RESUMO
Hepatocellular carcinoma (HCC) is assumed to be an immunogenic malignancy since 90% of cases develop in environments with ongoing inflammation. Monocyte subsets contribute to tumoral immunity. Most HCC patients are discovered at late stages, which lowers their survival chances. We aimed to determine whether altered frequency of monocyte subsets contribute to post hepatitis C virus infection-liver cirrhosis (HCV-LC) development to HCC. This cross-sectional study enrolled 105 patients classified as post HCV-HCC (n=72) and post HCV-LC (n=33) patients. The monocyte subsets frequency was assessed by flow-cytometry. There was a significant increase in intermediate monocytes and decrease in non-classical monocytes in HCC group when compared to the LC group (P = 0.001 and 0.006, respectively). Intermediate monocyte frequency was positively correlated with cholesterol and triglycerides (r = 0.296, P < 0.002 and r = 0.247, P < 0.011, respectively). The receiver operating characteristic (ROC) curve revealed that intermediate monocytes percentage at a cutoff ≥ 0.625% and non-classical monocytes percentage at a cutoff ≤ 0.61% differentiated between patients with HCV-LC and those with HCV-HCC with a sensitivity of 76.4% and 69.4%, respectively, while both revealed low specificity of 51.5%. According to logistic regression analysis, only the triglyceride level was found to be an independent risk factor for HCC development [OR =1.014 (11.001-1.026), P = 0.031]. Finally, we concluded that post-HCV-HCC is characterized by an upregulation of intermediate monocytes and a downregulation of non-classical monocytes when compared to Post-HCV-LC. Intermediate and non-classical monocytes frequency can aid to screening biomarkers for HCC development. Intermediate monocyte frequency may be linked to hyperlipemia. The level of triglycerides is proposed as an independent risk factor for HCC emergence.
Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Estudos Transversais , Citometria de Fluxo , Hepacivirus , Hepatite C/complicações , Hepatite C/patologia , Humanos , Cirrose Hepática , Neoplasias Hepáticas/etiologia , Monócitos , TriglicerídeosRESUMO
AIMS: We aimed to compare the diagnostic performance of two 2D-Shear Wave Elastography (2D-SWE) techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection using Transient Elas-tography (TE) as reference. MATERIAL AND METHODS: We enrolled 208 consecutive patients with chronic HCV infection, in which liver stiffness (LS) was evaluated in the same session using two 2D-SWE techniques: 2D-SWE.GE and 2D-SWE.SSI using TE as the method of reference. LS measurements were considered failures when no value was obtained after 10 attempts. RESULTS: Valid LSMs were obtained in 95.6% (199/208) of cases by 2D-SWE.GE, 92.7% (193/208) of cases by 2D-SWE.SSI, and in 94.7% (197/208) of cases by TE (p>0.05). The mean LS values by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI: 10.3±3.8 kPa vs. 15±10.4 kPa (p<0.0001). 2D-SWE.GE LSMs correlated better with TE than 2D-SWE.SSI (r=0.75, p<0.0001 vs. r=0.57, p<0.0001, z test p=0.0012). Linear regression analysis showed a moderate correlation between LSMs obtained by 2D-SWE.GE and 2D-SWE.SSI (r=0.63, R2=0.4, P<0.0001). Pairwise comparison of receiver operating characteristics curves (ROC) found no significant differences between 2D-SWE.GE and 2D-SWE.SSI in identifying F≥2 fibrosis (0.97 vs. 0.96, P = 0.5650), F≥3 (0.97 vs. 0.95, P = 0.2935), or F=4 (0.97 vs. 0.96, p = 0.6914). CONCLUSIONS: Both 2D-SWE techniques had good feasibility for the noninvasive assessment of liver fibrosis. LS values obtained by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI. No significant differences were found between both methods in staging liver fibrosis in patients with chronic HCV.
Assuntos
Técnicas de Imagem por Elasticidade , Hepatite C Crônica , Hepatite C , Cirrose Hepática , Hepatite C/patologia , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Curva ROCRESUMO
BACKGROUND: The recurrence of hepatitis C (HCV) after liver transplant (LTX) leads to graft fibrosis and cirrhosis. Liver biopsy remains the criterion standard for their diagnosis and monitoring. Our objective was evaluation of shear wave elastography (SWE) in patients with HCV recurrence after LTX and its comparison with histopathologic fibrosis assessment scoring systems. METHODS: A total of 101 LTX recipients with HCV recurrence (42 women [41.6%] and 59 men [58.4%]) were evaluated by graft biopsy specimens (Ishak, Scheurer, and meta-analysis of histologic data in viral hepatitis [Metavir] score) and SWE (liver stiffness). Median age of patients was 59.4 years; median time from LTX was 84.9 months. The study protocol conforms with the Declaration of Helsinki. RESULTS: Median liver stiffness was 21.3 kPa. To differentiate between liver fibrosis and cirrhosis, patients were divided into 2 subgroups: Ishak score fibrosis (1-4 [85.2%]) and cirrhosis (5-6 [13.9%]); Scheurer score fibrosis (0-3 [85.2%]) and cirrhosis (4 [12.9%]); Metavir score fibrosis (0-3 [85.2%]) and cirrhosis (4 [14.9%]). We have observed statistically significant differences between liver fibrosis and liver cirrhosis groups defined on the basis of Ishak, Scheurer, and Metavir scoring systems: 20.8 kPa vs 29.6 kPa (P = .001), 20.7 kPa vs 30.3 kPa (P = .0005), and 20.7 kPa vs 28.8 kPa (P = .002), respectively. CONCLUSIONS: Our results indicate that SWE may be useful in differentiating patients with advanced cirrhosis from those with fibrosis and may be helpful in the noninvasive diagnosis and monitoring of HCV recurrence after LTX.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico , Transplante de Fígado , Adulto , Biópsia/métodos , Feminino , Hepatite C/complicações , Hepatite C/patologia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown. DESIGN AND METHODS: HIV-positive MSM from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 ≤â1.45 and >â1.45 were examined using multistate Markov models. RESULTS: Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range â=â8-18) and median follow-up following AHCVI was 3.5 years (interquartile rangeâ=â1.9-5.6). FIB-4 measurements averaged at 1.00 [95% confidence interval (CI)â=â0.95-1.05] before AHCVI, 1.31 (95% CIâ=â1.25-1.38) during the first year of AHCVI and 1.10 (95% CIâ=â1.05-1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (Pâ=â0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4 cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45-3.25 and ≥â3.25, respectively. Older age, lower CD4 cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 >â1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 ≤â1.45. CONCLUSION: In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 ≥â3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression.
Assuntos
Coinfecção/virologia , Progressão da Doença , Infecções por HIV/fisiopatologia , Hepatite C/patologia , Homossexualidade Masculina , Cirrose Hepática/patologia , Adulto , Hepatite C/complicações , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Masculino , Cadeias de Markov , Países Baixos/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: American Indian/Alaska Natives (AI/ANs) are disproportionately affected by hepatitis C virus (HCV), with more than double the national rate of HCV-related mortality as well as the highest rates of acute HCV. The "cascade of care" for HCV consists of screening, confirmation, treatment, and sustained virologic clearance (SVR)/cure. At each stage of this process, patients can be lost to follow-up. Federal health care facilities in an administrative area of the Indian Health Service conducted a review to identify and address gaps in HCV treatment. Facilities generally treated HCV with a strong pharmacy component using a collaborative practice agreement and HCV telehealth services to external specialists. METHODS: All facilities had a pharmacist HCV program point of contact. Each pharmacist conducted a chart review of HCV patients and submitted aggregate results on HCV antibody status, HCV confirmation testing, stage of liver disease, initiation of treatment, and SVR/cure. Each facility also ranked current barriers to scaling up HCV treatment services from a defined list of options. RESULTS: Of 1789 HCV antibody positive patients, 77% (1381) had a confirmation test, of which 67% (929) were positive. Of these patients, 62% (576) had their liver fibrosis scored, and 58% (335) had initiated treatment. Of patients with an SVR/cure test, all (274/274) were negative. DISCUSSION: These data indicate that rural clinics can be successful providing HCV diagnosis and treatment. Pharmacists can play a key role in HCV clinical services. The outcomes of each step in the treatment process at the facility level can vary widely due to local factors. The barriers to HCV care that persist are nonclinical.
Assuntos
Antivirais/administração & dosagem , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Farmacêuticos/organização & administração , United States Indian Health Service/organização & administração , Antivirais/uso terapêutico , Comportamento Cooperativo , Acessibilidade aos Serviços de Saúde/organização & administração , Hepatite C/patologia , Humanos , Indígenas Norte-Americanos , Oklahoma , Papel Profissional , Serviços de Saúde Rural/organização & administração , Índice de Gravidade de Doença , Telemedicina/organização & administração , Estados UnidosRESUMO
INTRODUCTION: Direct acting antivirals (DAA's) have revolutionized the treatment of hepatitis C (HCV). However, questions persist concerning their efficacy in minority populations. AREAS COVERED: In this review, the authors review outcomes for treatment of HCV by race and ethnicity among the clinical trials that have led to the current recommended treatments for HCV. The authors highlight the efficacy and safety differences by race and ethnicity. They also highlight deficiencies within the literature including small populations of racial/ethnic minorities within HCV clinical trials. DAA's can achieve cure rates for HCV over 95% with the use of once daily medications that have minimal side effects and few significant drug-drug interactions. Regimens with high pan-genotypic efficacy have further simplified treatment paradigms. The purpose of this review is to describe the data on DAA's in treating HCV in racial/ethnic populations. EXPERT OPINION: While the overall data in racial/ethnic minority populations is sparse, DAA's appear to have high efficacy in curing HCV in diverse racial/ethnic populations. Although achieving high sustained virologic response (SVR) rates, there are also data that suggests that some disparities in SVR persist, especially when considering shorter regimens for HCV treatment in racial/ethnic populations.
Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Benzimidazóis/uso terapêutico , Benzofuranos/uso terapêutico , Carbamatos/uso terapêutico , Quimioterapia Combinada , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/economia , Hepatite C/etnologia , Hepatite C/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Imidazóis/uso terapêuticoRESUMO
BACKGROUND AND AIM: Observational studies showed significant liver stiffness regression after sustained virological response, but long-term effects of antiviral therapy are still unknown. The aim of this study was to assess the magnitude of change in stiffness up to 5 years after therapy in hepatitis C patients undergoing antiviral treatment. METHODS: Data of 153 patients were retrieved. Stiffness was assessed by Fibroscan at baseline, end of treatment, 6 months after treatment, and every year hereafter up to 5 years. RESULTS: Seventy patients were treated with interferon-based regimens and 83 with direct antiviral agents. Baseline cirrhosis was diagnosed in 53 (34.6%) patients. Sustained virological response was achieved in 112 patients, whereas 41 were non-responders. In responders, stiffness decreased from 12.3 kPa (9-17.8) to 6.6 kPa (5.3-7.4) at 5 years. A sharper decline was observed immediately after treatment (-2.5 kPa at the end of treatment and -3.7 kPa at 6 months), while from 1 year onwards, the magnitude of stiffness decrease was progressively lower. In non-responders, stiffness showed a slight decrease at the end of treatment (from 19.2 to 18.1 kPa), then returned to baseline levels at 6 months (19.4 kPa), and finally increased over time up to 23.7 kPa (15-32.5) at 5 years. The proportion of cirrhotic patients decreased by 50% at 6 months and finally fell < 5% at 4 years after treatment. CONCLUSIONS: Stiffness declines significantly after achieving response, and the magnitude of decline is greater in the first year after treatment, while it tends to plateau from 1 year onwards.
Assuntos
Antivirais/administração & dosagem , Elasticidade , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Interferon-alfa/administração & dosagem , Fígado/patologia , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Idoso , Estudos de Coortes , Técnicas de Imagem por Elasticidade/métodos , Feminino , Hepatite C/virologia , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Resposta Viral Sustentada , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Accurate assessment of liver fibrosis is crucial for the management of patients with hepatitis C virus (HCV) infection. OBJECTIVES: To evaluate the performance of liver segment-to-spleen volume ratio in predicting the severity of liver fibrosis. METHODS: Sixty-four consecutive HCV patients were enrolled in this retrospective study. All patients underwent contrast-enhanced computed tomography (CT) and were divided into three groups based on their hepatic fibrosis stage evaluated by shear-wave elastography (SWE): non-advanced (F0-F1, n=29), advanced (F2, n=19) and severe fibrosis (F3-F4, n=16). Using semi-automated liver segmentation software, we calculated the following liver segments and spleen volumes for each participant: total liver volume (TLV), caudate lobe (CV), left lateral segment (LLV), left medial segment (LMV), right lobe (RV) and spleen (SV), a well as their ratios: CV/SV, RV/SV, LLV/SV, LMV/SV and TLV/SV. RESULTS: RV/SV was found to discriminate between patients with non-advanced and advanced fibrosis (P = 0.001), whereas SV, CV, RV, TLV/SV, LMV/SV and RV/SV discriminated between patients with advanced and severe fibrosis (P < 0.05). RV/SV ≤ 3.6 and RV ≤ 2.9 were identified as the best cutoff values to differentiate non-advanced from advanced fibrosis and advanced from severe fibrosis with sensitivities of 72.2% and 92.7%, specificities of 72.7% and 77.8%, and with an area under the receiver operating characteristic (ROC) curve of 0.797 and 0.847, respectively (P ≤ 0.002). CONCLUSIONS: RV/SV may be used for the assessment and monitoring of liver fibrosis in HCV patients prior to the administration of antiviral therapy, considering SWE as the reference method.
Assuntos
Antivirais/administração & dosagem , Hepatite C , Cirrose Hepática , Fígado/patologia , Baço/patologia , Pesquisa Comparativa da Efetividade , Técnicas de Imagem por Elasticidade/métodos , Feminino , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/patologia , Humanos , Israel/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática/terapia , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Tamanho do Órgão , Seleção de Pacientes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Access to treatment for hepatitis C virus (HCV) in sub-Saharan Africa is extremely limited. With the advent of direct acting antivirals (DAAs), highly effective and easy-to-deliver oral regimens are now available on the global market. This study was conducted to understand the background and characteristics of a national cohort of patients with HCV infection enrolled in care and awaiting therapy with DAAs. METHODS AND FINDINGS: We conducted a retrospective chart review of all adult patients with confirmed HCV infection who were currently enrolled in care and treatment at the four existing hepatitis referral centers in Rwanda. Patient charts at these centers were reviewed, and routinely collected data were recorded and analyzed. Overall, 253 patients were identified; median age was 56 years (IQR: 43, 65), and 149 (58.9%) were female. Median viral load was 688,736 IU/ml and 96.7% were HCV genotype 4. As classified by FIB-4 score, 64.8% of the patients had moderate to severe fibrosis. Fibrosis stage was associated with age (OR 1.12, CI 1.09-1.17), but not with time since diagnosis, gender, treatment center, or type of insurance. There was a low frequency of documented co-morbid conditions, including hypertension, diabetes, HIV, and hepatitis B virus. CONCLUSIONS: Compared to an estimated 55,000 patients eligible for HCV treatment in Rwanda, this study identified only 253 patients currently diagnosed and engaged in care, highlighting an immense treatment gap in HCV, likely due to the lack of accessible and affordable screening, diagnostic, and treatment modalities. The patients that were enrolled in care had a disproportionately advanced fibrosis stage, possibly indicating late presentation to care or lack of treatment options. In the context of newly available and effective treatment options, this study supports the overall need to accelerate access to HCV screening, diagnostics, and care and treatment services in resource-limited settings in sub-Saharan Africa.
Assuntos
Antivirais/economia , Acessibilidade aos Serviços de Saúde , Hepatite C/epidemiologia , Cirrose Hepática/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Gastos em Saúde , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/patologia , Hepatite C/virologia , Humanos , Seguro Saúde/estatística & dados numéricos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ruanda/epidemiologia , Carga Viral , Adulto JovemRESUMO
AIM: To identify the prevalence and effect of hepatopathies of different etiologies among pediatric patients with type 1 diabetes mellitus (T1DM) using transient elastography (TE) and its relation to glycemic control. METHODS: One hundred T1DM patients were studied focusing on liver functions, fasting lipid profile, hemoglobin A1c (HbA1c), hepatitis C virus (HCV), serum immunoglobulins, autoimmune antibodies; anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver kidney microsomal antibody (anti-LKM). Abdominal ultrasound was performed and TE was done for patients with HCV, positive autoimmune antibody and/or abnormal ultrasound findings. RESULTS: Thirty-one patients were found to have one or more hepatic abnormalities; clinical hepatomegaly in 8%, elevated alanine aminotransferase (ALT) in 10%, HCV in 6%, autoimmune hepatitis (AIH) in 11% (10 were positive for ASMA and 2 were positive for ANA while anti-LKM antibodies were negative) and abnormal hepatic ultrasound in 20% (12 non-alcoholic fatty liver disease, 5 AIH, 2 HCV, 1 Mauriac syndrome). Mean liver stiffness in those 31 patients was 7.0±2.1kPa (range, 3.1-11.8kPa); 24 were Metavir F0-F1, 7 were F2-F3 while none was F4. Type 1 diabetic patients with abnormal hepatic ultrasound had higher fasting blood glucose, HbA1c and total cholesterol than those with normal findings. Liver stiffness was significantly higher in patients with abnormal liver ultrasound compared with normal sonography. Liver stiffness was positively correlated to HbA1c and ALT. CONCLUSIONS: Hepatic abnormalities are prevalent in T1DM and related to poor metabolic control. TE provides a non-invasive method for detection of hepatopathy-induced fibrosis.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Insuficiência Hepática/diagnóstico por imagem , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Fígado/diagnóstico por imagem , Adolescente , Biomarcadores/sangue , Biópsia , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/terapia , Egito/epidemiologia , Técnicas de Imagem por Elasticidade , Feminino , Hemoglobinas Glicadas/análise , Hepacivirus/isolamento & purificação , Insuficiência Hepática/complicações , Insuficiência Hepática/patologia , Insuficiência Hepática/virologia , Hepatite C/complicações , Hepatite C/epidemiologia , Hepatite C/patologia , Hepatite C/virologia , Hepatite Autoimune/complicações , Hepatite Autoimune/epidemiologia , Hepatite Autoimune/patologia , Hepatite Autoimune/virologia , Hepatomegalia/complicações , Hepatomegalia/diagnóstico por imagem , Hepatomegalia/epidemiologia , Hepatomegalia/patologia , Humanos , Incidência , Fígado/patologia , Fígado/virologia , Masculino , Prevalência , UltrassonografiaRESUMO
Virtual Touch™ Quantification (VTq) is a software application used with Siemens Acuson ultrasound scanners to assess the stiffness of liver tissue. The National Institute for Health and Care Excellence (NICE) Medical Technologies Advisory Committee (MTAC) selected VTq for evaluation and invited the company to submit clinical and economic evidence. King's Technology Evaluation Centre, an External Assessment Centre (EAC) commissioned by NICE, independently assessed the evidence submitted. The EAC conducted its own systematic review, meta-analysis and economic analysis to supplement the company's submitted evidence. The meta-analyses comparing VTq and transient elastography (TE) with liver biopsy (LB) provided pooled estimates of liver stiffness and stage of fibrosis for the study populations (hepatitis B, hepatitis C or combined populations). When comparing significant fibrosis (Metavir score F ≥ 2) for both hepatitis B and C, VTq had slightly higher values for both sensitivity and specificity (77 and 81 %) than TE (76 and 71 %). The overall prevalence of cirrhosis (F4, combined populations) was similar with VTq and TE (23 vs. 23 %), and significant fibrosis (F ≥ 2) was lower for VTq than for TE (55 vs. 62 %). The EAC revised the company's de novo cost model, which resulted in a cost saving of £53 (against TE) and £434 (against LB). Following public consultation, taking into account submitted comments, NICE Medical Technology Guidance MTG27 was published in September 2015. This recommended the adoption of the VTq software to diagnose and monitor liver fibrosis in patients with hepatitis B or hepatitis C.
Assuntos
Hepatite B/diagnóstico , Hepatite C/diagnóstico , Cirrose Hepática/diagnóstico , Hepatite B/complicações , Hepatite B/patologia , Hepatite C/complicações , Hepatite C/patologia , Humanos , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Sensibilidade e Especificidade , Software , Medicina Estatal/normas , Avaliação da Tecnologia Biomédica , Resultado do Tratamento , Reino UnidoAssuntos
Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Cirrose Hepática/virologia , Antivirais/economia , Congressos como Assunto , Análise Custo-Benefício , Quimioterapia Combinada , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/economia , Hepatite C/patologia , Humanos , Hungria , Interferons/uso terapêutico , Cirrose Hepática/prevenção & controle , Inibidores de Proteases/uso terapêutico , Relatório de Pesquisa , Ribavirina/uso terapêuticoRESUMO
Selenium is an essential trace mineral of fundamental importance to human healthy and exerts its biological function through selenoproteins. In particular, Selenoprotein M (SELM) is located in the endoplasmic reticulum and contains the common redox motif of cysteine-X-X-selenocysteine type. It attracts great attention due to its high expression in brain and its potential roles as antioxidant, neuroprotective, and cytosolic calcium regulator. Recently, our group found SELM over-expression in human hepatocellular carcinoma (HCC) cell lines. In this report some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV)-related cirrhosis and HCC were immunohistochemically stained and SELM expression scoring was evaluated. Our results evidence for the first time an increase of SELM expression in HCC liver tissues, and its gradual expression raise associated with an increased malignancy grade. Therefore, we propose to use i) SELM as putative marker for HCC as well as ii) simple immunohistochemistry technique to distinguish between the different grades of malignancy.
Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Proteínas de Neoplasias/biossíntese , Selenoproteínas/biossíntese , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Hepatite C/metabolismo , Hepatite C/patologia , Humanos , Imuno-Histoquímica , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p < 0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.
Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepatite B/patologia , Hepatite C/patologia , Cirrose Hepática/patologia , Síndrome da Imunodeficiência Adquirida/enzimologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Biomarcadores/sangue , Estudos de Coortes , Coinfecção , Feminino , Seguimentos , Hepatite B/enzimologia , Hepatite B/mortalidade , Hepatite C/enzimologia , Hepatite C/mortalidade , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/enzimologia , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Social determinants of health (SDOH) may influence the probability of people living with HIV also being infected with hepatitis C virus (HCV). We compared the SDOH of adults co-infected with HCV/HIV with that of HIV mono-infected adults to identify factors independently associated with HCV infection. METHODS: In this cross-sectional study, face-to-face interviews were conducted with 509 HIV-infected adults affiliated with or receiving services from community-based AIDS service organizations (CBAOs). The primary outcome measure was self-reported HCV infection status. Chi-square, Student's t tests, and Wilcoxon rank-sum tests were performed to compare SDOH of HCV/HIV co-infected participants with that of HIV mono-infected participants. Multivariable hierarchical logistic regression was used to identify factors independently associated with HCV co-infection. RESULTS: Data on 482 (95 HCV/HIV co-infected and 387 HIV mono-infected) adults were analyzed. Compared with participants infected with HIV only, those who were co-infected with HIV and HCV were more likely to be heterosexual, Aboriginal, less educated and unemployed. They were more likely to have a low income, to not be receiving antiretroviral treatment, to live outside the Greater Toronto Area (GTA), to use/abuse substances, experience significant depression, and utilize addiction counselling and needle-exchange services. They also were more likely to report a history of homelessness and perceived housing-related discrimination and to have moved twice or more in the previous 12 months. Factors independently associated with HCV/HIV co-infection were history of incarceration (odds ratio [OR] 8.81, 95% CI 4.43-17.54), history of homelessness (OR 3.15, 95% CI 1.59-6.26), living outside of the GTA (OR 3.13, 95% CI 1.59-6.15), and using/abusing substances in the past 12 months (OR 2.05, 95% CI 1.07-3.91). CONCLUSION: Differences in SDOH exist between HIV/HCV co-infected and HIV mono-infected adults. History of incarceration, history of homelessness, substance use, and living outside the GTA were independently associated with HCV/HIV co-infection. Interventions that reduce homelessness and incarceration may help prevent HCV infection in people living with HIV.
Assuntos
Fatores Epidemiológicos , Infecções por HIV/patologia , Nível de Saúde , Hepatite C/patologia , Adulto , Comorbidade , Intervalos de Confiança , Estudos Transversais , Depressão/diagnóstico , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Serviços de Saúde/estatística & dados numéricos , Indicadores Básicos de Saúde , Inquéritos Epidemiológicos , Hepatite C/epidemiologia , Hepatite C/psicologia , Pessoas Mal Alojadas , Humanos , Entrevista Psicológica , Masculino , Razão de Chances , Ontário/epidemiologia , Psicometria , Qualidade de Vida/psicologia , Características de Residência , Fatores de Risco , Autorrelato , Meio SocialRESUMO
BACKGROUND/AIM: The main objective of this study was to describe the profile of patients who were benefitted in a collective effort to perform liver biopsies in Bahia, Brazil. METHOD: A cross-sectional study was conducted with a sample composed of all the patients who were submitted to liver biopsy during a collective effort carried out in Bahia between July 2007 and November 2009. At the time of the procedure, date on the age and gender of patients and the reason for performing the biopsy were recorded. Data on the degree of fibrosis and the presence of co-morbidities. Following statistical analysis, the frequency of the liver diseases that led to the biopsy procedure was described, and the profile of the patients was stratified into groups according to the most prevalent etiologies. RESULTS: Of the 550 patients evaluated, 55.3% were men and 44.7% women. Mean age was 46.63 ± 11.59 years and there was no statistically significant difference in age between males and females. Of the 550 patients, 72% had hepatitis C and the mean age of these patients was 48.49 ± 10.1 years, significantly higher than the mean age of the patients with hepatitis B (40.41 ± 12.43 years). Furthermore, 70.7% of the patients with hepatitis C were between 41 and 60 years of age. The most frequent fibrosis grade was F2 (44%) and the prevalence of advanced fibrosis was 27.7%. Overall, 85 patients, most of them men, had some degree of iron overload. With respect to the safety of the biopsy procedure, severe complications occurred in only two patients. CONCLUSION: Hepatitis C is the predominant liver disease that demanded liver biopsy. The profile of the patients who benefitted from this collective effort is similar to that of patients in the rest of the country. Moreover, non-Ultrasonography guided liver biopsy is safe and the collective effort to carry out liver biopsies in Bahia was found to be a viable venture.
Assuntos
Biópsia/normas , Hepatopatias/epidemiologia , Fígado/patologia , Adulto , Biópsia/efeitos adversos , Brasil/epidemiologia , Distribuição de Qui-Quadrado , Comorbidade , Estudos Transversais , Feminino , Hepatite B/epidemiologia , Hepatite B/patologia , Hepatite C/epidemiologia , Hepatite C/patologia , Hepatite Autoimune/epidemiologia , Hepatite Autoimune/patologia , Humanos , Hipertensão Portal/epidemiologia , Hipertensão Portal/patologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Hepatopatias/diagnóstico , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Encaminhamento e Consulta/normas , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
AIM: To assess hepatic fibrosis and factors associated with its progression in children with HCV infection. METHODS: At the Hepatology Unit, Cairo University Children's Hospital, a single liver biopsy was performed to 43 children with HCV infection after an informed consent between 1998-2004. Their mean age at liver biopsy was 8.67 +/- 4.3 years. RESULTS: Among the 43 patients' biopsies, 12 (27.9%) were having no fibrosis, 20 (46.5%) mild fibrosis and 11 (25.6%) moderate to severe fibrosis. The median time for development of fibrosis was estimated to be 5.5 years. Developing fibrosis was significantly associated with shorter duration from first detected ALT elevation to biopsy (12 mo vs 1.2 mo, P=0.015) and having higher levels of direct serum bilirubin (0.3 mg/dL vs 0.5 mg/dL, P=0.048). No association was found between fibrosis stage and the presence of co-morbid conditions (P=0.33). CONCLUSION: Hepatic fibrosis was present in 72.1% of children with HCV infection. The development of fibrosis was associated with higher levels of direct serum bilirubin. There was no significant association between fibrosis and age, duration of infection, risk factors, co-morbid conditions and most biochemical parameters.
Assuntos
Hepatite C/complicações , Cirrose Hepática/virologia , Fígado/patologia , Adolescente , Alanina Transaminase/metabolismo , Bilirrubina/sangue , Biópsia , Criança , Pré-Escolar , Estudos Transversais , Progressão da Doença , Egito , Feminino , Hepacivirus/patogenicidade , Hepatite C/etnologia , Hepatite C/patologia , Humanos , Incidência , Lactente , Fígado/metabolismo , Fígado/virologia , Cirrose Hepática/etnologia , Cirrose Hepática/metabolismo , Masculino , Fatores de RiscoRESUMO
This study explores the experiences of people with hepatitis C within two models of chronic illness--illness trajectory and shifting perspectives--and examines the effects of clinical markers of disease in relation to perceived health. The findings show some support for both models and suggest how they can be seen as complementary and inter-related. The social consequences of living with hepatitis C, such as potential social limitations and isolation, were more significant and had greater impact than clinical markers of disease progress and should be emphasized in understandings of transformation experiences in chronic illness.
Assuntos
Adaptação Psicológica , Atitude Frente a Saúde , Efeitos Psicossociais da Doença , Hepatite C/psicologia , Perfil de Impacto da Doença , Biomarcadores , Doença Crônica , Progressão da Doença , Hepatite C/patologia , Humanos , Entrevistas como Assunto , Modelos Teóricos , New South Wales , Psicologia SocialRESUMO
OBJECTIVES: To estimate hepatitis C virus (HCV) progression rates between disease stages prior to cirrhosis, using data from liver biopsies in three observational cohorts. To demonstrate how the method of cohort recruitment can influence the estimation of HCV-progression rates. STUDY DESIGN AND SETTING: Data came from three United Kingdom observational cohorts, assembled from different referral sources. In total, 987 HCV-infected patients with an estimated (or known) date of infection and at least one histologically scored liver biopsy were eligible for inclusion in the analysis. Liver biopsy scores were used to determine the stage of HCV-related liver disease. A three-state continuous time Markov model was used to estimate covariate-specific average probabilities of progression of disease. RESULTS: After adjusting for confounders, considerably different rates of disease progression were estimated in the three cohorts. For a group of patients with the same demographics, the estimated 20-year probability of progression to cirrhosis was 12% (95% confidence interval CI = 6-22) in a hospital-based cohort, 6% (95% CI = 3-13) in a posttransfusion cohort, and 23% (95% CI = 14-37) in a cohort recruited from a tertiary referral center. CONCLUSION: Researchers using estimates of disease progression should be aware that the method of cohort recruitment has considerable influence on the progression rates that are derived.