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Rev. Soc. Bras. Med. Trop ; 52: e20180455, 2019. tab, graf
Article in English | LILACS | ID: biblio-985155


Abstract INTRODUCTION: The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. METHODS: The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. RESULTS: The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. CONCLUSIONS: The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response.

Humans , Male , Female , C-Reactive Protein/analysis , Hepatitis B, Chronic/blood , Hepatitis C, Chronic/blood , Liver Cirrhosis/virology , Severity of Illness Index , C-Reactive Protein/genetics , Biomarkers/blood , Case-Control Studies , Cross-Sectional Studies , Viral Load , Hepatitis B, Chronic/genetics , Hepatitis C, Chronic/genetics , Genotype , Liver Cirrhosis/blood
Rev. Soc. Bras. Med. Trop ; 52: e20170427, 2019. tab
Article in English | LILACS | ID: biblio-1041583


Abstract INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.

Humans , Male , Female , Antigens, Human Platelet/genetics , Carcinoma, Hepatocellular/virology , Hepatitis C, Chronic/genetics , Liver Neoplasms/virology , Prognosis , Genetic Markers , Polymerase Chain Reaction , Risk Factors , Carcinoma, Hepatocellular/genetics , Disease Progression , Hepatitis C, Chronic/virology , Genotype , Liver Neoplasms/genetics , Middle Aged
Braz. j. infect. dis ; 22(4): 317-322, July-Aug. 2018. tab
Article in English | LILACS | ID: biblio-974227


ABSTRACT Introduction Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. Methods A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. Results A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p= 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p= 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p= 0.047). Conclusion The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.

Humans , Male , Female , Adult , Middle Aged , Aged , Antiviral Agents/therapeutic use , Public Health/statistics & numerical data , Hepatitis C, Chronic/drug therapy , Sustained Virologic Response , Ribavirin/therapeutic use , Brazil , Retrospective Studies , Practice Guidelines as Topic , Hepacivirus/genetics , Viral Load , Hepatitis C, Chronic/genetics , Drug Therapy, Combination , Simeprevir/therapeutic use , Sofosbuvir/therapeutic use , Genotype , Imidazoles/therapeutic use , Liver Cirrhosis
Rev. méd. Chile ; 146(7): 823-829, jul. 2018. tab
Article in Spanish | LILACS | ID: biblio-961467


Background. Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. Aim: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. Material and Methods: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR. Fibrosis present in liver biopsies was assessed using the METAVIR score, comparing patients with either no fibrosis, mild fibrosis, or intermediate fibrosis (F0+F1+F2, n = 96), with patients with severe fibrosis or cirrhosis (F3+F4, n = 54). Results: In F0-F2 patients the distribution of rs12979860 genotypes was 22 CC, 57 CT and 17 TT, whereas in patients F3-F4 the distribution was 10, 29 and 15, respectively. No association between IFNL4 rs12979860 genotype and risk of fibrosis was observed in uni or multivariate analyses. Conclusions: IFNL4 rs12979860 C>T polymorphism is not associated with risk of liver fibrosis in this group of patients with CHC.

Humans , Male , Female , Middle Aged , Interleukins/genetics , Hepatitis C, Chronic/genetics , Liver Cirrhosis/genetics , Antiviral Agents/therapeutic use , Chile , Retrospective Studies , Risk Factors , Interferons/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/blood , Polymorphism, Single Nucleotide , Genotype , Liver Cirrhosis/blood
Rev. Soc. Bras. Med. Trop ; 51(2): 146-154, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-897067


Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

Humans , Male , Female , Adult , Aged , Antiviral Agents/administration & dosage , Protease Inhibitors/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Oligopeptides/administration & dosage , Oligopeptides/adverse effects , Antiviral Agents/adverse effects , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Protease Inhibitors/adverse effects , Ribavirin/administration & dosage , Ribavirin/adverse effects , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Proline/administration & dosage , Proline/analogs & derivatives , Proline/adverse effects , Retrospective Studies , Treatment Outcome , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Hepacivirus/drug effects , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions , Interferon alpha-2 , Genotype , Middle Aged
Rev. Soc. Bras. Med. Trop ; 50(6): 861-863, Nov.-Dec. 2017. tab
Article in English | LILACS | ID: biblio-897030


Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.

Humans , Female , Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Sofosbuvir/administration & dosage , Imidazoles/administration & dosage , Treatment Outcome , Hepacivirus/genetics , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Drug Therapy, Combination , Sustained Virologic Response , Genotype , Middle Aged
Arq. gastroenterol ; 53(4): 246-249, Oct.-Dec. 2016. tab
Article in English | LILACS | ID: lil-794596


ABSTRACT Background Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies.Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients. Objective The present study analyzes the MDR1 gene C3435T polymorphism in HCV-HIV co-infected patients. Methods A total of 99 HCV-HIV patients were included in the study. The DNA was extracted from blood samples, and the SNP rs1045642 was assessed by Real Time PCR (qPCR). Risk factors for acquiring the virus and the SVR after HCV treatment with pegylated interferon-alpha and ribavirin were also analyzed. Results Among the patients, 54 (54.5%) were male and 45 (45.5%) were female. The average age was 46.1±9.8 years. The SVR after HCV treatment was 40%. The frequencies of MDR1 genotypes CC, CT and TT were 28.3%, 47.5% and 24.2%, respectively. Allele frequencies were 52% for the C allele and 48% for the T allele. No association was found for SNP rs1045642 (C3435T) regarding response to treatment (P=0.308). Conclusion - In this study, the C3435T polymorphism in the MDR1 gene appears not to be associated with SVR in HCV-HIV co-infected individuals.

RESUMO Contexto Em virtude da elevada prevalência da coinfecção pelos vírus da hepatite C (HCV) e da imunodeficiência humana (HIV) e às inúmeras complicações que esses vírus acarretam, é fundamental o maior entendimento do comportamento biológico dos mesmos. O polimorfismo de nucleotídeo único rs1045642 C3435T do gene de resistência a múltiplas drogas MDR1, no qual ocorre modificação do códon ATC para ATT, parece estar relacionado à resposta virológica sustentada ao tratamento do HCV em coinfectados HCV-HIV. Objetivo Mapear o polimorfismo C3435T do gene MDR1 em pacientes coinfectados HCV-HIV e correlacionar com dados clínicos e laboratoriais. Métodos Foram analisados 99 pacientes coinfectados HCV-HIV. A identificação molecular do polimorfismo de nucleotídeo único rs1045642 do gene MDR1 foi realizada pela técnica de PCR em tempo real (qPCR) alelo-específico com primers e sondas específicos para a identificação desse polimorfismo. Fatores de risco para a aquisição do HCV e a resposta virológica sustentada ao tratamento do HCV com interferon-alfa peguilado e ribavirina foram analisados. Resultados Dentre os pacientes avaliados, 54 (54,5%) eram do gênero masculino e 45 (45,5%) do gênero feminino. A média de idade foi de 46,1 anos (±9,8). As frequências dos genótipos CC, CT e TT foram 28,3%, 47,5% e 24,2% respectivamente, e as frequências alélicas foram 52% para alelo C e 48% para alelo T. Não houve associação entre o gene MDR1 e a resposta virológica sustentada (P=0,308). Conclusão Neste estudo, o polimorfismo C3435T no gene MDR1 não apresentou associação com a resposta virológica sustentada ao tratamento em indivíduos coinfectados HCV-HIV.

Humans , Male , Female , HIV Infections/genetics , Genes, MDR , Hepatitis C, Chronic/genetics , Polymorphism, Single Nucleotide , Antiviral Agents/therapeutic use , Ribavirin/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/virology , Cross-Sectional Studies , HIV , Interferon-alpha/therapeutic use , Hepacivirus , Viral Load , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Coinfection/virology , Real-Time Polymerase Chain Reaction , Genotype , Middle Aged
Braz. j. med. biol. res ; 49(11): e5504, 2016. tab, graf
Article in English | LILACS | ID: lil-797884


Hepatitis C virus (HCV) genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of direct-acting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR) rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN), sofosbuvir (SOF), daclatasvir (DCV) and ribavirin (RBV). Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83–100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contraindications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82–96% among patients without cirrhosis and 62–92% among those with cirrhosis. Finally, SOF plus DCV provides 94–97% SVR rates in non-cirrhotic patients, but 59–69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection.

Humans , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C/genetics , Liver Cirrhosis/etiology , Drug Therapy, Combination , Genotype , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/genetics , Imidazoles/therapeutic use , Interferon-alpha/therapeutic use , Ribavirin/therapeutic use , Sofosbuvir/therapeutic use
Arq. gastroenterol ; 52(4): 315-320, Oct.-Dec. 2015. tab
Article in English | LILACS | ID: lil-771919


Background - Different factors are responsible for the progression of hepatic fibrosis in chronic infection with hepatitis C virus, but the role of nutritional factors in the progression of the disease is not clearly defined. This study aimed to evaluate the nutritional status and dietary profile among patients with chronic hepatitis C who were candidates for treatment and its association with histopathological features. Methods - A crossectional study was conducted on treatment-naïve patients with chronic hepatitis C genotype 1, between 2011 and 2013. The following assessments were performed before treatment: liver biopsy, anthropometric measurements and qualitative/quantitative analysis of food intake. Results - Seventy patients were studied. The majority of patients was classified as obese (34%) or overweight (20%) according to body mass index [BMI] and as at risk for cardiovascular diseases by waist circumference (79%). Unhealthy food intake was presented by 59% according to qualitative parameters and several patients showed an insufficient intake of calories (59%), excessive intake of protein (36%) and of saturated fat (63%), according to quantitative analysis. With respect to histology, 68% presented activity grade ≥2, 65% had steatosis and 25% exhibited fibrosis stage >2. Comparative analysis between anthropometric parameters and histological features showed that elevated waist circumference was the only variable associated to hepatic steatosis ( P =0.05). There was no association between qualitative and quantitative food intake parameters with histological findings. Conclusion - In this study, most of the patients with hepatitis C presented inadequate qualitative food intake and excessive consumption of saturated fat; in addition, excess of abdominal fat was associated to hepatic steatosis. Therefore, nutritional guidance should be implemented prior to treatment in patients with chronic hepatitis C, in order to avoid nutritional disorders and negative impact on the management of patients.

Contexto - Diferentes fatores são responsáveis pela progressão da fibrose na infecção crônica pelo vírus da hepatite C, mas o papel dos fatores nutricionais na progressão da doença não está definido. Este estudo teve como objetivo avaliar o estado nutricional e o perfil dietético de pacientes com hepatite C crônica candidatos a tratamento e sua associação com achados histopatológicos. Métodos - Foi conduzido um estudo transversal em pacientes com hepatite C crônica genótipo 1 virgens de tratamento, entre 2011 e 2013. Foram analisados, antes do tratamento, os seguintes aspectos: biópsia hepática, medidas antropométricas e análise qualitativa e quantitativa do consumo alimentar. Resultados - Setenta pacientes foram estudados. A maioria dos pacientes apresentava obesidade (34%) ou sobrepeso (20%) de acordo com índice de massa corporal e risco para doenças cardiovasculares de acordo com a circunferência da cintura elevada (79%). Na análise qualitativa do consumo alimentar, 59% apresentavam uma dieta inadequada. Conforme análise quantitativa, 59% tinham consumo insuficiente de calorias, 36% consumo excessivo de proteínas e 63% consumo excessivo de gorduras saturadas. Com relação à histologia, 68% apresentavam grau de atividade inflamatória ≥2, 65% mostraram esteatose hepática e 25% possuíam grau de fibrose >2. Na análise comparativa entre as medidas antropométricas e achados histológicos, somente a circunferência da cintura elevada mostrou associação com esteatose hepática ( P =0,05). Não houve associação entre consumo alimentar qualitativo e quantitativo com parâmetros histológicos. Conclusão - A maioria dos pacientes apresentava consumo alimentar inadequado de acordo com parâmetros qualitativos e consumo excessivo de gordura saturada, além de excesso de gordura abdominal, que esteve associada à esteatose hepática. Portanto, aconselhamento nutricional deveria ser implementado em pacientes candidatos a tratamento para hepatite C crônica visando evitar distúrbios nutricionais que podem impactar negativamente no manejo dos pacientes.

Female , Humans , Male , Middle Aged , Energy Intake/physiology , Feeding Behavior/physiology , Hepatitis C, Chronic/complications , Body Mass Index , Chronic Disease , Cross-Sectional Studies , Disease Progression , Fatty Liver/etiology , Fatty Liver/physiopathology , Genotype , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/physiopathology , Liver Cirrhosis/etiology , Liver Cirrhosis/physiopathology , Obesity/complications , Obesity/physiopathology , Risk Factors , Severity of Illness Index
Rev. Soc. Bras. Med. Trop ; 48(4): 406-409, July-Aug. 2015. tab
Article in English | LILACS | ID: lil-755969



Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients.


Genomic deoxyribonucleic acid from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was genotyped to determine the presence of human platelet antigens-1, -3, or -5 polymorphisms. Fibrosis progression was evaluated using the Metavir scoring system, and the patients were assigned to two groups, namely, G1 that comprised patients with F1, portal fibrosis without septa, or F2, few septa (n = 23) and G2 that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13). Fisher's exact test was utilized to determine possible associations between the human platelet antigen polymorphisms and fibrosis progression.


There were no deviations from the Hardy-Weinberg equilibrium in the human platelet antigen systems evaluated. Statistically significant differences were not observed between G1 and G2 with respect to the distributions of the allelic and genotypic frequencies of the human platelet antigen systems.


The greater stimulation of hepatic stellate cells by the human immunodeficiency virus and, consequently, the increased expression of transforming growth factor beta can offset the effect of human platelet antigen polymorphism on the progression of fibrosis in patients coinfected with the human immunodeficiency virus-1 and the hepatitis C virus.


Adult , Humans , Male , Antigens, Human Platelet/genetics , HIV Infections/genetics , HIV-1 , Hepacivirus/genetics , Hepatitis C, Chronic/genetics , Liver Cirrhosis/virology , Coinfection , Disease Progression , Genotype , HIV Infections/complications , HIV Infections/immunology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/immunology , Polymorphism, Genetic
Rev. Soc. Bras. Med. Trop ; 48(2): 136-142, mar-apr/2015. tab, graf
Article in English | LILACS | ID: lil-746219


INTRODUCTION: The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS: No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. CONCLUSIONS: This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection. .

Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Hepatitis B, Chronic/genetics , Hepatitis C, Chronic/genetics , /genetics , Alleles , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Disease Progression , Genotype , Haplotypes , Polymorphism, Single Nucleotide/genetics , Risk Factors , gamma-Glutamyltransferase/blood
Mem. Inst. Oswaldo Cruz ; 109(3): 345-351, 06/2014. tab
Article in English | LILACS | ID: lil-711738


Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a sustained virological response (SVR) to treatment in subjects infected with hepatitis C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896), myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of having a null virological response was observed in patients carrying at least one A allele at positions -308 [odds ratios (OR) = 2.58, 95% confidence intervals (CI) = 1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI = 1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple logistic regression of TNF diplotypes showed that patients with at least two copies of the A allele had an even higher risk of having a null virological response (OR = 16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI = 2.18-20.66, p = 0.001). No statistically significant association was found between the other SNPs under study and anti-HCV therapy response.

Female , Humans , Male , Middle Aged , Antiviral Agents/administration & dosage , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Promoter Regions, Genetic , Ribavirin/administration & dosage , Tumor Necrosis Factor-alpha/genetics , Drug Therapy, Combination , Genotype , Hepatitis C, Chronic/genetics , /genetics , Myxovirus Resistance Proteins/genetics , Polymorphism, Single Nucleotide , Treatment Failure , Viral Load
Gut and Liver ; : 70-78, 2014.
Article in English | WPRIM | ID: wpr-36650


BACKGROUND/AIMS: This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. METHODS: Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. RESULTS: The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. CONCLUSIONS: The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.

Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/genetics , Female , Hepatitis C, Chronic/genetics , Humans , Interleukins/genetics , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide , Prognosis , Republic of Korea , Retrospective Studies
Braz. j. infect. dis ; 17(5): 555-563, Sept.-Oct. 2013. ilus, tab
Article in English | LILACS | ID: lil-689881


BACKGROUND/AIMS: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. METHODS: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCVRNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. RESULTS: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. CONCLUSION: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.

Humans , Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Hepatitis C/genetics , Insulin Resistance/physiology , RNA, Viral/genetics , Drug Therapy, Combination , Genotype , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/physiopathology , Hepatitis C/classification , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Recombinant Proteins/administration & dosage , Ribavirin/administration & dosage , Viral Load
Mem. Inst. Oswaldo Cruz ; 108(1): 48-53, Feb. 2013. graf, tab
Article in English | LILACS | ID: lil-666043


A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Interleukins/genetics , Polyethylene Glycols/administration & dosage , Polymorphism, Single Nucleotide/genetics , Ribavirin/administration & dosage , Alleles , Cohort Studies , Drug Therapy, Combination , Genotype , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Polymerase Chain Reaction , Prospective Studies , Recombinant Proteins/administration & dosage , Treatment Outcome
Mem. Inst. Oswaldo Cruz ; 107(7): 888-892, Nov. 2012. tab
Article in English | LILACS | ID: lil-656044


Single nucleotide polymorphisms (SNPs) in the interleukin (IL)28B locus have been associated with a sustained virological response (SVR) in interferon-ribavirin (IFN-RBV)-treated chronic hepatitis C virus (HCV)-infected patients in European and African populations. In this study, the genotype frequency of two IL28B SNPs (rs129679860 and rs8099917) in a cohort of chronic HCV-monoinfected patients in Brazil was evaluated and the SNP sufficient to predict the treatment response outcome was determined. A total of 66 naïve genotype-1 chronic HCV-infected patients were genotyped and the associated viral kinetics and SVR were assessed. The overall SVR was 38%. Both the viral kinetics and SVR were associated with rs129679860 genotypes (CC = 62% vs. CT = 33% vs. TT = 18%, p = 0.016). However, rs8099917 genotypes were only associated with SVR (TT = 53% vs. TG = 33% vs. GG = 18%; p = 0.032). In this population, the analysis of a single SNP, rs12979860, successfully predicts SVR in the IFN-RBV treatment of HCV.

Female , Humans , Male , Middle Aged , Hepatitis C, Chronic/genetics , Interleukins/genetics , Polymorphism, Single Nucleotide/genetics , Antiviral Agents/therapeutic use , Brazil , Cohort Studies , Drug Therapy, Combination , Genotype , Hepacivirus , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , RNA, Viral/genetics , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Treatment Outcome , Viral Load
Braz. j. med. biol. res ; 45(1): 72-77, Jan. 2012. tab
Article in English | LILACS | ID: lil-610549


The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson’s disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8 percent of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3 percent of the patients with fibrosis grade 1+2 (OR = 1.8; 95 percentCI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95 percentCI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.

Adult , Female , Humans , Carrier Proteins/genetics , Fatty Liver/genetics , Hepatitis C, Chronic/genetics , Polymorphism, Genetic/genetics , Disease Progression , Fatty Liver/metabolism , Fatty Liver/pathology , Genetic Predisposition to Disease , Genotype , Hepatitis C, Chronic/metabolism , Hepatitis C, Chronic/pathology , Polymerase Chain Reaction
Article in English | IMSEAR | ID: sea-135752


Background & objectives: Hepatitis C virus (HCV) induces an immune response of the host, manifested by the formation of anti-HCV antibodies mediated by adaptive and innate immunity. Toll-like receptors (TLRs) play a pivotal role in innate immunity system. This study was aimed to investigate the promoter region polymorphism and expression of TLR3 gene in patients with chronic HCV infection. Methods: Patients with chronic HCV infection (N=180) and an equal number of age-sex matched controls were included in the study. Patients positive for HCV-RNA were subjected to analysis of TLR3 polymorphism by direct sequencing of PCR products verified by comparing with the sequences reported in the National Centre for Biotechnology Information (NCBI) database (accession number: NT 022792). Expression of TLR3 gene was analyzed by semiquantitative RT-PCR using housekeeping β-actin gene as the internal control. Results: Polymorphisms at position -288G/A and -705A/G were identified. The results were significant in -705 allele (P=0.004) OR 2.79(1.46-5.42) and were associated with high risk of HCV infection. In silico sequence analysis showed the presence of ectropic viral integration site 1 encoded factor, in which G at -705 results in the loss of this site. The -7C/A polymorphism was not seen in our study cohort. The expression of TLR3 was upregulated in chronic HCV patients compared to healthy controls. Interpretation & conclusions: Polymorphism in the -705A/G allele at the promoter region of the TLR3 gene may predispose individual to HCV infection. However association of TLR3 expression with polymorphism of TLR3 promoter was not found.

Adult , Cohort Studies , Female , Hepacivirus/immunology , Hepacivirus/pathogenicity , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/genetics , Humans , India , Male , Middle Aged , Polymorphism, Genetic/genetics , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics , Retrospective Studies , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism
Article in English | WPRIM | ID: wpr-82228


Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea.

Adult , Aged , Female , Genes, MHC Class I , Genotype , HLA-C Antigens/genetics , Hepacivirus/immunology , Hepatitis C, Chronic/genetics , Humans , Killer Cells, Natural/immunology , Male , Middle Aged , Receptors, KIR/genetics , Republic of Korea , T-Lymphocyte Subsets/immunology