RESUMEN
Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Anciano , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Hepacivirus/clasificación , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Proteínas Recombinantes , Ribavirina/uso terapéutico , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
The authors investigated the dose-effect relation between alcohol drinking and hepatocellular carcinoma (HCC) in men and women separately, also considering hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380 men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected by hepatic diseases as controls; all were hospitalized in Brescia, northern Italy, in 1995-2000. Spline regression models showed a steady linear increase in the odds ratio of HCC for increasing alcohol intake, for values of >60 g of ethanol per day, with no substantial differences between men and women. Duration of drinking and age at start had no effect on the odds ratio when alcohol intake was considered. Former drinkers who had stopped 1-10 years previously had a higher risk of HCC than current drinkers did. The effect of alcohol drinking was evident even in the absence of hepatitis B or hepatitis C virus infection. In addition, a synergism between alcohol drinking and either infection was found, with approximately a twofold increase in the odds ratio for each hepatitis virus infection for drinkers of >60 g per day.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/virología , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/virología , Adulto , Edad de Inicio , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores SexualesRESUMEN
The objective of our study was to evaluate the association between occupation and risk of liver cancer. A hospital-based case-control study was carried out during 1997-1999 in the Province of Brescia, a highly industrialized area in Northern Italy with a high incidence of this neoplasm. The cases were 144 male patients with incident liver cancer (96% hepatocellular carcinoma). Controls were 283 male patients, matched to cases on age (+/-5 years), period and hospital of admission. Information on lifetime occupational history and alcohol consumption was obtained via interview. Specific occupational exposures to pesticides, solvents and other suspected hepatocarcinogens were evaluated. A blood sample was collected to detect hepatitis B and C infections. Odds ratios (OR) of occupational exposure and 95% confidence intervals (CI), adjusted for age, residence, education, heavy alcohol intake, hepatitis B surface antigen and hepatitis C virus antibodies positivity were computed. A statistically significant increased OR was observed for employment in repair of motor vehicles (OR 3.7; 95% CI 1.1-12.3; 9 exposed cases, 10 exposed controls). Increased ORs, although not statistically significant, were found for field-crop farm workers, food and beverage processors, blacksmiths and machine-tool operators, electrical fitters, clerical workers, manufacture of industrial machinery and personal and household services. A slightly increased OR was noted in workers exposed to toluene and xylene (OR 1.4; 95% CI 0.7-3.0, 23 cases, 36 controls); the OR was 2.8 (95% CI 1.0-7.6, 11 cases, 12 controls) for 20 or more years of exposure and 2.0 (95% CI 0.9-4.1, 21 cases, 28 controls) for 30 or more years of time since first exposure. The increase in OR seemed to be independent from that of alcohol or viral infections. Our study showed that the role of occupational exposures in liver carcinogenesis is limited. However, prolonged exposure to organic solvents such as toluene and xylene may represent a risk factor for liver cancer.
Asunto(s)
Neoplasias Hepáticas/etiología , Exposición Profesional/efectos adversos , Adulto , Anciano , Estudios de Casos y Controles , Humanos , Incidencia , Italia/epidemiología , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The aim of this study was to evaluate the distribution and clinical significance of hepatitis C virus (HCV) genotypes in European patients with compensated cirrhosis due to hepatitis C (Child class A) seen at tertiary referral centres. HCV genotypes were determined by genotype-specific primer PCR in 255 stored serum samples obtained from cirrhotics followed for a median period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, absence of complications of cirrhosis and exclusion of all other potential causes of chronic liver disease. The proportion of patients with types 1b, 2, 3a, 1a, 4 and 5 were 69%, 19%, 6%, 5%, 0.5% and 0.5%, respectively. Kaplan-Meier 5-year risk of hepatocellular carcinoma (HCC) was 6% and 4% for patients infected by type 1b and non-1b, respectively (P=0.8); the corresponding figures for decompensation were 18% and 7% (P=0.0009) and for event-free survival were 79% and 89% (P=0.09), respectively. After adjustment for baseline clinical and serological features, HCV type 1b did not increase the risk for HCC [adjusted relative risk=1.0 (95% confidence interval=0.47-2.34)], whereas it increased the risk for decompensation by a factor of 3 (1.2-7.4) and decreased event-free survival by a factor of 1.7 (0.9-3.10). In conclusion, type 1b and, to a lesser extent, type 2, are the most common HCV genotypes in European patients with cirrhosis. HCV type 1b is not associated with a greater risk for HCC, but increases the risk for decompensation by threefold in patients with cirrhosis.
Asunto(s)
Hepacivirus/genética , Hepatitis C/epidemiología , Cirrosis Hepática/virología , Adulto , Factores de Edad , Anciano , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , Supervivencia sin Enfermedad , Europa (Continente)/epidemiología , Femenino , Hepacivirus/química , Hepacivirus/clasificación , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , ARN Viral/genética , Factores Sexuales , Estadísticas no Paramétricas , Reacción a la Transfusión , Resultado del TratamientoAsunto(s)
Antivirales/uso terapéutico , Hepatitis C/prevención & control , Interferón-alfa/uso terapéutico , Trasplante de Hígado , Complicaciones Posoperatorias/prevención & control , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/virología , Proteínas Recombinantes , Prevención SecundariaRESUMEN
OBJECTIVE: Intrahepatic cholangiocarcinoma (ICC) is a rare type of primary liver cancer (PLC) arising from intrahepatic bile ducts. We carried out a case-control study to assess the association between ICC and hepatitis B and C virus (HBV and HCV) infections, alcohol intake, and hepatolithiasis in Brescia, North Italy. METHODS: Among 370 subjects with histology-based diagnosis of PLC who were resident in the area and hospitalized in 1995-2000, 26 (7%) ICC cases were identified. A total of 824 subjects unaffected by hepatic diseases and frequency-matched with PLC cases by age, sex, date, and hospital of admission were recruited as controls. RESULTS: Among ICC cases the mean age was 65 years, 80.8% were males, and 38.5% had cirrhosis. Seropositivity for anti-HCV, HBsAg, alcohol intake >80 g/day and history of hepatolithiasis were found in 25%, 13%, 23.1%, and 26.9% of ICC cases and in 5.8%, 6.7%, 32.9%, and 10.6% of controls, respectively. The odds ratios adjusted for demographic factors by logistic regression (95% confidence interval; 95% CI) were 9.7 (1.6-58.9) for anti-HCV, 2.7 (0.4-18.4) for HBsAg, and 6.7 (1.3-33.4) for hepatolithiasis, whereas no association was found with alcohol drinking. CONCLUSIONS: HCV and hepatolithiasis may be risk factors for ICC in Western countries.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Neoplasias de los Conductos Biliares/etiología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/etiología , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Litiasis/complicaciones , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Italia/epidemiología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
The IgMk rheumatoid factors (RF) of type II mixed cryoglobulinaemia (MC) react, in 95% of cases, with MoAbs against the cross-reactive idiotypes (CRI) Cc1 or Lc1 (corresponding to the products of the VH1 and VH4 genes). MC is closely associated with HCV infection, a virus which infects lymphocytes and may replicate in B cells. It has been suggested that HCV may induce clonal selection of B cells producing monoclonal IgMk RF in type II MC. To verify whether HCV is enriched in B cells, and in the subsets expressing Cc1 and Lc1 CRI, we studied peripheral blood lymphocytes from eight patients with MC and HCV RNA-positive sera. Seven patients had RF reacting with anti-Cc1, the other with anti-Lc1 CRI. Total lymphocytes, T cells, B cells, and Cc1+ or Lc1+, Cc1- or Lc1- B cells were purified using MoAb-coated magnetic beads. Lymphocyte subsets were then diluted to give a range of 1 x 106-1 x 103 cells and tested for HCV RNA by reverse transcriptase-polymerase chain reaction. HCV was found exclusively in B cells in seven out of eight patients. In three patients HCV was enriched in the Cc1+ cells. In one of these patients, HCV was found exclusively in Cc1+ cells, with Cc1- cells being HCV-. The data indicate that B cells from type II MC patients are almost constantly infected by HCV. In selected cases, B cell subsets expressing IgMk RF CRI are the prevalent cell type infected by HCV. Our data suggest HCV involvement in B cell dysregulation leading to cryoprecipitable IgMk RF production.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Linfocitos B/virología , Crioglobulinemia/virología , Hepacivirus/aislamiento & purificación , Subgrupos Linfocitarios/virología , Factor Reumatoide/inmunología , Adulto , Anciano , Autoantígenos/análisis , Linfocitos B/inmunología , Reacciones Cruzadas , Crioglobulinemia/inmunología , Crioglobulinas/análisis , Femenino , Hepacivirus/genética , Hepacivirus/inmunología , Humanos , Inmunoglobulina M/inmunología , Inmunoglobulinas/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/virología , Subgrupos Linfocitarios/inmunología , Masculino , Persona de Mediana Edad , ARN Viral/análisis , Linfocitos T/inmunología , Linfocitos T/virologíaRESUMEN
We performed a case-control study to assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV), GB virus C/hepatitis G virus (HGV), TT virus, alcohol intake, and tobacco smoking as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis. We prospectively recruited 174 patients with a first diagnosis of HCC admitted to the main hospitals in Brescia, North Italy. On the basis of histological, clinical, and radiological criteria, the presence of cirrhosis was established in 142 cases, excluded in 21 cases, and remained undefined in 11 cases. Among the HCC cases without cirrhosis, a histological picture of normal liver was found in a single patient, chronic viral hepatitis was found in 11 patients, alcoholic hepatitis was found in 5 patients, nonspecific reactive hepatitis was found in 3 patients, and hemochromatosis was found in 1 patient. As controls, we also included 610 subjects unaffected by hepatic diseases and admitted to the same hospitals as cases. The odds ratios for having HCC according to positivity for HCV RNA, HBsAg and/or HBV DNA, and alcohol intake > 80 g/day (95% confidence interval) were as follows, in the presence and absence of cirrhosis, respectively: (a) 33.5 (17.7-63.4) and 19.7 (6-64.8) for HCV RNA; (b) 17.6 (9.0-34.4) and 20.3 (5.7-72.6) for HBsAg; and (c) 5.5 (3.1-9.7) and 4.6 (1.5-13.8) for alcohol intake. No association was found with HGV or TT virus infections or tobacco. This study has shown that most HCC cases arising in the area are due to HBV, HCV, or alcohol intake, in both the presence and absence of cirrhosis.
Asunto(s)
Carcinoma Hepatocelular/etiología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/etiología , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma Hepatocelular/epidemiología , Estudios de Casos y Controles , Femenino , Flaviviridae/patogenicidad , Hepacivirus/patogenicidad , Hepatitis B/complicaciones , Virus de la Hepatitis B/patogenicidad , Hepatitis C/complicaciones , Humanos , Italia/epidemiología , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Fumar/efectos adversosRESUMEN
The relationship between clinical features and specific alterations of heme metabolism allows the accurate diagnosis and classification of porphyrias. The acute porphyric attack is characterized by frequently confusing clinical pattern of abdominal-psiquic- and neurological symptoms. An increased urinary excretion of porphobilinogen, which can be quickly detected by the Hoesch test, confirms the diagnosis of this acute attack. Increased plasma porphyrin levels are associated with skin lesions, which are the characteristic features of the cutaneous porphyrias. Their presence is easily and rapidly detected by a fluorimetric scanning of PBS (phosphate buffer saline) diluted samples. Characterization of the molecular defects in genes coding for the enzymes involved in the heme synthetic pathway is complementary to the biochemical methods. Molecular analysis permits an accurate classification of those biochemically unclassified patients and allows prenatal diagnosis in those homozygotic cases where a severe prognosis is suspected.
Asunto(s)
Porfirias/diagnóstico , Algoritmos , Humanos , Porfirias/clasificaciónRESUMEN
OBJECTIVES: We carried out a case-control study to investigate the role of history of liver cancer in a first-degree relative as a risk factor for hepatocellular carcinoma (HCC). METHODS: Two hundred eighty-seven HCC incident cases and 450 subjects unaffected by liver disease (controls) were enrolled in the study. Family history of liver cancer and other malignancies and history of alcohol intake were collected by face-to-face interview. Blood samples were analyzed for HBsAg, anti-HCV and HCV RNA positivity. RESULTS: Family history of liver cancer was associated with HCC (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.2-4.7), whereas family history of other malignancies was not (OR = 1.0; 95% CI = 0.61.5). An increased OR for family history of liver cancer was found among subjects negative for the other risk factors (OR = 2.0; 95% CI = 0.6-6.9). A synergism of family history of liver cancer was also evident with hepatitis B and hepatitis C virus infection and with heavy alcohol intake. CONCLUSIONS: This study suggests a role of family history independent from and interacting with known risk factors for hepatocellular carcinoma.
Asunto(s)
Carcinoma Hepatocelular/genética , Predisposición Genética a la Enfermedad , Neoplasias Hepáticas/genética , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma Hepatocelular/etiología , Estudios de Casos y Controles , Salud de la Familia , Femenino , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Humanos , Italia/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
We performed a case-control study to evaluate the association of a new human DNA virus named TT virus (TTV) with hepatocellular carcinoma (HCC). We recruited 174 subjects hospitalized for HCC (84% males; mean age: 64 years) and 118 patients hospitalized for non-liver diseases in Brescia, northern Italy, as controls (94% males; mean age: 66 years). TTV DNA was found in serum by polymerase chain reaction (PCR) in 26 cases (15%) and 11 controls (9.3%) (P >. 1). TTV group 2 infection was identified in 16 cases (61.5%) and 4 controls (36.4%) (P >.1) using a type-specific PCR method. Sequence analysis of 222 nt of TTV DNA demonstrated that the remaining 10 cases and 7 controls were all infected by group 1. The odds ratio (OR) for TTV-DNA positivity, adjusted for demographic variables, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, and heavy alcohol intake was 1.8 (95% CI: 0.7-4.8; P >.1). The OR did not change when the analysis was restricted to 14 HCC cases and 56 controls who were negative for each known risk factor for HCC (OR = 1.7; 95% CI: 0.8-4.0). TTV-DNA positivity was not associated with transfusion history. The prevalence of TTV DNA was higher among HCC cases positive for HBsAg (10 of 38 [26.3%]) than among those positive for HCV RNA (8 of 62 [12.9%]) or negative for hepatitis B virus (HBV), HCV, and hepatitis G virus (HGV) infections (5 of 62 [8. 1%]) (P =.02). This study does not support the hypothesis of an association between TTV infection and HCC.
Asunto(s)
Carcinoma Hepatocelular/virología , Infecciones por Virus ADN/complicaciones , Virus ADN/genética , ADN Viral/sangre , Neoplasias Hepáticas/virología , Adulto , Anciano , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Secuencia de Bases , Carcinoma Hepatocelular/epidemiología , Estudios de Casos y Controles , Cartilla de ADN , Infecciones por Virus ADN/epidemiología , Virus ADN/clasificación , Virus ADN/aislamiento & purificación , ADN Viral/genética , Evolución Molecular , Femenino , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/epidemiología , Humanos , Italia/epidemiología , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Factores de RiesgoRESUMEN
We performed a case-control study to evaluate the risk of hepatocellular carcinoma (HCC) for hepatitis C virus (HCV) infection. A total of 305 newly diagnosed HCC cases (80% males) and 610 subjects (81% males) unaffected by clinically evident hepatic disease admitted to the 2 main hospitals in Brescia, North Italy, were recruited as cases and controls, respectively. Among the 122 HCC cases positive for HCV RNA, genotype 1b was found in 83 patients (68%), genotype 2 in 36 (29.5%) and genotype 1a in 3 (2.5%). Among the controls, 15 were infected with genotype 1b and 15 with type 2. Analysis of HCV envelope 1 nucleotide sequence among 25 cases and 8 controls infected with genotype 2 showed subtype 2c in 96% of cases and in all controls, and subtype 2a in 1 HCC case. The odds ratio (OR) for HCV RNA positivity adjusted for hepatitis B virus (HBV) markers and alcohol intake was 26.3 [95% confidence interval (CI): 15.8-44], and it was higher for genotype 1b (OR = 34.2) than type 2 (OR = 14.4). The OR for HCV RNA was 35.6 (95% CI: 14.5-87.1) when the HBV markers were all negative and 132 (15.3-890) when HBsAg positivity was present; the OR was 26.1 (95% CI: 12.6-54.0) among subjects with alcohol intake of 0-40 g/day and increased to 62.6 (23.3-168) and 126 (42.8-373) with an alcohol intake of 41-80 and >80 g/day, respectively. In conclusion, synergism was found between HCV infection and HBV infection and alcohol intake in causing HCC.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma Hepatocelular/etiología , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/complicaciones , Neoplasias Hepáticas/etiología , Adulto , Factores de Edad , Anciano , Anticuerpos Antivirales/sangre , Antígenos Virales/sangre , Carcinoma Hepatocelular/epidemiología , Estudios de Casos y Controles , Femenino , Genotipo , Hepacivirus/genética , Hepatitis B/sangre , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Hepatitis C/sangre , Hepatitis C/epidemiología , Humanos , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , ARN Viral/sangre , Factores de Riesgo , Estudios Seroepidemiológicos , SexoRESUMEN
OBJECTIVE: To assess the role of hepatitis G virus (HGV) in cryptogenic chronic liver disease (CLD), we investigated the prevalence of HGV RNA among patients with cryptogenic CLD, patients with nonviral CLD (primary biliary cirrhosis [PBC] and Wilson's disease [WD]) and subjects without clinically evident liver disease (controls). METHODS: Ninety patients with cryptogenic CLD (43 with chronic hepatitis, 20 with cirrhosis, and 27 with hepatocellular carcinoma [HCC]), 143 patients with PBC, 22 patients with WD, and 134 controls were recruited. HGV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) and antibodies against HGV E2 protein (anti-E2) by an immunoassay test. RESULTS: HGV RNA was detected in 7.8% of patients with cryptogenic CLD (chronic hepatitis, 9.3%; cirrhosis, 5.0%; HCC, 7.4%), in 2.4% of patients with PBC or WD, and in 2.2% of controls. As a consequence, a positive association of HGV infection with cryptogenic CLD was found (odds ratio, 3.1; 95% confidence interval [CI], 1.0-9.7; p = 0.05). No difference was observed between HGV RNA-positive and -negative patients by age, sex, histology, or liver function tests. Anti-E2 prevalence did not differ between patients with cryptogenic CLD (26.5%), patients with PBC (28.1%), and controls (22.1%). Transfusion history was associated with HGV RNA but not with anti-E2 seropositivity. CONCLUSIONS: Although an association was found between cryptogenic CLD and HGV infection, the role of the virus seems far from important, the proportion of cryptogenic CLD attributable to it being only 5.2%.
Asunto(s)
Flaviviridae/aislamiento & purificación , Hepatitis Viral Humana/epidemiología , Degeneración Hepatolenticular/virología , Cirrosis Hepática Biliar/virología , Hepatopatías/virología , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Estudios de Casos y Controles , Enfermedad Crónica , Ensayo de Inmunoadsorción Enzimática , Femenino , Flaviviridae/genética , Hepatitis Viral Humana/virología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , ARN Viral/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
AIMS/BACKGROUND: The clinical significance of GB virus-C/hepatitis G virus (GBV-C/HGV) infection in chronic hepatitis B is not well known and its role in the outcome of liver disease was investigated. METHODS: HGV-RNA and antibody to HGV (anti-E2) were studied in 125 patients with chronic hepatitis B (41 with multiple hepatitis virus exposure), 82 asymptomatic HBsAg carriers and 103 healthy adults. RESULTS: In chronic hepatitis B, HGV-RNA was more frequent in patients with HDV infection and/or anti-HCV positivity than in those without (29% vs 6%, p<0.0001), mainly in drug addicts (38%). At diagnosis the overall prevalence of any marker (HGV-RNA plus anti-E2) was similar in chronic hepatitis due to HBV alone (17%), in HBsAg carriers (16%) and in healthy adults (17%) and increased to 58% in those exposed to HDV and/or HCV. During 1-11 years of follow-up, HGV infection persisted in 70% of patients with chronic hepatitis B. About 400% of HGV persistently coinfected patients underwent sustained biochemical remission, whereas continuing disease activity was observed in 80% of patients who cleared HGV-RNA. CONCLUSIONS: In chronic HBV infection the rate of exposure to HGV is similar to that in healthy adults, except for high risk patients. Long lasting HGV coinfection or anti-E2 seroconversion did not modify the course of chronic hepatitis B.
Asunto(s)
Flaviviridae , Virus de la Hepatitis B , Hepatitis B Crónica/fisiopatología , Hepatitis Viral Humana/fisiopatología , Adulto , Anciano , Cartilla de ADN/química , Femenino , Flaviviridae/genética , Flaviviridae/inmunología , Flaviviridae/aislamiento & purificación , Estudios de Seguimiento , Anticuerpos Antihepatitis/análisis , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/virología , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/aislamiento & purificación , Hepatitis Viral Humana/virología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , ARN Viral/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas del Envoltorio Viral/análisisRESUMEN
Whether sustained biochemical response and absence of serum HCV RNA in the 6-12 months following suspension of interferon-alpha (IFN-alpha) therapy reflect definitive viral clearance in patients with chronic hepatitis C virus (HCV) infection is controversial. To obtain more information on this topic, HCV RNA was sought in both liver and serum samples of 25 long-term responders who were followed for a median period of 39 months (range 21-79) after discontinuation of IFN-alpha. Liver biopsy was undertaken before and 6 to 12 months after IFN-alpha withdrawal. Liver and serum HCV RNA were tested by a nested polymerase chain reaction. Twenty-two patients (88%) tested negative for both liver and serum HCV RNA, two patients had detectable HCV RNA in both liver and serum, and one patient showed persistent HCV RNA only in the liver. Post-treatment liver histology improved markedly in all patients, including those with viral persistence. During further follow-up, biochemical remission was maintained in all patients except one in whom both serum and liver specimens remained HCV RNA positive. The data indicate that the large majority of long-term responders test negative for HCV RNA in the liver, which suggests definitive eradication of HCV RNA infection.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Interferón-alfa/uso terapéutico , Hígado/virología , ARN Viral/análisis , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Femenino , Estudios de Seguimiento , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/sangre , Hepatitis C Crónica/patología , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Infection with the hepatitis G virus (HGV), as indicated by the presence of HGV ribonucleic acid, was sought in 57 children with chronic hepatitis C virus infection. HGV infection was found in 2 children (3.5%), or 14% of the babies whose mothers were former drug abusers. Maternal drug abuse is an important risk factor for hepatitis G and C virus coinfection in children in our area.
Asunto(s)
Flaviviridae , Hepatitis C/complicaciones , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/virología , Adolescente , Niño , Preescolar , Enfermedad Crónica , ADN Viral , Femenino , Flaviviridae/genética , Genotipo , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis Viral Humana/diagnóstico , Humanos , Lactante , Masculino , ARN Viral , Factores de RiesgoRESUMEN
A new hepatitis-associated RNA virus of the Flaviviridae family has been identified and named GB virus C/ hepatitis G virus (HGV). We carried out a case-control study to evaluate the association of HGV infection with hepatocellular carcinoma (HCC). We recruited 170 patients hospitalized for HCC (143 male and 27 female, mean age 64 years) and 306 patients hospitalized for nonliver diseases (controls) in Brescia, Italy. HGV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) and antibodies against HGV E2 protein (anti-E2) by an immunoassay test. HGV RNA was found in 8 cases (4.7%) and 4 controls (1.3%). The relative risk (RR) for HGV RNA positivity adjusted for demographic variables and hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, and alcohol was 7.3 (95% confidence interval, 1.7-30.6; P = .009). No HGV RNA-positive subject was also positive for anti-E2. Anti-E2 prevalence did not differ significantly between cases (20%) and controls (15.3%), and no RR increase was found by this marker. Among subjects with HGV exposure (HGV RNA plus anti-E2 positive), a greater proportion of cases (40%) than controls (14%) had transfusion history. The possible role of HGV in HCC etiology seems modest because the population-attributable risk is lower (4%) than those for HBsAg (22%), HCV RNA (36%), and heavy alcohol intake (52%). This study supports the hypothesis of an association between HGV infection and HCC, although at present there are insufficient data on the causality of the association.
Asunto(s)
Carcinoma Hepatocelular/complicaciones , Flaviviridae/aislamiento & purificación , Hepatitis Viral Humana/complicaciones , Neoplasias Hepáticas/complicaciones , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma Hepatocelular/inmunología , Estudios de Casos y Controles , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Anticuerpos Antihepatitis/análisis , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis Viral Humana/inmunología , Humanos , Neoplasias Hepáticas/inmunología , Masculino , Persona de Mediana Edad , ARN Viral/análisis , Factores de Riesgo , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
We performed a case-control study to assess the association of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol drinking. We recruited as cases 172 subjects with an initial diagnosis of HCC, who were admitted to the two major hospitals in the province of Brescia, northern Italy, and 332 subjects, sex-, age-, and hospital-matched, who were admitted to the Departments of Ophthalmology, Dermatology, Urology, Cardiology, and Internal Medicine, as controls. Of the HCC cases, 23.8% were positive for HBsAg and 37.8% for HCV RNA; among the controls, 5.4% were positive for HBsAg and 4.8% for HCV RNA. History of heavy alcohol intake (>80 g of ethanol per day for at least 5 years) was found among 58.1% of the cases and among 36.4% of the controls. The relative risks (RRs) for HBsAg, HCV RNA positivity, and heavy alcohol intake were, respectively: 11.4 (95% confidence interval: 5.7-22.8), 23.2 (95% confidence interval: 11.8-45.7), and 4.6 (95% confidence interval: 2.7-7.8). Positive interactions (synergisms) between both HBsAg positivity and HCV RNA positivity and heavy alcohol intake were found, suggesting more than additive effects of viral infections and alcohol drinking on the risk of HCC. Infection with HCV genotype 1b showed a higher risk than type 2 (RR = 2.9; 95% confidence interval: 0.9-10), suggesting a major role for the former type in causing HCC. On the basis of population attributable risks (AR), heavy alcohol intake seems to be the single most relevant cause of HCC in this area (AR: 45%), followed by HCV (AR: 36%), and HBV (AR: 22%) infection.
Asunto(s)
Consumo de Bebidas Alcohólicas , Carcinoma Hepatocelular/epidemiología , Hepacivirus/genética , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Neoplasias Hepáticas/epidemiología , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Femenino , Genotipo , Hepacivirus/aislamiento & purificación , Hepatitis C/diagnóstico , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Población Rural , Factores Sexuales , Población UrbanaRESUMEN
The prevalence of antibodies for one or more HCV antigens was 2.3% of 1,347 mothers at childbirth. Compared with the principal factors studied, the presence of antibodies was more frequent in women who were carriers of HIV infection (3/3), in those who had suffered liver diseases (5/37) or who had had transfusion (3/25). This was as opposed to women who did not have any risk factor (p < 0.001). The prevalence of HCV-RNA was 1.3%; in relation to the antibody state, such a condition was more frequent in subjects with antibodies for 3 or 4 antigens (about 80%) compared with those who were positive for 1 or 2 antigens. HCV-RNA of the same genotype as the mother (type 1; 1a) was also found in the funicular blood of 2 of the 18 babies born to mothers who were positive for HCV-RNA. In the course of the follow-up (from the 3rd to the 18th month) the viral RNA was not found in any of the babies, nor was it found in the 2 who were positive at birth. Even the antibodies gradually disappeared, although slowly. At the 10th month, 91% of the babies resulted as having no antibodies and at the 18th month none of the babies resulted as having antibodies. Breast-feeding also appeared to have no influence on the transmission of the infection; out of 18 viremic mothers indeed 12 (67%) breast-fed their babies.