Reviewer's report
Title:Anticoagulant therapy for nodular regenerative hyperplasia in a
HIV-infected patient
Version: 2Date:29 July 2009
Reviewer: Vincent Mallet
Reviewer's report:
The case of a Human Immunodeficiency Virus (HIV)-infected patient with nodular
regenerative hyperplasia (NRH) and severe portal hypertension that improved
under anticoagulants is presented. The patient had been previously exposed to
didanosine and harbored protein S deficiency. This case adds further evidence
that HIV-associated NRH is linked to thrombophilia, but still, there is not enough
data to recommend the use of anticoagulants in HIV-associated NRH. The
manuscript should be modified to focus on the putative mechanism(s) of
HIV-associated NRH. With their observation, the authors should highlight the
relation between thrombophilia and HIV-associated NRH which is, to date, not so
clear.
1. Major revisions
This patient had several episodes of gastrointestinal hemorrhage, one of them
under vitamin K antagonist (VKA). Please explain and discuss how you managed
these complications before and under anticoagulants.
The following mechanisms: HIV-1 vasculotropism and toxicity, didanosine and
thrombophilia (especially Protein S deficiency) should be better discussed.
Please reference the recent studies on the subject.
The conclusion of this paper is that anticoagulants should be evaluated in
controlled studies.
2. Minor revisions
Please reference the recent papers on the subject [1-5].
In the introduction, first paragraph, it is inaccurate to state that the central veins
are squeezed by the enlarged hepatocytes in NRH, especially in HIV-associated
NRH where obliterative venopathy seems to be the main mechanism [3, 6].
1. Mallet VO, Varthaman A, Lasne D, Viard JP, Gouya H, Borgel D,
Lacroix-Desmazes S, Pol S: Acquired protein S deficiency leads to obliterative
portal venopathy and to compensatory nodular regenerative hyperplasia in
HIV-infected patients. Aids 2009, 23:1511-1518.
2. Kovari H, Ledergerber B, Peter U, Flepp M, Jost J, Schmid P, Calmy A,
Mueller NJ, Muellhaupt B, Weber R: Association of noncirrhotic portal
hypertension in HIV-infected persons and antiretroviral therapy with didanosine:
a nested case-control study. Clin Infect Dis 2009, 49:626-635.
3. Chang PE, Miquel R, Blanco JL, Laguno M, Bruguera M, Abraldes JG, Bosch
J, Garcia-Pagan JC: Idiopathic portal hypertension in patients with HIV infection
treated with highly active antiretroviral therapy. Am J Gastroenterol 2009,
104:1707-1714.
4. Saifee S, Joelson D, Braude J, Shrestha R, Johnson M, Sellers M, Galambos
MR, Rubin RA: Noncirrhotic Portal Hypertension in Patients With Human
Immunodeficiency Virus-1 Infection. Clin Gastroenterol Hepatol 2008.
5. Maida I, Garcia-Gasco P, Sotgiu G, Rios MJ, Vispo ME, Martin-Carbonero L,
Barreiro P, Mura MS, Babudieri S, Albertos S, et al: Antiretroviral-associated
portal hypertension: a new clinical condition? Prevalence, predictors and
outcome. Antivir Ther 2008, 13:103-107.
6. Reshamwala PA, Kleiner DE, Heller T: Nodular regenerative hyperplasia: not
all nodules are created equal. Hepatology 2006, 44:7-14.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
Honoraria received from Schering-Plough, Bristol-Myers Squibb, Gilead Science.
Reviewer's report
Title:Anticoagulant therapy for nodular regenerative hyperplasia in a
HIV-infected patient
Version: 2Date:29 July 2009
Reviewer: Vincent Mallet
Reviewer's report:
The case of a Human Immunodeficiency Virus (HIV)-infected patient with nodular
regenerative hyperplasia (NRH) and severe portal hypertension that improved
under anticoagulants is presented. The patient had been previously exposed to
didanosine and harbored protein S deficiency. This case adds further evidence
that HIV-associated NRH is linked to thrombophilia, but still, there is not enough
data to recommend the use of anticoagulants in HIV-associated NRH. The
manuscript should be modified to focus on the putative mechanism(s) of
HIV-associated NRH. With their observation, the authors should highlight the
relation between thrombophilia and HIV-associated NRH which is, to date, not so
clear.
1. Major revisions
This patient had several episodes of gastrointestinal hemorrhage, one of them
under vitamin K antagonist (VKA). Please explain and discuss how you managed
these complications before and under anticoagulants.
The following mechanisms: HIV-1 vasculotropism and toxicity, didanosine and
thrombophilia (especially Protein S deficiency) should be better discussed.
Please reference the recent studies on the subject.
The conclusion of this paper is that anticoagulants should be evaluated in
controlled studies.
2. Minor revisions
Please reference the recent papers on the subject [1-5].
In the introduction, first paragraph, it is inaccurate to state that the central veins
are squeezed by the enlarged hepatocytes in NRH, especially in HIV-associated
NRH where obliterative venopathy seems to be the main mechanism [3, 6].
1. Mallet VO, Varthaman A, Lasne D, Viard JP, Gouya H, Borgel D,
Lacroix-Desmazes S, Pol S: Acquired protein S deficiency leads to obliterative
portal venopathy and to compensatory nodular regenerative hyperplasia in
HIV-infected patients. Aids 2009, 23:1511-1518.
2. Kovari H, Ledergerber B, Peter U, Flepp M, Jost J, Schmid P, Calmy A,
Mueller NJ, Muellhaupt B, Weber R: Association of noncirrhotic portal
hypertension in HIV-infected persons and antiretroviral therapy with didanosine:
a nested case-control study. Clin Infect Dis 2009, 49:626-635.
3. Chang PE, Miquel R, Blanco JL, Laguno M, Bruguera M, Abraldes JG, Bosch
J, Garcia-Pagan JC: Idiopathic portal hypertension in patients with HIV infection
treated with highly active antiretroviral therapy. Am J Gastroenterol 2009,
104:1707-1714.
4. Saifee S, Joelson D, Braude J, Shrestha R, Johnson M, Sellers M, Galambos
MR, Rubin RA: Noncirrhotic Portal Hypertension in Patients With Human
Immunodeficiency Virus-1 Infection. Clin Gastroenterol Hepatol 2008.
5. Maida I, Garcia-Gasco P, Sotgiu G, Rios MJ, Vispo ME, Martin-Carbonero L,
Barreiro P, Mura MS, Babudieri S, Albertos S, et al: Antiretroviral-associated
portal hypertension: a new clinical condition? Prevalence, predictors and
outcome. Antivir Ther 2008, 13:103-107.
6. Reshamwala PA, Kleiner DE, Heller T: Nodular regenerative hyperplasia: not
all nodules are created equal. Hepatology 2006, 44:7-14.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
Honoraria received from Schering-Plough, Bristol-Myers Squibb, Gilead Science.
Please review this paper.
user
Reviewer's report
Title:Anticoagulant therapy for nodular regenerative hyperplasia in a
HIV-infected patient
Version: 2Date:29 July 2009
Reviewer: Vincent Mallet
Reviewer's report:
The case of a Human Immunodeficiency Virus (HIV)-infected patient with nodular
regenerative hyperplasia (NRH) and severe portal hypertension that improved
under anticoagulants is presented. The patient had been previously exposed to
didanosine and harbored protein S deficiency. This case adds further evidence
that HIV-associated NRH is linked to thrombophilia, but still, there is not enough
data to recommend the use of anticoagulants in HIV-associated NRH. The
manuscript should be modified to focus on the putative mechanism(s) of
HIV-associated NRH. With their observation, the authors should highlight the
relation between thrombophilia and HIV-associated NRH which is, to date, not so
clear.
1. Major revisions
This patient had several episodes of gastrointestinal hemorrhage, one of them
under vitamin K antagonist (VKA). Please explain and discuss how you managed
these complications before and under anticoagulants.
The following mechanisms: HIV-1 vasculotropism and toxicity, didanosine and
thrombophilia (especially Protein S deficiency) should be better discussed.
Please reference the recent studies on the subject.
The conclusion of this paper is that anticoagulants should be evaluated in
controlled studies.
2. Minor revisions
Please reference the recent papers on the subject [1-5].
In the introduction, first paragraph, it is inaccurate to state that the central veins
are squeezed by the enlarged hepatocytes in NRH, especially in HIV-associated
NRH where obliterative venopathy seems to be the main mechanism [3, 6].
1. Mallet VO, Varthaman A, Lasne D, Viard JP, Gouya H, Borgel D,
Lacroix-Desmazes S, Pol S: Acquired protein S deficiency leads to obliterative
portal venopathy and to compensatory nodular regenerative hyperplasia in
HIV-infected patients. Aids 2009, 23:1511-1518.
2. Kovari H, Ledergerber B, Peter U, Flepp M, Jost J, Schmid P, Calmy A,
Mueller NJ, Muellhaupt B, Weber R: Association of noncirrhotic portal
hypertension in HIV-infected persons and antiretroviral therapy with didanosine:
a nested case-control study. Clin Infect Dis 2009, 49:626-635.
3. Chang PE, Miquel R, Blanco JL, Laguno M, Bruguera M, Abraldes JG, Bosch
J, Garcia-Pagan JC: Idiopathic portal hypertension in patients with HIV infection
treated with highly active antiretroviral therapy. Am J Gastroenterol 2009,
104:1707-1714.
4. Saifee S, Joelson D, Braude J, Shrestha R, Johnson M, Sellers M, Galambos
MR, Rubin RA: Noncirrhotic Portal Hypertension in Patients With Human
Immunodeficiency Virus-1 Infection. Clin Gastroenterol Hepatol 2008.
5. Maida I, Garcia-Gasco P, Sotgiu G, Rios MJ, Vispo ME, Martin-Carbonero L,
Barreiro P, Mura MS, Babudieri S, Albertos S, et al: Antiretroviral-associated
portal hypertension: a new clinical condition? Prevalence, predictors and
outcome. Antivir Ther 2008, 13:103-107.
6. Reshamwala PA, Kleiner DE, Heller T: Nodular regenerative hyperplasia: not
all nodules are created equal. Hepatology 2006, 44:7-14.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
Honoraria received from Schering-Plough, Bristol-Myers Squibb, Gilead Science.
assistant