Hair cortisol levels in pregnancy as a possible determinant of fetal sex: a longitudinal study.

Stress during pregnancy has been widely studied and associated to different variables, usually with negative results for the health of the mother and the newborn, such as having a higher risk of suffering postpartum depression, premature birth, obstetrics complications or low birthweight, among others. However, there are not many lines of research that study the role that the sex of the baby plays on this specific stress and vice versa. Thus, the main objective was to analyse the relationship between the sex of the offspring and the stress of the mothers in the first trimester of pregnancy. In order to achieve this, 108 women had their biological stress measured (trough hair cortisol levels) and psychological stress evaluated (the Prenatal Distress Questionnaire (PSS), the Perceived Stress Scale (PDQ) and the Stress Vulnerability Inventory (IVE)). The results revealed significant differences in maternal hair cortisol levels in the first trimester based on the sex of the baby they had given birth to (t = -2.04; P < 0.05): the concentration of the hormone was higher if the baby was a girl (164.36:54.45-284.87 pg/mg) than if it was a boy (101.13:37.95-193.56 pg/mg). These findings show that the sex of the future baby could be conditioned, among many other variables, by the mother´s stress levels during conception and first weeks of pregnancy. Further research is needed in this area to support our findings.

Cap-fitted endoscopic mucosal resection of ≥ 20 mm colon flat lesions followed by argon plasma coagulation results in a low adenoma recurrence rate.

Background and study aims Endoscopic mucosal resection (EMR) is increasingly used for the treatment of large colonic polyps (≥ 20 mm). A drawback of EMR is local adenoma recurrence. Therefore, we studied the impact of argon plasma coagulation (APC) of the EMR edge on local adenoma recurrence. Patients and methods This was a retrospective study of patients with laterally spreading tumors (LST) ≥ 20 mm, who underwent EMR from January 2009 to August 2018 and follow-up endoscopic assessment. A cap-fitted endoscope was used to assess completeness of resection by systematically inspecting the EMR defect for any macroscopic disease. This was followed by forced APC of the resection edge followed by clip closure of the defect. Surveillance colonoscopy was performed at 6 months after resection to detect recurrence. Results Two hundred forty-six patients met the inclusion criteria. Most were female (53 %) and white (80 %), with a Median age of 64 years. Median polyp size was 35 mm (interquartile range, 30-45 mm). Most polyps were located in the right colon (77 %) and were removed by piecemeal EMR (70 %). Eleven patients (5 %) had residual tumor at the resection site. Conclusions We observed low adenoma recurrence after argon plasma coagulation of the EMR edge with a cap fitted colonoscope in patients with LST ≥ 20 mm of the colon, which requires further validation in a randomized controlled study.

Evaluación de dos secuencias de código de barras de ADN en germoplasmas de Arracacia xanthorrhiza (Apiaceae) de Ecuador / Evaluation of two sequences of DNA barcodes in germplasms of Arracacia xanthorrhiza (Apiaceae) from Ecuador

El presente estudio evalua el gen de cloroplasto rbcL y la región espaciadora no codificante psbA-trnH de Arracacia xanthorrhiza como posible secuencia de código de barra. Se colectó material vegetal de A. xanthorrhiza en huertos de las provincias de Pichincha, Tungurahua y Cotopaxi, las cuales fueron sembradas en condiciones homogéneas en la Facultad de Ciencias Agropecuarias de la Universidad Técnica. El análisis del locus rbcL identificó los cinco materiales de A. xanthorrhiza con entre 97 y 99% de homología. La alineación de secuencias del locus rbcL y de psbA-trnH permitió diferenciar dos grupos, el primer grupo con SJ, QU, PP y B, observándose poca diversidad entre ellos, mientras que el segundo grupo está conformado por el material CH cultivado a 3260 m de altitud. En el segundo árbol, se demostró la divergencia entre los materiales colectados en diferentes provincias de la Sierra ecuatoriana, separándolos de acuerdo a su localidad, así como al color de la pulpa de la raíz. La región intergénica no codificadora (psbA-trnH) permitió identificar y obtener la diversidad genética de materiales cultivados de A. xanthorrhiza, provenientes de diversas zonas geográficas de la sierra ecuatoriana, con características morfológicas distintivas. Adicionalmente, esta secuencia pudo diferenciar a A. xanthorrhiza de otras especies de la familia Apiaceae, con lo cual se recomienda como código de barra.

The present study aimed to evaluate the Arracacia xanthorrhiza rbcL chloroplast gene and the non-coding spacer region psbA-trnH as a possible barcode sequence. Plant material of A. xanthorrhiza was collected in orchards of Pichincha, Tungurahua and Cotopaxi provinces. This material were cultivated in standard conditions in the la Facultad de Ciencias Agropecuarias de la Universidad Técnica. The rbcL locus analysis identified the five materials of A. xanthorrhiza with between 97 and 99% homology. The sequence alignment of rbcL locus and psbA-trnH allowed to differentiate two groups, the first group with SJ, QU, PP and B, showing low diversity among them, while the second group consisted of the CH material grown in 3260 m of altitude. In the second tree, the divergence between the materials collected in different provinces of the Ecuadorian Sierra was demonstrated, separating them according to their locality, as well as the color of the root pulp The non-coding intergenic region (psbA-trnH) allowed identify and obtain the genetic diversity of cultivated materials of A. xanthorrhiza, from various geographical areas of the Ecuadorian Sierra, with distinctive morphological characteristics. Additionally, this sequence was able to differentiate A. xanthorrhiza from other species of the Apiaceae family, which is recommended as a bar code.

Quality of endoscopy reporting at index colonoscopy significantly impacts outcome of subsequent EMR in patients with > 20 mm colon polyps.

Background and study aims Endoscopic mucosal resection (EMR) is safe and cost-effective in management of patients with colon polyps. However, very little is known about the actions of the referring endoscopist following identification of these lesions at index colonoscopy, and the impact of those actions on the outcome of subsequent referral for EMR. The aim of this study was to identify practices at index colonoscopy that lead to failure of subsequent EMR. Patients and methods Two hundred and eighty-nine consecutive patients with biopsy-proven non-malignant colon polyps (> 20 mm) referred for EMR were analyzed to identify practices that could be improved from the time of identifying the lesion at index colonoscopy until completion of therapy. Results EMR was abandoned at colonoscopy at the EMR center in 71 of 289 patients (24.6 %). Reasons for abandoning EMR included diagnosis of invasive carcinoma (n = 9; 12.7 %), tethered lesions (n = 21; 29.6 %) from prior endoscopic interventions, and overly large (n = 22; 31 %) and inaccessible lesions (n = 17; 24 %) for complete and safe resection whose details were not recorded in the referring endoscopy report, or polyposis syndromes (n = 2; 2.8 %) that were not recognized. Conclusions In our practice, one in four EMR attempts were abandoned as a result of inadequate diagnosis or management by the referring endoscopist, which could be improved by education on optical diagnosis of polyps, comprehensive documentation of the procedure and avoidance of interventions that preclude resection.

Barrett's Esophagus after Bimodality Therapy in Patients with Esophageal Adenocarcinoma.

INTRODUCTION: Barrett's esophagus (BE) may be present in patients with esophageal adenocarcinoma (EAC) after bimodality therapy (BMT). There is no specific guidance for follow-up of these patients with regard to the presence of BE or dysplasia. In this study, we assessed the outcomes of patients who, after BMT, had BE and those who did not. METHOD: Patients with EAC who had BMT were identified and analyzed retrospectively in two groups, with and without BE. We compared patient characteristics and outcome variables (local, distant, and no recurrence). RESULTS: Of 228 patients with EAC, 68 (29.8%) had BE before BMT. Ninety-eight (42.9%) had BE after BMT, and endoscopic intervention was done in 11 (11.2%). With a median follow-up of 37 months, the presence of post-BMT BE was not significantly associated with overall survival (OS) and local recurrence-free survival (LRFS). Similarly, endoscopic intervention was not significantly associated with OS and LRFS. Fifty (73.5%) patients with BE before BMT had BE after BMT (p < 0.0001). CONCLUSION: The presence of BE after BMT was not associated with increased risk of local recurrence. The local recurrence rate was not influenced by endoscopic intervention. Prospective studies are warranted to generate guidance for intervention, if necessary, for this group of EAC patients.

Outcomes after endoscopic mucosal resection or esophagectomy for submucosal esophageal adenocarcinoma.

OBJECTIVES: Endoscopic mucosal resection (EMR) is a diagnostic and potentially therapeutic option for patients with submucosal esophageal adenocarcinoma. However, there are significant concerns regarding the risk of lymph node metastasis. Our purpose was to construct a comparative effectiveness analysis comparing recurrence patterns after therapeutic EMR or esophagectomy. METHODS: Patients who underwent therapeutic EMR or esophagectomy from 2007 to 2015 with pathologically staged submucosal adenocarcinoma were identified from a departmental database. Cancer-related outcomes were compared among an unmatched as well as a propensity matched cohort. Risk stratification was also used to compare results among those with a low, medium, or high risk of nodal metastasis. RESULTS: Seventy-two patients met criteria for analysis, among whom 23 underwent therapeutic EMR with esophageal preservation and 49 underwent esophagectomy. Median follow-up was 43 months. Patients who underwent esophagectomy had larger, deeper tumors. Esophageal preservation was associated with an increased risk of local recurrence (P = .01), but not distant recurrence (P = .44). After propensity matching, there continued to be no difference in distant recurrence rate (P = .66). In a risk-stratified analysis, low-risk patients showed no recurrences or cancer-related deaths, however, high-risk patients showed a trend toward increased distant recurrence after therapeutic EMR. CONCLUSIONS: Esophageal preservation after therapeutic EMR was associated with an increased risk of local recurrence. Among low-risk patients, either strategy resulted in excellent cancer control. However, among high-risk patients, esophageal preservation showed a trend toward increased distant failure. These findings should prompt further investigation to determine optimal treatment for patients with submucosal esophageal adenocarcinoma.

Loss of the transforming growth factor-ß effector ß2-Spectrin promotes genomic instability.

Exposure to genotoxins such as ethanol-derived acetaldehyde leads to DNA damage and liver injury and promotes the development of cancer. We report here a major role for the transforming growth factor ß/mothers against decapentaplegic homolog 3 adaptor ß2-Spectrin (ß2SP, gene Sptbn1) in maintaining genomic stability following alcohol-induced DNA damage. ß2SP supports DNA repair through ß2SP-dependent activation of Fanconi anemia complementation group D2 (Fancd2), a core component of the Fanconi anemia complex. Loss of ß2SP leads to decreased Fancd2 levels and sensitizes ß2SP mutants to DNA damage by ethanol treatment, leading to phenotypes that closely resemble those observed in animals lacking both aldehyde dehydrogenase 2 and Fancd2 and resemble human fetal alcohol syndrome. Sptbn1-deficient cells are hypersensitive to DNA crosslinking agents and have defective DNA double-strand break repair that is rescued by ectopic Fancd2 expression. Moreover, Fancd2 transcription in response to DNA damage/transforming growth factor ß stimulation is regulated by the ß2SP/mothers against decapentaplegic homolog 3 complex. CONCLUSION: Dysfunctional transforming growth factor ß/ß2SP signaling impacts the processing of genotoxic metabolites by altering the Fanconi anemia DNA repair pathway. (Hepatology 2017;65:678-693).

Mutational Profiles Reveal an Aberrant TGF-ß-CEA Regulated Pathway in Colon Adenomas.

Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-ß pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-ß signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-ß signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-ß in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.

Outcome of EMR as an alternative to surgery in patients with complex colon polyps.

BACKGROUND AND AIMS: Patients with complex colon polyps were traditionally referred for surgery to avoid adverse events associated with endoscopic resection. Recent advances in endoscopic imaging as well as endoscopic hemostasis and clip closure allow for the use of EMR as an alternative to surgery for such lesions. To determine the outcome of treatment of complex colon polyps with EMR as an alternative to surgery, we conducted a retrospective observational study. METHODS: Two hundred three patients with complex colon polyps were referred to an EMR center as an alternative to surgery. Patients underwent a protocol-driven EMR. The primary endpoint was the complete resection rate. Secondary endpoints were safety, residual adenoma rate, and incidence of missed synchronous polyps. RESULTS: EMR was performed in 155 patients and was deferred in 48 patients who were referred to surgery. EMR specimens revealed benign polyps in 149 and cancer in 6 patients. EMR adverse events occurred in 7 patients, requiring hospitalization in 5 of them. None of the patients died as a result of their adverse events. Surveillance colonoscopy at 4 to 6 months after resection of a benign lesion in 137 patients revealed residual adenoma at the scar site in 6 patients and additional synchronous precancerous lesions in 117 patients that were not removed by the referring endoscopist. None underwent surgery for failure of EMR. The overall precancerous lesion burden was 2.83 per patient, the adenoma burden was 2.13 per patient, and the serrated polyp burden was .69 per patient. CONCLUSIONS: EMR can be used instead of surgery for complex colon polyps in 75% of patients with few adverse events and few residual adenomas at resection sites. In addition, careful repeat examination of the entire colon for synchronous lesions overlooked by the referring endoscopist is required for most patients. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01827241.).

TGF-ß/ß2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a human stem cell disorder, and individuals with this disease have a substantially increased risk (~800-fold) of developing tumors. Epigenetic silencing of ß2-spectrin (ß2SP, encoded by SPTBN1), a SMAD adaptor for TGF-ß signaling, is causally associated with BWS; however, a role of TGF-ß deficiency in BWS-associated neoplastic transformation is unexplored. Here, we have reported that double-heterozygous Sptbn1+/- Smad3+/- mice, which have defective TGF-ß signaling, develop multiple tumors that are phenotypically similar to those of BWS patients. Moreover, tumorigenesis-associated genes IGF2 and telomerase reverse transcriptase (TERT) were overexpressed in fibroblasts from BWS patients and TGF-ß-defective mice. We further determined that chromatin insulator CCCTC-binding factor (CTCF) is TGF-ß inducible and facilitates TGF-ß-mediated repression of TERT transcription via interactions with ß2SP and SMAD3. This regulation was abrogated in TGF-ß-defective mice and BWS, resulting in TERT overexpression. Imprinting of the IGF2/H19 locus and the CDKN1C/KCNQ1 locus on chromosome 11p15.5 is mediated by CTCF, and this regulation is lost in BWS, leading to aberrant overexpression of growth-promoting genes. Therefore, we propose that loss of CTCF-dependent imprinting of tumor-promoting genes, such as IGF2 and TERT, results from a defective TGF-ß pathway and is responsible at least in part for BWS-associated tumorigenesis as well as sporadic human cancers that are frequently associated with SPTBN1 and SMAD3 mutations.

Natural language processing as an alternative to manual reporting of colonoscopy quality metrics.

BACKGROUND AND AIMS: The adenoma detection rate (ADR) is a quality metric tied to interval colon cancer occurrence. However, manual extraction of data to calculate and track the ADR in clinical practice is labor-intensive. To overcome this difficulty, we developed a natural language processing (NLP) method to identify adenomas and sessile serrated adenomas (SSAs) in patients undergoing their first screening colonoscopy. We compared the NLP-generated results with that of manual data extraction to test the accuracy of NLP and report on colonoscopy quality metrics using NLP. METHODS: Identification of screening colonoscopies using NLP was compared with that using the manual method for 12,748 patients who underwent colonoscopies from July 2010 to February 2013. Also, identification of adenomas and SSAs using NLP was compared with that using the manual method with 2259 matched patient records. Colonoscopy ADRs using these methods were generated for each physician. RESULTS: NLP correctly identified 91.3% of the screening examinations, whereas the manual method identified 87.8% of them. Both the manual method and NLP correctly identified examinations of patients with adenomas and SSAs in the matched records almost perfectly. Both NLP and the manual method produced comparable values for ADRs for each endoscopist and for the group as a whole. CONCLUSIONS: NLP can correctly identify screening colonoscopies, accurately identify adenomas and SSAs in a pathology database, and provide real-time quality metrics for colonoscopy.

Endoscopic management of Barrett's esophagus with high-grade dysplasia and early-stage esophageal adenocarcinoma.

Several endoscopic procedures have been recently developed for the treatment of Barrett's esophagus and early esophageal cancer, including endoscopic resection, radiofrequency ablation, and cryoablation. This review article discusses ideal candidates for endoscopic therapies, current treatment modalities, clinical and safety outcomes, and specific management recommendations.

Comparison of the utility of covered metal stents versus uncovered metal stents in the management of malignant biliary strictures in 749 patients.

BACKGROUND: Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstruction. OBJECTIVE: To compare outcomes between covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (USEMSs) in malignant biliary obstruction. DESIGN: Retrospective cohort study. SETTING: Tertiary cancer center. PATIENTS: Patients with malignant biliary obstruction. INTERVENTIONS: Placement of CSEMS or USEMS. MAIN OUTCOME MEASUREMENTS: Time to recurrent biliary obstruction (TRO), overall survival (OS), and adverse events. RESULTS: From January 2000 to June 2011, 749 patients received SEMSs: 171 CSEMSs and 578 USEMSs. At 1 year, there was no significant difference in the percentage of patients with recurrent obstruction (CSEMSs, 35% vs USEMSs, 38%) and survival (CSEMSs, 45% vs USEMSs, 49%). There was no significant difference in the median OS (CSEMSs, 10.4 months vs USEMSs, 11.8 months; P = .84) and the median TRO (CSEMSs, 15.4 months vs USEMSs, 26.3 months; P = .61). The adverse event rate was 27.5% for the CSEMS group and 27.7% for the USEMS group. Although tumor ingrowth with recurrent obstruction was more common in the USEMS group (76% vs 9%, P < .001), stent migration (36% vs 2%, P < .001) and acute pancreatitis (6% vs 1%, P < .001) were more common in the CSEMS group. LIMITATIONS: Retrospective study. CONCLUSIONS: There was no significant difference in the patency rate or overall survival between CSEMSs and USEMSs for malignant distal biliary strictures. The CSEMS group had a significantly higher rate of migration and pancreatitis than the USEMS group. No significant SEMS-related adverse events were observed in patients undergoing neoadjuvant chemoradiation or surgical resection.

Loss of TGF-ß adaptor ß2SP activates notch signaling and SOX9 expression in esophageal adenocarcinoma.

TGF-ß and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-ß signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-ß adapter ß2SP (SPNB2) activates Notch signaling and its target SOX9 in primary fibroblasts or esophageal adenocarcinoma cells. Expression of the stem cell marker SOX9 was markedly higher in esophageal adenocarcinoma tumor tissues than normal tissues, and its higher nuclear staining in tumors correlated with poorer survival and lymph node invasion in esophageal adenocarcinoma patients. Downregulation of ß2SP by lentivirus short hairpin RNA increased SOX9 transcription and expression, enhancing nuclear localization for both active Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into esophageal adenocarcinoma cells of ß2SP and a dominant-negative mutant of the Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor sphere formation and invasive capacity in vitro and tumor growth in vivo were increased in ß2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of ß2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of ß2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-ß targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of ß2SP switches TGF-ß signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9.

Acute exacerbation and reactivation of chronic hepatitis C virus infection in cancer patients.

BACKGROUND & AIMS: Data on acute exacerbation and reactivation of chronic hepatitis C virus (HCV) infection following chemotherapy are very limited. We sought to characterize the episodes of acute exacerbation and viral reactivation of HCV infection in cancer patients. METHODS: The medical records of HCV-infected patients seen at our institution (2008-2009) were analyzed retrospectively. Acute exacerbation was defined as greater than 3-fold increase in serum level of alanine aminotransferase, and viral reactivation as ≥ 1 log(10) IU/ml increase of HCV viral load following chemotherapy. RESULTS: Acute exacerbation occurred in 33 (11%) of 308 patients with proven HCV infection. Patients with acute exacerbation more often had underlying hematological malignancies (73% vs. 29%; p<0.001) and lymphopenia (6% vs. 0%; p=0.01) than patients without it. In multivariate analysis, underlying hematological malignancies (p=0.02; odds ratio, 3.2; 95% confidence interval, 1.2-8.7) and use of rituximab (p=0.004; odds ratio, 4.2; 95% confidence interval, 1.6-10.9) were associated with acute exacerbation. Patients with acute exacerbation received higher median cumulative dose of rituximab than those without exacerbation. Discontinuation of chemotherapy due to liver dysfunction was more common in patients with acute exacerbation than in patients without it (45% vs. 11%; p<0.001). Eight (36%) of 22 patients with known pre- and post-chemotherapy viral load had viral reactivation. CONCLUSIONS: Acute exacerbation and reactivation of chronic HCV infection occur often after chemotherapy. Liver dysfunction can lead to discontinuation of potentially life-saving chemotherapy in nearly one-half of the patients with exacerbation of HCV infection.

Barrett's Esophagus: A Review of Biology and Therapeutic Approaches.

Despite advances in diagnosis and therapy, esophageal cancer remains a highly lethal disease. The incidence of esophageal adenocarcinoma (EAC) has risen faster than that of any other cancer in the western world, and Barrett's esophagus (BE) may be a significant contributing factor. In-depth knowledge of biology of cancer progression and cancer could lead to the identification of biomarkers that are the hallmark of BE's progression. By integrating validated biomarkers of progression into clinical practice, there is a possibility of identifying high-risk patient population for targeted surveillance, and such biomarkers may serve as novel therapeutic targets for chemoprevention and therapy. Clinical management of BE has improved considerably due to the improvements in endoscopic resection and ablation techniques. We discuss the current status of biology and therapeutic approaches to BE.

Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer.

Infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) are associated with significant morbidity and mortality among patients with cancer, especially in patients with hematologic malignancies and those who undergo hematopoietic stem-cell transplantation. Reported rates of HBV reactivation in HBV carriers who undergo chemotherapy range from 14-72%. In these patients, mortality rates range from 5-52%. HCV reactivation seems to be less common than HBV reactivation and is usually associated with a good outcome and low mortality. However, once severe hepatitis develops, as a result of viral reactivation, mortality rates seem to be similar among patients infected with HBV or HCV. Liver damage owing to viral reactivation frequently leads to modifications or interruptions of chemotherapy, which can negatively affect patients' clinical outcome. Risk factors for the development of severe HBV or HCV reactivation need to be better defined to permit identification of patients who may benefit from preventive measures, early diagnosis, and therapy. In this article, we review the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with reactivation of HBV and HCV during immunosuppressive therapy. We also discuss strategies for the prevention and treatment of viral reactivation, including the management of reactivation with new antiviral agents.