RESUMO
AIM: To determine the feasibility of magnetic resonance imaging T2 mapping in the quantification of liver steatosis in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and to assess the effect of inflammation and fibrosis on T2 values of the liver. MATERIAL AND METHODS: Twenty-three consecutive patients with biopsy-proven NAFLD who underwent T2 mapping between December 2013 and September 2014 were included in this study. All patients underwent fast spin echo multi-echo sequence with eight echoes for T2 measurements. RESULTS: The mean liver T2 value and percentage of histological steatosis was 64.9 ± 7.4 ms and 46.5 ± 27.6%, respectively. There was a good correlation between the liver T2 value and histology-determined steatosis (r = 0.780, p<0.001) and grade of steatosis (rs = 0.779, p<0.001). The mean T2 value in patients with definitive non-alcoholic steatohepatitis (NASH) was significantly higher in comparison with patients without NASH (69 ± 7.37 versus 61.73 ± 5.99 ms, p=0.016). The correlation between T2 value and NAFLD activity score (NAS) was significant (rs = 0.443, p=0.034); however, the correlation disappeared after adjustment for hepatic steatosis and fibrosis (r=0.131, p=0.572). There was a close inverse correlation between T2 value and fibrosis stage after adjusting for hepatic steatosis (r=-0.536, p=0.012). CONCLUSION: T2 mapping can be used for quantification of hepatic steatosis, as there is a close correlation between T2 relaxation values and histology-determined steatosis. Patients with definite NASH have increased T2 values and there is an inverse correlation between the T2 value and fibrosis stage of the liver. T2 mapping in NAFLD may be a useful clinical tool for disease assessment and prognostication.
Assuntos
Fígado Gorduroso/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Fígado Gorduroso/complicações , Estudos de Viabilidade , Feminino , Fibrose , Humanos , Inflamação/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Chronic hepatitis D is caused by coinfection of hepatitis B and hepatitis D virus. While HDV is the dominant virus over HBV in the majority of cases, mechanisms and consequences of viral dominance are largely unknown. We aimed to investigate associations between viral dominance patterns and patients' characteristics and inflammatory features; 109 HDV-infected patients treated with PEG-IFNa-2α within the international multicentre, prospective HIDIT-2 trial were studied. Patients were classified as D- or B-dominant if the viral load of one virus exceeded that of the other virus by more than 1log10 . Otherwise, no viral dominance (ND) was described. We used Luminex-based multiplex technology to study 50 soluble immune mediators (SIM) in pretreatment samples of 105 HDV RNA-positive patients. Dominance of HDV was evident in the majority (75%) of cases. While only 7% displayed B-dominance, 17% showed nondominance. D-dominance was associated with downregulation of 4 interleukins (IL-2ra, IL-13, IL-16 and IL-18) and 5 chemokines/cytokines (CTACK (CCL27), MCP-1 (CCL2), M-CSF, TRAIL and ICAM-1) while no analyte was increased. In addition, D-dominance could be linked to a delayed HDV RNA response to pegylated interferon as patients with B-dominance or nondominance showed higher early HDV RNA responses (61% at week 12) than D-dominant patients (11%; P < .001). In conclusion, this study revealed unexpected effects of viral dominance on clinical and immunological features in chronic hepatitis delta patients. Individualizing PEG-IFNa-2α treatment duration should consider viral dominance. Overall, our findings suggest an activated but exhausted IFN system in D-dominant patients.
Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/fisiologia , Hepatite D Crônica/tratamento farmacológico , Hepatite D Crônica/virologia , Vírus Delta da Hepatite/fisiologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Citocinas/sangue , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite D Crônica/imunologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
The aim of this study was to determine the long-term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the natural course of disease in chronic hepatitis B patients (CHB) with/without cirrhosis in clinical practice. A total of 355 treatment-naïve CHB patients were enrolled into the study. The primary outcome measure was viral suppression as defined by serum HBV DNA level <20 IU/mL. A secondary outcome measure was to determine the development of Hepatocellular carcinoma (HCC). Virological and biochemical responses were similar between the two treatment groups over time. The presence of cirrhosis and hepatitis B e antigen (HBeAg) positivity did not appear to impact viral suppression. The cumulative probability of HBeAg loss was 41% at 4 years of therapy. Hepatitis B surface antigen (HBsAg) loss occurred in four patients. Model for End-Stage Liver Disease score was significantly improved from baseline to week 48 and 96 under antiviral therapy (P = 0.013, P = 0.01). HCC was diagnosed in 17 patients (4.8%). The cumulative probability of the development of HCC was 3.3% at 1 year and 7.3% at 4 years of therapy. The development of HCC was independently associated with older age (P = 0.031) and the presence of cirrhosis (P = 0.004). Serum creatinine levels and creatinine clearance remained stable over time. ETV and TDF effectively maintained virological and biochemical responses in long-term follow-up of CHB patients with/without cirrhosis. HCC may still develop, although at a lower rate, and is more likely to develop in patients with cirrhosis, especially in older patients.
Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Carcinoma Hepatocelular/epidemiologia , Creatinina/sangue , DNA Viral/sangue , Feminino , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Carga ViralRESUMO
No data exist to assess certain polymorphisms that have a potential effect on the immune response in patients with chronic hepatitis delta (CHD). The aim of this study was to investigate polymorphisms in 6 polymorphic sites: IL-10 -1082 (rs1800896), IL-10 -627 (rs1800872), IFN-γ +874 (rs62559044), TNF-α -308 (rs1800629), vitamin D receptor (VDR) FokI (rs2228570) and VDR TaqI (rs731236). The genotypes of 67 patients with CHD and 119 patients with chronic hepatitis B (CHB) were compared. In addition, 56 individuals with resolved hepatitis B virus (HBV) infection were used as a control group for patients with CHB. Polymorphisms in TNF-α, IL-10, and VDR genes were analysed using polymerase chain reaction/restriction fragment length polymorphism methods. The IFN-γ gene polymorphism was detected by allele-specific polymerase chain reaction (PCR). Patients with CDH were more likely to have advanced liver disease compared with patients with CHB (P < 0.0001). IL-10 -1082 and VDR TaqI polymorphisms showed significant differences between patients with CHD and CHB. The high secretory IL-10 -1082 genotype GG was less frequent in CHD compared with patients with CHB and resolved HBV (17.7%, 37.4% and 47.1%, respectively (P < 0.05 for CHD vs CHB and resolved HBV). The frequency of the high secretory VDR TaqI TT genotype was 86.6% in patients with CHD, 62.7% in patients with CHB and 62.5% in resolved HBV individuals (CHD vs CHB: P < 0.05). None of the polymorphisms analysed had an effect on HBV persistence. IL-10 -1082 and VDR TaqI polymorphisms may contribute to the more severe liver disease associated with CHD compared with CHB.
Assuntos
Hepatite D Crônica/genética , Vírus Delta da Hepatite/fisiologia , Interferon gama/genética , Interleucina-10/genética , Receptores de Calcitriol/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Hepatite D Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Turquia , Carga ViralRESUMO
Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
Assuntos
Hepatite C Crônica/epidemiologia , Antivirais/uso terapêutico , Saúde Global , Hepatite C Crônica/mortalidade , Hepatite C Crônica/terapia , Humanos , Incidência , Transplante de Fígado , Prevalência , Análise de SobrevidaRESUMO
The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Diagnósticos de Rotina/estatística & dados numéricos , Erradicação de Doenças , Quimioterapia Combinada/métodos , Feminino , Saúde Global , Hepatite C Crônica/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Adulto JovemRESUMO
The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Quimioterapia Combinada/métodos , Feminino , Saúde Global , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Adulto JovemRESUMO
The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg-negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg-negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti-HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti-HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on-treatment in four patients after a median treatment duration of 30 months and off-treatment in the remaining five patients in a median 61 months after LMV discontinuation. The cumulative probability of HBsAg seroconversion increased from 0.6% at 1 year and 1.9% at 5 years to 21.5% at 10 years of LMV during and after LMV treatment. HBsAg clearance was preceded by undetectable serum hepatitis B virus (HBV) DNA. The majority of the patients responding to treatment had undetectable HBV DNA levels at 24 weeks of treatment. The cumulative probability of LMV resistance increased from 2.2% at 1 year to 37.3% at 5 years. No baseline parameter predicting either HBsAg seroconversion or the emergence of LMV resistance was identified. None of the patients with HBsAg seroconversion experienced virological breakthrough or disease progression during the follow-up period. These results indicate that HBsAg seroclearance can occur in patients with HBeAg-negative CHB under LMV therapy and predicts better clinical outcome.
Assuntos
Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Adulto , Idoso , Anticorpos Antivirais/sangue , Antivirais/administração & dosagem , DNA Viral/sangue , Feminino , Fibrose/patologia , Fibrose/virologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Humanos , Interferon-alfa/uso terapêutico , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead to disease in humans through co-infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV-HDV co-infection compared to HBV mono-infection. Chronic infection after acute hepatitis B + D co-infection is infrequent and similar to the rate in mono-infected patients. CDH develops in 70-90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10-15% of patients. However, as with any immune-mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.
Assuntos
Vírus da Hepatite B/patogenicidade , Hepatite D Crônica/tratamento farmacológico , Hepatite D Crônica/patologia , Vírus Delta da Hepatite/efeitos dos fármacos , Vírus Delta da Hepatite/patogenicidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Hepatite D Crônica/complicações , Humanos , Fatores Imunológicos/uso terapêutico , Interferons/uso terapêutico , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologiaRESUMO
The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/40, mean age: 42.9+/-13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (<10(7) copies/mL) was a significant predictor of response to ADV treatment (P<0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.
Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Farmacorresistência Viral , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Substituição de Aminoácidos/genética , Antivirais/farmacologia , DNA Viral/sangue , DNA Viral/genética , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Organofosfonatos/farmacologia , Terapia de Salvação/métodos , Análise de Sequência de DNA , Resultado do Tratamento , Carga ViralRESUMO
Living donor liver transplantation is a widely accepted option to treat liver diseases in several indications. Risk of liver donation is being discussed and quality of life of donors is also studied. Changes and the change pattern of quality of life were analyzed in this prospective longitudinal study. PATIENTS AND METHODS: Fifty-five donors were included. The Medical Outcomes Study Short Form 36 (SF-36) was fulfilled either in-person or during a telephone interview each donor preoperatively and at the end of the third, sixth, and 12th months. RESULTS: Physical subdomain scores of SF-36 decreased significantly in the third postoperative month compared to preoperative score. The scores recovered in the sixth postoperative month, except for the bodily pain domain. The pain score recovered at the end of the 12th month. While social functioning score among mental subdomains of SF-36 temporarily decreased and recovered at postoperative 12th month, other mental subdomain scores and mental composition summary scores did not show a significant change. CONCLUSION: The quality of life of living liver donors is not permanently affected by donation. There are well-defined changes in the physical aspects of the quality of life that all seem to recover within 1 year. Donors should be preoperatively informed about this temporary change as well as complications.
Assuntos
Hepatectomia/efeitos adversos , Transplante de Fígado/métodos , Doadores Vivos , Qualidade de Vida , Adulto , Feminino , Hepatectomia/métodos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Adulto JovemRESUMO
The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.
Assuntos
Trato Gastrointestinal/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas , Hepatócitos/patologia , Quimeras de Transplante , Adolescente , Adulto , Cromossomos Humanos Y , Epitélio/lesões , Epitélio/patologia , Feminino , Trato Gastrointestinal/lesões , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Hepatitis B virus reactivation-related hepatitis is a serious cause of liver-related morbidity and mortality in inactive hepatitis B virus carriers with hemato/oncological malignancies who receive chemo/immunosuppressive therapy. It occurs in 14% to 50% of such individuals and the mortality ranges from 3.7% to 60%. The aims of the present review were 1) to determine the effect of lamivudine prophylaxis in inactive hepatitis B virus carriers with hemato/oncological malignancies who receive chemo/immunosuppressive therapy, and 2) to define the safety and duration of lamivudine in such individuals. The data currently available suggest that all individuals with hemato/oncological malignancies who undergo chemo/immunosuppressive therapy should be screened for hepatotropic viruses. Lamivudine prophylaxis in inactive hepatitis B virus carriers with hemato/oncological malignancies who receive chemo/immunosuppressive therapy prevents chemo/immunosuppressive-induced hepatitis B virus reactivation. Lamivudine also prevents interruptions in treatment as a result of hepatitis B virus reactivation. Lamivudine is safe and tolerable in such individuals. The ideal protocol of lamivudine prophylaxis for the prevention of hepatitis B virus reactivation in such individuals is not yet established. However, it would appear prudent to begin lamivudine at the time of the initiation of the chemo/immunosuppressive therapy and to continue it throughout the period of chemo/immunosuppressive administration and for at least one but possibly two years following the therapy discontinuation.
Assuntos
Antivirais/uso terapêutico , Portador Sadio/prevenção & controle , Neoplasias Hematológicas/tratamento farmacológico , Hepatite B/prevenção & controle , Neoplasias Hematológicas/complicações , Hepatite B/complicações , HumanosRESUMO
BACKGROUND: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. AIM: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. METHODS: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 µg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. RESULTS: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. CONCLUSIONS: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.
Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Tenofovir/administração & dosagem , Administração Oral , Adulto , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteínas Recombinantes/administração & dosagem , Resultado do TratamentoRESUMO
The frequency of sexual dysfunction (SD) is not very well known in patients with chronic hepatitis C. In this study, the prevalence of SD and its correlations with psychological and biological variables was assessed in 46 HCV positive patients. The mean age of patients was 46.4+/-9.4 y; the mean duration of HCV infection was 43.4+/-34.0 months; 52% were male; 89% were living with a spouse. SD was assessed using the Arizona Sexual Experiences Scale (ASEX), the level of anxiety and depression measured with the Hospital Anxiety and Depression Scale (HADS). Biochemical parameters were also assessed. Overall, as indicated by ASEX criteria, SD was observed in 35% of our patients. Of 24 males, 21% described SD; problems with drive (25%), arousal (17%) and erection (17%) were the most frequent complaints. Of 22 female patients, 50% described SD; problems with drive (55%) arousal (50%), and reaching orgasm (59%) were the most frequent complaints. Total ASEX scores were correlated with age (P<0.07, significant at trend level), education (P<0.001), and was higher in female patients (P<0.02). After controlling for the effects of age, sex, education, duration of HCV and marital status, depression levels could still significantly predict the SD (P<0.05). Moreover, even after controlling the effects of all other variables, gamma glutamyl transpeptidase (GGT) levels could predict the SD status of the patients (P<0.05). Our results indicate that the prevalence of SD was 35% in HCV-infected patients and the level of depression and GGT levels were predictive of patients SD status.
Assuntos
Hepatite C Crônica/psicologia , Disfunções Sexuais Fisiológicas/psicologia , Adulto , Idoso , Ansiedade/epidemiologia , Ansiedade/psicologia , Arizona/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Feminino , Hepatite C Crônica/complicações , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Orgasmo , Valor Preditivo dos Testes , Prevalência , Análise de Regressão , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Psicogênicas/epidemiologia , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/psicologia , Classe Social , gama-Glutamiltransferase/sangueRESUMO
The present study was designed to determine the seroprevalence of hepatitis B and C virus (HBV, HCV) infections and risk factors in the Turkish general population. Participants were enrolled from urban and rural areas of the predetermined 23 EUROSTAT NUTS 2 region. A two-stage stratified sampling method was used to select participants from these regions (n = 5460; 50.9% females; mean (SD) age: 40.8 (14.7) years). Sociodemographics, clinical characteristics and risk factors were recorded at home visits. The seropositivity rates for hepatitis B surface antigen (HBsAg), anti-HCV, anti-HBs and anti-HBc total were 4.0%, 1.0%, 31.9% and 30.6%, respectively. Among HBsAg-positive cases, 94.5% were anti-HBe-positive, 70.2% were HBV-DNA-positive and 2.8% were anti-HDV total positive; 99.1% of HBV infections were of genotype D. Close contact with a hepatitis patient (OR 3.24; 95% CI 2.25-4.66; p < 0.001), living in the southeastern region (OR 2.74; 95% CI 1.7-4.45; p < 0.001), male gender (OR 1.77; 95% CI 1.28-2.46; p < 0.001), being married (OR 1.62; 95% CI 1.02-2.57; p 0.038), educational level less than high school (OR 1.53; 95% CI 1.04-2.26; p 0.03), orodental interventions (OR 1.54; 95% CI 1.01-2.35; p 0.047) and a history of non-disposable syringe use (OR 1.4; 95% CI 1.01-1.96; p 0.045) were significant determinants of HBsAg positivity. Age ≥50 years (OR 2; 95% CI 1.09-4.3; p 0.026) was the only significant predictor of anti-HCV positivity. In conclusion, our findings revealed an HBsAg positivity in 4% and anti-HCV positivity in 1% of the adult population and at least one-third of the population has been exposed to HBV infection in Turkey.
Assuntos
Hepatite B/epidemiologia , Hepatite C/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , Estudos Soroepidemiológicos , Turquia/epidemiologia , População Urbana , Adulto JovemRESUMO
A case of cryptogenic cirrhosis in a patient with Turner's syndrome is presented. The individual was admitted for upper gastrointestinal bleeding due to oesophageal varices. After failure of medical treatment, a transjugular intra-hepatic portal systemic shunt was used to control the bleeding. A liver biopsy revealed cirrhosis with minimal necro-inflammatory activity and no steatosis. Immunohistochemical staining for HCV, HBsAg and HBcAg was negative. No other risk factor for liver disease was recognized and none of the known causes of chronic liver disease was identified after a thorough evaluation for such. Turner's syndrome is a genetic disorder due to X chromosome monosomy in which a wide range of congenital anomalies can occur. Cardiac, renal and skeletal anomalies are all well recognized. The possible association of Turner's syndrome with cirrhosis is herein discussed along with a review of the published literature.
Assuntos
Cirrose Hepática/complicações , Síndrome de Turner/complicações , Adulto , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal , HumanosRESUMO
Organ transplantation has become a practical and effective option for patients with acute and/or chronic irreversible organ disease. However, solid organ transplantation is associated with many different complications which depend upon the specific surgical procedure and/or confounding medical problems (e.g. rejection, infection, adverse effect of immunosuppressive agents) experienced by a given patient. Tacrolimus and cyclosporin A are immunosuppressive drugs used to prevent rejection following allogeneic solid organ transplantation. Adverse events are common with both drugs and include long-term organ dysfunction, opportunistic infections, haematopoietic alterations, nephrotoxicity and neurotoxicity. Neurological complications, both central and peripheral, occur in 10-42% of transplant recipients using either of these two immunosuppressive agents. Two cases of reversible posterior leukoencephalopathy manifested by headache, nausea and seizures associated with the use of immunosuppressive drugs following liver transplantation are reported.
Assuntos
Encefalopatias/induzido quimicamente , Ciclosporina/efeitos adversos , Imunossupressores/uso terapêutico , Transplante de Fígado , Tacrolimo/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , MasculinoRESUMO
The physiopathology, diagnosis and treatment of hepatic osteodystrophy are discussed in this review. Hepatic osteodystrophy (HO) is a generic definition for the metabolic bone disease that may occur in individuals with chronic liver disease. Two distinct bone metabolic processes, osteoporosis (OP) and osteomalacia (OM) are combined together in various proportions in HO syndromes. The relative importance of these two diseases in a given case is quite variable. HO is a common complication among individuals with long time lasting hepatic disease, particularly those with cholestasis. Since advanced HO is difficult to treat and adversely affects both the quality of life and the long-term prognosis of patients with chronic liver disease, special care is required in order to prevent the development of clinical bone disease in individuals with advanced hepatic disease.
Assuntos
Hepatopatias/complicações , Osteomalacia/etiologia , Osteoporose/etiologia , Doenças Autoimunes/complicações , Colestase/complicações , Doença Crônica , Humanos , Hepatopatias/imunologia , Hepatopatias Alcoólicas/complicações , Osteomalacia/diagnóstico , Osteomalacia/tratamento farmacológico , Osteomalacia/fisiopatologia , Osteomalacia/prevenção & controle , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Osteoporose/prevenção & controle , Prognóstico , Qualidade de Vida , SíndromeRESUMO
Based upon all of the available data relating to the natural history, chemical course, and response to therapy of HCV, the following recommendations are made: 1) The primary end point for HCV therapy should be HCV clearance from all tissue sites, eg plasma, liver and others 2) Therapy should be provided for patients with early infections as they have the best chance of achieving a virologic response 3) Therapy should be offered to patients with cirrhotic disease, as prevention of hepatic decompensation and degeneration to hepatic cancer is possible 4) End stage decompensated disease should be treated, particularly if liver transplantation is being considered, in an effort to either eliminate or ameliorate disease recurrence 5) Combination therapies are preferable to monotherapy as they enhance the likelihood of a therapeutic response. Some of these include agents that reduce the frequency of IFN-induced untoward events (NSAIDs) 6) The approach to HCV infection should be to view it as an infectious disease. In this way, multi-agent therapy could be used to prevent the emergence of drug resistant mutants as well as to obtain earlier clearance of the infection than is possible with monotherapy.