Subject(s)
Antifungal Agents/administration & dosage , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Practice Guidelines as Topic , Humans , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/prevention & control , Japan , Risk Factors , Time FactorsABSTRACT
BACKGROUND: Hypersplenism is a common complication in cirrhotic patients, and liver transplantation would be one of the effective treatments. However, detailed dynamics, especially over a long term, are not fully understood. We investigated the long-term dynamics of hematological data and spleen volumes, as well as their correlation in cirrhotic patients who underwent liver transplantation. PATIENTS AND METHODS: We studied 53 cirrhotic patients who underwent liver transplantation at our institute and followed for more than 1 year. Hematological data were collected from medical records, while spleen volumes were determined by CT volumetry at 0, 1, 3, 6, 12, 24, 36, 48, 60 postoperative months (POM). RESULTS: (1) Platelet (Plt) and hemoglobin (Hb) levels were gradually increased up to 18 and 10 POM, respectively, in contrast with white blood cells (WBC), which remained mostly unchanged from pretransplantation levels. (2) Spleen volume was sharply decreased in the first POM, then showed a slower but steady decline up to 48 POM. (3) Spleen volume was significantly correlated with hematological data, though the levels were generally weak (Plt: r = 0.433, p < 0.001; Hb: r = 0.233, p < 0.001; WBC: r = 0.217, p = 0.001). (4) Spleen volume was strongly correlated with all hematological parameters in HBV patients (Plt: r = 0.617, p < 0.0001; Hb: r = 0.401, p < 0.001; WBC: r = 0.387, p < 0.001), in contrast with that in other etiologies, which had generally weak correlations though some were statistically significant. CONCLUSIONS: We investigated the long-term dynamics of hematological data and spleen volume in cirrhotic patients after liver transplantation. Unique dynamics and correlations between them were found among the different etiologies investigated.
ABSTRACT
OBJECTIVE: To elucidate the effect of liver transplantation (LT) on brain dysfunctions in cirrhotic patients who had no clinical evidence of hepatic encephalopathy (HE), we performed a prospective study of voxel-based diffusion tensor imaging (DTI) and detailed cognitive examination. METHODS: We assessed 12 consecutive patients as transplant candidates by DTI, with neurological and cognitive examinations just before and at 6 months after LT. RESULTS: After LT, cirrhotic patients showed significant improvement in visual reproduction, digit symbol, digit span, Stroop test, and Trail-making test scores, suggesting recovery of frontal-temporal function. As for voxel-based DTI, increased mean diffusivity (MD) and reduced fractional anisotropy (FA) values were found before LT in the frontal and temporal lobes of cirrhotic patients. After LT, the unusual FA and MD values observed in the frontal and temporal lobes preoperatively were significantly reduced. CONCLUSION: End-stage cirrhotic patients without clinical evidence of HE showed increased MD and decreased FA values in both frontal and temporal lobes. These parameters improved after LT, in line with cognitive function. MD and FA values might be of value as a biomarker in end-stage cirrhotic patients for investigating brain tissue dysfunctions and evaluating the efficacy of LT.
Subject(s)
Brain/diagnostic imaging , Cognition/physiology , Fibrosis/surgery , Liver Transplantation/adverse effects , Adult , Aged , Anisotropy , Brain/physiopathology , Diffusion Magnetic Resonance Imaging/methods , Hepatic Encephalopathy , Humans , Male , Middle Aged , Prospective Studies , Radiography , Treatment OutcomeABSTRACT
Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010-11 influenza season, and 53 adult and 21 pediatric recipients in the 2011-12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50-94% to all three antigens among adults and 27-80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32-56% among adults and 13-67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011-12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010-11 and 0/53 vs. 3/21 in 2011-12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups.
Subject(s)
Influenza Vaccines/immunology , Influenza, Human/prevention & control , Liver Transplantation , Transplantation , Adolescent , Adult , Aged , Antibodies, Viral/blood , Child , Child, Preschool , Female , Hemagglutination Inhibition Tests , Humans , Incidence , Infant , Influenza Vaccines/administration & dosage , Influenza, Human/epidemiology , Male , Middle Aged , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Young AdultABSTRACT
The purpose of this prospective, randomized, multicenter trial was to evaluate the effects of a steroid-avoiding immunosuppression protocol on hepatitis C virus (HCV)-positive recipients of living donor liver transplantation (LDLT). Seventy-five HCV-positive LDLT recipients were included in this study, and they were randomized to receive tacrolimus (TAC) plus a corticosteroid (ST; n = 35) or TAC plus mycophenolate mofetil (MMF; n = 40). Biopsy-proven acute rejection (BPAR) was treated with steroid pulse therapy in both groups. Protocol biopsy was performed 3, 6, and 12 months after LDLT and annually thereafter. Histological recurrence of HCV (fibrosis stage ≥ F1 according to the METAVIR score), BPAR resistant to 2 sets of steroid pulse therapy, hepatocellular carcinoma (HCC) recurrence, retransplantation, and patient death were defined as events, and the primary endpoint was event-free survival. The median follow-up was 55 months. The event-free survival rates at 1, 3, and 5 years were 38.2%, 11.8%, and 5.9%, respectively, for the ST group and 25.0%, 17.5%, and 14.6%, respectively, for the MMF group (P = 0.45). The overall 5-year patient survival rates were similar for the ST group (82.7%) and the MMF group (81.0%, P = 0.28). Steroid-resistant BPAR occurred in only 1 patient from the MMF group. HCC recurrence occurred for 1 patient from the ST group and 2 patients from the MMF group. HCV recurrence rates with a fibrosis stage ≥ F1 1 and 3 years after LDLT were 59.4% and 85.9%, respectively, for the ST group and 74.2% and 81.9%, respectively, for the MMF group (P = 0.57). In conclusion, our steroid-avoidance regimen had no apparent impact on LDLT outcomes for HCV-positive recipients.
Subject(s)
Hepatitis C/therapy , Immunosuppressive Agents/therapeutic use , Liver Failure/therapy , Liver Transplantation/methods , Mycophenolic Acid/analogs & derivatives , Steroids/administration & dosage , Tacrolimus/administration & dosage , Adult , Aged , Biopsy , Disease-Free Survival , Female , Follow-Up Studies , Hepacivirus , Hepatitis C/complications , Humans , Liver Cirrhosis/pathology , Liver Failure/complications , Living Donors , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Prospective Studies , Recurrence , Treatment Outcome , Young AdultABSTRACT
Although postoperative serum thyroglobulin (Tg) is a prognostic indicator for papillary thyroid carcinoma (PTC), it is unreliable when Tg antibody (TgAb) is positive. We evaluated the prognostic significance of changes in serum TgAb levels of pre- and post-total thyroidectomy in TgAb-positive PTC patients. We reviewed our medical charts of 225 TgAb-positive PTC patients in whom TgAb levels were measured before and 1-2 years after total thyroidectomy, performed between April 2002 and March 2007. We divided them into 3 groups based on changes in TgAb levels. Postoperative serum TgAb levels decreased by ≥ 50% in 181 patients (80.4%) (Group 1), by <50% in 22 patients (9.8%) (Group 2), and increased in 22 patients (9.8%) (Group 3). During the follow-up, 3 patients died of the disease and 14 patients had recurrences. All 3 patients who died of PTC were seen only in Groups 2 and 3. Groups 2 and 3 showed similar prognostic outcomes, thus were analyzed together as Group 2+3. Group 1 had significantly better lymph node recurrence-free survival and distant recurrence-free survival than Group 2+3 (96.9% vs. 90.5%, p <0.001, and 98.9% vs. 90.1%, p = 0.004, respectively at 5 years). Multivariate analyses on prognostic factors revealed that classification to Group 2+3 was the strongest indicator for poor prognosis. The present results suggest that changes in TgAb levels following total thyroidectomy can be an important dynamic prognostic factor of PTC patients. Prospective periodical measurements of TgAb are necessary to confirm these findings.
Subject(s)
Autoantibodies/blood , Carcinoma/diagnosis , Carcinoma/surgery , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroidectomy , Adolescent , Adult , Aged , Carcinoma/blood , Carcinoma/mortality , Carcinoma, Papillary , Child , Female , Humans , Male , Middle Aged , Postoperative Period , Predictive Value of Tests , Preoperative Period , Prognosis , Retrospective Studies , Survival Analysis , Thyroid Cancer, Papillary , Thyroid Neoplasms/blood , Thyroid Neoplasms/mortality , Treatment Outcome , Young AdultABSTRACT
AIM: Recently, knowledge for indications of living donor liver transplantation (LDLT) has been robustly accumulated in. For further improvement, risks should be reexamined in recent cases. In this study, we investigated preoperative risk factors in cirrhotic patients who underwent LDLT in recent era. METHODS: Seventy-four cirrhotic patients who underwent LDLT at our institution between 2003 and 2011 were included. Recipient and donor age and sex, existence of hepatocellular carcinoma (HCC), preoperative Model for End-Stage Liver Disease score, fasting blood glucose (FBG), triglyceride, total cholesterol, serum creatinine, hemoglobin A1c, graft : recipient weight ratio, ABO compatibility and choice of calcineurin inhibitor were analyzed. A proportional hazard model was applied and P < 0.05 was considered statistically significant. RESULTS: In multivariate analysis, recipient age (hazard ratio = 1.188, P = 0.011) and FBG (hazard ratio = 1.009, P = 0.016) showed as significant independent factors. Theoretical mortalities were 9.2%, 21.9% and 51.7% in patients with normal FBG at 55, 60 and 65 years old, respectively, and 34.3% and 53.6% in patients with FBG of 150 and 200 mg/dL, respectively, at 60 years old. CONCLUSION: Recipient age and FBG remain important risk factors for LDLT in cirrhotic patients even in the recent era. These factors should be considered for selecting liver transplant candidates in cirrhotic patients.
ABSTRACT
PURPOSE: Surgical treatment of local recurrent papillary thyroid carcinoma is still controversial because of the increased morbidity in comparison to primary surgery, and the unclear efficacy. This study analyzed the efficacy and safety of surgery for recurrent disease. METHODS: A retrospective cohort analysis of 86 patients who underwent surgery for local recurrent papillary thyroid carcinoma at a single institution during the period 1979-2009. RESULTS: The cause-specific survival rates of all patients at 5, 10, and 20 years were 86 % (95 % CI 77-95 %), 74 % (95 % CI 62-87 %), and 36 % (95 % CI 18-54 %), respectively. A univariate analysis found that gender, age >45 years at reoperation and macroscopic non-curative surgery for recurrence affected the cause-specific survival rates. The latter two features remained significant in a multivariate analysis. Permanent recurrent nerve paralysis and hypoparathyroidism developed in 4 (4.7 %) and 5 (5.8 %) patients, respectively. CONCLUSIONS: Surgery for local recurrent papillary thyroid carcinoma could be effective when macroscopic curative dissection was possible, and that the procedure was safe and was associated with minimal morbidity. Therefore, repeat surgery for local recurrent papillary thyroid carcinoma is worthwhile.
Subject(s)
Carcinoma, Papillary/surgery , Neoplasm Recurrence, Local/surgery , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Carcinoma, Papillary/mortality , Child , Cohort Studies , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Reoperation , Retrospective Studies , Sex Factors , Survival Rate , Thyroid Neoplasms/mortality , Thyroidectomy/mortality , Time Factors , Young AdultABSTRACT
INTRODUCTION: Information related to the long-term follow-up of neuropathy in patients with familial amyloid polyneuropathy after liver transplantation is still scarce. METHODS: We describe the neuropathic features of 3 patients with the transthyretin Val30Met mutation. Each patient underwent liver transplantation at an early stage of neuropathy, as indicated by the absence of motor dysfunction and relative preservation of myelinated fibers in sural nerve biopsy specimens. RESULTS: Although the patient with late-onset disease (at age 60 years) presented with the least amount of amyloid deposition, he had neuropathic progression after liver transplantation. An older early-onset (at age 40 years) patient reported a slight exacerbation of both somatic and autonomic neuropathic symptoms 10 years after transplantation. However, the younger early-onset (at age 28 years) patient did not exhibit characteristics suggestive of neuropathy 7 years after transplantation. CONCLUSION: Aging may determine the progression of neuropathy after liver transplantation.
Subject(s)
Aging , Amyloid Neuropathies, Familial/etiology , Liver Transplantation/adverse effects , Methionine/genetics , Prealbumin/genetics , Valine/genetics , Adult , Humans , Liver Diseases/surgery , Longitudinal Studies , Male , Middle AgedABSTRACT
A 53-year-old woman visited us for a neurological consultation before her liver transplantation. She had a history of primary biliary cirrhosis that began at 37 years of age. She showed falling episodes and met with a traffic accident at 52 years old. Since then, her symptoms had worsened. The neurological examination showed masked face, rigidity on bilateral arms and legs, and lack of balance. Her Mini-Mental State Examination Score was 28/30, but she suffered from loss of memory and had trouble with executive function in detailed examinations. Her T(1) weighted image showed hyperintensity in bilateral globus pallidus, putamen, dentate nucleus and cerebral peduncle. There was a significant improvement in intellectual function and neurological signs 6 months after her orthotopic liver transplantation. In addition, post-liver transplantation images showed a decrease in the area of hyperintensities. This case suggests that even in a patient with severe liver cirrhosis a complete cure of neurological manifestations can be obtained after the liver transplantation.
Subject(s)
Cognition Disorders/etiology , Hepatolenticular Degeneration/etiology , Hepatolenticular Degeneration/surgery , Liver Cirrhosis, Biliary/complications , Liver Cirrhosis, Biliary/surgery , Liver Transplantation , Living Donors , Parkinsonian Disorders/etiology , Female , Hepatolenticular Degeneration/pathology , Humans , Magnetic Resonance Imaging , Middle Aged , Treatment OutcomeABSTRACT
Organ transplant therapy is becoming a usual practice also in Japan, which dramatically improves the length and quality of life in patients with end-stage organ disease. Liver transplantation was resumed in Japan much later than that in the West and is continued now under unique circumstances where more than 90% of grafts come from living donors. Nevertheless the number of liver transplantation for alcohol-related liver failure shows a sharp rise to the level comparable to the West, and not a few physical and/or psychosocial problems caused by recidivism after transplantation are coming up. To find appropriate solutions to how to predict recidivism and define psychosocial indication of liver transplantation in our society, and to how to monitor and support sobriety after transplantation, there is an urgent need for multidisciplinary management by hepatologist, transplant surgeon, psychiatrist, and dependence specialist. Life-saving therapy and dependence management are expected to work closely together from the viewpoints of transparency, equity, utility, and autonomy requested in transplant therapy, protection of living donors, and consideration for donor family and public emotion.
Subject(s)
Alcohol Drinking/psychology , Liver Diseases, Alcoholic/psychology , Liver Failure/chemically induced , Liver Transplantation/psychology , Living Donors/psychology , Alcohol Drinking/prevention & control , Health Services Needs and Demand , Humans , Japan , Liver Diseases, Alcoholic/surgeryABSTRACT
AIM: We investigated a protocol that lowered the necessary dose of anti-hepatitis B surface immunoglobulin (HBIg) with frequent monitoring of hepatitis B surface antigen (HBsAg) and antibody (HBsAb) levels in the early post-transplant period. METHODS: Fifteen hepatitis B virus (HBV)-positive patients were studied. We administered a nucleoside analog from the preoperative period, high dose HBIg was used intraoperatively (200 IU/kg in the patients who weighed less than 50 kg, and 10 000 IU in those who weighed more than or equal to 50 kg) and was continued every day (5000-10 000 IU/day). Thereafter, HBIg was administered to keep the target trough titers. We evaluated the effectiveness and safety of this protocol for preventing HBV reactivation. RESULTS: The average use of HBIg during the first three postoperative months (POM) was 27.9 ± 9.6 Kilo International Units. The average cost was $US11 800 in the first three postoperative months, compared with other previously reported protocols (about $20 000-40 000). HBV reactivation was detected in only one patient (6.7%) during the median follow up of 64 months (range: 12-86 months). CONCLUSIONS: The present protocol for HBIg administration, which used frequent monitoring of HBsAg and HBsAb levels to determine the minimum required dose, was both safe and effective, and contributed to overall cost saving after liver transplantation.
ABSTRACT
To analyse the phenotype of Epstein-Barr virus (EBV)-infected lymphocytes in EBV-associated infections, cells from eight haematopoietic stem cell/liver transplantation recipients with elevated EBV viral loads were examined by a novel quantitative assay designed to identify EBV-infected cells by using a flow cytometric detection of fluorescent in situ hybridization (FISH) assay. By this assay, 0.05-0.78% of peripheral blood lymphocytes tested positive for EBV, and the EBV-infected cells were CD20+ B-cells in all eight patients. Of the CD20+ EBV-infected lymphocytes, 48-83% of cells tested IgD positive and 49-100% of cells tested CD27 positive. Additionally, the number of EBV-infected cells assayed by using FISH was significantly correlated with the EBV-DNA load, as determined by real-time PCR (r2 â= 0.88, P < 0.0001). The FISH assay enabled us to characterize EBV-infected cells and perform a quantitative analysis in patients with EBV infection after stem cell/liver transplantation.
Subject(s)
B-Lymphocytes/virology , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/isolation & purification , Liver/virology , Stem Cell Transplantation/adverse effects , Transplantation , Tumor Necrosis Factor Receptor Superfamily, Member 7/analysis , B-Lymphocytes/chemistry , Blood/virology , Child , Child, Preschool , DNA, Viral/analysis , Female , Flow Cytometry , Humans , In Situ Hybridization, Fluorescence , Infant , Male , Middle Aged , Viral LoadSubject(s)
Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Liver Transplantation , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/secondary , Carcinoma, Hepatocellular/surgery , Chemotherapy, Adjuvant , Evidence-Based Medicine , Health Status Indicators , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Neoplasm Recurrence, Local/prevention & control , Patient Selection , Practice Guidelines as Topic , Risk Assessment , Risk Factors , Survival Rate , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: In patients with papillary thyroid carcinoma (PTC), the appropriate extent of lymph node dissection has not yet been established due to lack of accurate patterns of lymph node metastases (LNM). The aim of this study was to clarify the LNM pattern in PTC patients based on our institution's experience with a consistent technique of bilateral neck dissection, and to consider the rational extent of lymph node dissection. METHODS: Between 1990 and 1999, 152 consecutive patients with PTC who underwent curative total thyroidectomy and bilateral neck dissection as initial treatment were analyzed. The patterns of LNM according to clinicopathological classification were analyzed using the lymph node ratio (LNR; number of metastatic lymph nodes/number of dissected nodes) and frequency (FLNM; number of patients with LNM/number of dissected patients) in cervical compartments. RESULTS: Regardless of clinicopathological classification, LNR in the central compartment was consistently higher than in other compartments, and FLNM in the ipsilateral lateral compartment was consistently higher than in other compartments except for multifocal tumors. The LNR and FLNM in the contralateral lateral compartment were significantly higher in advanced (≥T3) cases than in cases with smaller tumors (T1) and were comparable to those in the ipsilateral lateral compartment in advanced (≥T3) cases. CONCLUSIONS: The pattern of LNR provided a better reflection of the patterns of LNM. In terms of the LNR, central neck dissection is the basic extent of lymph node dissection for all clinically apparent PTC. In advanced patients, it is also advisable to include bilateral lateral neck dissection.
Subject(s)
Lymph Node Excision/methods , Thyroid Neoplasms/secondary , Thyroid Neoplasms/surgery , Adolescent , Adult , Aged , Carcinoma , Carcinoma, Papillary , Child , Female , Humans , Lymphatic Metastasis , Middle Aged , Retrospective Studies , Thyroid Cancer, Papillary , Young AdultABSTRACT
To assess the safety and immunogenicity of 2009 H1N1 influenza vaccination, 13 pediatric liver transplant recipients and 31 immunocompetent controls received inactivated influenza vaccine without adjuvant according to Japanese guidelines. Serious adverse events and acute allograft rejections were not observed in participants. Seroprotection rates (hemagglutinin-inhibition (HI) antibody titer ≥ 1:40) were 53.8% among recipients and 58.1% among controls (p=0.797). Seroconversion rates (4-fold or more HI antibody rise) were 46.2% for the recipient group and 51.6% for the control group (p=0.741). Geometric mean titers were elevated after vaccination in both groups. In comparison with the seasonal influenza vaccination, the seroconversion rate for 2009 H1N1 appeared to be higher than that for seasonal influenza antigens, and the seroprotection rate for 2009 H1N1 clearly increased after vaccination. These findings suggest that pediatric liver transplant patients may respond safely to inactivated 2009 H1N1 influenza vaccines in a manner similar to immunocompetent children.
Subject(s)
Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Liver Transplantation/immunology , Transplantation , Adolescent , Antibodies, Viral/blood , Child , Child, Preschool , Female , Hemagglutination Inhibition Tests , Humans , Infant , Influenza Vaccines/administration & dosage , Influenza, Human/immunology , Male , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunologyABSTRACT
BACKGROUND: More than 80% of all thyroid cancers, the most common endocrine malignancy, are papillary thyroid cancer (PTC). It is well established that CITED1 (Cbp/p300 Interacting Transactivators with glutamic acid [E] and aspartic acid [D]-rich C-terminal domain) mRNA is characteristically overexpressed in PTC. Our previous study suggested a positive association of BRAF mutation with CITED1 overexpression. However, the mechanism of CITED1 expression in PTC remains to be elucidated. In the present study, we analyzed whether aberrant methylation of CITED1 gene promotes CITED1 overexpression in PTC. METHOD: CITED1 mRNA expression levels were analyzed by quantitative polymerase chain reaction in three PTC-derived cell lines, TPC1, K1, and KTC-1, and in surgically dissected PTC and surrounding normal tissues from 19 patients. The BRAF mutation status of the cells and clinical specimens was determined by direct sequencing. The methylation status of the deoxycitidine-phosphate-deoxyguanosine dinucleotides (CpGs) in the CITED1 promoter was analyzed by the bisulfite-sequencing method using genomic DNA. Finally, the expression of CITED1 mRNA in TPC1 cells, when subjected to pharmacological inhibition of methylation, was analyzed. RESULTS: CITED1 mRNA was expressed at lower levels in TPC1 than in K1 and KTC-1 cells. A BRAF mutation was present in K1 and KTC-1 cells, but not in TPC1 cells. CITED1 promoter was hypomethylated in K-1 and KTC-1 cells, but not in TPC1 cells. In surgically dissected specimens, the mean expression level of CITED1 mRNA was 30-fold higher in PTC tissues than in normal tissues. CpGs in the CITED1 promoter were more heavily methylated in normal tissues than in PTC tissues. In PTC specimens without a BRAF mutation, two CpGs were more heavily methylated than in PTC specimens with the BRAF V600E mutation. Pharmacological inhibition of methylation in TPC1 cells by 5'-aza-2'-deoxycitidine resulted in increased expression of CITED1 mRNA. CONCLUSION: Hypomethylation of the CpGs in the promoter region of CITED1 is associated with higher expression of CITED1 mRNA in PTC tissues, consistent with the hypothesis that epigenetic regulation is involved in the overexpression of CITED1. This hypothesis is supported by pharmacologic inhibition studies in TPC1 cells.
Subject(s)
DNA Methylation , Gene Expression Regulation, Neoplastic , Gene Expression Regulation , Nuclear Proteins/genetics , Promoter Regions, Genetic , Thyroid Neoplasms/genetics , Transcription Factors/genetics , Adult , Aged , Apoptosis Regulatory Proteins , Azacitidine/analogs & derivatives , Azacitidine/pharmacology , Carcinoma , Carcinoma, Papillary , Cell Line, Tumor , CpG Islands , Decitabine , Female , Humans , Male , Middle Aged , Mutation , Thyroid Cancer, Papillary , Trans-ActivatorsABSTRACT
BACKGROUND: Combination of nucleos(t)ide analogue and anti-HBs immunoglobulin (HBIg) is the standard protocol for prevention of HBV reactivation after liver transplantation, but because of the extremely high cost of HBIg, HBV vaccine is tried as a much cheaper and potentially safer substitute. Here we show the different effect of HBV vaccine between chronic HBV carrier and non-HBV patients who received grafts from HBc antibody-positive donors. METHODS: Fifteen chronic HBV carriers and 6 non-HBV patients who received grafts from HBc antibody-positive donors were included in this study. These patients received double dose of pre-S-containing HBV vaccine every month from later than 12 months after liver transplantation. Successful vaccination was defined as HBsAb >100 IU/l without HBIg administration for 3 months. RESULTS: None of the 15 chronic HBV carriers succeeded in maintaining high enough HBsAb titers. In contrast, 5 of 6 non-HBV patients with HBcAb-positive donors achieved HBsAb >100 IU/l without HBIg coadministration. Recipient HBV status (HBV carrier/non-HBV) was considered to have a stronger effect on vaccine success (p < 0.001) though recipient age (p = 0.006) was also selected as a significant factor. CONCLUSIONS: Recipient HBV status seems to be the most important factor affecting success of HBV vaccine after liver transplantation. In non-HBV patients who received grafts from HBcAb-positive donors, HBV vaccination is an effective, cost-saving, and safe method for prevention of HBV reactivations. In contrast in chronic HBV patients, response rate was quite poor, so some modifications such as combination with adjuvant or modification of administration schedules should be considered.
Subject(s)
Carrier State/immunology , Hepatitis B Antibodies/blood , Hepatitis B Vaccines/therapeutic use , Hepatitis B/prevention & control , Liver Transplantation/immunology , Adult , Age Factors , Child , Female , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/adverse effects , Hepatitis B virus/immunology , Humans , Infant , Male , Middle Aged , Tissue Donors , Transplants , Treatment Outcome , Young AdultABSTRACT
Annual influenza vaccination is recommended for pediatric liver transplant recipients, who are at high risk of influenza-related complications. However, effectiveness and safety of vaccination may differ among influenza seasons in this population and have not been fully evaluated. Subjects comprised 38 pediatric liver transplant recipients with or without influenza vaccination through the 2006-2007, 2007-2008 and 2008-2009 influenza seasons. Recipients received inactivated trivalent (AH1/AH3/B) influenza vaccine, and comparisons were made to non-vaccinated recipients with regard to effectiveness and safety. No significant differences were seen between recipient groups for acute allograft rejection, acute febrile illness, or influenza virus infection. No serious systemic adverse events were observed in vaccinated recipients. Seroprotection rate (defined as the proportion of recipients with HI antibody titer ≥ 1:40), seroconversion rate (proportion of recipients with a ≥ 4-fold increase in HI titers), and geometric mean titers were mostly elevated after vaccination for the three influenza antigens in each season. These three indicators of immunogenicity showed similar results in both vaccinated recipients and vaccinated healthy children in the 2007-2008 season. These findings suggest that pediatric liver transplant patients may respond safely to inactivated seasonal influenza vaccines in a similar manner to healthy children, and effectiveness varies among influenza seasons.
Subject(s)
End Stage Liver Disease/complications , End Stage Liver Disease/therapy , Influenza Vaccines/therapeutic use , Influenza, Human/complications , Influenza, Human/prevention & control , Liver Transplantation/methods , Pediatrics/methods , Adolescent , Antigens/chemistry , Child , Child, Preschool , Female , Hemagglutination , Humans , Male , Seasons , Treatment OutcomeABSTRACT
Living donor liver transplantation (LDLT) has evolved based on the premise that donor safety is most important. In 2005, we encountered a donor who developed a pulmonary embolism during the early post-operative period. As it is important for donors to be healthy, most risk factors related to perioperative thrombosis, such as obesity, age, and malignancy are used as exclusion criteria during the evaluation process. We speculated that thrombophilia not detected by conventional laboratory examinations may cause post-operative thrombotic complications and should be investigated by application of additional parameters, including protein S, protein C, antithrombin III, anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulant. From July 2005 to June 2007, we evaluated 44 donor candidates for LDLT using our novel algorithm for screening of thrombophilia, which revealed two suspected candidates (one with low protein S, one with low protein C, and positive anti-ß2GPI findings), who were subsequently excluded from the donor pool. Thereafter, all donor hepatectomies, which included two borderline donors given anticoagulants perioperatively, were performed without complications. Four donors (two suspected, two borderline) would not have been recognized without additional screening. In conclusion, we were able to detect thrombophilia and avoid donor thrombosis using additional screening criteria and our novel algorithm.