Remission of Epstein‐Barr virus‐positive post‐transplant lymphoproliferative disorder by conversion to everolimus in a kidney transplant recipient

Post‐transplant lymphoproliferative disorder (PTLD) is a fatal complication of transplantation. There is no clear consensus on the treatment of PTLD. In most cases, the pathogenetic mechanism of PTLD involves the Epstein‐Barr virus (EBV). We report the case of an elderly kidney transplant recipient who developed EBV‐positive monomorphic T‐cell PTLD 14 years after transplantation. Conversion from conventional immunosuppressants to everolimus induced complete remission of PTLD accompanied by a decrease in blood EBV‐DNA level without chemotherapy.     

Long‐term remission in an adult heart transplant recipient with advanced Burkitt’s lymphoma post‐transplant lymphoproliferative disorder after anthracycline‐free chemotherapy: A case report and literature review

Incidence of Burkitt's lymphoma post‐transplant lymphoproliferative disorder (BL‐PTLD) in solid organ transplant (SOT) recipients in 1.4%‐1.6% with unknown cure rate. We report a case of Epstein‐Barr virus (EBV) positive, late‐onset BL‐PTLD in a 24‐year‐old EBV donor positive/recipient negative female. This is the first reported case of advanced BL‐PTLD post‐heart transplant in an adult. This is also the first reported case of treatment of advanced BL‐PTLD in a heart transplant recipient with a combined chemotherapy regimen without anthracyclines to avoid cardiotoxicity. The patient received 6 cycles of R‐COEP (rituximab with cyclophosphamide, vincristine, etoposide, prednisone) over 6 months and subsequently 3 cycles of high‐dose methotrexate (MTX) over 3 months for CNS prophylaxis. She remains without evidence of disease at 19 months post‐treatment. This case demonstrates that an anthracycline‐free regimen can be the therapy option for patients with BL‐PTLD after heart transplantation.     

Subacute immune response to primary EBV infection leading to post‐transplant lymphoproliferative disease in a renal transplant patient

A 23‐year‐old man sero‐negative for Epstein–Barr virus (EBV) developed recurrent sore throats 3 and 6 months after a renal transplant from an EBV sero‐positive donor. Tonsillar biopsy at 9 months post‐transplant showed post‐transplant lymphoproliferative disease (PTLD) caused by EBV. Following reduction of immunosuppressive treatment, he developed further signs and symptoms, and serological evidence of infectious mononucleosis followed by resolution of lymphadenopathy. This case emphasizes the difficulty in interpreting EBV serology in immunosuppressed patients and the importance of pre‐transplant EBV serology.     

Acute cellular rejection and Epstein–Barr virus‐related post‐transplant lymphoproliferative disorder in a pediatric lung transplant with low viral load

F. Calabrese, M. Loy, F. Lunardi, D. Marino, S.M.L. Aversa, F. Rea. Acute cellular rejection and Epstein–Barr virus‐related post‐transplant lymphoproliferative disorder in a pediatric lung transplant with low viral load.
Transpl Infect Dis 2010: 12: 342–346. All rights reserved. Abstract: We report the case of an 18‐year‐old male who underwent bilateral lung transplantation for end‐stage cystic fibrosis. No Epstein–Barr virus (EBV) or cytomegalovirus serology mismatch was detected on pre‐transplant evaluation (donor and recipient were both positive). Two months after lung transplantation a computed tomography scan showed multiple nodules throughout both lungs. At that time a low EBV DNA blood level was detected (<300 copies/100,000 lymphomonocytes). Scheduled follow‐up transbronchial biopsy (TBB) revealed a prevalent finding characterized by perivascular lymphoid infiltrates with endothelitis. Extensive tissue coagulative necrosis with peripheral areas of dense aggregates of larger lymphoid cells were detected in the trans‐thoracic fine needle core biopsy (FNCB) performed on the largest nodule. The immunophenotypic profile characterized the perivascular lymphoid cells in TBB as mainly composed of T lymphocytes (CD3 positive) while the larger number of lymphocytes in FNCB as B cells (CD20 positive). In situ hybridization for EBV (EBER mRNA) was negative in TBB while it was positive in many lymphocytes of the FNCB. Real‐time polymerase chain reaction (PCR) for EBV was performed on paraffin‐embedded FNCB and detected a high quantity of EBV genomes (1260 copies/cell). IgH gene rearrangement using a fragment size PCR technique revealed a monoclonal B‐cell population in FNCB. Morphological and molecular findings suggest a final diagnosis of acute cellular rejection and a post‐transplant lymphoproliferative disorder (PTLD) EBV‐related in a lung transplant recipient with a low EBV DNA blood level. A possible coexistence of PTLD and acute rejection should be considered both for diagnosis and treatment. EBV PCR in the peripheral blood is a useful screening tool in transplant recipients; however, rare cases with PTLD may not have detectable levels of EBV DNA. This aspect should be taken into consideration to avoid false negatives.     

First‐line use of rituximab correlates with increased overall survival in late post‐transplant lymphoproliferative disorders: retrospective,single‐centre study

This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single‐centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29–69), median time to diagnosis 50 months (range 0–100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B‐cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non‐rituximab; P = 0.5). R‐CHOP‐like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31–96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58–79 months; non‐rituximab 1–30 months). Post‐transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single‐centre series, and it should be considered as first‐line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.     

Hashimoto's encephalopathy after interferon therapy for hepatitis C virus in adult liver transplant recipient accompanied by post‐transplant lymphoproliferative disorder related to Epstein–Barr virus infection

T. Hori, F. Oike, K. Hata, M. Nishikiori, Y. Ogura, K. Ogawa, Y. Takada, H. Egawa, J.H. Nguyen, S. Uemoto. Hashimoto's encephalopathy after interferon therapy for hepatitis C virus in adult liver transplant recipient accompanied by post‐transplant lymphoproliferative disorder related to Epstein–Barr virus infection
Transpl Infect Dis 2010: 12: 347–352. All rights reserved Abstract: A 55‐year‐old woman underwent living‐donor liver transplantation (LDLT). She had no history of autoimmune diseases. Spleen was preserved. Steroids were withdrawn at 3 months after LDLT. Epstein–Barr virus (EBV) infection occurred at 3.5 years after LDLT. Recurrent hepatitis C virus infection was confirmed at 4.5 years after LDLT, and pegylated interferon was introduced. Diagnosis of EBV‐positive post‐transplant lymphoproliferative disorder (PTLD) was made at 4.8 years after LDLT, and tacrolimus (Tac) was stopped completely. Then, unconsciousness, convulsion, and cervical stiffness appeared suddenly. Electroencephalography, cerebrospinal fluid analysis, and image studies revealed normal or only nonspecific findings. The patient was in a state of exhaustion; therefore, steroid pulse therapy (SPT) was attempted. Surprisingly, her general condition, including consciousness disturbance, was improved markedly, and Hashimoto's encephalopathy (HE) was suspected, based on this reaction to SPT. Elevations of anti‐thyroglobulin antibody and anti‐thyroid peroxidase antibody were confirmed. After withdrawal of Tac, and treatment with acyclovir and steroids, EBV‐positive PTLD and HE improved, although they recurred at 5.1 years after LDLT. SPT improved only neurological symptoms. Molecular‐targeted therapy was given for recurrent PTLD, based on analysis of sampling specimens. This therapy was effective, but tumor lysis syndrome occurred, and the patient died at 5.3 years after LDLT.     

Isolated cerebral manifestation of Epstein–Barr virus‐associated post‐transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: a case of clinical and diagnostic challenges

N.A. Kittan, F. Beier, K. Kurz, H.H. Niller, L. Egger, W. Jilg, R. Andreesen, E. Holler, G.C. Hildebrandt. Isolated cerebral manifestation of Epstein–Barr virus‐associated post‐transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: a case of clinical and diagnostic challenges.
Transpl Infect Dis 2011: 13: 524–530. All rights reserved Abstract: We present the case of a 49‐year‐old male patient with Epstein–Barr virus (EBV)‐associated post‐transplant lymphoproliferative disorder (PTLD) limited to the brain that occurred 6 months after allogeneic hematopoietic stem cell transplantation (HSCT). Clinical symptoms included mental confusion, ataxia, and diplopia. Magnetic resonance imaging (MRI) revealed cerebellar and periventricular lesions consistent with an inflammatory process. Cerebrospinal fluid (CSF) analysis, but not peripheral blood, was positive for EBV‐DNA, but no malignant cells were found. Brain biopsy was not feasible because of low platelet counts. As we considered a diagnosis of either EBV‐associated encephalitis or PTLD, the patient was treated with rituximab combined with antiviral therapy. However, the cerebral lesions progressed and follow‐up CSF testing revealed immunoglobulin H clonality as evidence of a malignant process. Subsequent treatment attempts included 2 donor lymphocyte infusions (DLI). Despite treatment, the patient died from autopsy‐proven PTLD within 8 weeks of the onset of symptoms. This case demonstrates the clinical and diagnostic challenges of primary cerebral PTLD in a patient following allogeneic HSCT.     

Liver transplant listing for hepatitis C‐associated cirrhosis and hepatocellular carcinoma has fallen in the United Kingdom since the introduction of direct‐acting antiviral therapy

Following the introduction of direct‐acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV)‐related liver disease as a liver transplantation indication. In this study, we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA. Registration UKELD scores and 1‐year waiting list outcomes were also compared. The proportion of waiting list patients registered with HCV‐related cirrhosis reduced after the introduction of DAA from 10.5% in 2013 to 4.7% in 2016 (P < 0.001). Alcohol‐related liver disease (ARLD) was the leading indication for liver transplantation followed by liver cancer (26.1% and 18.4% in 2016, respectively). The proportion of registrations with Hepatocellular carcinoma (HCC) associated with HCV reduced from 46.4% in 2013 to 33.7% in 2016 (P = 0.002). For patients with HCV‐related cirrhosis at one year the outcomes of death, transplantation, delisting due to improvement or deterioration and awaiting a graft at 1 year were similar. For patients with HCV‐related HCC, the proportion dying at 1 year reduced significantly from 2.9% to 0.0% (P = 0.04). These data demonstrate an association between DAA and reduced listing rates for HCV‐related cirrhosis and HCC, but no significant changes in waiting list outcomes other than reduced mortality in the HCC group.     

Severe post‐transplant lymphoproliferative disorder after living donor liver transplantation

Post‐transplant lymphoproliferative disorder (PTLD) is a well‐known complication after transplantation. A living donor liver transplantation was performed on a 31‐year‐old man for fulminant hepatitis. He again developed liver dysfunction after 7 months. He was diagnosed as having acute cellular rejection and the steroid pulse therapy introduced resulted in little improvement. He gradually developed a high fever and right axillary lymphadenopathy appeared. Chest computed tomography (CT) was performed revealing small lung nodules and axillary lymphadenopathy. Because his serological status for Epstein–Barr virus was positive, PTLD was highly suspected and immunosuppression treatment was withdrawn with little improvement. One week later, he developed tachycardia. Chest CT was re‐performed revealing an infiltration to the left cardiac chamber. For diagnosis, axillary lymph node biopsy was performed and during the procedure, he developed ventricular tachycardia (VT). Immunohistological staining revealed PTLD of T lymphocytes, and chemotherapy was introduced on the same day he developed VT. After two cycles of tetrahydropyranyl, adriamycin, cyclophosphamide, vincristine, prednisolone and etoposide treatment, he completely recovered. This is a first case report of severe PTLD with VT, and our case implies the feasibility of chemotherapy after the appearance of dissemination symptoms.     

Direct‐acting antivirals and hepatitis B virus (HBV) reactivation in co‐infected HBV/HCV kidney‐transplant recipients

Direct‐acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg‐positive and HBsAg‐negative patients. We report on 3 cases of HBV reactivation that were detected after achieving a DAA‐associated sustained virological response in 3 kidney‐transplant recipients initially HBsAg‐negative. In the first case, retrospective virological analysis revealed that HBsAgs had become positive and HBV DNA was detectable before initiating DAA therapy. In the second and third cases, HBV reactivation occurred 2 months and more than 1 year after stopping anti‐HCV therapy. These cases underline the discrepancies and highlight the need for comprehensive information before making definitive conclusions regarding the causal link between DAAs and HBV reactivation.     

Epstein–Barr virus‐associated pneumonia in patients with post‐transplant lymphoproliferative disease after hematopoietic stem cell transplantation

Q.‐F. Liu, Z.‐P. Fan, X.‐D. Luo, J. Sun, Y. Zhang, Y.‐Q. Ding. Epstein–Barr virus‐associated pneumonia in patients with post‐transplant lymphoproliferative disease after hematopoietic stem cell transplantation.
Transpl Infect Dis 2010: 12: 284–291. All rights reserved. Abstract: Epstein–Barr virus (EBV) reactivation or infection after hematopoietic stem cell transplantation (HSCT) most often induces post‐transplant lymphoproliferative disease (PTLD), but it also may be associated with clinical symptoms such as pneumonia. Our aim was to investigate and describe the clinical manifestations of PTLD and PTLD accompanied by EBV‐associated pneumonia in 323 patients after HSCT. PTLD within extravisceral lymphoid tissue was identified in 7 cases (5 with CD20⁺ diffuse large B‐cell lymphoma, 1 with CD20⁺ polymorphic B‐cell hyperplasia, and 1 with CD3⁺CD45RO⁺ peripheral T‐cell lymphoma unspecified). Six of the patients with PTLD were EBV positive. Three patients had EBV‐associated pneumonia, and chest computed tomography revealed multifocal patchy and diffuse ground‐glass attenuation in both lungs. EBV‐DNA was positive in bronchoalveolar lavage (BAL) fluid, which contained mainly CD3⁺ T cells but no CD19⁺ or CD20⁺ B cells. Lung biopsy showed interstitial intra‐alveolar infiltrates of mainly CD3⁺ T cells and some CD68⁺ macrophages without CD19⁺ and CD20⁺ B cells. The patients with PTLD accompanied by EBV‐associated pneumonia developed hyperpyrexia and dyspnea, which progressed rapidly, and eventually all died within 2 weeks of the onset of PTLD. EBV‐associated PTLD accompanied by EBV‐associated pneumonia after HSCT is rare. Cytology of BAL fluid and lung biopsy may help establish the diagnosis.     

Treatment of rare co‐occurrence of Epstein–Barr virus‐driven post‐transplant lymphoproliferative disorder and hemophagocytic lymphohistiocytosis after allogeneic stem cell transplantation

In both conditions, post‐transplant lymphoproliferative disorder (PTLD) and hemophagocytic lymphohistiocytosis (HLH), infection with Epstein–Barr virus (EBV) is a key mechanism: almost all PTLD in allogeneic stem cell transplantation (alloSCT) is caused by EBV‐related neoplastic lymphoproliferation, and secondary HLH is most frequently triggered by EBV infection. Therefore, concomitant EBV‐driven PTLD and HLH early after alloSCT require an approach to eliminate EBV and balance immune activation simultaneously. We report on a patient who developed simultaneous PTLD and signs of HLH on day 64 after alloSCT. Treatment was comprised of stopping cyclosporine, short‐course dexamethasone, and 3 courses of rituximab. The patient showed full recovery and complete remission of lymphadenopathy. This result indicates that immediate reduction in EBV‐carrying B cells by rituximab, suppression of general inflammation, and parallel support of reconstitution of long‐term T‐cell function, might be an appropriate therapeutic approach in this rare situation.     

Successful treatment of donor‐derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens

We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)‐negative donor to three HCV‐negative recipients—two renal transplants and one liver. Both renal recipients underwent standard deceased‐donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39‐year‐old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV‐infected male partner. Recipient 1 was a 45‐year‐old man with a history of end‐stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62‐year‐old woman with a history of end‐stage renal disease caused by hypertension and insulin‐dependent diabetes. Recipient 3 was a 42‐year‐old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post‐transplant follow‐up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor‐derived HCV in transplant recipients.     

Post‐transplant recurrent hepatitis C: immunohistochemical detection of hepatitis C virus core antigen and possible pathogenic implications

Introduction: The mechanisms by which severe cholestatic hepatitis develops after liver transplantation are not fully understood. Reports on immunohistochemical distribution of hepatitis C virus (HCV) antigens are still scarce, but recently, HCV immunostaining was suggested for early diagnosis of cholestatic forms of recurrent hepatitis C in liver grafts. After purification, Rb246 pab anticore (aa1‐68) yielded specific, granular cytoplasmic staining in hepatocytes. Signal amplification through the Envision‐Alkaline Phosphatase System avoided endogenous biotin and peroxidase. Aims/Methods: Rb246 was applied to liver samples of explants of 12 transplant recipients, six with the most severe form of post‐transplantation recurrence, severe cholestatic hepatitis (group 1) and six with mild recurrence (group 2). We also assessed immuno‐reactivity at two time‐points post‐transplantation (median 4 and 22 months) in both groups. HCV‐core Ag was semiquantified from 0 to 3+ in each time point. Serum HCV‐RNA was also measured on the different time points by branched DNA. Results: In the early post‐transplant time point, one patient had a mild staining (1+), two patients had a moderate staining (2+) and the other three had no staining in group 1, compared with five patients with no staining (0) and one patient with mild staining (1+) in group 2. Late post‐transplant liver samples were available in nine patients, and two out of four samples in group 1 showed a mild staining, compared with no staining patients in five patients in group 2. Strikingly, on the explant samples, HCV immunostaining was strongly positive in group 1, and mildly positive in group 2. Two out of five samples showed 3+ staining, and three samples showed 2+ staining in group 1; two out of five samples showed no staining, two samples showed 1+ staining and one sample showed 2+ staining in group 2. Serum HCV‐RNA was significantly higher in group 1, on both time‐points post‐transplantation. HCV‐core Ag was not directly associated with serum HCV‐RNA on the different time points. Conclusion: These preliminary results suggest that strong HCV immunostaining in the explant is predictive of more severe disease recurrence.     

A retrospective analysis of post‐transplant lymphoproliferative disorder following liver transplantation

Objective

To evaluate response rates and survival in adults developing post‐transplant lymphoproliferative disorder (PTLD) following liver transplantation.

Methods

Patients were identified retrospectively and data collected through local liver and haematology electronic databases and pharmacy records.

Results

Forty‐five patients were identified. The median age at first transplant and at development of PTLD was 48 and 54 years, respectively, with the median time from transplant to PTLD diagnosis of 56 months. The majority of cases (76%) were monomorphic B‐cell lymphomas, and 36% of tumours were EBV positive. Treatment involved reduction in immune‐suppression (RIS) in 30 (67%) with RIS the only treatment in 3. Ten (22%) patients were treated with rituximab alone, 13 (29%) with chemotherapy alone and 14 (31%) patients were treated with rituximab and chemotherapy. Twenty‐six (58%) patients achieved a complete response (CR). At a median follow‐up of 27 months, the median overall survival (OS) was 50 months. Response and OS were not associated with clinical factors or the use of rituximab.

Conclusion

Outcomes reported in this study are favourable and comparable to those reported previously. The addition of rituximab did not appear to have improved outcomes in this series, although a significant proportion of patients were able to avoid chemotherapy.     

Reactivation of hepatitis B virus during interferon‐free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co‐infection

Direct‐acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti‐HBe hepatitis during interferon (IFN)‐free DAA therapy in HBV/HCV co‐infected patients with inactive HBV. A 69‐year‐old male patient was diagnosed with chronic hepatitis due to HBV/HCV co‐infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core‐related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug‐induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti‐HCV DAA therapy and the commencement of anti‐HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co‐infection.     

Low viral load post‐transplant lymphoproliferative disease localized within the tongue

Abstract: Post‐transplant lymphoproliferative disease (PTLD) can occur in different sites, such as lymph nodes, allograft, and central nervous system. We report a 6‐year‐old girl with end‐stage renal disease secondary to hypoplastic–dysplastic kidneys, who received a kidney transplant. Thirty months post transplant, she developed PTLD in the tongue, an area of muscular tissue only. At that time her peripheral blood Epstein–Barr viral (EBV) load was only 40 copies/10⁵ lymphocytes, though the tumor was EB early RNA (EBER) positive. Immunosuppression was reduced with initial improvement in her symptoms. One month later, she returned with abdominal complaints and a contained cecal abscess. The excised cecal tissue revealed CD20 and EBER‐positive lymphoid cells. At the same time, her peripheral blood EBV copy number rose to 400 copies/10⁵ lymphocytes. She was successfully treated for the progressive PTLD by complete cessation of immunosuppression and a modified reduced‐dose chemotherapy protocol plus rituximab. Partial immunosuppression was eventually re‐introduced with sirolimus and prednisone. She remains in remission 60 months post transplant, and 30 months post PTLD, with serum creatinine value maintained at 1.3 mg/dL. Unusual localization of PTLD to areas in non‐lymphoid tissue without regional lymphoid involvement may result in misleading low peripheral blood EBV viral loads.     

Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.     

Occult hepatitis B in renal transplant patients

BACKGROUND: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not have HB surface antigen (HBsAg) detectable in sera, and is frequently described in patients with hepatitis C virus (HCV) infection. These viral liver diseases are common and may have a negative impact on the survival of renal transplant patients, especially if they are both present. In this study we aimed to evaluate the prevalence of occult HB in renal transplant patients either with or without HCV infection. PATIENTS AND METHODS: In a cross-sectional survey 101 HbsAg-negative renal transplant patients were evaluated; 51 were anti-HCV positive. Sera were analyzed for the presence of the S and core genes of the HBV-DNA by a nested polymerase chain reaction technique. Markers of HBV infection and liver function tests were also analyzed. RESULTS: The core gene was identified in 1 HCV-infected patient and 1 anti-HCV-negative patient who also presented the S gene (prevalence: 2% and 1% for each gene, respectively). HCV-infected patients had longer pre-transplant dialysis time (50.8 +/- 34.6 vs. 32.0 +/- 20.9; P < 0.001). Liver function tests were also increased in the HCV-infected group: alanine aminotransferase (P < 0.001), aspartate aminotransferase (P < 0.05), gamma-glutamyl transpeptidase (P<0.02), and alkaline phosphatase (P < 0.04). Multivariate analysis revealed that HCV infection was the only determinant of the altered results of the liver function tests. CONCLUSION: We found that occult HB is a condition present in our population of renal transplant patients and that HCV infection does not seem to be associated with occult HB infection in this setting.     

Epstein‐Barr virus post‐transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell transplantation

Epstein‐Barr virus (EBV) viremia and post‐transplant lymphoproliferative disease (PTLD) are severe complications after hematopoietic stem cell transplantation (HSCT). A series of risk factors have been found to predict EBV viremia and PTLD, including the T‐cell depletion, reduced intensity conditioning, and alternative donor. The rituximab pre‐emptive therapy could improve PTLD prognosis significantly, but the trigger of initiating rituximab pre‐emptive therapy has not been well established. Additionally, EBV‐specific cytotoxic T cell (CTL) is a promising approach to treat EBV‐PTLD.