, and discuss this point.
5. Residents older than 70 years were excluded in this study. IFN treatment may
not be indicated for those residents, this exclusion seems not to be necessary.
6. Mortality or liver related death in HCV infected patients in hospital based study
thought to be higher than those in cohort study (resident based study). This
difference may be affected by patients’ characteristics. In this study, LC was
observed in 177 patients with HCV infection, and these patients were excluded in
figure 5. How are cumulative survival and liver related death in LC patients
compared to Group B? In addition, ALT is important factor for HCC occurrence.
Untreated group (Group B) included many patients with normal ALT compared to
treated group (Group A). How is cumulative survival in patients with abnormal
ALT (#40) compared to that with normal ALT (<40)?
7. Methods for diagnosis of HCC should be indicated.
8. The numbers of patients at risk in Group A in Figure 5C or 5D (15 years of
follow up) seem to be mistake.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Effects and Outcomes of Interferon Treatment in Japanese Hepatitis C
Patients
Version: 1Date:13 July 2012
Reviewer: Hirofumi Uto
Reviewer's report:
This study examined the long-term prognosis of HCV-positive residents in an
isolated Japanese island and investigated the effects of IFN treatment in
comparison with the HCV-negative general population. This study is interesting
because it elucidates the mortality in HCV-infected patients with IFN treatment is
similar to that of general resident groups, although the mortality in HCV-infected
patients without IFN treatment was higher than that of general resident groups.
However, several points should be considered.
Specific Comments:
1. Authors stated that this study is prospective. However, gender- and
age-matched general resident may be enrolled to this study after the follow-up
period. If so, is this study prospective? Please indicate this point clearly.
2. Authors stated that the survival rate of members of the hepatitis C group who
received IFN treatment was comparable to that of the general resident group
irrespective of the effect of IFN treatment (Page 12, line 21-). However, these
results should be due to the small number of patients. The survival rate in
patients with Non-SVR seems to be lower compared to that with SVR (Figure 5C
and D), even if there is no statistical difference. Authors should show the
difference of survival rate between SVR group and non SVR group, and discuss
this point clearly.
3. The effect of IFN treatment for improvement of survival rate though to be due
to the reduction of liver-related death (Table 3). Please indicate the mortality
associated with liver-related death in Group A1, Group A2 and Group B using the
Kaplan-Meier method; these survival curves should be different. In addition, the
other disease mortality in these Groups should be shown using Kaplan-Meier
method; those survival curves would be similar. Furthermore, it was reported that
patients with the risk factors of high age at HCV eradication and heavy alcohol
intake might be at heightened risk for the development of HCC within 5 years
after HCV eradication (J Gastroenterol. 2011; 46: 799-808). Because liver-related
death had been occurred in IFN treatment group, the authors should discuss this
point.
4. Previous reports (J Hepatol 2010; 53: 36-42) have already shown that chronic
HCV infection is associated with a higher mortality and liver-related deaths. In
addition, the percentage of cause of death in this study is similar to the previous
reports (Hepatology 2009; 50:393-9). This study used gender- and age-matched
general resident as control and this comparison is interesting. However, authors
should add the resident positive for HCV antibody and negative for HCV RNA as
a control in addition to general resident in Figure 2, and discuss this point.
5. Residents older than 70 years were excluded in this study. IFN treatment may
not be indicated for those residents, this exclusion seems not to be necessary.
6. Mortality or liver related death in HCV infected patients in hospital based study
thought to be higher than those in cohort study (resident based study). This
difference may be affected by patients’ characteristics. In this study, LC was
observed in 177 patients with HCV infection, and these patients were excluded in
figure 5. How are cumulative survival and liver related death in LC patients
compared to Group B? In addition, ALT is important factor for HCC occurrence.
Untreated group (Group B) included many patients with normal ALT compared to
treated group (Group A). How is cumulative survival in patients with abnormal
ALT (#40) compared to that with normal ALT (<40)?
7. Methods for diagnosis of HCC should be indicated.
8. The numbers of patients at risk in Group A in Figure 5C or 5D (15 years of
follow up) seem to be mistake.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Effects and Outcomes of Interferon Treatment in Japanese Hepatitis C
Patients
Version: 1Date:13 July 2012
Reviewer: Hirofumi Uto
Reviewer's report:
This study examined the long-term prognosis of HCV-positive residents in an
isolated Japanese island and investigated the effects of IFN treatment in
comparison with the HCV-negative general population. This study is interesting
because it elucidates the mortality in HCV-infected patients with IFN treatment is
similar to that of general resident groups, although the mortality in HCV-infected
patients without IFN treatment was higher than that of general resident groups.
However, several points should be considered.
Specific Comments:
1. Authors stated that this study is prospective. However, gender- and
age-matched general resident may be enrolled to this study after the follow-up
period. If so, is this study prospective? Please indicate this point clearly.
2. Authors stated that the survival rate of members of the hepatitis C group who
received IFN treatment was comparable to that of the general resident group
irrespective of the effect of IFN treatment (Page 12, line 21-). However, these
results should be due to the small number of patients. The survival rate in
patients with Non-SVR seems to be lower compared to that with SVR (Figure 5C
and D), even if there is no statistical difference. Authors should show the
difference of survival rate between SVR group and non SVR group, and discuss
this point clearly.
3. The effect of IFN treatment for improvement of survival rate though to be due
to the reduction of liver-related death (Table 3). Please indicate the mortality
associated with liver-related death in Group A1, Group A2 and Group B using the
Kaplan-Meier method; these survival curves should be different. In addition, the
other disease mortality in these Groups should be shown using Kaplan-Meier
method; those survival curves would be similar. Furthermore, it was reported that
patients with the risk factors of high age at HCV eradication and heavy alcohol
intake might be at heightened risk for the development of HCC within 5 years
after HCV eradication (J Gastroenterol. 2011; 46: 799-808). Because liver-related
death had been occurred in IFN treatment group, the authors should discuss this
point.
4. Previous reports (J Hepatol 2010; 53: 36-42) have already shown that chronic
HCV infection is associated with a higher mortality and liver-related deaths. In
addition, the percentage of cause of death in this study is similar to the previous
reports (Hepatology 2009; 50:393-9). This study used gender- and age-matched
general resident as control and this comparison is interesting. However, authors
should add the resident positive for HCV antibody and negative for HCV RNA as
a control in addition to general resident in Figure 2, and discuss this point.
5. Residents older than 70 years were excluded in this study. IFN treatment may
not be indicated for those residents, this exclusion seems not to be necessary.
6. Mortality or liver related death in HCV infected patients in hospital based study
thought to be higher than those in cohort study (resident based study). This
difference may be affected by patients’ characteristics. In this study, LC was
observed in 177 patients with HCV infection, and these patients were excluded in
figure 5. How are cumulative survival and liver related death in LC patients
compared to Group B? In addition, ALT is important factor for HCC occurrence.
Untreated group (Group B) included many patients with normal ALT compared to
treated group (Group A). How is cumulative survival in patients with abnormal
ALT (#40) compared to that with normal ALT (<40)?
7. Methods for diagnosis of HCC should be indicated.
8. The numbers of patients at risk in Group A in Figure 5C or 5D (15 years of
follow up) seem to be mistake.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
assistant