Journal Information
Vol. 40. Issue. 4.July - August 2020
Pages 371-490
Vol. 40. Issue. 4.July - August 2020
Pages 371-490
Letter to the Editor
DOI: 10.1016/j.nefroe.2019.06.008
Open Access
Reactivation of hepatitis B virus in patient that rests dialysis after renal transplantation. How can we prevent it or anticipate it in diagnosis?
Reactivación silenciosa del virus de la hepatitis b en paciente que reinicia diálisis tras trasplante renal ¿Cómo podemos prevenirlo o anticiparlo en el diagnóstico?
Visits
...
Leonardo Calle Garcíaa,
Corresponding author
, Pilar Tajada Alegreb, Victoria M. Villalta Roblesb, Ana Avellón Calvoc, M. Astrid Rodríguez Gómeza, Manuel Heras Benitod, Rebeca Amo Alonsoe, Carmen Martín Varasa, Giomar Urzola Rodrígueza, M. José Fernández-Reyes Luisa
a Servicio de Nefrología, Complejo Asistencial de Segovia, Segovia, Spain
b Servicio de Análisis Clínicos, Complejo Asistencial de Segovia, Segovia, Spain
c Centro Nacional de Microbiología, Majadahonda, Madrid, Spain
d Servicio de Nefrología, Hospital Clínico Universitario de Salamanca, Salamanca, Spain
e Servicio de Digestivo, Complejo Asistencial de Segovia, Segovia, Spain
Article information
Full Text
Bibliography
Download PDF
Statistics
Tables (1)
Table 1. The patient's clinical, clinical chemistry and serology course.
Full Text
Dear Editor,

Hepatitis B virus (HBV) infection has high rates of morbidity and mortality in the general population. In chronic kidney disease (CKD), these vary depending on patient characteristics. In dialysis, its prevalence ranges from 0 to 7% to 10–20 %.1 According to the PIBHE study, its prevalence in Spain is 1.03%.2 Vaccination and use of universal protective measures have contributed to its decline.1–4 In kidney transplantation (KT), its prevalence increases as a result of risk of reactivation due to immunosuppressants.1,5–7 We report a case of HBV reactivation in a patient with previously managed infection who restarted peritoneal dialysis (PD), following failed KT, in whom immunosuppression was maintained to prevent graft intolerance syndrome (GIS).

A 64-year-old man had CKD secondary to IgA glomerulonephritis. In January 2004, he presented anti-HBV markers consistent with a prior resolved infection (negative HBsAg and anti-HBc markers and positive anti-HBs markers). He had never been vaccinated against HBV. In March 2004, he started PD. Six months later, he received a KT and started immunosuppression with tacrolimus, mycophenolate mofetil (MMF) and prednisone. During the KT, MMF was replaced with everolimus. He restarted PD in July 2016 due to chronic allograft nephropathy. He had a normal liver panel and the same anti-HBV serology markers of resolved infection (Table 1). Low-dose immunosuppression with everolimus, prednisone and tacrolimus was maintained to prevent GIS. In December 2016 he was admitted due to febrile syndrome of unknown origin. It was decided to suspend everolimus and decrease the doses of prednisone and tacrolimus, with significant patient improvement. In March 2017, routine laboratory testing showed elevated transaminases. The patient was asymptomatic. An HBV DNA serology study confirmed the presence of active infection due to probable HBV reactivation (Table 1). To amplify the study, a sample was sent to the Centro Nacional de Microbiología [Spanish National Microbiology Centre (CNM)]. The results indicated: genotype H; mutation 145R in HBsAg associated with vaccine escape, resistance to immunotherapy and escape on detection of HBsAg in certain immunoassays; and two mutations in the polymerase (possible resistance) for 169 L (entecavir) and 173A (lamivudine). At first, he was treated with entecavir 0.5 mg every five days, but given his lack of response and the results from the CNM, this was replaced with tenofovir 245 mg/week. Thereafter, the patient improved considerably (Table 1). In December 2017, he was placed again on the KT waiting list. In February 2018, he underwent KT again. In May 2018, his dose of tenofovir was increased to 245 mg/24 h as he showed normal kidney function and increased HBV DNA. At present, the patient is asymptomatic and has normal laboratory and serology parameters (Table 1).

Table 1.

The patient's clinical, clinical chemistry and serology course.

[0,1−10]Date
  14/01/04  18/07/16  08/12/16  09/03/17  21/06/17  19/10/17  22/11/17  21/05/18  03/09/18 
[0,1−10]Laboratory tests
HBsAg  Negative  Negative    Positive    Positive       
anti-HBs (mIU/mL)  >10  34.34    313.28    243.62       
anti-HBc  Positive  Positive    Positive    Positive       
anti-HBc IgM        Positive    Negative       
HBeAg        Positive    Positive       
anti-HBe        Negative    Negative       
HBV DNA (IU/mL)      <10  40,891  1449  317  65  5890  97 
anti-HCV  Negative  Negative    Negative    Negative       
HIV  Negative  Negative  Negative  Negative    Negative       
P creatinine (mg/dl)    4.6  4.6  5.4  4.7  5.1  0.9  0.9 
AST (U/l)    17  12  103  34  36  23  34  53 
ALT (U/l)    16  10  163  36  45  24  32  54 
GGT (U/l)    58  60  177  153  137  72  55  98 
AP (U/l)    71  83  137  90  149  97  67  122 
LDH (U/l)    206  245  258  283  261  247  213  288 
CRP (mg/dl)    0.5  8.1  1.1  0.8  0.7  0.7  1.2  0.6 
[0,1−10]
[0,1−10]Pharmacological data
Entecavir doses (mg/5 days)        0.5           
Tenofovir doses (mg/7 days)          245  245  245     
Tenofovir doses (mg/24 h)                245  245 
Tacrolimus doses (mg/24 h)    2.5  2.5  2.5 
Tacrolimus levels (ng/mL)    5.3  10.2  4.2  3.5  3.9  5.8  4.2  3.2 
Everolimus doses (mg/24 h)      1.25a          1.75  1.25 
Everolimus levels (ng/mL)      4.98          5.8  4.4 
Kidney status  ACKD  PD  PD  PD  PD  PD  PD  KT  KT 

ACKD: advanced chronic kidney disease; ALT: alanine aminotransferase; AP: alkaline phosphatase; AST: aspartate aminotransferase; CRP: C-reactive protein; GGT: gamma-glutamyl transferase; KT: kidney transplantation; LDH: lactate dehydrogenase; P creatinine: plasma creatinine; PD: peritoneal dialysis.

a

Everolimus suspended.

HBV reactivation in the kidney patient population has higher rates of morbidity and mortality than in the general population.1,5,6 Several authors have warned of HBV reactivations in patients on dialysis or following immunosuppressive therapy in KT.1 Risk factors (RFs) such as advanced age, graft rejection, use of rituximab and/or everolimus and loss or absence of anti-HBs markers have been reported.1,2,5,7 Our patient did not present any of these; therefore, reactivation was unlikely, but did happen. Clinical guidelines recommend annual serology monitoring for patients who test positive for anti-HBc markers, regardless of whether they test positive or negative for anti-HBs markers.1,3 Some authors recommend testing for HBV DNA in cases of negative HBsAg markers and positive anti-HBc markers to detect potential occult HBV infection.1,6 In our case, all this testing was performed, but it was a routine liver panel that alerted us. If an anti-HBc‒positive patient presents liver abnormalities, full HBV and HBV DNA serology should be performed. Early diagnosis enabled us to start immediate treatment as well as isolate and protect healthcare workers and patients on dialysis. Some authors advise starting PD in HBsAg-positive kidney patients and patients with a history of resolved HBV infection (negative HBsAg, positive anti-HBc), clinical conditions permitting.4 In our case, the patient freely chose PD. This facilitated the non-transmission of the infection. A debate on prioritising a patient's free choice of dialysis versus the safety of other patients on dialysis may be warranted. Regarding drugs, at present, entecavir and tenofovir are considered first-line options.1,6 Early molecular study enabled detection of drug resistances and an unusual genotype in Spain (genotype H, common in South America8). This allowed the patient to follow a favourable clinical course and be put back on a KT list.

Finally, patients with CKD and resolved HBV infection represent a challenge for the nephrologist. HBV reactivation may happen at any time. Liver panel monitoring may be a good method for early detection. Provided there is no medical contraindication, anti-HBc‒positive patients should start PD or home haemodialysis to prevent massive spread of infection. Molecular study of HBV is very useful for optimising treatment.

References
[1]
S. Marikani, K. Kolovou, S. Sakellariou, J.N. Boletis, I.K. Delladetsima.
Hepatitis B in renal transplant patients.
World J Hepatol, 9 (2017), pp. 1054-1063
[2]
R. García Agudo, S. Aoufi Rabih, G. Barril Cuadrado, B. Proy Vega, A. Arias Arias, J.A. Herruzo Gallego.
Estudio multicéntrico español PIBHE: prevalencia e inmunización de la infección crónica por el virus de la hepatitis B en pacientes en hemodiálisis en España.
Nefrología, 36 (2016), pp. 126-132
[3]
G. Barril, E. González Parra, R. Alcázar, D. Arenas, J.M. Campistol, et al.
Guías sobre enfermedades víricas en hemodiálisis (HD).
Nefrología. Vol. XXIV. Número Extraordinario (II)., (2004),
[4]
J. Arrieta, M.A. Bajo, F. Caravaca, F. Coronel, H. García-Pérez, et al.
Guías de práctica clínica en diálisis peritoneal.
Nefrología, 26 (2006), pp. 1-184
[5]
C. Meng, C. Belino, L. Pereira, Ana Pinho, S. Sampaio, et al.
Reactivation of hepatitis B virus in kidney transplant recipients with previous clinically resolved infection: a single-center experience.
Nefrología, 38 (2018), pp. 545-550
[6]
R. Loomba, T.J. Liang.
Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: current concepts, management strategies and future directions.
Gastroenterology, 152 (2017), pp. 1297-1309
[7]
S. Sezgin Göksu, S. Bilal, H.S. Coskun.
Hepatitis B reactivation related to everolimus.
World J Hepatol, 5 (2013), pp. 43-45
[8]
S. Schlabe, K. van Bremen, S. Aldabbagh, D. Glebe, C.M. Bremer, et al.
Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations: A case report and review of the literature.
World J Hepatol, 10 (2018), pp. 509-516

Please cite this article as: García LC, Alegre PT, Villalta Robles VM, Calvo AA, Gómez MAR, Benito MH, et al. Reactivación silenciosa del virus de la hepatitis b en paciente que reinicia diálisis tras trasplante renal ¿Cómo podemos prevenirlo o anticiparlo en el diagnóstico? Nefrologia. 2020;40:477–479.

Copyright © 2019. Sociedad Española de Nefrología
Idiomas
Nefrología (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.