Molecular Epidemiology of Norovirus (NoV) Infection in Mie Prefecture: The Kinetics of Norovirus Antigenemia in Pediatric Patients

Few studies have shown the presence of norovirus (NoV) RNA in blood circulation but there is no data on norovirus antigenemia. We examined both antigenemia and RNAemia from the sera of children with NoV infections and studied whether norovirus antigenemia is correlated with the levels of norovirus-specific antibodies and clinical severity of gastroenteritis. Both stool and serum samples were collected from 63 children admitted to Mie National Hospital with acute NoV gastroenteritis. Norovirus antigen and RNA were detected in sera by ELISA and real-time RT-PCR, respectively. NoV antigenemia was found in 54.8% (34/62) and RNAemia in 14.3% (9/63) of sera samples. Antigenemia was more common in the younger age group (0–2 years) than in the older age groups, and most patients were male. There was no correlation between stool viral load and norovirus antigen (NoV-Ag) levels (r_s = −0.063; Cl −0.3150 to 0.1967; p = 0.6251). Higher levels of acute norovirus-specific IgG serum antibodies resulted in a lower antigenemia OD value (n = 61; r = −0.4258; CI −0.62 to −0.19; p = 0.0006). Norovirus antigenemia occurred more commonly in children under 2 years of age with NoV-associated acute gastroenteritis. The occurrence of antigenemia was not correlated with stool viral load or disease severity.     

Rotavirus antigenemia in patients with acute gastroenteritis

Although rotavirus infections are generally considered to be confined to the intestine, recent reports suggest that extraintestinal disease occurs. We studied whether rotavirus infection was associated with antigenemia during a major outbreak of gastroenteritis in the Kingston metropolitan area, during July-August 2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples (including from 2 deceased individuals) but in only 1 of 53 control samples. Serum antigen levels were inversely associated with time since symptom onset and were directly associated with antigen levels in stool (P = .02). Serum antigen levels were significantly elevated during primary infections (acute-phase serum immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections (acute-phase serum IgG titers, > or = 25) (P = .02). Antigenemia was common in this outbreak and might provide a mechanism to help explain rare but well-documented reports of findings of extraintestinal rotavirus. In situations in which stool samples are not readily available (i.e., patients with severe dehydration or those recently recovered or deceased), serum testing by enzyme immunoassay offers a new and practical diagnostic tool.     

Human herpesvirus 6 infection of the gastroduodenal mucosa.

BACKGROUND: Human herpesvirus 6 (HHV-6) infections are usually asymptomatic reactivations in adult liver transplant recipients, but they may also cause fever or graft dysfunction. HHV-6 infection can also present symptoms of gastroenteritis. In this study, we investigated the presence of HHV-6 in the gastroduodenal mucosa of liver transplant recipients and in immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms. METHODS: HHV-6 and cytomegalovirus (CMV) examinations were performed on gastroduodenal biopsy specimens obtained during upper gastrointestinal endoscopic examinations from 90 liver transplant recipients and from 31 immunocompetent patients with upper gastrointestinal symptoms. In the gastroduodenal mucosa, HHV-6 and CMV was demonstrated by immunohistochemistry in frozen sections using monoclonal antibodies against HHV-6- and CMV-specific antigens. RESULTS: HHV-6-positive cells were found in biopsy specimens from 21 (23%) of the liver transplant recipients and 6 (19%) of the immunocompetent patients, CMV-positive cells were found in specimens from 55 (61%) of the transplant recipients and 7 (23%) of the immunocompetent patients, and 12 transplant recipients were found to have both HHV-6 and CMV infection. Fifteen transplant recipients with positive HHV-6 findings in the gastroduodenal mucosa also had HHV-6 antigenemia, whereas 30 patients with HHV-6 antigenemia did not have gastroduodenal involvement. Endoscopic findings in these patients included biliary complications in 10 patients and gastritis in 2 patients. Histopathological findings were nonspecific and included very mild inflammation. A total of 30 (94%) of the transplant recipients with biliary complications also had HHV-6 or CMV detected in the duodenal mucosa. CONCLUSIONS: HHV-6-positive cells and CMV-positive cells were frequently found in the gastroduodenal mucosa of liver transplant recipients and of immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms.     

Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation

To evaluate the clinical significance of a cytomegalovirus (CMV) antigenemia assay in the prediction and diagnosis of CMV gastrointestinal (CMV-GI) disease after hematopoietic stem cell transplantation (HSCT), 19 allogeneic HSCT recipients developing CMV-GI disease were retrospectively reviewed. All patients were monitored by a CMV antigenemia assay, at least once weekly after engraftment. The median onset of CMV-GI disease occurred 31 days post transplant (range: 19-62). Only four of 19 patients (21%) developed a positive CMV antigenemia test before developing CMV-GI diseases. Although all 19 patients subsequently developed positive CMV antigenemia tests during their clinical courses, the values remained at a low-level in nine (47%) patients. Among the 14 patients in whom results of real-time polymerase chain reaction (PCR) were available, seven (50%) yielded positive results of real-time PCR before developing CMV-GI disease. In contrast to the values of CMV antigenemia, all 14 patients exclusively yielded high viral loads (median: 2.8 x 10(4) copies/ml plasma). We conclude that CMV antigenemia testing has limited value in prediction or early diagnosis of CMV-GI disease, and that real-time PCR could have a more diagnostic significance.     

Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective,randomized, open-label trial

In the search for better protocols of preemptive therapy of human cytomegalovirus (HCMV) infection in hematopoietic stem cell transplant (HSCT) recipients, we conducted a randomized trial comparing antigenemia with the nucleic acid sequence-based assay (NASBA) for determination of HCMV immediate-early messenger RNA (IEmRNA) as the guiding assay for initiation of pre-emptive antiviral treatment. In the IEmRNA arm, antiviral therapy was started upon IEmRNA positivity confirmed the following day, whereas in the antigenemia arm, therapy was started in the presence of either at least 2 pp65-positive leukocytes/2 x 105 examined or a single positive leukocyte confirmed the following day. In both arms, treatment was stopped upon 2 consecutive negative results. All patients were monitored for 3 months after HSCT. The primary end point of the study was duration of anti-HCMV therapy. On the whole, 80 children (41 in the IEmRNA and 39 in the antigenemia arm), recipients of transplants from either a relative or an unrelated donor, completed the study. No patient developed HCMV disease. In the IEmRNA arm, the incidence of HCMV infection was higher compared to the antigenemia arm (80% vs 51%, respectively, P =.0069), as well as the percentage of treated patients (66% vs 44%, respectively, P =.045). However, the percentage of relapses and treated relapses was comparable in the 2 arms. There was no significant difference in median duration of therapy per patient. Although these data indicate that IEmRNA determination does not offer advantages in terms of treatment duration, it can safely replace antigenemia, while semiautomation is the major advantage of the NASBA procedure.     

Cytomegalovirus antigenemia assay or PCR can be used to monitor ganciclovir treatment in bone marrow transplant recipients.

The antigenemia assay, polymerase chain reaction (PCR) and rapid culture technique on buffy coat cells (DEAFF test) were used to monitor 37 cytomegalovirus (CMV) seropositive bone marrow transplant (BMT) recipients for active CMV infection during the first 3 months after BMT. The antigen assay and PCR demonstrated a comparable sensitivity for the detection of CMV in blood: discordant results were only obtained in the early or late phase of infection when the viral load was low. The antigen assay was more sensitive than the DEAFF test. Only 12 out of 40 antigen-positive samples yielded a positive result with DEAFF test, whereas viremia without antigenemia was never found. The discordance between these two tests increased further during antiviral therapy with ganciclovir. A correlation was observed between the duration of antigenemia during treatment and the recurrence of systemic CMV reactivation. Ten out of 11 patients with antigen-positive leukocytes present for more than 1 week after starting the treatment subsequently exhibited a relapse of active infection, whereas only three out of nine patients who resolved their antigenemia within 1 week did so. In conclusion, the antigen assay and PCR are useful techniques for detection of CMV infection in BMT patients. Test results obtained during therapy give reliable information regarding the viral load and the possibility of recurrence of antigenemia, and can be taken into account when prolonged administration of ganciclovir is considered.     

Evaluation of viral load and antigenemia as markers for relapse cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) is a pathogen, commonly found in the donors and recipients of solid organ transplantation. CMV is one of the major causes of morbidity and mortality in these patients. Relapsing episodes of CMV infection occur in 23-33% of transplant patients which is likely a reflection of incomplete suppression of viral replication following antiviral treatment with intravenous ganciclovir. We have studied CMV DNA load and antigenemia as markers for relapse of CMV infection in 49 renal transplant patients out of 68 with CMV infection who received a course of intravenous ganciclovir among 300 transplants carried out between January of 2001 and June of 2005. Viral load and antigenemia were measured in blood samples obtained before, during and at the completion of treatment. We also studied different viral load as predictors of relapse CMV infection. Twelve (24.5%) of 49 recipients developed relapsing CMV infection. The relapsing group had higher viral loads after treatment than the no relapsing group. There was no difference in antigenemia level between both groups. The viral loads before and during the treatment, the age and sex of donors and recipients, inmunosupresión, percentage of seronegative recipients with seropositive donors, duration of the therapy and the percentage of patients with heavy immunosuppression were similar in the two groups, but the incidence of acute rejection was higher in the relapsing group. We also evaluated the range of viral load after treatment which is able to trigger the relapse of CMV infection. We conclude that CMV DNA load after treatment is a useful marker for individualizing antiviral treatment of CMV infection in renal transplant recipients. Acute rejection is a risk factor to the relapsing CMV infection.     

Persistence of recipient human leucocyte antigen (HLA) antibodies and production of donor HLA antibodies following reduced intensity allogeneic haematopoietic stem cell transplantation

The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)‐alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo‐HSCT) are unknown. We studied HLA‐alloantibodies in a cohort of 16 patients (eight HLA‐alloimmunized with pre‐transplant histories of PTR and eight non‐alloimmunized controls) undergoing Allo‐HSCT using fludarabine/cyclophosphamide‐based RIC. Pre‐ and post‐transplant serum samples were analysed for HLA‐antibodies and compared to myeloid, T‐cell and bone marrow plasma cell chimaerism. Among alloimmunized patients, the duration that HLA‐antibodies persisted post‐transplant correlated strongly with pre‐transplant HLA‐antibody mean fluorescence intensity (MFI) and PRA levels (Spearman's rank correlation = 0·954 (P = 0·0048) and 0·865 (P = 0·0083) respectively). Pre‐transplant MFI >10 000 was associated with post‐transplant HLA antibody persistence >100 d (P = 0·029). HLA‐antibodies persisted ≥100 d in 3/8 patients despite recipient chimaerism being undetectable in all lympho‐haematopoietic lineages including plasma cells. Post‐transplant de‐novo HLA‐antibodies developed in three control patients with two developing PTR; the donors for two of these patients demonstrated pre‐existing HLA‐antibodies of equivalent specificity to those in the patient, confirming donor origin. These data show HLA‐antibodies may persist for prolonged periods following RIC. Further study is needed to determine the incidence of post‐transplant PTR as a consequence of donor–derived HLA alloimmunization before recommendations on donor HLA‐antibody screening can be made.     

Clinical trial of quantitative real-time polymerase chain reaction for detection of cytomegalovirus in peripheral blood of allogeneic hematopoietic stem-cell transplant recipients

The preemptive therapy of cytomegalovirus (CMV) reactivation is useful for the prevention of CMV disease in allogeneic hematopoietic stem-cell transplant (HSCT) recipients. We compared results of the pp65 CMV antigenemia test with quantitative touch-down polymerase chain reaction (Q-PCR) on unfractionated whole blood for the detection of CMV reactivation in 51 HSCT recipients. Forty episodes of reactivation in 28 patients were detected by antigenemia and treated by antiviral drugs. Q-PCR detected CMV DNA in 39 (97.5%) of 40 reactivation episodes. False-positive results occurred in 3% of tests, of which 63% were borderline positive. Q-PCR results were positive earlier than antigenemia results in 30 (77%) of 39 episodes detected by antigenemia. Q-PCR remained positive after treatment was discontinued in 14 (36%) of 39 episodes and predicted the return of CMV reactivation in 4 (31%) of 13 episodes. Q-PCR was more sensitive than the antigenemia test and had sufficient specificity for clinical use.     

Use of a DNAemia cut-off for monitoring human cytomegalovirus infection reduces the number of preemptively treated children and young adults receiving hematopoietic stem-cell transplantation compared with qualitative pp65 antigenemia

We performed a randomized trial comparing the use of quantitative DNAemia versus positive antigenemia for starting preemptive antihuman cytomegalovirus (HCMV) therapy in hematopoietic stem-cell transplantation (HSCT) recipients. In the DNAemia arm, antiviral therapy was initiated on reaching a DNAemia cut-off of 10 000 DNA copies/mL of whole blood, whereas in the antigenemia arm, therapy was started in the presence of a positive antigenemia. The aim of the study was to compare the number of patients treated in the 2 arms. On the whole, 178 patients (89 in each arm), receiving unmanipulated HSCT from either a relative or an unrelated donor, completed the study. Although the incidence of HCMV infection was comparable in DNAemia and antigenemia arms (34% vs 42%, respectively, P = .259), the number of patients treated was significantly lower in the DNAemia arm (18% vs 31%, P = .026). No patient developed HCMV disease. The use of a DNAemia cut-off avoids unnecessary antiviral treatment.     

Virus-specific IgM antibodies in acute gastroenteritis due to a reovirus-like agent (rotavirus).

62 serum samples from 24 patients with rotavirus gastroenteritis were tested for IgM antibodies against a bovine rotavirus by an indirect fluorescent antibody technique. IgM antibodies were detected in one or more of the serum samples from all but one of the patients. IgM antibodies were not detected in samples obtained from 11 of the patients after the 5th week of illness. Absorption of sera for IgG with Staphylococcus aureus increased the sensitivity of the IgM antibody test. It is concluded that the presence of IgM antibodies against bovine rotavirus in a patient's serum, as measured by the present technique, does suggest a recent rotavirus infection. On the other hand, the lack of IgM antibodies in the serum of a child with acute gastroenteritis between the second and the 5th week of illness tends to exclude rotavirus as a cause of the disease.     

Surveillance of Active Human Herpesvirus 6 Infection in Chinese Patients after Hematopoietic Stem Cell Transplantation with 3 Different Methods

Human herpesvirus 6 (HHV-6) reactivation was studied in 72 consecutive allogeneic hematopoietic stem cell transplant (HSCT) recipients and 53 "healthy" donors. The feasibilities of real-time quantitative polymerase chain reaction (RQ-PCR), nested-PCR, and antigenemia assays in the assessment of HHV-6 reactivation were also evaluated. HHV-6 DNA was detected in 62.5% and 48.6% of post-HSCT patients with the nested-PCR assay and RQ-PCR analysis, respectively, and HHV-6B was identified as the predominant variant. The incidence of HHV-6 infection peaked from the second to the seventh week, whereas the HHV-6B DNA loads peaked from the second to the third week. Compared with RQ-PCR analysis, the sensitivity and specificity of the nested-PCR assay were 100% and 88%, respectively, with positive and negative predictive values of 60% and 99%, respectively. For the HHV-6 antigenemia assay, the sensitivity and specificity were 89% and 97%, respectively, and the positive and negative predictive values were both 94%. Conditioning with antithymocyte globulin in HLA-mismatched or unrelated HSCT increased the possibility of HHV-6B reactivation after HSCT (hazard ratio, 5.92; 95% confidence interval, 1.99-17.59; P = .001). In conclusion, HHV-6B reactivation is commonly encountered after HSCT. Of the 3 methods we adopted for HHV-6 detection, both RQ-PCR analysis and the antigenemia assay could be seen as essential tests for predicting HHV-6 reactivation.     

Genetic variability of cytomegalovirus glycoprotein O in hematopoietic stem cell transplant recipients

K. Roubalova, O. Strunecky, A. Vitek, S. Zufanova, B. Prochazka. Genetic variability of cytomegalovirus glycoprotein O in hematopoietic stem cell transplant recipients.
Transpl Infect Dis 2011: 13: 237–243. All rights reserved Abstract: Genetic variation of cytomegalovirus (CMV) strains can correlate with their pathogenicity for immunocompromised patients. Glycoprotein O (gO), together with glycoprotein L and glycoprotein H, mediate the fusion of the viral envelope with the cell membrane and promotes virus penetration, envelopment, and release. The variability of gO might play a role in CMV cell tropism. The goal was a retrospective analysis of gO variability in a cohort of hematopoietic stem cell transplant (HSCT) recipients to determine the distribution of gO genotypes and to investigate their impact on clinical outcome and manifestation of CMV infection. Methods. In archived blood samples from 51 adult allogeneic HSCT recipients with active CMV infection, gO was analyzed by sequencing the N‐terminal domain of the UL74 gene using the dye deoxy termination method. Results. The gO1 and gO2 clades were most common (39% and 20%, respectively, and gO3 was associated with higher risk of symptomatic infection (P=0.026 in multivariant analysis). Despite being associated with higher antigenemia levels (P=0.02), gO4 had the best survival and lower rate of CMV recurrence. No significant differences were found in clinical manifestation and outcome of CMV disease between patients with various gO clades. Because CMV strains sharing an identical gO sequence differed in glycoprotein B genotypes, sequencing the N‐terminal part of the gO gene does not seem to be optimal for the identification of strains. Conclusions. gO genotyping may contribute to the biological characterization of CMV strains in HSCT recipients.     

Predictors for persistent cytomegalovirus reactivation after T-cell-depleted allogeneic hematopoietic stem cell transplantation

Cytomegalovirus (CMV) reactivation occurs in up to 60% of CMV-seropositive recipients after allogeneic hematopoietic stem cell transplantation (HSCT). The incidence of CMV disease among T-cell-depleted HSCT patients has been reported from 5-15%. The incidence of reactivation refractory to antivirals in this population is not well studied. METHODS: In this retrospective study we characterized the outcome of CMV reactivation in a cohort of 255 adult and pediatric patients who underwent T-cell-depleted HSCT at Memorial Sloan-Kettering Cancer Center from September 1999 through August 2004. CMV infection was monitored by the pp65 antigenemia assay (CMV Ag). Persistent reactivation was defined as antigenemia positivity >21 days on antiviral therapy. RESULTS: Of 118 CMV-seropositive recipients, 69 (58.4%) had reactivated CMV. Twenty of 69 (29%) developed persistent reactivation at first episode of reactivation, and 7 (10%) in subsequent episode. All patients with persistent reactivation received >/=2 antivirals and CMV hyperimmune globulin; 45% received combination antiviral therapy. The median duration of persistent reactivation was 98 days, range 31-256 days. In multivariate analysis, maximum CMV Ag >25 cells/slide was associated with persistent reactivation (odds ratio 16.2%, 95% confidence interval 4-64, P<0.0001). CMV disease occurred in 6/27 (22%) patients with persistent reactivation. Patients with persistent reactivation had lower CD4(+) and CD8(+) lymphocyte counts compared with those with non-persistent reactivation at day +90 post HSCT (P=0.01 and 0.02, respectively). CONCLUSIONS: Persistent reactivation occurred in 39% of T-cell-depleted HSCT despite treatment with currently available antivirals. Maximum CMV Ag >25 cells/slide was associated with persistent CMV reactivation. More effective treatment modalities are needed for this high-risk population to reduce CMV-associated morbidity and mortality.     

母胎微嵌合在单倍体相合活化外周造血干细胞治疗肿瘤中的作用初探

目的 探讨母胎微嵌合在单倍体相合活化外周造血干细胞治疗实体瘤中的作用.方法 选取25例进行无预处理的人类白细胞抗原单倍体相合活化外周造血干细胞治疗的实体肿瘤患者,采用巢式PCR-序列特异引物法检测供、受者之间母胎微嵌合状态,比较不同母胎微嵌合状态的供、受者混合淋巴细胞增殖反应(MTT法),供者细胞植入情况(FISH法),血清Th1/Th2细胞因子水平(ELISA法)及生存时间.结果 母子(女)移植的患者中母胎微嵌合检出率40%,父子(女)移植的患者中为0.母胎微嵌合阳性患者对其供者的增殖反应显著低于对无关第三人(P=0.03),而阴性患者则无此现象.FISH结果显示,只有1例母胎微嵌合阳性的男性患者供者干细胞植入.母胎微嵌合阴性17例患者IFNγ值从治疗后1周的171.4(26.3～258.4)ng/L,治疗后1个月急剧降至29.4(1.2～39.9)ng/L.比较所有母子(女)移植患者,发现母胎微嵌合阳性组生存时间(31.2±4.3)个月显著长于阴性组的生存时间(11.1±3.3)个月(P=0.036).结论 患者体内的母胎微嵌合可能通过诱导其对单倍体相合供者的特异性免疫耐受,延长供者细胞的体内停留时间,维持体内的正向免疫微环境,并延长生存时间.     

The value of Pneumocystis carinii antibody and antigen detection for diagnosis of Pneumocystis carinii pneumonia after marrow transplantation.

Thirty-three marrow transplant patients with Pneumocystis carinii pneumonia were studied to determine the usefulness of antibody and antigen detection in the diagnosis of pneumocystis infection. Antibody against P. carinii was present in one half of all patients tested, and changes in antibody titer were not helpful diagnostically. P. carinii antigen was detected by counterimmunoelectrophoresis in the serum of 22 of 28 patients tested. Fifteen of 28 patients had antigen detected before or within 72 h after diagnosis. However, antigen was also present in 35 of 52 marrow transplant patients with viral or idiopathic pneumonia, in 11 of 25 transplant patients with no pneumonia, and in 22 of 28 other patients with pulmonary infiltrates. Only 1 of 50 normal marrow donors had detectable antigenemia. Detection of this antigen does not appear to establish the diagnosis of P. carinii pneumonia in the absence of other clinical or histologic data. The data may suggest that subclinical infection with this agent is more common than was previously recognized.     

Antigenemia in the diagnosis and monitoring of active cytomegalovirus infection after liver transplantation.

In 45 liver transplant recipients, the value of weekly monitoring of cytomegalovirus (CMV) antigenemia for early diagnosis of active CMV infection was compared with serology and rapid viral isolation. Active CMV infection occurred in 23 patients. The sensitivities of the antigenemia assay and serology (of blood) and rapid viral isolation (from blood or urine) were 96%, 96%, 57%, and 70%, respectively. First diagnostic results of these methods were obtained a median of 25, 36, 31, and 49 days, respectively, after transplant. CMV infection was symptomatic in 20 patients; antigenemia was present at the onset of disease in 13 of these. Maximum CMV antigenemia levels were higher in patients with severe disease than in those with mild or asymptomatic infection. CMV antigenemia is a sensitive, early, quantitative marker of active CMV infection after liver transplantation.     

Bone marrow may be the preferable graft source in recipients homozygous for HLA-C group 2 ligands for inhibitory killer Ig-like receptors

HLA class I molecules participate in natural killer cell regulation by acting as ligands for inhibitory killer cell Ig-like receptors (KIRs). One individual may express one or more inhibitory KIR lacking the corresponding HLA ligand. The role of this 'missing KIR ligand' constellation in hematopoietic SCT (HSCT) remains controversial and depends on incompletely defined transplant variables. We have retrospectively analyzed the effects of missing HLA-C group 1/2 and Bw4 KIR ligands in the recipients on the outcome in 382 HSCT, comparing 118 BMT to 264 PBSC transplants (PBSCT). In the multivariate Cox analysis of PBSCT, poor PFS was observed in homozygous HLA-C group 2 (C2/2) recipients (risk ratio (RR), 1.59; P=0.026). In contrast, C2 homozygosity was not unfavorable after BMT (RR, 0.68; P=0.16). C2 homozygous recipients (n=68) had better PFS after BMT than after PBSCT (RR, 0.17; P=0.001), due to fewer relapses (RR, 0.27; P=0.018). Missing Bw4 favorably influenced PFS after BMT (RR, 0.56; P=0.04), but not after PBSCT. These data suggest opposite effects of missing KIR ligands in BMT vs PBSCT. Larger studies are required to reassess whether BMT should be preferred to PBSCT as an option for C2/C2 recipients.     

Human leukocyte antigen DR markers as predictors of progression to liver transplantation in patients with chronic hepatitis C

OBJECTIVE: Because many patients with chronic viral hepatitis do not progress to end-stage liver disease, it is possible that host factors such as human leukocyte antigen (HLA) differences are important. Our aims were to determine HLA marker-specific rates of progression to liver transplantation among patients with chronic hepatitis C; and to determine if polymerase chain reaction (PCR)-based HLA DRB1 typing can be performed on stored serum samples. METHODS: Forty-two hepatitis C virus RNA-positive liver transplant patients and 87 untransplanted patients were included in a Cox proportional hazards model to test whether the occurrence of certain HLA DRB1 markers were associated with progression to liver transplantation. HLA DRB1 typing was performed on stored serum samples using a PCR method. RESULTS: There were no differences among the HLA DRB1 markers with regard to the HLA marker-specific rate of progression to transplantation among patients with chronic hepatitis C. CONCLUSIONS: HLA DRB1 markers do not appear to be associated with progression of disease in chronic viral hepatitis C. It is possible to perform PCR-based HLA DRB1 typing on stored frozen serum samples.     

Loss of hepatitis A virus antibodies after bone marrow transplantation

Reimmunization guidelines have recommended the inactivated HAV vaccine for hematopoietic stem cell transplant (HSCT) recipients living in or traveling to areas where hepatitis A is endemic. As a shift from high to medium hepatitis A endemicity has been observed in several countries in Latin America, we conducted a retrospective study to evaluate the prevalence of hepatitis A pre-bone marrow transplant (BMT) and the loss of specific antibodies in consecutive stored serum samples from 77 BMT recipients followed up from 82 to 1530 days. The prevalence of HAV antibodies was 92.2% before BMT. As vaccine was not available in Brazil when the samples were taken, it was assumed that this prevalence reflects natural infection. Survival analysis showed that the probability of becoming seronegative was 4.5% (+/-2.6%), 7.9% (+/-3.4%), 10.1% (+/-4.0%), 23.4% (+/-9.6%) at 1, 2, 3 and 4 years after transplant, respectively. The loss of HAV antibodies was significantly associated with longer follow-up (P=0.0015), younger age (P=0.049) and acute graft-versus-host disease (P=0.035). As most reimmunization protocols start around day +365, in developing countries with similar HAV endemicity, BMT recipients should have serological screening before HAV vaccination and the inactivated vaccine should be advised to those seronegative.