Human pegivirus-1 infection in kidney transplant recipients: A single-center experience.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. In the posttransplant period, the induced immunosuppression leads to an increased risk of developing infectious diseases, a leading cause of death after kidney transplantation. Human pegivirus-1 (HPgV-1) is considered a nonpathogenic human virus and is highly frequent in individuals parenterally exposed, however, its impact on kidney transplantation outcome is poorly understood. Given the scarcity of epidemiological data for this infection on organ recipients in Brazil, we conducted a study in a single center for kidney transplantation in Rio de Janeiro, aiming to determine HPgV-1 prevalence and genotypic distribution. Serum samples from 61 renal recipients, followed up for the first year after transplantation, were evaluated for viral RNA and genotypes were determined by sequencing of the 5'-untranslated region. HPgV-1 RNA was detected in 36.1% (22/61) of patients. Genotype 2 was the most commonly found (80.9%), followed by genotypes 3 (9.5%), 1, and 5, in 4.8% each. Statistical comparisons did not reveal any significant impact of HPgV-1 in patient outcome. Further epidemiologic studies are needed to understand if immunosuppression may interfere in HPgV-1 persistence rates and if viremia might impact graft dysfunction rates in kidney recipients.

Impact assessment and investigation of factors associated with herpesviruses viremia in the first year of renal transplantation.

The increased risk for opportunistic infections after a renal transplant requires monitoring of viral infections to avoid future complications. Our goal was to investigate the impact and factors associated with Epstein-Barr virus (EBV), human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) viremia in renal transplant recipients. Whole blood samples were collected monthly from 82 patients during the first semester and then quarterly up to 1 year after transplantation. EBV, HCMV, and HHV-6 were detected and quantified by TaqMan real-time polymerase chain reaction. The results showed that EBV and HCMV viremia were detected in 32 patients (39% each), while HHV-6 viremia in only 3 patients (3.7%). EBV was significantly associated with age (P = .050), thymoglobuline induction (P = .019), mTOR inhibitor-based therapy (P = .003), and female gender (P = .044). HCMV was significantly associated with basiliximab induction (P = .015), mycophenolate mofetil (MMF)-based therapy (P = .003) and allograft acute rejection (P = .033). Moreover, HCMV-disease was correlated with MMF-based therapy (P = .021) and female gender (P = .003). In conclusion, EBV and HCMV viremia were associated with different immunosuppressive induction and maintenance strategies. Additionally, higher HCMV viremia (> 10 4 copies/mL) was related to acute allograft rejection.

Investigation of three oncogenic epitheliotropic viruses shows human papillomavirus in association with non-melanoma skin cancer.

Non-melanoma skin cancers (NMSC) share similar risk factors with other virus-related cancers, despite the lack of proved causal association between viral infection and NMSC development. We investigated the presence of Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) DNA in 83 NMSC fresh-frozen and 16 non-cancerous skin biopsies and evaluated viral infection according to demographical data, histopathological diagnosis, and ultraviolet exposure. Our results showed that 75% of NMSC biopsies were positive for at least one out of three viruses, whereas only 38% of non-cancerous skin biopsies were positive (p = 0.02). Notably, HPV detection was frequent in NMSC (43%) and nearly absent (one sample, 6.7%) in non-cancerous biopsies (p = 0.007). MCPyV was associated with sites of higher exposure to ultraviolet radiation (p = 0.010), while EBV was associated with a compromised immune system (p = 0.032). Our study showed that HPV was strongly associated with NMSC while EBV and MCPyV with other risk factors. Though further studies are required to elucidate the role of viral infection in NMSC development and management, this study supports the possible role of oncogenic viruses in skin cancers, especially HPV.

Screening for BKV-DNAEMIA after renal transplantation in a resource limited setting.

Costs may hinder the implementation of BK polyomavirus (BKV)-DNAemia screening in resource-limited kidney transplant (KT) centers. We analyzed data from two studies to assess the performance and potential cost saving of a dual-step screening strategy based on the use of a preliminary qualitative semi-nested PCR (snPCR) assay followed by BKV-DNAemia quantification after KT. In the preliminary study, in which 130 samples from 33 KT recipients were screened for BKV-DNAemia, the estimated positive and negative predictive values of snPCR, as compared to quantitative PCR (qPCR), were 88% and 99%, respectively. In the second study, which included 84 KT recipients, BKV-DNAemia was detected by snPCR in 28/472 (5.9%) samples and confirmed by qPCR in 26 samples of 21 (25%) subjects. No graft loss occurred among KT recipients who developed BKV-DNAemia. Cost analyses suggested that this strategy might be a cost saving alternative for BKV-DNAemia screening for some resource-limited settings.

A globally applicable PCR-based detection and discrimination of BK and JC polyomaviruses.

BKV and JCV belong to the Polyomaviridae family and are opportunistic agents associated with complications in immunocompromised individuals. Although a single screening assay for both viruses would be convenient, the diversity of BKV and JCV serotypes and genotypes is a methodological challenge. In this paper, we developed a PCR method able to detect and segregate BKV and JCV, despite these genetic discrepancies. A duplex semi-nested PCR (duplex snPCR) was designed to target a conserved region (639nt-1516nt) within the VP2 gene. In the first PCR, a primer set common to all BKV and JCV serotypes/ genotypes was used, followed by a semi-nested PCR with internal primers for BKV and JCV segregation. The limit of detection of the duplex snPCR was as low as 10 copies of BKV or JCV plasmids/µL. Specific products were observed when JCV and BKV plasmids were mixed in the same reaction. In field sample testing, the duplex snPCR detected and distinguished both viruses in different biological samples. Results were confirmed by Sanger's sequencing. The geographical complexity of BKV and JCV serotypes and genotypes imposes limits to a simple and universal method that could detect each virus. However, we describe here a sensitive and reliable PCR technique for BKV and JCV diagnosis that overcomes these limitations and could be universally applied.

Prevalence of occult hepatitis B virus infection and Torque teno virus infection and their association with hepatocellular carcinoma in chronic hepatitis C patients.

BACKGROUND: The role of occult hepatitis B virus (HBV) infection and Torque teno virus (TTV) infection in the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients is still uncertain. AIM: The aim of the present study was to investigate the prevalence and significance of OBI and TTV infection, and to examine the genetic diversity of these viruses, in chronic hepatitis C patients with and without HCC. METHODS: Sera from 151 hepatitis C virus (HCV)-infected patients (49 patients with HCC and 102 without HCC) negative for HBV surface antigen (HBsAg) were tested for the presence of OBI and TTV infection by semi-nested and group-specific multiplex PCR assays, respectively. Nucleotide sequencing of HBV S region was further performed. RESULTS: OBI and TTV infection were detected in 5 (3.3%) and 68 (45%) patients, respectively. HBV isolates were classified into genotypes A (4/5, 80%) and D (1/5, 20%), and no HBsAg escape mutation was observed. TTV phylogenetic group 3 was the most prevalent among both HCC and non-HCC patients. OBI and TTV infection were significantly more frequent in patients with HCC than patients without HCC (p=0.003, and p=0.009, respectively). Moreover, TTV infection was associated with HCC (OR=2.23, 95%CI=1.04-4.80, p=0.040), independently of liver cirrhosis. CONCLUSIONS: A low prevalence of OBI was observed in patients with HCV-related chronic liver disease, and TTV infection was an independent factor associated with the occurrence of HCC. Whether TTV influences the progression of liver disease in chronic hepatitis C patients remains to be elucidated.

ASSOCIATION OF EPSTEIN-BARR VIRUS (EBV) BUT NOT HUMAN PAPILLOMAVIRUS (HPV) WITH GINGIVITIS AND/OR PERIODONTITIS IN TRANSPLANTED INDIVIDUALS.

The aim of this study was to investigate the association of EBV and HPV with gingivitis and/or periodontitis according to the immunologic status. To this end, 74 oral biopsies from transplanted and non-transplanted individuals with the abovementioned oral manifestations were submitted to a screening by PCR for both viruses. According to the results, EBV was strongly associated with gingivitis and/or periodontitis in transplanted individuals (p = 0.011) but not HPV (p = 0.766). EBV-HPV co-detections did not enhance the presence of tissue injury as well. Although a causal relationship was not investigated in this study, the higher frequency of these two oncoviruses in lesion tissues must be investigated in follow-up studies, especially among immunocompromised individuals.

Prevalence, risk factors and genotypes of hepatitis B infection among HIV-infected patients in the State of MS, Central Brazil.

OBJECTIVES: A cross-sectional study on prevalence of HBV and HDV infection, risk factors and genotype distribution of HBV infection was conducted among 848 HIV-infected patients in Mato Grosso do Sul, Central Brazil. METHODS: Serum samples of 848 participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis surface antibody (anti-HBs). HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV, and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction. Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi-square test and Fisher's exact test were used to compare variables and to evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg positivity) and risk factors. RESULTS: Among the 848 HIV infected patients investigated 222 had serological markers of HBV infection. The prevalence rate of HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4-3.5%); 484 (57.1%) patients were susceptible for HBV infection. There were no cases of anti-HDV positive and only one (0.1%) anti-HCV-positive case among the HIV-HBV coinfected patients. Male gender, increasing age, family history of hepatitis, use of illicit drug, and homosexual activity were independent factors associated with HBV exposure. The phylogenetic analysis based on the S gene region revealed the presence of genotypes D (76.9%), F (15.4%) and A (7.7%) in the study sample. CONCLUSION: This study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals.

Prevalence, risk factors and genotypes of hepatitis B infection among HIV-infected patients in the State of MS, Central Brazil

Objectives: A cross-sectional study on prevalence of HBV and HDV infection, risk factors and genotype distribution of HBV infection was conducted among 848 HIV-infected patients in Mato Grosso do Sul, Central Brazil. Methods: Serum samples of 848 participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis surface antibody (anti-HBs). HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV, and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction. Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi-square test and Fisher's exact test were used to compare variables and to evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg positivity) and risk factors. Results: Among the 848 HIV infected patients investigated 222 had serological markers of HBV infection. The prevalence rate of HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4–3.5%); 484 (57.1%) patients were susceptible for HBV infection. There were no cases of anti-HDV positive and only one (0.1%) anti-HCV-positive case among the HIV-HBV coinfected patients. Male gender, increasing age, family history of hepatitis, use of illicit drug, and homosexual activity were independent factors associated with HBV exposure. The phylogenetic analysis based on the S gene region revealed the presence of genotypes D (76.9%), F (15.4%) and A (7.7%) in the study sample. Conclusion: This study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals. .