Brief Article Open Access
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 21, 2009; 15(43): 5449-5454
Published online Nov 21, 2009. doi: 10.3748/wjg.15.5449
G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence
Francesca Lodato, Francesco Azzaroli, Maria Rosa Tamè, Maria Di Girolamo, Federica Buonfiglioli, Natalia Mazzella, Paolo Cecinato, Enrico Roda, Giuseppe Mazzella, Department of Digestive Diseases and Internal Medicine, University of Bologna, Bologna 40138, Italy
Author contributions: Lodato F performed the majority of the study and wrote the paper; Azzaroli F, Tamè MR and Di Girolamo M performed the study and contributed to writing of the paper; Buonfiglioli F, Mazzella N and Cecinato P contributed to editing of the paper; Roda E revised the paper; Mazzella G designed the study, performed the statistical analysis and revised the paper.
Correspondence to: Dr. Francesca Lodato, MD, Department of Digestive Diseases and Internal Medicine, Sant’Orsola-Malpighi University Hospital, Via Massarenti, Bologna 40138, Italy.
Telephone: +39-51-6364120 Fax: +39-51-6364120
Received: August 1, 2009
Revised: September 10, 2009
Accepted: September 17, 2009
Published online: November 21, 2009


AIM: To evaluate the efficacy of granulocyte colony stimulating factors (G-CSF) in liver transplanted patients with hepatitis C (HCV) recurrence and Pegylated-IFN α-2b induced neutropenia, and to evaluate the impact of G-CSF administration on virological response.

METHODS: Sixty-eight patients undergoing antiviral treatment for post-liver transplantation (OLT) HCV recurrence were enrolled. All patients developing neutropenia received G-CSF.

RESULTS: Twenty three (34%) received G-CSF. Mean neutrophil count at the onset of neutropenia was 700/mmc (range 400-750/mmc); after 1 mo of G-CSF it increased to 1210/mmc (range 300-5590/mmc) (P < 0.0001). Three patients did not respond to G-CSF. Treatment duration was similar in neutropenic and non-neutropenic patients. No differences in the rate of discontinuation, infections or virological response were observed between the two groups. G-CSF was protective for the onset of de novo autoimmune hepatitis (P < 0.003).

CONCLUSION: G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasing neutrophil count, prolonging treatment and leading to sustained virological response (SVR) rates comparable to non-neutropenic patients. It prevents the occurrence of de novo autoimmune hepatitis.

Key Words: Granulocyte colony stimulating factors, Liver transplantation, Hepatitis C virus recurrence, Antiviral treatment


Both interferons (IFNs) and pegylated interferons (Peg-IFNs) may induce neutropenia[1-4]. This side effect may limit adherence to treatment which is one of the most important factors related to virological response[1,5-7].

In immunocompetent patients, neutropenia has not been associated with infections. However, in oncological immunodepressed patients neutropenia is associated with infections[8-10] and liver transplanted patients are immunosuppressed. In fact, liver transplanted patients have a high rate of infections reaching 56% within the first year post transplantation[11-13]. This ease at infections coupled to the baseline leucopenia induced by the immunosuppressive regimens challenging the management of these patients by the clinician.

There are no guidelines on the use of granulocyte colony stimulating factors (G-CSF) for the treatment of IFN induced neutropenia. Moreover, the impact of G-CSF administration during antiviral therapy for chronic hepatitis C has not been determined yet. Nevertheless, the use G-CSF is becoming a standard of care in this setting, especially in liver transplanted patients, and is recommended by several authors[5,14-19].

A recent study by our group showed that G-CSF administration has a protective effect for the development of de novo autoimmune hepatitis during antiviral therapy in transplanted patients[20].

This effect is not surprising as G-CSF has been shown to have several immunological properties: induces T-regulator (T-regs) mobilization and activity, both directly and through the expansion of tolerogenic myeloid precursor and type 2 dendritic cells mobilization; moreover it skews the cytokine profile, inducing tolerogenic dendritic cells and T-regs, which finally suppresses T cell activity[21-26].

The aims of the present study were to evaluate the efficacy of G-CSF use in liver transplanted patients with hepatitis C virus (HCV) recurrence and Peg-IFN α-2b induced neutropenia, and to evaluate the impact of G-CSF administration on virological response.


Patients undergoing antiviral treatment for post orthotopic liver transplantation (OLT) HCV recurrence were consecutively enrolled in Bologna Liver Transplantation Centre between October 2001 and April 2005. All patients received Peg-IFN α-2b at the dose of 1.0 mcg/kg once weekly (Peg-Intron®, Schering-Plough, Italy), and Ribavirin (Rebetol®, Schering-Plough, Italy) at a dose of 8-10 mg/kg per day. Transplanted patients had to fulfil the following criteria for antiviral treatment: detectable HCV-RNA by PCR, elevated (> 1.0 ×) serum alanine aminotransferase (ALT) levels and histological features of HCV hepatitis on liver biopsy. Exclusion criteria were: evidence of decompensated liver disease, histological evidence of rejection and drug-related injury, HBsAg positivity, human immunodeficiency virus (HIV) positivity, moderate to severe anemia (Hb < 10 g/dL), neutropenia (neutrophil count < 1000/mm3), thrombo-cytopenia (PLT < 50 000/mm3), impaired renal function (creatinine clearance < 50 mL/min), significant history of cardiovascular and psychiatric diseases, ongoing alcohol abuse and previous post-LT treatment with PEG-IFN. Hematologic determinations were carried out using conventional tests at baseline and weekly for the first month, then monthly until the end of the study.

All patients developing neutropenia during antiviral treatment received Granulocyte Colony-Stimulating Factor (G-CSF) (Granulokine®, Roche, Italy). Below 750/mmc neutrophils, G-CSF 300 μg/wk was administered and in case of non significant response the dose was increased to 600 μg/wk. When the neutrophil count did not increase satisfactorily, despite G-CSF administration, Peg-IFN dose was reduced. When neutrophils fell below 500/mmc despite G-CSF administration, antiviral treatment was discontinued. G-CSF treatment was continued until restoration of neutrophil count to values comparable to the patient’s baseline. None of the patients received azathioprine or mycophenolate mofetil.

All patients gave written informed consent according to the Ethical Committee Procedures of our Hospital for the administration of off label drugs.

Statistical analysis

Data were analyzed on an intention-to-treat-basis. Results are presented as median (range). Non parametric tests were used to compare variables between groups (Wilcoxon, χ2 test). All P < 0.05 by the two-tailed test were considered significant. All data analyses were conducted using the MedCalc Package.


Sixty-eight patients (46 males and 22 females), median age 59 (22-68 years) were enrolled in the study (Table 1). Ten patients were cirrhotic at enrolment. Twenty three (34%) received G-CSF according to our study design. Table 2 shows the baseline characteristics of patients developing neutropenia or not and of all patients together. The only factor related to neutropenia development was pre-treatment neutrophil count, which was significantly lower in patients who later developed neutropenia and were treated with G-CSF. Median neutrophil count at the onset of neutropenia was 700/mmc (range 400-750/mmc) and after one month of G-CSF administration it increased to 1210/mmc (range 300-5590/mmc) (P < 0.0001) (Figure 1). Mean G-CSF treatment duration was 4.9 ± 3.6 mo. Three patients did not respond to G-CSF administration after one month; two patients had an improved neutrophil count with an increased dose of G-CSF and a reduction of Peg-IFN dose and continued treatment until the end of the planned 48 wk period, the other discontinued treatment. No patient had to reduce their Peg-IFN dose in the non-neutropenic group. Table 3 shows Ribavirin (RBV) and Peg-IFN dose modification during treatment in both groups. At multivariate analysis, several factors were evaluated (age, sex, time from OLT, type of immunosuppression, presence of cirrhosis, basal neutrophil count) but none was associated with non response to G-CSF.

Table 1 Baseline characteristics of patients at enrolment.
Sex (M/F)46/22
Age, median (range)59 (22-68)
BMI, median (range)24.2 (15.5-40.5)
Months since LT, median (range)15.5 (1-151)
Previous acute cellular rejection n (%)13 (19)
Days since OLT, mean36.4
Previous CMV infection n (%)14 (21)
Genotype n (%)
153 (76.5)
26 (9)
34 (6)
45 (7)
Viral load (MEq/mL), median (range)10.6 (0.009-40)
ALT (IU/L), median (range)136 (52-945)
Neutrophil count (× 103/mmc) mean ± SD3 ± 1.2
Hemoglobin (g/dL) mean ± SD12.9 ± 1.5
Cirrhosis n (%)10 (15)
Pre-LT antiviral treatment n (%)29 (45)
Post-LT antiviral treatment n (%)15 (22)
Induction immunosuppression n (%)
Monoclonal antibodies10 (14)
Steroids49 (72)
Other3 (4)
NA6 (10)
Maintenance immunosuppression n (%)
Cyclosporine30 (44)
Tacrolimus22 (32)
Cyclosporine + steroids6 (9)
Tacrolimus + steroids9 (13)
Other1 (1.5)
Figure 1
Figure 1 Neutrophil count response after 1 mo of granulocyte colony stimulating factors administration.
Table 2 Characteristics of patients developing neutropenia.
Sex (M/F)10/13Dec-33NS
Age, median (range)60 (41-68)58 (22-67)NS
Months since LT, median (range)15 (2-151)19 (1-148)
Genotype n (%)
117 (73)36 (80)NS
22 (8.6)4 (8.8)NS
32 (8.6)2 (4.4)NS
42 (8.6)3 (6.6)NS
Neutrophil count (× 103/mmc) mean ± SD2.23 ± 0.963.14 ± 1.220.0021
Cirrhosis n (%)10 (15)
Induction immunosuppression n (%)
Monoclonal antibodies4 (17)6 (13)NS
Steroids17 (73)32 (71)NS
Other1 (3)2 (4)NS
NA1 (3)5 (1)NS
Maintenance immunosuppression n (%)
Cyclosporine10 (43)20 (44)NS
Tacrolimus8 (34)14 (31)NS
Cyclosporine + steroids1 (4)5 (11)NS
Tacrolimus + steroids3 (13)6 (13)NS
Other1 (4)0NS
Table 3 Peg-IFN and RBV dose reductions n (%).
RBV reduction6 (26)17 (37)0.4
RBV withdrawal4 (17)3 (6)0.2
Peg-IFN + RBV reduction2 (8)1 (2)0.2

The mean treatment duration was similar in neutropenic and non-neutropenic patients regardless of G-CSF administration and genotype (Figure 2A).

Figure 2
Figure 2 Comparison of treatment duration, premature discontinuation rate, infections rate and sustained virological response (SVR) rate between neutropenic patients treated with G-CSF and untreated non-neutropenic patients.

Causes of premature discontinuation are shown in Table 4. No significant differences in the rate of discontinuation were observed between the two groups (neutropenic and non-neutropenic) (Figure 2B).

Table 4 Causes of premature discontinuation in the two groups.
Discontinuation causeG-CSF groupNon neutropenic group
Liver decompensation33
Severe asthenia21
Toxic hepatitis1
Non response1
Liver abscess1
De novo AIH9
De novo HBV infection1

Two severe infections were observed in the G-CSF group (1 pneumonia and 1 urinary infection) and 5 in the non-neutropenic patients (3 pneumonias, 1 liver abscess and 1 cytomegalovirus) (P = No significance) (Figure 2C). Among neutropenic patients, the neutrophil counts were 700/mm3 and 900/mm3 respectively at the onset of infections. In non-neutropenic patients developing infections, the neutrophil count was > 1000/mm3 in all at the onset of neutropenia.

Viral response

Sustained virological response was 30% in the G-CSF group versus 35% in the non-neutropenic patients (P = NS) (Figure 2D).

Autoimmune diseases

In the G-CSF group no de novo hepatic autoimmune disease was observed, while 9 patients in the other group developed autoimmune hepatitis (P < 0.03) (Figure 3). This pathological entity has already been extensively described by our group[20] and therefore won’t be discussed in detail here. De novo autoimmune hepatitis diagnosis was performed in patients with an unexplained cause of graft dysfunction, after the exclusion of other known causes (infections, anastomoses complications, acute or chronic rejection) and the application of the International Autoimmune Hepatitis Group score[27]. This disease was related to severe patient and graft outcome; in fact two patients died and two had a graft failure with one patient re-enlisted for transplant. In our series no rejection episodes were observed.

Figure 3
Figure 3 Incidence of hepatic and systemic autoimmune diseases in neutropenic patients treated with G-CSF and untreated non-neutropenic patients.

The incidence of non hepatic autoimmune manifestations was similar in the two groups. One patient had autoimmune thyroiditis and another had systemic lupus erythematosus (SLE) responding to steroid treatment[28] in the G-CSF group, while among non-neutropenic patients, one had autoimmune gastritis.


Our data shows that G-CSF administration is effective in resolving neutropenia in transplanted patients treated with Peg-IFN α-2b for HCV recurrence. The improvement or the resolution of neutropenia allowed us to prolong treatment duration to a time which is comparable to that of non-neutropenic patients and presumably contributed to patients reaching an SVR rate which was comparable in the two groups. G-CSF administration did not affect the rate of infections or the occurrence of non hepatic autoimmune diseases, while it was a protective factor for the development of de novo autoimmune hepatitis. The only predictive factor related to the development of neutropenia during antiviral treatment was pre-treatment neutrophil count.

Clinical experience, mainly from studies in immunocompetent patients, suggests that maintenance of optimal dosages of Peg-IFN and RBV results in higher rates of SVR. Previous studies on liver transplanted patients have shown that, overall, a SVR between 30% and 45% is achievable[29-35]. Therefore, in our opinion, adjunctive treatments allowing the maintenance of optimal dosages of Peg-IFN and RBV during treatment are advisable. In our series the rate of SVR was not significantly different among patients treated and not treated with G-CSF. The lack of a statistically significant difference could be affected by the small number of patients, but the rate of SVR in neutropenic patients treated with G-CSF is comparable to what is reported in literature. Moreover, although not statistically significant, a larger proportion of patients had to reduce or suspend RBV in the G-CSF group, and this factor might have contributed to the smaller SVR rate in this group.

There are currently no guidelines on the use of G-CSF in IFN induced neutropenia. Therefore, no established common approach to its use is defined in both the immunocompetent and the transplanted patient. In this context we arbitrarily defined cut off values to begin G-CSF administration. In consideration of the immune depression of our patients we chose a high cut off level of 750 neutrophils/mmc for initiation of treatment in order to prevent infections. We are aware that previous studies in immunocompetent patients did not show a correlation between the absolute number of neutrophils and infections[2,36,37], but in immunodepressed oncological patients this correlation exists[8-10]; this induced us to choose a safer cut off value. Unfortunately ours was not a randomised study, because in our opinion it would be not ethical not to treat a severe neutropenia in a transplanted immunosuppressed patient. Nevertheless, in our study infections seemed to be independent of neutrophil count. Anyway, our study shows that G-CSF use in transplanted patients is safe and effective.

With regard to autoimmune diseases, our study suggests that G-CSF protected from de novo autoimmune hepatitis but not from other systemic autoimmune manifestations. This is not surprising, as G-CSF has been reported to have different effects in different autoimmune diseases[38-40]. This probably depends on the immune pathogenetic mechanisms underlying the different diseases. However, the apparently induced non hepatic autoimmune manifestations did not significantly impact on patients outcome while de novo hepatitis was severe and related to high patient and graft loss, suggesting that the onset of non hepatic autoimmune manifestations does not contraindicate G-CSF use in this population.

In conclusion, our study supports G-CSF administration in transplanted patients with HCV recurrence developing Peg-IFN induced neutropenia because it is effective in increasing the neutrophil count. G-CSF administration prolongs treatment duration in neutropenic patients leading to SVR rates which are comparable to that of non-neutropenic patients. A pre-emptive treatment with G-CSF could be advisable in patients with very low pre-treatment neutrophil counts. G-CSF seems to have a protective role against the occurrence of de novo autoimmune hepatitis, a recently defined pathogenetic entity related to a severe outcome. Prospective randomized studies are needed in order to evaluate the protective effect of prophylactic G-CSF administration to prevent this form of autoimmune hepatitis.


The treatment of liver transplanted patients with hepatitis C virus (HCV) recurrence is based on a combination of Pegylated Interferon (PegIFN) and Ribavirin, with disappointing results. A key factor for response to IFNs is adherence to treatment, which is challenging in immunodepressed patients in whom PegIFN dose reductions for neutropenia are often required. This study aims to evaluate the efficacy and the impact on virological response of granulocyte colony stimulating factors (G-CSF) administration in transplanted patients developing PegIFN related neutropenia.

Research frontiers

There are no guidelines on the use of G-CSF for the treatment of IFN induced neutropenia. Moreover, the impact of G-CSF administration during antiviral therapy for chronic hepatitis C has not been determined yet. Nevertheless, the use of G-CSF is becoming a standard of care in this setting, especially in liver transplanted patients, and is recommended by several authors. A recent study by the authors’ group showed that G-CSF administration has a protective effect on the development of de novo autoimmune hepatitis during antiviral therapy in transplanted patients.

Innovations and breakthroughs

This is the first study conducted to investigate the efficacy of G-CSF in liver transplanted patients with PegIFN induced neutropenia. It shows that G-CSF administration is effective at increasing the neutrophil count, prolonging treatment and leading to SVR rates comparable to those in non-neutropenic patients. Moreover, it confirms the observation that G-CSF has a protective role with regard to the occurrence of de novo autoimmune hepatitis.


This study is of clinical interest to physicians treating recurrent HCV after liver transplantation. Based on the results, the use of G-CSF in liver transplanted patients with PegIFN induced neutropenia is advisable.


HCV recurrence: the reinfection of the graft by HCV post-liver transplantation is universal and is associated with a worse outcome. G-CSF is granulocyte colony stimulating factor hormone, which stimulates the bone marrow to produce granulocytes and stem cells

Peer review

This work is an interesting pilot study describing the potential benefits of using G-CSF to treat IFN-induced neutropenia in recurrent HCV infection after liver transplantation.


Peer reviewers: Juan-Ramón Larrubia, PhD, Gastroenterology Unit and Liver Research Unit., Guadalajara University Hospital, Donante de Sangre s/n, 19002 Guadalajara, Spain; Raymund R Razonable, MD, Division of Infectious Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States

S- Editor Li LF L- Editor O’Neill M E- Editor Yin DH

1.  Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Soza A, Everhart JE, Ghany MG, Doo E, Heller T, Promrat K, Park Y, Liang TJ, Hoofnagle JH. Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. Hepatology. 2002;36:1273-1279.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Antonini MG, Babudieri S, Maida I, Baiguera C, Zanini B, Fenu L, Dettori G, Manno D, Mura MS, Carosi G. Incidence of neutropenia and infections during combination treatment of chronic hepatitis C with pegylated interferon alfa-2a or alfa-2b plus ribavirin. Infection. 2008;36:250-255.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Fried MW. Side effects of therapy of hepatitis C and their management. Hepatology. 2002;36:S237-S244.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, Dienstag J, Lee WM, Mak C, Garaud JJ. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology. 2002;123:1061-1069.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology. 2003;38:645-652.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, Neumann TA, Schwartzberg LS. First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol. 2005;23:1178-1184.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Lyman GH, Kuderer NM. Epidemiology of febrile neutropenia. Support Cancer Ther. 2003;1:23-35.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Timmer-Bonte JN, Adang EM, Smit HJ, Biesma B, Wilschut FA, Bootsma GP, de Boo TM, Tjan-Heijnen VC. Cost-effectiveness of adding granulocyte colony-stimulating factor to primary prophylaxis with antibiotics in small-cell lung cancer. J Clin Oncol. 2006;24:2991-2997.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Piselli P, Zanfi C, Corazza V, Ferretti S, Scuderi M, Arana MG, Secchia SB, Lauro A, Dazzi A, Pinna A. Incidence and timing of infections after liver transplant in Italy. Transplant Proc. 2007;39:1950-1952.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Blair JE, Kusne S. Bacterial, mycobacterial, and protozoal infections after liver transplantation--part I. Liver Transpl. 2005;11:1452-1459.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Kusne S, Blair JE. Viral and fungal infections after liver transplantation--part II. Liver Transpl. 2006;12:2-11.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Collantes RS, Younossi ZM. The use of growth factors to manage the hematologic side effects of PEG-interferon alfa and ribavirin. J Clin Gastroenterol. 2005;39:S9-S13.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Thomas RM, Brems JJ, Guzman-Hartman G, Yong S, Cavaliere P, Van Thiel DH. Infection with chronic hepatitis C virus and liver transplantation: a role for interferon therapy before transplantation. Liver Transpl. 2003;9:905-915.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Neumann U, Puhl G, Bahra M, Berg T, Langrehr JM, Neuhaus R, Neuhaus P. Treatment of patients with recurrent hepatitis C after liver transplantation with peginterferon alfa-2B plus ribavirin. Transplantation. 2006;82:43-47.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Ong JP, Younossi ZM. Managing the hematologic side effects of antiviral therapy for chronic hepatitis C: anemia, neutropenia, and thrombocytopenia. Cleve Clin J Med. 2004;71 Suppl 3:S17-S21.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Keeffe EB, Kowdley KV. Hematologic side effects of PEG interferon and ribavirin. Management with growth factors. J Clin Gastroenterol. 2005;39:S1-S2.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Aspinall RJ, Pockros PJ. The management of side-effects during therapy for hepatitis C. Aliment Pharmacol Ther. 2004;20:917-929.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Berardi S, Lodato F, Gramenzi A, D'Errico A, Lenzi M, Bontadini A, Morelli MC, Tamè MR, Piscaglia F, Biselli M. High incidence of allograft dysfunction in liver transplanted patients treated with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis? Gut. 2007;56:237-242.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  Kusnierz-Glaz CR, Still BJ, Amano M, Zukor JD, Negrin RS, Blume KG, Strober S. Granulocyte colony-stimulating factor-induced comobilization of CD4- CD8- T cells and hematopoietic progenitor cells (CD34+) in the blood of normal donors. Blood. 1997;89:2586-2595.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Rutella S, Zavala F, Danese S, Kared H, Leone G. Granulocyte colony-stimulating factor: a novel mediator of T cell tolerance. J Immunol. 2005;175:7085-7091.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Zou L, Barnett B, Safah H, Larussa VF, Evdemon-Hogan M, Mottram P, Wei S, David O, Curiel TJ, Zou W. Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res. 2004;64:8451-8455.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Rutella S, Lemoli RM. Regulatory T cells and tolerogenic dendritic cells: from basic biology to clinical applications. Immunol Lett. 2004;94:11-26.  [PubMed]  [DOI]  [Cited in This Article: ]
25.  Arpinati M, Green CL, Heimfeld S, Heuser JE, Anasetti C. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood. 2000;95:2484-2490.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Rutella S, Bonanno G, Pierelli L, Mariotti A, Capoluongo E, Contemi AM, Ameglio F, Curti A, De Ritis DG, Voso MT. Granulocyte colony-stimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-alpha. Eur J Immunol. 2004;34:1291-1302.  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929-938.  [PubMed]  [DOI]  [Cited in This Article: ]
28.  Lodato F, Tame MR, Colecchia A, Racchini C, Azzaroli F, D'Errico A, Casanova S, Pinna A, Roda E, Mazzella G. Systemic lupus erythematosus following virological response to peginterferon alfa-2b in a transplanted patient with chronic hepatitis C recurrence. World J Gastroenterol. 2006;12:4253-4255.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Dumortier J, Scoazec JY, Chevallier P, Boillot O. Treatment of recurrent hepatitis C after liver transplantation: a pilot study of peginterferon alfa-2b and ribavirin combination. J Hepatol. 2004;40:669-674.  [PubMed]  [DOI]  [Cited in This Article: ]
30.  Rodriguez-Luna H, Khatib A, Sharma P, De Petris G, Williams JW, Ortiz J, Hansen K, Mulligan D, Moss A, Douglas DD. Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon alpha2b and ribavirin: an open-label series. Transplantation. 2004;77:190-194.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  Mukherjee S. Pegylated interferon alfa-2a and ribavirin for recurrent hepatitis C after liver transplantation. Transplant Proc. 2005;37:4403-4405.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Castells L, Vargas V, Allende H, Bilbao I, Luis Lázaro J, Margarit C, Esteban R, Guardia J. Combined treatment with pegylated interferon (alpha-2b) and ribavirin in the acute phase of hepatitis C virus recurrence after liver transplantation. J Hepatol. 2005;43:53-59.  [PubMed]  [DOI]  [Cited in This Article: ]
33.  Neff GW, Montalbano M, O'Brien CB, Nishida S, Safdar K, Bejarano PA, Khaled AS, Ruiz P, Slapak-Green G, Lee M. Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy. Transplantation. 2004;78:1303-1307.  [PubMed]  [DOI]  [Cited in This Article: ]
34.  Angelico M, Petrolati A, Lionetti R, Lenci I, Burra P, Donato MF, Merli M, Strazzabosco M, Tisone G. A randomized study on Peg-interferon alfa-2a with or without ribavirin in liver transplant recipients with recurrent hepatitis C. J Hepatol. 2007;46:1009-1017.  [PubMed]  [DOI]  [Cited in This Article: ]
35.  Carrión JA, Navasa M, García-Retortillo M, García-Pagan JC, Crespo G, Bruguera M, Bosch J, Forns X. Efficacy of antiviral therapy on hepatitis C recurrence after liver transplantation: a randomized controlled study. Gastroenterology. 2007;132:1746-1756.  [PubMed]  [DOI]  [Cited in This Article: ]
36.  Juarez-Navarro A, Vera-de-León L, Navarro JM, Chirino-Sprung R, Díaz-Hernandez M, Casillas-Davila L, Dehesa-Violante M. Incidence and severity of infections according to the development of neutropenia during combined therapy with pegylated interferon-alpha2a plus ribavirin in chronic hepatitis C infection. Methods Find Exp Clin Pharmacol. 2005;27:317-322.  [PubMed]  [DOI]  [Cited in This Article: ]
37.  Puoti M, Babudieri S, Rezza G, Viale P, Antonini MG, Maida I, Rossi S, Zanini B, Putzolu V, Fenu L. Use of pegylated interferons is associated with an increased incidence of infections during combination treatment of chronic hepatitis C: a side effect of pegylation? Antivir Ther. 2004;9:627-630.  [PubMed]  [DOI]  [Cited in This Article: ]
38.  Dejaco C, Lichtenberger C, Miehsler W, Oberhuber G, Herbst F, Vogelsang H, Gangl A, Reinisch W. An open-label pilot study of granulocyte colony-stimulating factor for the treatment of severe endoscopic postoperative recurrence in Crohn's disease. Digestion. 2003;68:63-70.  [PubMed]  [DOI]  [Cited in This Article: ]
39.  Lawlor KE, Campbell IK, Metcalf D, O'Donnell K, van Nieuwenhuijze A, Roberts AW, Wicks IP. Critical role for granulocyte colony-stimulating factor in inflammatory arthritis. Proc Natl Acad Sci USA. 2004;101:11398-11403.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Zavala F, Masson A, Hadaya K, Ezine S, Schneider E, Babin O, Bach JF. Granulocyte-colony stimulating factor treatment of lupus autoimmune disease in MRL-lpr/lpr mice. J Immunol. 1999;163:5125-5132.  [PubMed]  [DOI]  [Cited in This Article: ]