Pharmacology and therapeutics
Outcome of patients with serology suggestive of past hepatitis B virus infection during antitumor necrosis factor therapy for psoriasis Raquel Navarro1, MD, Marıa Jose Concha-Garz on1, MD, Carlos Casta~ no2, MD, Cristina Casal3, PhD, Alba Guiu3, MD, and Esteban Dauden1, PhD
1 Department of Dermatology, Hospital Universitario La Princesa, Madrid, Spain, 2 Department of Gastroenterology, Hospital Universitario La Princesa, Madrid, Spain, and 3Department of Microbiology, Hospital Universitario La Princesa, Madrid, Spain
Abstract Background Recently, the reactivation during treatment with tumor necrosis factor (TNF) blockers has exceptionally been described in patients with hepatitis B virus (HBV) antigennegative (HBsAg). The objective was to evaluate the influence of anti-TNF agents in patients with psoriasis and serology suggesting past hepatitis B state. Methods The inclusion criteria were chronic plaque psoriasis treated with anti-TNF
Correspondence Raquel Navarro, MD n 62 c/ Diego de Leo 28006 Madrid Spain E-mail: [email protected]
therapy, HBsAg-negative, and HBcAb-positive. We gathered the demographic data and type and duration of anti-TNF agent. Serum aminotransferase levels and HBV serologic status were requested at baseline and during follow-up. Results We have included 13 patients (four women, nine men) (mean age of 62.1 years). The agent was etanercept in seven cases, infliximab in four patients, and adalimumab in the other two. The mean duration of TNF therapy was 28.6 months. None of them became
Conflicts of interest: None.
HBsAg-positive. Neither signs nor symptoms of acute hepatitis were reported. Conclusion The management of HBsAg-negative patients is unresolved. Only nine cases of HBV reactivation during treatment with TNF blockers have been reported. Despite the low risk of reactivation in these patients, we recommend the monitoring of serum aminotransferase levels, HBsAb titers, HBsAg and, if possible, viral load.
To evaluate the security of anti-TNFa agents in patients with psoriasis and serology suggesting a past hepatitis B state.
● Moderate-to-severe chronic plaque psoriasis treated with anti-TNF therapy in monotherapy for at least nine months. ● HBsAg negative and hepatitis B core antibody (HBcAb) positive. We gathered from their clinical histories the demographic features, sex and age, personal history, and concomitant treatments, with special emphasis on hepatotoxic factors. Regarding the psoriasis, we collected data including the subtype, duration of disease, previous treatments, and, in relation to the biological therapy, dose, and duration. Clinical history records and serum liver test (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin) were collected. The HBV serologic status and HBV viral load were investigated, and complementary studies (echography, fibroscan) were performed in some cases.
Patients and methods
Results
We retrospectively evaluated the outcomes of patients with psoriasis with a serology that was suggestive of past HBV infection during the treatment with anti-TNF therapy. The inclusion criteria were as follows:
Thirteen patients, four women and nine men (mean age 62.1 years, range 34–80 years), were evaluated. Baseline patient data are reviewed in Table 1. The mean duration of anti-TNF treatment was 28.6 months (9–86 months).
Background Tumor necrosis factor (TNF) is known to reduce hepatitis B virus (HBV) replication.1 There is evidence indicating a risk of HBV reactivation or aggravation in patients with chronic hepatitis B infection when using anti-TNF agents. There are even some reports of fulminant hepatitis during treatments with biological therapy.2 Recently, a few reports have suggested the possible HBV reactivation in hepatitis B surface antigen (HBsAg)-negative patients following treatment with biological agents.3 Objective
ª 2014 The International Society of Dermatology
International Journal of Dermatology 2014, 53, 909–911
909
910
Pharmacology and therapeutics
Table 1 Features of HBsAg-negative/HBcAb-positive patients at baseline 1 2 3 4 5 6 7 8 9 10 11 12 13
M M F M M F F M F M M M M
71 61 80a 53 61 34 74 77 47 63 57 68 62
PL PL PL PL PL PL PL PL PL PL PL PL PL
Navarro et al.
Past HBV infection during anti-TNF therapy for psoriasis
Infliximab Etanercept Etanercept Etanercept Infliximab Etanercept Adalimumab Etanercept Infliximab Infliximab Etanercept Adalimumab Etanercept
+ +
13 86 23 24 38 38 11 9 27 24 45 26 9
listed as an absolute contraindication, and it is recommended not to treat chronic carriers of hepatitis B with anti-TNF agents.4 Nevertheless, the management of HBsAg-negative patients is unresolved; optimal management strategies have not yet been elucidated. HBV may persist in HBsAg-negative cases after HBV infection,5 with a prevalence ranging from 6 to 15.3% in countries where HBV infection is endemic.6,7 There are few reports of HBV reactivation after transplantation or during chemotherapy in patients with a serological status indicating past HBV infection.8 To the best of our knowledge, only nine cases of HBV reactivation during treatment with TNF blockers in HBcAb-positive/HBsAg-negative patients have been reported; none of the cases was in a dermatological patient. They are included in the review by Perez-Alvarez et al. They found a total of 168 patients with past HBV infection treated with anti-TNF agents reported in the literature. HBV was reactivated in 5% of the cases after a mean follow-up of 11 months. Two patients presented clinical symptoms of liver disease, one of whom died due to fulminant liver failure. The management was not uniform in all cases; it consisted in the anti-TNF agent cessation and/or the antiviral therapy addition.2 Only one case involving a patient with psoriasis who became HBsAgpositive has been reported, although this patient did not exhibit an increase in the viral load.9 By contrast, Kim et al.10 demonstrated the safety of anti-TNF drugs in 88 HBsAg-negative patients with rheumatic diseases in a series in which no patient showed reactivation. Charpin et al.11 commented that the titer of HBsAb can decrease in some patients during treatment with anti-TNF drugs, as was observed in three of our cases. Kato et al.12 concluded that a lower titer of baseline HBsAb may carry a risk of reactivation by immunosuppressive therapy in cases with autoimmune diseases, but this fact has not been observed in our patients. In dermatologic literature, Prignano et al.13 reported 11 patients with past HBV infection and concomitant psoriasis treated with etanercept. None of the patients
No No HCV No No No No No No No No No No
+ + + + + +
F, female; HBcAb, hepatitis B virus core antibody; HBsAb, hepatitis B virus surface antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus infection; M, male; PL, plaque psoriasis; TNF, tumor necrosis factor. a Exitus.
The most frequently prescribed agent was etanercept (seven cases), followed by infliximab (four cases) and adalimumab (two cases). Of the nine patients who had at least two different HBV serologic measurements (at baseline and at the end of follow-up), none became HBsAg positive. All patients remained positive for HBcAb, except for patient 9. The HBsAb titer decreased in three and increased in one (case 4) of the eight patients who were HBsAbpositive at screening. Cases 4 and 13 became HBsAb-positive (Table 2). During the follow-up period, no significant differences were found in liver enzyme levels, except in patient 10, who presented periodic increases in gammaglutamyl transferase with a normal hepatic echography. In two of two cases, HBV DNA was undetectable. Neither signs nor symptoms of acute hepatitis were reported. Conclusion In European guidelines for the use of anti-TNF therapy in psoriasis published in 2009, active chronic hepatitis B is
Table 2 Evolution of hepatitis B surface antibody titer and serum liver enzymes during the follow-up period Case
1
2
3
4
5
6
7
8
9
HBsAb titer (UI/l) At baseline At the end AST (UI/ml) At baseline At the end ALT (UI/ml) At baseline At the end
18 ND 30 53 47 26
+ 13.92 41 37 54 14
ND 64 81 79 70
12.4 35 33 60 41
384 307.2 30 24 32 15
202.2 92.9 18 23 11 14
88.4 105.17 17 19 20 20
51.2 ND 33 29 50 36
(HBcAb 17 19 11 10
)
10
11
12
13
504.6 410.08 37 27 31 28
+ 58.7 30 21 29 34
ND 9 21 14 43
11.26 23 19 25 21
, negative; +, positive (not quantified); ALT, alanine aminotransferase; AST, aspartate aminotransferase; HBcAb, hepatitis B virus core antibody; HBsAb, hepatitis B virus surface antibody; ND, not determined. International Journal of Dermatology 2014, 53, 909–911
ª 2014 The International Society of Dermatology
Navarro et al.
Past HBV infection during anti-TNF therapy for psoriasis
showed significant changes in serum aminotransferases or HBsAg positivity, and HBV-DNA remained undetectable at the end of the follow-up period. In our series, none of the patients became HBsAg-positive or showed a significant increase in aspartate aminotransferase or alanine aminotransferase levels. In case 9, HBcAb became negative, suggesting that the baseline measurement was a false positive. No uniform diagnostic criteria are available for HBV reactivation.14 It has been defined as an increase in HBV replication from a low to a high level in patients with chronic or past HBV infection.15 The increase in the liver enzyme test might not be enough to evaluate reactivation, as the increase in HBV DNA levels usually precedes that of liver enzymes by days or weeks.14,15 Monitoring of HBsAg might be useful to detect HBV reactivation, despite some reported cases of reactivation while HBsAg remained negative in patients who were treated with tacrolimus, rituximab, or cyclophosphamide.12 The possibility of HBsAg-negative patients developing HBV reactivation is lower than that for HBsAg-positive patients. For heavily immunodepressed patients the risk of reactivation is higher, and some authors defend that an alternative approach would be the close monitoring of their serum HBV DNA and liver transaminases.5 The limitations of our study include having only a limited number of patients and the fact that the complementary test data were not available for all patients, as the monitoring of HBsAg-negative patients was not recommended a few years ago. Based on data from the literature, despite the low risk of reactivation (as we have observed in our results), we recommend the monitoring of serum aminotransferase levels, HBsAb titers, HBsAg and, if possible, viral load in HBsAg-negative/HBcAb-positive patients during treatment with TNF blockers.
4
5
6
7
8
9
10
11
12
13
References 1 Ganem D, Prince AM. Hepatitis B virus infection–natural history and clinical consequences. N Engl J Med 2004; 350: 1118–1129. 2 Perez-Alvarez R, Díaz-Lagares C, García-Hernandez F, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 patients. Medicine (Baltimore) 2011; 90: 359–371. 3 Navarro R, Iba~ nes S, Llamas M, et al. Awareness about possible reactivation of HBsAg-negative patients when
ª 2014 The International Society of Dermatology
14
15
Pharmacology and therapeutics
prescribing biological therapy. J Eur Acad Dermatol Venereol 2011; 25: 1232–1233. Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009; 23: 1–70. Liang R. How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hematopoietic stem cell transplantation. Blood 2009; 113: 3147–3153. Chen MH, Hsiao LT, Chiou TJ, et al. High prevalence of occult hepatitis B infection in patients with B-cell nonHodgkins lymphoma. Ann Hematol 2008; 87: 475–480. Hui CK, Sun J, Au WY, et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol 2005; 42: 813–819. Lee IC, Huang YH, Chu CJ, et al. Hepatitis B virus reactivation after 23 months of rituximab-based chemotherapy in an HBsAg-negative, anti-HBs-positive patient with follicular lymphoma. J Chin Med Assoc 2010; 73: 156–160. Cassano N, Mastrandrea V, Principi M, et al. Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a retrospective analysis of 62 patients with psoriatic disease. J Biol Regul Homeost Agents 2011; 25: 285–289. Kim YJ, Bae SC, Sung YK, et al. Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-alpha blocker in the treatment of rheumatic diseases. J Rheumatol 2010; 37: 346–350. Charpin C, Guis S, Colson P, et al. Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients. Arthritis Res Ther 2009; 11: R179. Kato M, Atsumi T, Kurita T, et al. Hepatitis B virus reactivation by immunosuppressive therapy in patients with autoimmune diseases: risk analysis in hepatitis B surface antigen-negative cases. J Rheumatol 2011; 38: 2209–2214. Prignano F, Ricceri F, Pescitelli L, et al. Tumour necrosis factor-a antagonists in patients with concurrent psoriasis and hepatitis B or hepatitis C: a retrospective analysis of 17 patients. Br J Dermatol 2011; 164: 645–647. Lalazar G, Rund D, Shouval D, et al. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007; 136: 699–712. Lau GK, Hepatitis B. reactivation after chemotherapy: two decade of clinical research. Hepatol Int 2008; 2: 152–162.
International Journal of Dermatology 2014, 53, 909–911
911
Outcome of patients with serology suggestive of past hepatitis B virus infection during antitumor necrosis factor therapy for psoriasis Raquel Navarro1, MD, Marıa Jose Concha-Garz on1, MD, Carlos Casta~ no2, MD, Cristina Casal3, PhD, Alba Guiu3, MD, and Esteban Dauden1, PhD
1 Department of Dermatology, Hospital Universitario La Princesa, Madrid, Spain, 2 Department of Gastroenterology, Hospital Universitario La Princesa, Madrid, Spain, and 3Department of Microbiology, Hospital Universitario La Princesa, Madrid, Spain
Abstract Background Recently, the reactivation during treatment with tumor necrosis factor (TNF) blockers has exceptionally been described in patients with hepatitis B virus (HBV) antigennegative (HBsAg). The objective was to evaluate the influence of anti-TNF agents in patients with psoriasis and serology suggesting past hepatitis B state. Methods The inclusion criteria were chronic plaque psoriasis treated with anti-TNF
Correspondence Raquel Navarro, MD n 62 c/ Diego de Leo 28006 Madrid Spain E-mail: [email protected]
therapy, HBsAg-negative, and HBcAb-positive. We gathered the demographic data and type and duration of anti-TNF agent. Serum aminotransferase levels and HBV serologic status were requested at baseline and during follow-up. Results We have included 13 patients (four women, nine men) (mean age of 62.1 years). The agent was etanercept in seven cases, infliximab in four patients, and adalimumab in the other two. The mean duration of TNF therapy was 28.6 months. None of them became
Conflicts of interest: None.
HBsAg-positive. Neither signs nor symptoms of acute hepatitis were reported. Conclusion The management of HBsAg-negative patients is unresolved. Only nine cases of HBV reactivation during treatment with TNF blockers have been reported. Despite the low risk of reactivation in these patients, we recommend the monitoring of serum aminotransferase levels, HBsAb titers, HBsAg and, if possible, viral load.
To evaluate the security of anti-TNFa agents in patients with psoriasis and serology suggesting a past hepatitis B state.
● Moderate-to-severe chronic plaque psoriasis treated with anti-TNF therapy in monotherapy for at least nine months. ● HBsAg negative and hepatitis B core antibody (HBcAb) positive. We gathered from their clinical histories the demographic features, sex and age, personal history, and concomitant treatments, with special emphasis on hepatotoxic factors. Regarding the psoriasis, we collected data including the subtype, duration of disease, previous treatments, and, in relation to the biological therapy, dose, and duration. Clinical history records and serum liver test (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin) were collected. The HBV serologic status and HBV viral load were investigated, and complementary studies (echography, fibroscan) were performed in some cases.
Patients and methods
Results
We retrospectively evaluated the outcomes of patients with psoriasis with a serology that was suggestive of past HBV infection during the treatment with anti-TNF therapy. The inclusion criteria were as follows:
Thirteen patients, four women and nine men (mean age 62.1 years, range 34–80 years), were evaluated. Baseline patient data are reviewed in Table 1. The mean duration of anti-TNF treatment was 28.6 months (9–86 months).
Background Tumor necrosis factor (TNF) is known to reduce hepatitis B virus (HBV) replication.1 There is evidence indicating a risk of HBV reactivation or aggravation in patients with chronic hepatitis B infection when using anti-TNF agents. There are even some reports of fulminant hepatitis during treatments with biological therapy.2 Recently, a few reports have suggested the possible HBV reactivation in hepatitis B surface antigen (HBsAg)-negative patients following treatment with biological agents.3 Objective
ª 2014 The International Society of Dermatology
International Journal of Dermatology 2014, 53, 909–911
909
910
Pharmacology and therapeutics
Table 1 Features of HBsAg-negative/HBcAb-positive patients at baseline 1 2 3 4 5 6 7 8 9 10 11 12 13
M M F M M F F M F M M M M
71 61 80a 53 61 34 74 77 47 63 57 68 62
PL PL PL PL PL PL PL PL PL PL PL PL PL
Navarro et al.
Past HBV infection during anti-TNF therapy for psoriasis
Infliximab Etanercept Etanercept Etanercept Infliximab Etanercept Adalimumab Etanercept Infliximab Infliximab Etanercept Adalimumab Etanercept
+ +
13 86 23 24 38 38 11 9 27 24 45 26 9
listed as an absolute contraindication, and it is recommended not to treat chronic carriers of hepatitis B with anti-TNF agents.4 Nevertheless, the management of HBsAg-negative patients is unresolved; optimal management strategies have not yet been elucidated. HBV may persist in HBsAg-negative cases after HBV infection,5 with a prevalence ranging from 6 to 15.3% in countries where HBV infection is endemic.6,7 There are few reports of HBV reactivation after transplantation or during chemotherapy in patients with a serological status indicating past HBV infection.8 To the best of our knowledge, only nine cases of HBV reactivation during treatment with TNF blockers in HBcAb-positive/HBsAg-negative patients have been reported; none of the cases was in a dermatological patient. They are included in the review by Perez-Alvarez et al. They found a total of 168 patients with past HBV infection treated with anti-TNF agents reported in the literature. HBV was reactivated in 5% of the cases after a mean follow-up of 11 months. Two patients presented clinical symptoms of liver disease, one of whom died due to fulminant liver failure. The management was not uniform in all cases; it consisted in the anti-TNF agent cessation and/or the antiviral therapy addition.2 Only one case involving a patient with psoriasis who became HBsAgpositive has been reported, although this patient did not exhibit an increase in the viral load.9 By contrast, Kim et al.10 demonstrated the safety of anti-TNF drugs in 88 HBsAg-negative patients with rheumatic diseases in a series in which no patient showed reactivation. Charpin et al.11 commented that the titer of HBsAb can decrease in some patients during treatment with anti-TNF drugs, as was observed in three of our cases. Kato et al.12 concluded that a lower titer of baseline HBsAb may carry a risk of reactivation by immunosuppressive therapy in cases with autoimmune diseases, but this fact has not been observed in our patients. In dermatologic literature, Prignano et al.13 reported 11 patients with past HBV infection and concomitant psoriasis treated with etanercept. None of the patients
No No HCV No No No No No No No No No No
+ + + + + +
F, female; HBcAb, hepatitis B virus core antibody; HBsAb, hepatitis B virus surface antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus infection; M, male; PL, plaque psoriasis; TNF, tumor necrosis factor. a Exitus.
The most frequently prescribed agent was etanercept (seven cases), followed by infliximab (four cases) and adalimumab (two cases). Of the nine patients who had at least two different HBV serologic measurements (at baseline and at the end of follow-up), none became HBsAg positive. All patients remained positive for HBcAb, except for patient 9. The HBsAb titer decreased in three and increased in one (case 4) of the eight patients who were HBsAbpositive at screening. Cases 4 and 13 became HBsAb-positive (Table 2). During the follow-up period, no significant differences were found in liver enzyme levels, except in patient 10, who presented periodic increases in gammaglutamyl transferase with a normal hepatic echography. In two of two cases, HBV DNA was undetectable. Neither signs nor symptoms of acute hepatitis were reported. Conclusion In European guidelines for the use of anti-TNF therapy in psoriasis published in 2009, active chronic hepatitis B is
Table 2 Evolution of hepatitis B surface antibody titer and serum liver enzymes during the follow-up period Case
1
2
3
4
5
6
7
8
9
HBsAb titer (UI/l) At baseline At the end AST (UI/ml) At baseline At the end ALT (UI/ml) At baseline At the end
18 ND 30 53 47 26
+ 13.92 41 37 54 14
ND 64 81 79 70
12.4 35 33 60 41
384 307.2 30 24 32 15
202.2 92.9 18 23 11 14
88.4 105.17 17 19 20 20
51.2 ND 33 29 50 36
(HBcAb 17 19 11 10
)
10
11
12
13
504.6 410.08 37 27 31 28
+ 58.7 30 21 29 34
ND 9 21 14 43
11.26 23 19 25 21
, negative; +, positive (not quantified); ALT, alanine aminotransferase; AST, aspartate aminotransferase; HBcAb, hepatitis B virus core antibody; HBsAb, hepatitis B virus surface antibody; ND, not determined. International Journal of Dermatology 2014, 53, 909–911
ª 2014 The International Society of Dermatology
Navarro et al.
Past HBV infection during anti-TNF therapy for psoriasis
showed significant changes in serum aminotransferases or HBsAg positivity, and HBV-DNA remained undetectable at the end of the follow-up period. In our series, none of the patients became HBsAg-positive or showed a significant increase in aspartate aminotransferase or alanine aminotransferase levels. In case 9, HBcAb became negative, suggesting that the baseline measurement was a false positive. No uniform diagnostic criteria are available for HBV reactivation.14 It has been defined as an increase in HBV replication from a low to a high level in patients with chronic or past HBV infection.15 The increase in the liver enzyme test might not be enough to evaluate reactivation, as the increase in HBV DNA levels usually precedes that of liver enzymes by days or weeks.14,15 Monitoring of HBsAg might be useful to detect HBV reactivation, despite some reported cases of reactivation while HBsAg remained negative in patients who were treated with tacrolimus, rituximab, or cyclophosphamide.12 The possibility of HBsAg-negative patients developing HBV reactivation is lower than that for HBsAg-positive patients. For heavily immunodepressed patients the risk of reactivation is higher, and some authors defend that an alternative approach would be the close monitoring of their serum HBV DNA and liver transaminases.5 The limitations of our study include having only a limited number of patients and the fact that the complementary test data were not available for all patients, as the monitoring of HBsAg-negative patients was not recommended a few years ago. Based on data from the literature, despite the low risk of reactivation (as we have observed in our results), we recommend the monitoring of serum aminotransferase levels, HBsAb titers, HBsAg and, if possible, viral load in HBsAg-negative/HBcAb-positive patients during treatment with TNF blockers.
4
5
6
7
8
9
10
11
12
13
References 1 Ganem D, Prince AM. Hepatitis B virus infection–natural history and clinical consequences. N Engl J Med 2004; 350: 1118–1129. 2 Perez-Alvarez R, Díaz-Lagares C, García-Hernandez F, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 patients. Medicine (Baltimore) 2011; 90: 359–371. 3 Navarro R, Iba~ nes S, Llamas M, et al. Awareness about possible reactivation of HBsAg-negative patients when
ª 2014 The International Society of Dermatology
14
15
Pharmacology and therapeutics
prescribing biological therapy. J Eur Acad Dermatol Venereol 2011; 25: 1232–1233. Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009; 23: 1–70. Liang R. How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hematopoietic stem cell transplantation. Blood 2009; 113: 3147–3153. Chen MH, Hsiao LT, Chiou TJ, et al. High prevalence of occult hepatitis B infection in patients with B-cell nonHodgkins lymphoma. Ann Hematol 2008; 87: 475–480. Hui CK, Sun J, Au WY, et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol 2005; 42: 813–819. Lee IC, Huang YH, Chu CJ, et al. Hepatitis B virus reactivation after 23 months of rituximab-based chemotherapy in an HBsAg-negative, anti-HBs-positive patient with follicular lymphoma. J Chin Med Assoc 2010; 73: 156–160. Cassano N, Mastrandrea V, Principi M, et al. Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a retrospective analysis of 62 patients with psoriatic disease. J Biol Regul Homeost Agents 2011; 25: 285–289. Kim YJ, Bae SC, Sung YK, et al. Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-alpha blocker in the treatment of rheumatic diseases. J Rheumatol 2010; 37: 346–350. Charpin C, Guis S, Colson P, et al. Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients. Arthritis Res Ther 2009; 11: R179. Kato M, Atsumi T, Kurita T, et al. Hepatitis B virus reactivation by immunosuppressive therapy in patients with autoimmune diseases: risk analysis in hepatitis B surface antigen-negative cases. J Rheumatol 2011; 38: 2209–2214. Prignano F, Ricceri F, Pescitelli L, et al. Tumour necrosis factor-a antagonists in patients with concurrent psoriasis and hepatitis B or hepatitis C: a retrospective analysis of 17 patients. Br J Dermatol 2011; 164: 645–647. Lalazar G, Rund D, Shouval D, et al. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007; 136: 699–712. Lau GK, Hepatitis B. reactivation after chemotherapy: two decade of clinical research. Hepatol Int 2008; 2: 152–162.
International Journal of Dermatology 2014, 53, 909–911
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