Review for 10.1186/1471-230X-9-5 (2009)

Reviewer's report
Title:Studies on best positive predictors for sustained virologic response to
interferon alpha plus ribavirin therapy in Naive Chronic Hepatitis C Patients
Version: 2Date:12 July 2008
Reviewer: Gloria Taliani
Reviewer's report:
Major comments:
In the present study a really good rate of SVR (51.56%) is reported in HCV
patients treated with non-pegylated IFN and ribavirin. Although this result may
depend on racial and/or virological characteristics of the study population, it is
quite different from the results reported in other populations treated with the
same schedule and IFN type. To this high response rate could, at least in part,
contribute the exclusion of some patients from the analysis. In fact, on page 9 we
find the following sentence: “Out of these 400 patients, 280 were males and 120
females. Six patients (four males and two females) discontinued treatment due to
severe side effect of treatment at month 2 and were excluded from data
analysis”. This is not correct because these patients have received the treatment
for 2 months and should be computed as non-responders on intention to treat
analysis. Thus, SVR rate should be recalculated after inclusion of these patients
and the result should be correctly reported in all the sections of the manuscript,
including the abstract. In addition, although the PCR method employed in the
present study has a quite low sensitivity (100copies/ml of HCV-RNA) which may
contribute to misclassify partial responders with low residual HCV-RNA titer as
end treatment responders, the relapse rate after therapy withdrawal is
surprisingly low (16%), and this is an unexpected result which deserves some
comments and some clarification from the authors.
Table 2, which reports the results of the analysis of virological response at week
8, end of treatment and end of follow up, is difficult to understand. I made the
calculation myself with either Fisher’s exact test and Chi square test and found
no significant difference between males and females in any type of virological
response. Thus I wonder which test has been applied for the calculation of such
a significant difference reported by the Authors. Besides, I did not find any
difference between males and females by Chi Square test and Fisher’s exact test
based on the data reported in table 5. Thus, a revision of the statistical analysis
is strongly advised.
The definition of Rapid Virological Response (RVR) given by the Authors in not
correct. By definition, the RVR is the negative HCV-RNA by week 4 of therapy
and not by week 8 as indicated by the Authors. The wrong definition should be
corrected along all the manuscript.
The number of patients who had a liver biopsy examination is really low (57
patients) compared to the cohort of treated patients (400 patients) and this
makes impossible to infer data about the response rate of different ethnic groups
(Pashtoon versus Punjabj), of cirrhotic patients or make a multivariate analysis
concerning the predictors of response. In addition, no data about the compliance
of the patients to the therapy are reported, which introduces a further uncertainty
about the reliability of the predictors of response.
In Table 3, the groups of patients divided according to the infecting genotype are
too many and some groups include less than 5 patients, which is useless:
genotypes may be grouped in 1 and non-1. This last group can be sub-divided in
genotype 2 and 3. Finally, it could be interesting to examine in deeper detail
those patients with mixed genotypes who did not respond to the treatment in
order to evaluate which genotype was the resistant one.
Also Table 4 is too detailed. A ROC of age and response could be done to
determine the best age cut-point and age analysis should be done according to
it.
Finally, the discussion is too long. It should be shortened and focused on really
relevant points regarding data correctly re-analyzed. The manuscript should
undergo a careful revision by an English mother tongue reviewer.
Minor Comments:
In the text it is reported that some examined factors are “…..independent risk
factors for low SVR”…. Which is not correct. These factors are independent
PREDICTORS OF NON RESPONSE. The concept of “low response” is not
applicable to HCV treatment: there is only the possibility of “response” or “non
response”.
In the abstract, the following sentence should be reworded ” the patients data
collected prospectively was at this Centre from 2001 to 2007 was analyzed”.
On page 7, the following sentence should be reworded “Further the patients were
required to negative for hepatitis B surface antigen…”
On page 7, the following sentence should be reworded “Patients were excluded
from the studies that were <18 years or above 70 years..”
Tables should be carefully revised because of typing errors (e.g. Table 1, the
percentage of genotype 3 females is not 18.78) or mistakes (Table 2 P values;
Table 5 sex P value).
Many other misspelling, grammar and syntax errors are present in the
manuscript and should be corrected.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
No competing interests exist