Download - Annals of Gastroenterology

September 27, 2016
Ioannis Koutroubakis MD PhD
Editor-in-Chief; Annals of Gastroenterology
Associate Professor of Medicine
University Hospital Heraklion
Department of Gastroenterology
P.O BOX 1352 , 71110 Heraklion, Crete, Greece
e-mail:[email protected]
Tel: + 30.2810392254
fax: +30.2810542085
Re: Annals of Gastroenterology, manuscript #2972
Dear Dr. Koutroubakis,
Kindly find attached our revised manuscript entitled “Viral hepatitis status does not affect
survival in hepatocellular carcinoma” for consideration of publication in Annals of
Gastroenterology.
The manuscript has been edited based on the comments of the reviewers and following is the
letter of itemized responses.
Thank you for considering our revised manuscript
Sincerely,
Eyas Alkhalili, MD
Response to reviewers.
Re: Annals of Gastroenterology, manuscript #2972
Reviewer A:
The present study tries to address the question of the impact of viral
etiology on the prognosis of patients with HCC , analyzed as an independent
factor . It is however, limited as an one center retrospective study with
233 patients with Viral (HBV or HCV positive) etiology of HCC, and 133 HCC
cases virus negative whose main etiology is alcohol induced chronic liver
disease or NASH. Although sample size is rather small to produce firm
conclusions, one of the important strengths of this study in comparison to
previous studies, is the inclusion of one third of the cases of non viral
etiology HCC. On multivariate analysis , disease stage and Child-Pugh class
were independent factors affecting survival, but viral factor was not.
Patients with V-HCC presented with more advanced cirrhosis and had a lower
likelihood to undergo hepatectomy.
The study although has limitations such as particular ethnic groups in new
Mexico and the fact that it did not accounted for difference in surveillance
patterns between etiologies of HCC, (viral cirrhosis has more solid
surveillance in general clinical practice ) puts into consideration the
important question of adjuvant antiviral treatment possible effect on
survival in V-HCC ,without a counterpart available for NBNC-HCC.
Thank you for your encouraging review. We have no additions or comments.
Reviewer B:
1) The survival in Fig 2 (according to disease stage) should be changed in
stage two disease. The x-axis (months of survival) should change according
to the other three stages so the comparisons are straigtforward. Moreover
the median survival of the four stages should be reported along with the
overall median survival at the appropriate paragraph at the results section.
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We have edited figure 2 and reloaded the new version to the revised manuscript. The new
paragraph now reads as follows:
“No differences were found for stage-specific median survivals for stage I (36 months in
V-HCC vs. 29 months NBNC-HCC), stage II (13 vs 14 months), stage III (6 vs. 7
months), and stage IV (5 vs 6 months) (Figure 2).”
2) The authors should include any previous antiviral treatment the viral
cases have received. This might have influenced the result. If the number of
treated with antivirals cirrhotics is relatively large this parameter should
be included in the multivariate analysis.
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The first agents to treat viral hepatitis agents (Boceprevir and Telaprevir) were only
approved by the FDA in 2011 and as such the vast majority of our patients were not on
antiviral therapy in the study period (2000-2014). The effect of these treatments would
have an impact on patients’ liver disease, however, the vast majority of patients
diagnosed and treated prior to approval of these medications. Moreover, this data is not
complete in our data and not available to us as some patients were referred to our cancer
institution for treatment of their HCC while treatment of their underlying liver disease
and hepatitis were performed elsewhere.
3) The authors should comment on the fact that the vast majority of their
viral cirrhotics are HCV cirrhosis who may have a better survival than HBV.
In our recent paper (World J Hepatology 6504-51,2014) we reported that HBV
cirrhotics have twice the risk of death compared to HCV cirrhotics.
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This has been edited and addressed in the discussion section. Manuscript now reads:
“ Another study by the ILCG demonstrated a difference in survival in advanced HCC
between different types of hepatitis; as patients with hepatitis B had better survival than
those associated with hepatitis C (HR 1.5, 95% CI 1-2.29, p=0.048) (23). This has not
been consistent in the literature, however. Samonakis et al. found contradictory results
with Hepatitis B being associated with twice the risk of death of HCV patients (24). The
majority of our V-HCC patients had hepatitis C which makes this patient group
overrepresented when compared to hepatitis B and the results group might be more
reflective of these patients’ prognosis.”
4) TNM classification may not be the best way of staging in HCC. Certainly
the Barcelona or the Italian classification are prognostically more
accurate,although even with the TNM system,stage is a significant prognostic
factor in their study. They should however comment in the discussion that an
other classification might have strengthened the significance.
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The discussion has been revised. The other staging systems were mentioned in the
discussion section and while these may be more prognostic and incorporate the stage of
cirrhosis into the classification, we use the TNM system which despite its limitations has
shown to be strongly predictive of survival in our survival and multivariate analysis.
Discussion now reads as follows:
“We used the TNM staging system and found similar stage distribution between the two
groups. Although the other staging systems account for cirrhosis while the TNM does
not, the TNM staging system was an independent factor of prognosis and it’s the
preferred staging system at our institution.”
Thank you for considering our revised manuscript.
Editor's comments:
1. A summary box according to Journal's guidelines (What is already known
about this subject: 3-4 bullet points What are the new findings: 3-4 bul
points) should be added
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These has been added to the manuscript.
2. All abbreviations used in each table should be explained at the bottom
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These have been added to the tables.
3. The references should follow the Journal's style
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These have been edited appropriately.
Thank you for considering our revised manuscript.