RESUMO
Recent studies have demonstrated that several cellular factors are involved in entry of hepatitis C virus (HCV) into host cells. Detailed gene expression profiles of these factors in HCV-infected livers have not been reported for humans. Transcriptional levels of LDL receptor (LDLR), CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin genes in liver samples from patients with chronic hepatitis C were investigated. Serum levels of LDL-cholesterol (LDL-C) and HCV core antigen were also evaluated, and expression of claudin-1 and occludin were immunohistochemically analyzed. Compared with normal liver, transcription of LDLR and claudin-1 genes was significantly suppressed (P < 0.0001) and occludin transcription was significantly up-regulated in HCV-infected livers (P < 0.0001). Significant positive correlations were found for LDLR versus occludin, LDLR versus claudin-1, occludin versus claudin-1, and CD81 versus SR-BI in HCV-infected (P = 0.0012, P < 0.0001, P = 0.0004, and P < 0.0001, respectively) and normal livers (P < 0.0001, P = 0.0051, P < 0.0001, and P < 0.0001, respectively). Positive correlation was observed between serum levels of HCV core antigen and LDL-C (P = 0.0147), with their levels negatively correlated to LDLR (P = 0.0270 and P = 0.0021, respectively). Immunohistochemically, hepatocellular expression of claudin-1 and occludin was increased in HCV-infected livers. Different levels of expression were demonstrated at the mRNA and protein levels for occludin and claudin-1 in HCV-infected and normal livers. Correlation of elements associated with viral entry was comparable in HCV-infected and normal livers.
Assuntos
Regulação da Expressão Gênica , Hepacivirus/fisiologia , Hepatite C Crônica/patologia , Interações Hospedeiro-Patógeno , Fígado/virologia , Internalização do Vírus , Adulto , Idoso , Antígenos CD/biossíntese , LDL-Colesterol/sangue , Claudina-1 , Feminino , Perfilação da Expressão Gênica , Hepacivirus/patogenicidade , Hepatite C Crônica/virologia , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Ocludina , Receptores de LDL/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptores Depuradores Classe B/biossíntese , Tetraspanina 28 , Proteínas do Core Viral/sangueRESUMO
We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan, to investigate the high mortality rate from liver disease. Antibodies to hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%). Multivariate logistic regression analyses showed that presence of anti-HCV, male gender, and history of liver disease were associated with the presence of liver dysfunction, and that age of more than 40 years and a particular district were associated with the presence of anti-HCV. HCV RNA was more frequently detected in anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05). The incidence of liver dysfunction was significantly higher in HCV RNA-positive men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings suggest that: (1) HCV was correlated with the high mortality rate from liver diseases, (2) there were district-related differences in the incidence of HCV, and (3) the lower frequency of elimination of HCV from men may explain why they showed a high mortality from liver disease.
Assuntos
Hepatite C/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepacivirus/genética , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Japão/epidemiologia , Hepatopatias/epidemiologia , Hepatopatias/mortalidade , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Estudos Soroepidemiológicos , Fatores SexuaisRESUMO
Previously, we reported the high prevalence of hepatitis C virus (HCV) infection in patients with oral cancer or oral lichen planus in Kyushu, Japan. We now report a 61-year-old man with chronic hepatitis C and no oral lesions who developed oral cancer 6 months after interferon therapy (interferon alpha [HLBI], 6 million units (MU) daily for 2 weeks and then 3 times a week for 14 weeks). This case emphasizes the need for periodic oral cavity examinations of hepatitis C patients and contributed to the investigation of oral cancer and HCV.
Assuntos
Hepacivirus , Hepatite C/complicações , Neoplasias Bucais/virologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
To determine the incidence of hepatocellular carcinoma among patients with chronic hepatitis C who received interferon (IFN) therapy, 63 patients with chronic hepatitis C who underwent IFN therapy (IFN alpha 2a 9 x 10(6) IU daily for 2 weeks and followed 9 x 10(6) IU three times weekly for 14 weeks) from January to December 1992, were studied. Selection criteria were as follows: within six months before IFN therapy patients were diagnosed with chronic active hepatitis without cirrhosis by hepatic histological examination, and were hepatitis C virus antibody positive. Furthermore, patients had records of follow-up liver function tests (once a month) for more than six months after IFN therapy completion, and of ultrasound scanning (once in three to four months) before and for at least more than six months after the therapy completion. An average period of observation was 2.7 years (0.6 to 3.8 years). Twenty five of 63 patients (39.7%) returned to normal values of serum ALT, whereas 38 of 63 (60.3%) still showed abnormal values at six months after IFN therapy completion. Nine of 63 (14.2%) and 6/63 (9.5%) developed cirrhosis and hepatocellular carcinoma, respectively. All patients who developed cirrhosis and hepatocellular carcinoma were from those (n = 38) that showed abnormal ALT values after therapy completion. The five of six patients that progressed to hepatocellular carcinoma were associated with cirrhosis. No patients who returned to normal ALT values developed hepatocellular carcinoma during the period of observation. These results suggest that IFN therapy is effective to prevent the development of hepatocellular carcinoma.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite Crônica/terapia , Interferon-alfa/uso terapêutico , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Feminino , Hepatite Crônica/complicações , Humanos , Incidência , Interferon alfa-2 , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Proteínas RecombinantesRESUMO
We conducted an epidemiological study to investigate the relation of food intake to Helicobacter pylori (H. pylori) infection in an area endemic for H. pylori. In this study, 365 subjects, 104 men and 261 women, were randomly selected from 7,389 adult (over age 20) inhabitants of town A, Japan. The prevalence of immunoglobulin G (IgG) class antibody to H. pylori (anti-H. pylori) was 83.7% and the prevalence of anti-H. pylori increased with age significantly (P < 0.05). Subjects with anamnesis of gastritis, gastroduodenal ulcer and gastric cancer tended to have a higher anti-H. pylori positive ratio (93.5%) than those without (81.0%). But there was no relationship between anti-H. pylori prevalence and sex, blood type, smoking or drinking habits. Daily intake of foods by food groups, nutrients and the concentrations of serum ingredients were compared between 37 anti-H. pylori-positive and 40 negative subjects selected from 365 inhabitants by matching up according to sex and age. The daily intake of cereals, potatoes and starches, and milks tended to be higher in positive than negative subjects, while the daily intake of algae and tea appeared to be a little higher in negative than in positive subjects. The daily zinc intake of antibody-positive subjects was significantly higher (P < 0.05) than in antibody negative subjects. On the other hand, the daily iron intake in negative subjects was significantly higher (P < 0.05) than in positive subjects. The serum concentrations of copper, zinc, and vitamin E tended to be higher in positive than negative subjects. But there were no significant differences in serum ingredients concentrations between antibody negative and positive subjects. Our findings suggest that iron and zinc intakes may effect on H. pylori infection.
Assuntos
Dieta , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ferro/administração & dosagem , Ferro/sangue , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Fatores Sexuais , Zinco/administração & dosagem , Zinco/sangueRESUMO
We examined the characteristics and usefulness of a third generation anti-HCV test kit, SYNPEP HCV-EIA II (Kyokuto Pharmaceutical Inc., Tokyo, Japan). The sera of inhabitants from a hepatitis C virus (HCV) hyperendemic area were used. The kit had even or more anti-HCV detection sensitivity and reproducibility than ORTHO HCV III ELISA Test System (Ortho-Clinical Diagnostic K.K., Tokyo, Japan) or HCV PHA 2nd Generation (Dinabot Co., Ltd., Tokyo, Japan). SYNPEP HCV-EIA II needed less total reaction time than other EIA kits, resulting in a simple procedure. Also, HCV RNA was detected in 90% of subjects who had a 7.5 or greater cut-off index (COI) of SYNPEP HCV-EIA II kit. In conclusion, SYNPEP HCV-EIA II require cheap cost and simple procedure and it could be applied to mass screening to find out HCV RNA positive persons who may need clinical care.
Assuntos
Anticorpos Antivirais/sangue , Doenças Endêmicas , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Técnicas Imunoenzimáticas , Estudos de Avaliação como Assunto , Hepacivirus/imunologia , Hepatite C/epidemiologia , Humanos , Japão/epidemiologia , Valor Preditivo dos Testes , Kit de Reagentes para DiagnósticoRESUMO
To elucidate the influence of chronic alcohol intake on interferon (IFN) therapy in patients with various diseases, 3 million units of natural IFN (nHuIFN-alpha Ly) was administered once to alcoholics, nonalcoholic chronic hepatitis C (CH-C) patients, and healthy subjects. The serial changes of serum activity of 2'-5' oligoadenylate synthetase, serum levels of beta 2-microglobulin, C-reactive protein (CRP), and body temperature were monitored. The increase in the activity of 2'-5' oligoadenylate synthetase, the response of serum-reactive protein, and body temperature after IFN administration were significantly lower in the alcoholics than those in CH-C group, and healthy subjects (control group). The serum beta 2-microglobulin level was already higher in the alcoholics before IFN administration than those of the control group and the CH-C group. These findings suggest that physiological responses to exogenous IFN in alcoholics are generally decreased. Hence, for the maximum effect of IFN therapy, it is important for patients to abstain from alcohol intake and for doctors to carefully consider the timing of initiation.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Alcoolismo/sangue , Alcoolismo/tratamento farmacológico , Interferons/farmacologia , Interferons/uso terapêutico , 2',5'-Oligoadenilato Sintetase/sangue , Adulto , Consumo de Bebidas Alcoólicas/sangue , Alcoolismo/metabolismo , Temperatura Corporal/efeitos dos fármacos , Proteína C-Reativa/análise , Hepatite C/sangue , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Microglobulina beta-2/análiseRESUMO
We have studied the prevalence, seroconversion rate of anti-hepatitis C virus (HCV), and the transmission of HCV in a cohort of individuals living in a hyperendemic area of HCV in Japan. We investigated 509 subjects, of which 375 could be studied again after 5 years. A remarkable high prevalence of anti-HCV (23.4-24.0%) was observed. Of 287 subjects negative at the first examination in 1990, 4 became positive until the second in 1995 (seroconversion rate: 0.28% per year). Furthermore, we investigated the route of transmission in HCV seroconverted subjects through a detailed interview. All of the HCV seroconverted subjects had past histories of medical treatment. Seroconversion rates of HCV in a hyperendemic area of HCV, were extremely high. Medical treatment was considered to be a causative route of HCV transmission.
Assuntos
Hepatite C/epidemiologia , Adulto , Idoso , Transmissão de Doença Infecciosa , Feminino , Hepatite C/imunologia , Hepatite C/transmissão , Anticorpos Anti-Hepatite C/análise , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos SoroepidemiológicosRESUMO
To determine the incidence of hepatitis C virus (HCV) infection in patients with alcoholic liver disease (ALD), serum samples from 252 patients with ALD were tested for anti-HCV and HCV RNA. Serial sera of these patients were collected and stored under optimal conditions to allow exact quantification of HCV RNA. Fifteen patients who visited our hospital during the same period of time with chronic HCV infections served as controls. In those with ALD, anti-HCV and HCV RNA were positive in 55.5% and 41.2%, respectively. Patients with histologically diagnosed chronic hepatitis and hepatocellular carcinoma had much higher prevalence rates of HCV RNA (84% and 100%, respectively) compared to those with fatty liver (4.3%), hepatic fibrosis (10.1%) and alcoholic hepatitis (22.2%) (P < 0.01). Although no difference in serum HCV RNA levels was observed between the patients with both ALD and chronic HCV infection and those with chronic HCV infection alone, HCV RNA levels significantly (10-fold) dropped after abstinence in nearly half of the patients (P < 0.01). These data indicate that HCV infection in patients with ALD promotes progression of liver disease, and abstinence from alcohol is associated with a reduction in serum HCV RNA levels.