Title: Hepatitis C Positive Organ Transplantation to Negative Recipients at a Multiorgan
Canadian Transplant Centre: Ready for Prime Time
Version: 2 Date: 30 Oct 2021
Reviewer's report:
The authors describe the success rate of eradication of HCV post-transplant in HCV seronegative
recipients transplanted with a seropositive donor, with or without positive NAT. There are not
many data on this issue, especially studies including other transplant types than kidney are scarse.
Therefore this publication is certainly welcome. However, there are some limitations and points
that need to be addressed:
1. Primary outcome was eradication of HCV posttransplant at 12 weeks. How did you define
eradication? Assume a negative HCV RNA in plasma, but should be stated in the methods
section.
2. You write “All of our patients who completed HCV treatment achieved SVR12”. Were there
any response prior to week 12? Fx week 4?
3. “One patient with metabolic syndrome that achieved SVR12 had persistently elevated
hepatocellular liver enzymes even after cure. This patient had long standing NAFLD pre-
transplant and post-transplant liver biopsy confirmed NASH with F2 fibrosis as the cause of liver
enzyme elevation. One patient experienced a complicated and prolonged hospital course due to
frailty with recurrent sepsis and eventually died from invasive pulmonary aspergillosis. ”. There
are studies suggesting that virus infection may increase risk of subsequent fungal infection, fx
influenza, covid and possibly also CMV. Could there be an associtation between HCV infection
leading to a more vulnerable patient, leading to fungal infection and death? And likewise, could
it be argued that the HCV infection had an adverse effect on an already vulnerable patient with
NASH? Thus, these concerns should be elaborated in the manuscript.
4. Were there any difference in the outcome (creatinine level at last follow up, graft survival
or other clinically relevant outcomes between the recipients who received a NAT positive vs
negative donor?
5. There were 11 patients that received NAT negative organs in this study and none of these
patients developed a donor derived HCV infection after 3 months of follow up post-transplant.
This is stated in the discussion section but this information is hard to find in the results section.
Should be more clear in the results section.
6. Could there be a difference in the risk of obtaining SVR in the different transplant organs?
One could suspect that liver tx are more at risk of having liver failure or impairment since the
location of the infections occurs in this organ. You have very few liver tx patients and may
therefore not be able to says much about this type of tx?
7. there could also be varying outcomes depending on immunosuppressive regimes, fx including
T cell depleting treatments. Can you comment on this in your paper?
Minor comments:
8. DCD: Donation After Circulatory Death should be explained the first time it is used in the
manuscript
9. suggestion for abstract: “Methods: We performed a retrospective review of HCV positive
organs to negative recipients transplanted over over 27 months. Primary outcome was
the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of
transmission of HCV, treatment adverse events, and graft failure. ”
Title: Hepatitis C Positive Organ Transplantation to Negative Recipients at a Multiorgan
Canadian Transplant Centre: Ready for Prime Time
Version: 2 Date: 30 Oct 2021
Reviewer's report:
The authors describe the success rate of eradication of HCV post-transplant in HCV seronegative
recipients transplanted with a seropositive donor, with or without positive NAT. There are not
many data on this issue, especially studies including other transplant types than kidney are scarse.
Therefore this publication is certainly welcome. However, there are some limitations and points
that need to be addressed:
1. Primary outcome was eradication of HCV posttransplant at 12 weeks. How did you define
eradication? Assume a negative HCV RNA in plasma, but should be stated in the methods
section.
2. You write “All of our patients who completed HCV treatment achieved SVR12”. Were there
any response prior to week 12? Fx week 4?
3. “One patient with metabolic syndrome that achieved SVR12 had persistently elevated
hepatocellular liver enzymes even after cure. This patient had long standing NAFLD pre-
transplant and post-transplant liver biopsy confirmed NASH with F2 fibrosis as the cause of liver
enzyme elevation. One patient experienced a complicated and prolonged hospital course due to
frailty with recurrent sepsis and eventually died from invasive pulmonary aspergillosis. ”. There
are studies suggesting that virus infection may increase risk of subsequent fungal infection, fx
influenza, covid and possibly also CMV. Could there be an associtation between HCV infection
leading to a more vulnerable patient, leading to fungal infection and death? And likewise, could
it be argued that the HCV infection had an adverse effect on an already vulnerable patient with
NASH? Thus, these concerns should be elaborated in the manuscript.
4. Were there any difference in the outcome (creatinine level at last follow up, graft survival
or other clinically relevant outcomes between the recipients who received a NAT positive vs
negative donor?
5. There were 11 patients that received NAT negative organs in this study and none of these
patients developed a donor derived HCV infection after 3 months of follow up post-transplant.
This is stated in the discussion section but this information is hard to find in the results section.
Should be more clear in the results section.
6. Could there be a difference in the risk of obtaining SVR in the different transplant organs?
One could suspect that liver tx are more at risk of having liver failure or impairment since the
location of the infections occurs in this organ. You have very few liver tx patients and may
therefore not be able to says much about this type of tx?
7. there could also be varying outcomes depending on immunosuppressive regimes, fx including
T cell depleting treatments. Can you comment on this in your paper?
Minor comments:
8. DCD: Donation After Circulatory Death should be explained the first time it is used in the
manuscript
9. suggestion for abstract: “Methods: We performed a retrospective review of HCV positive
organs to negative recipients transplanted over over 27 months. Primary outcome was
the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of
transmission of HCV, treatment adverse events, and graft failure. ”
Please review this paper.
user
Title: Hepatitis C Positive Organ Transplantation to Negative Recipients at a Multiorgan
Canadian Transplant Centre: Ready for Prime Time
Version: 2 Date: 30 Oct 2021
Reviewer's report:
The authors describe the success rate of eradication of HCV post-transplant in HCV seronegative
recipients transplanted with a seropositive donor, with or without positive NAT. There are not
many data on this issue, especially studies including other transplant types than kidney are scarse.
Therefore this publication is certainly welcome. However, there are some limitations and points
that need to be addressed:
1. Primary outcome was eradication of HCV posttransplant at 12 weeks. How did you define
eradication? Assume a negative HCV RNA in plasma, but should be stated in the methods
section.
2. You write “All of our patients who completed HCV treatment achieved SVR12”. Were there
any response prior to week 12? Fx week 4?
3. “One patient with metabolic syndrome that achieved SVR12 had persistently elevated
hepatocellular liver enzymes even after cure. This patient had long standing NAFLD pre-
transplant and post-transplant liver biopsy confirmed NASH with F2 fibrosis as the cause of liver
enzyme elevation. One patient experienced a complicated and prolonged hospital course due to
frailty with recurrent sepsis and eventually died from invasive pulmonary aspergillosis. ”. There
are studies suggesting that virus infection may increase risk of subsequent fungal infection, fx
influenza, covid and possibly also CMV. Could there be an associtation between HCV infection
leading to a more vulnerable patient, leading to fungal infection and death? And likewise, could
it be argued that the HCV infection had an adverse effect on an already vulnerable patient with
NASH? Thus, these concerns should be elaborated in the manuscript.
4. Were there any difference in the outcome (creatinine level at last follow up, graft survival
or other clinically relevant outcomes between the recipients who received a NAT positive vs
negative donor?
5. There were 11 patients that received NAT negative organs in this study and none of these
patients developed a donor derived HCV infection after 3 months of follow up post-transplant.
This is stated in the discussion section but this information is hard to find in the results section.
Should be more clear in the results section.
6. Could there be a difference in the risk of obtaining SVR in the different transplant organs?
One could suspect that liver tx are more at risk of having liver failure or impairment since the
location of the infections occurs in this organ. You have very few liver tx patients and may
therefore not be able to says much about this type of tx?
7. there could also be varying outcomes depending on immunosuppressive regimes, fx including
T cell depleting treatments. Can you comment on this in your paper?
Minor comments:
8. DCD: Donation After Circulatory Death should be explained the first time it is used in the
manuscript
9. suggestion for abstract: “Methods: We performed a retrospective review of HCV positive
organs to negative recipients transplanted over over 27 months. Primary outcome was
the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of
transmission of HCV, treatment adverse events, and graft failure. ”
assistant