RESUMEN
Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis.
Asunto(s)
Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/diagnóstico , Adulto , Anciano , Estudios Transversales , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Hepatitis C Crónica/patología , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Estudios Prospectivos , Adulto JovenRESUMEN
The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin ≤8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.
Asunto(s)
Anemia/etiología , Hepatitis C Crónica/tratamiento farmacológico , Oligopéptidos/administración & dosificación , Prolina/análogos & derivados , Inhibidores de Proteasas/administración & dosificación , Adulto , Anciano , Antivirales/administración & dosificación , Femenino , Tasa de Filtración Glomerular , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/administración & dosificación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oligopéptidos/efectos adversos , Polietilenglicoles/administración & dosificación , Prolina/administración & dosificación , Prolina/efectos adversos , Estudios Prospectivos , Inhibidores de Proteasas/efectos adversos , Proteínas Recombinantes/administración & dosificación , Ribavirina/administración & dosificación , Factores de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Respuesta Virológica Sostenida , Factores de Tiempo , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Since some authors referred to panhypopituitarism or central hypothyroidism during the treatment of chronic hepatitis C virus (HCV) infection using interferon-α, it is intended to evaluate the prevalence of central hypothyroidism (CH) in HCV patients before and during interferon-α therapy. PATIENTS AND METHODS: We evaluated 308 HCV patients treated with standard interferon-α (IFN) and/or pegylated-interferon-α (PEG-IFN) associated with ribavirin. Free thyroxine (FT4) and thyrotropin (TSH) levels were measured before, during and after treatment. CH was diagnosed when the level of FT4 was lower than normal values with concomitant normal or lower TSH as verified at least in two consecutive measures. RESULTS: Before treatment, 18 (5.8 %) patients presented CH Twelve patients maintained laboratory changes during the treatment and 17 new patients developed central hypothyroidism. Among the 29 patients (9.4 %) with CH, 11 used IFN, six used PEG-IFN and 12 patients used two or more therapeutic schedules. The differences in gender, age, cirrhosis, viral genotype, duration of treatment and the type of interferon used were not statistically significant. The absence of sustained virologic response was associated with central hypothyroidism (OR=3.83). CONCLUSION: HCV patients may develop CH due to viral infection or during the interferon treatment. These patients presented 3.83 times more chance of not obtaining sustained virologic response.
Asunto(s)
Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hipotiroidismo/etiología , Interferón-alfa/administración & dosificación , Adulto , Distribución de Chi-Cuadrado , Femenino , Hepacivirus , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/inducido químicamente , Hipotiroidismo/virología , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tirotropina/sangre , Tiroxina/sangreRESUMEN
Previous reports suggest cryoglobulinemia might influence the hepatitis C virus (HCV) infection clinical course and treatment response but this association has not been thoroughly evaluated. We aimed to assess the relationship between cryoglobulinemia and sustained viral response (SVR) in patients treated for HCV infection. We included patients with HCV infection treated from January 2003 through December 2006. Biochemical analyses, detection cryoglobulinemia, and liver biopsies were performed prior to treatment. Genotype 1 or 4 infections received Peg-interferon (IFN) alpha-2a or -2b for 48 weeks; genotypes 2 or 3 received IFN alpha for 24 weeks. All patients also received ribavirin. Of 329 enrolled patients, 242 (73%) were male and the median age was 43 years. Cryoglobulinemia was detected in 196 (59.6%) patients; liver biopsy was performed in 301. Multivariate analysis showed an association of cryoglobulinemia with severe active necroinflammation (A3) (adjusted odds ratio [AOR] = 9.48; 95% confidence interval [CI]: 1.50-59.92) and rheumatoid factor (RF) level (AOR = 1.01; 95% CI: 1.00-1.02). Variables associated with advanced fibrosis were age, aspartate aminotransferase and alkaline phosphatase levels, alcohol use, and presence of diabetes. Variables independently associated with SVR were cryoglobulinemia (AOR = 2.33, 95% CI: 1.26-4.32), absence of cirrhosis (AOR = 4.5, 95% CI: 1.4-14.80), and RF level (AOR = 1.008, 95% CI: 1.001-1.014). Our findings suggest cryoglobulinemia is associated with severe necroinflammatory activity in HCV-infected patients. We also provide the first evidence for an association between cryoglobulinemia and higher SVR rates, highlighting its potential role as a prognostic factor for treatment response.
Asunto(s)
Antivirales/administración & dosificación , Crioglobulinemia/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Carga Viral , Adulto , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Hígado/patología , Masculino , Persona de Mediana Edad , Necrosis/patología , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes , Ribavirina/administración & dosificación , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55% of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1%) and HLA-DQB1*02 (52.9 vs 38.7%) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0%) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1%) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.
Asunto(s)
Antivirales/uso terapéutico , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Hepatitis C Crónica/genética , Interferón-alfa/uso terapéutico , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/inmunología , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa/métodos , Adulto JovenRESUMEN
Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.
Asunto(s)
Crioglobulinemia/etiología , Hepatitis C/complicaciones , Polineuropatías/etiología , Antivirales/uso terapéutico , Electromiografía , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/tratamiento farmacológico , Humanos , Técnicas para Inmunoenzimas , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Polineuropatías/patología , Ribavirina/uso terapéuticoRESUMEN
Hepatitis C virus (HCV) infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62%) and white patients (80%). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64%) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77 kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.
Asunto(s)
Pesos y Medidas Corporales , Hepacivirus/genética , Hepatitis C Crónica/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Screening blood donations for anti-HCV antibodies and alanine aminotransferase (ALT) serum levels generally prevents the transmission of hepatitis C virus (HCV) by transfusion. The aim of the present study was to evaluate the efficiency of the enzyme immunoassay (EIA) screening policy in identifying potentially infectious blood donors capable to transmit hepatitis C through blood transfusion. We have used a reverse transcriptase (RT)-nested polymerase chain reaction (PCR) to investigate the presence of HCV-RNA in blood donors. The prevalence of HCV-RNA positive individuals was compared with the recombinant immunoblot assay (RIBA-2) results in order to assess the usefulness of both tests as confirmatory assays. Both tests results were also compared with the EIA-2 OD/C ratio (optical densities of the samples divided by the cut off value). ALT results were expressed as the ALT quotient (qALT), calculated dividing the ALT value of the samples by the maximum normal value (53UI/l) for the method. Donors (n=178) were divided into five groups according to their EIA anti-HCV status and qALT: group A (EIA> or = 3, ALT<1), group B (EIA> or = 3, ALT>1), grou (1< or = EIA< 3, ALT<1), group D (1< or = EIA<3, ALT>1) and group E (EIA< or = 0.7). HCV sequences were detected by RT-nested PCR, using primers for the most conserved region of viral genome. RIBA-2 was applied to the same samples. In group A (n=6), all samples were positive by RT-nested PCR and RIBA-2. Among 124 samples in group B, 120 (96.8%) were RIBA-2 positive and 4 (3.2%) were RIBA-2 indeterminate but were seropositive for antigen c22.3. In group B, 109 (87.9%) of the RIBA-2 positive samples were also RT-nested PCR positive, as well as were all RIBA-2 indeterminate samples. In group C, all samples (n=9) were RT-nested PCR negative: 4 (44.4%) were also RIBA-2 negative, 4 (44.4%) were RIBA-2 positive and 1 (11.1%) was RIBA-2 indeterminate. HCV-RNA was detected by RT-nested PCR in 3 (37.5%) out of 8 samples in group D. Only one of them was also RIBA-2 positive, all the others were RIBA-2 indeterminate. All of the group E samples (controls) were RT- nested PCR and RIBA-2 negative. Our study suggests a strong relation between anti-HCV EIA-2 ratio > or = 3 and detectable HCV-RNA by RT-nested PCR. We have also noted that blood donors with RIBA-2 indeterminate presented a high degree of detectable HCV-RNA using RT-nested PCR (75%), especially when the c22.3 band was detected.
Asunto(s)
Donantes de Sangre , Hepatitis C/diagnóstico , Immunoblotting , Técnicas para Inmunoenzimas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alanina Transaminasa/sangre , Distribución de Chi-Cuadrado , Hepacivirus/inmunología , Hepatitis C/sangre , Humanos , Prevalencia , ARN Viral/análisis , Proteínas RecombinantesRESUMEN
Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%). Blood transfusion was the second factor for HCV transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%). In 83. 5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89%) with mild or moderate grade in most of the cases (99.5%). The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50% of the histopathological exams of the anti-HCV EIA-2 reagent donors which were indeterminate RIBA-2. Among 18 blood donors with minimal changes histopathological exam 11 (61%) were HCV-RNA positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial and histopathological features observed in patients with chronic HCV hepatitis and a high proportion could be identified in interviews and medical evaluation realized in blood blanks. Generally, these HCV infected donors are identified and discharged only by the serological tests results.
Asunto(s)
Donantes de Sangre , Anticuerpos contra la Hepatitis C/aislamiento & purificación , Hepatitis C Crónica/diagnóstico , Adolescente , Adulto , Femenino , Hepatitis C Crónica/sangre , Hepatitis C Crónica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Factores de RiesgoRESUMEN
A case of a pregnant patient with chronic hepatitis C who gave birth to monozygotic twins that were infected with HCV is reported. One of the newborns was positive for HCV-RNA in blood sample collected 12 hours after delivery. The other newborn was negative for HCV-RNA at birth, but was detected HCV viremia at three months of age. The results have led to the conclusion that one of the twins was probably contaminated in the intrauterine period, while the other acquired the infection in the perinatal period. Both were negative for HCV-RNA and for anti-HCV in the serum samples collected at nine months of age. The report describes the changes in the laboratory tests conducted in mother and twins until 29 months after delivery.
Asunto(s)
Enfermedades en Gemelos , Hepatitis C Crónica/virología , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/virología , Adulto , Femenino , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Anticuerpos contra la Hepatitis C/sangre , Humanos , Lactante , Recién Nacido , Embarazo , Gemelos MonocigóticosRESUMEN
The prevalence of GB virus C (GBV-C) in candidate Brazilian blood donors with normal and elevated alanine aminotransferase levels was found to be 5.2% (5 of 95) and 6.5% (5 of 76), respectively. Among Brazilian patients, GBV-C was found in 9.5% (13 of 137) of cases of hepatitis not caused by hepatitis A virus (HAV), HBV, HCV, HDV, or HEV (non-A-E hepatitis) and in 18.2% (8 of 44) of individuals infected with HCV. Molecular characterization of GBV-C by partial sequencing of the NS3 region showed clustering between members of a single family, implying intrafamilial transmission. In conclusion, these results together suggest that contagion mechanisms which facilitate intrafamilial transmission of GBV-C may partially explain the high prevalence of viremic carriers worldwide.