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1.
Transplant Proc ; 52(1): 89-96, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32000943

RESUMO

BACKGROUND: After renal transplantation (RTx) hepatitis C virus (HCV) is associated with higher morbidity and mortality resulting in lower patient and graft survival. Few studies have investigated the evolution of renal transplant patients with cirrhosis owing to HCV. The objectives were to evaluate the post-transplant evolution of cirrhotic patients and to compare them with noncirrhotic patients considering the outcomes, including hepatic decompensation, graft loss, and death. METHODS: The retrospective-cohort study analyzed the data of patients undergoing RTx between 1993 and 2014, positive anti-HCV, HCV-RNA before RTx, and availability of data for assessment of cirrhosis. Demographic, clinical, and laboratory variables were compared between the groups according to the outcomes. The same were made between cirrhotic patients with and without portal hypertension (PH). Survival curves were constructed by the Kaplan-Meier test and compared by the log-rank test. Variables associated with the outcomes were analyzed using Cox regression. RESULTS: This study included noncirrhotic (n = 201) and cirrhotic patients (n = 23). In cirrhotic patients, they were significantly older (49 vs 41.6 years) and mostly male (87% vs 65%), with a greater number of previous RTx (48% vs 18%), less frequent use of azathioprine (26% vs 54%), cyclosporine (13% vs 46.5%), more frequent use of tacrolimus (87% vs 55%), lower count of platelets × 1000 cells/mm3(110 vs 187), and higher pre-RTx international normalized ratio (1.20 vs 1.1).The Kaplan-Meier survival differed in cirrhotic vs noncirrhotic patients only in hepatic decompensation. Cox regression analysis identified pretransplant cirrhosis (hazard ratio 6.64, 95% confidence interval, 2.59-17.06) and tacrolimus (hazard ratio 3.17,95% confidence interval, 1.05-9.58) as variables independently associated with decompensation. CONCLUSIONS: Patients with HCV and cirrhosis exhibit higher morbidity when submitted to RTx than noncirrhotic patients, with a higher risk of hepatic decompensation. However, no difference was observed in liver-related mortality, suggesting that RTx is a feasible option in cirrhotic patients without decompensation, even if they have PH.


Assuntos
Hepacivirus , Hepatite C/cirurgia , Transplante de Rim/mortalidade , Cirrose Hepática/cirurgia , Adulto , Feminino , Sobrevivência de Enxerto , Hepatite C/complicações , Hepatite C/virologia , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
2.
J MED VIROL, v. 9o, n. 3, p. 537-544, mar. 2018
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2417

RESUMO

New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment-naive patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD-HD patients presented HCV genotypes 1a (n=18), 1b (n=16), 2a (n=2), 2b (n=2), and 3a (n=4). Control subjects were infected with genotypes 1a (n=11), 1b (n=21), 2b (n=4), and 3a (n=8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD-HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD-HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.

3.
J MED VIROL ; 90(3): p. 537-544, 2018.
Artigo | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib14928

RESUMO

New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment-naive patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD-HD patients presented HCV genotypes 1a (n=18), 1b (n=16), 2a (n=2), 2b (n=2), and 3a (n=4). Control subjects were infected with genotypes 1a (n=11), 1b (n=21), 2b (n=4), and 3a (n=8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD-HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD-HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.

4.
Ann Hepatol ; 14(3): 317-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25864211

RESUMO

BACKGROUND: HBV/HCV coinfection is a common finding among hemodialysis patients. However, there is scarce information concerning the impact of HBV coinfection on the response to treatment of HCV-infected patients on hemodialysis. AIM: We aimed to compare the rate of sustained virologic response (SVR) to treatment with interferon-alfa (IFN) between hemodialysis patients with HBV/HCV coinfection and those with HCV-monoinfection. MATERIAL AND METHODS: HCV-infected patients on hemodialysis treated with IFN were included. Patients coinfected by HBV/HCV were compared to HCV-monoinfected patients, regarding clinical and biochemical features and rates of SVR. RESULTS: One hundred and eleven patients were treated. HBV/HCV coinfection was observed in 18/111 patients (16%). Coinfected patients were younger (p = 002), had more time on dialysis (p = 0.05) and showed a tendency to present a higher prevalence of septal fibrosis (p = 0.06). The analysis by intention to treat showed SVR of 56% among coinfected patients and 18% in HCV-monoinfected patients (p = 0.004). CONCLUSION: In conclusion, end-stage renal disease patients with HBV/HCV coinfection exhibit higher rate of SVR to HCV treatment than HCV-monoinfected patients. It is possible that factors related to the host immune response and viral interaction could explain the better response observed among coinfected patients.


Assuntos
Antivirais/uso terapêutico , Coinfecção , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal , Feminino , Seguimentos , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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