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Acute-on-chronic liver failure (ACLF) has come a long way as a clinical concept within the hepatology and liver transplant communities. Though the term was proposed in 1995, the first recognition of the entity along with a consensus definition emerged in 2009. Subsequently, the entity has sparked great interest, inspired several consensus conferences, and inspired national societies to form professional ACLF affinity groups (eg, special interest group). Multicenter consortia have been established all over the world to study this condition, including the North American Consortium for the Study of End-Stage Liver Disease, Chronic Liver Failure consortium, Asian Pacific Association for the Study of Liver Diseases ACLF Research Consortium, Chronic Liver disease Evolution And Registry for Events and Decompensation, and the LiverHope Consortium. Collectively, these consortia have enrolled tens of thousands of patients with or at risk for ACLF across dozens of countries and characterized in detail the predictors, pathogenesis, and progression of patients with ACLF. Perhaps most importantly, they have produced essential data characterizing the excess morbidity and mortality that patients with ACLF face, making a compelling case for the urgent need for therapeutic strategies for this condition.
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INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.
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Doença Hepática Terminal/etiologia , Hepatite Alcoólica/mortalidade , Fígado/fisiopatologia , Adulto , Análise Discriminante , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/fisiopatologia , Feminino , Seguimentos , Saúde Global , Hepatite Alcoólica/complicações , Hepatite Alcoólica/fisiopatologia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.
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Técnicas de Ablação/métodos , Neoplasias dos Ductos Biliares/terapia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Colangiocarcinoma/terapia , Neoplasias Hepáticas/terapia , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Ablação por Radiofrequência , Estudos Retrospectivos , Resultado do TratamentoRESUMO
While the COVID-19 pandemic evolves, we are beginning to understand the role the gastrointestinal tract plays in the disease and the impact of the infection on the care of patients with gastrointestinal (GI) and liver diseases. We review the data and understanding around the virus related to the digestive tract, impact of the pandemic on delivery of GI services and daily gastroenterology clinical practice, and the effects on patients with pre-existing GI diseases.
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Infecções por Coronavirus/epidemiologia , Gastroenterologia/organização & administração , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Controle de Infecções/organização & administração , Pandemias/estatística & dados numéricos , Equipe de Assistência ao Paciente/organização & administração , Pneumonia Viral/epidemiologia , COVID-19 , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/prevenção & controle , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/terapia , Pessoal de Saúde/organização & administração , Humanos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
Foamy viruses (FVs) or spumaviruses are retroviruses that are explored as vectors for gene therapy. The good feature of foamy viruses is its broad tropism; however, their infections result in non-targeted gene expression. Here, we attempted to design the liver targeted viral gene delivery by employing liver specific gene promoters like albumin (ALB), transthyretin (TTR) and hepatitis B virus (HBV) promoters. We compared the relative gene expression of liver specific promoters versus the U3 promoter in liver cell line (HepG2) and non-liver cell lines: human fibrosarcoma cell line (HT1080), baby hamster kidney cell line (BHK), human embryonic kidney cell line (HEK 293T) and cervical cancer cell line (HeLa). We have found that the promoter exchange didn't affect viral assembly. The ability to drive gene expression was best with TTR promoter which was followed by HBV and ALB promoter. The use of TTR, HBV and ALB promoters are helpful in achieving liver specific gene expression. Keywords: foamy virus; gene therapy; liver; albumin; transthyretin promoter; HBV promoter.
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Fígado , Regiões Promotoras Genéticas , Spumavirus , Adulto , Animais , Linhagem Celular , Cricetinae , Terapia Genética , Vetores Genéticos , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Fígado/metabolismo , Regiões Promotoras Genéticas/genética , Spumavirus/genéticaRESUMO
CONTEXT: To review the imaging spectrum, clinical profile and disease outcome of patients with H1N1 influenza at a tertiary liver hospital. AIM: To review the imaging spectrum, clinical profile and disease outcome of patients with H1N1 influenza at a tertiary liver hospital. SETTINGS AND DESIGN: A retrospective analysis of imaging findings of 21 patients with H1N1 flu, admitted to our hospital from September 2014-March 2015, was done. METHODS AND MATERIAL: All patients with H1N1 virus infection were included. Mode of hospital admission, concomitant liver disease, clinical findings, liver function tests and viral markers for hepatitis B and C infections were studied. Chest imaging findings on CXR or HRCT were analyzed. Correlation with CLD, clinical course, mortality and morbidity was reviewed. STATISTICAL ANALYSIS USED: Analysis was performed with SPSS version. Mean ± standard deviation (SD), number and percentage, chi-square or Fisher exact test, t-test and odds ratio were calculated as appropriate. RESULTS: The mean age was 43.52 ± 14.2 years (18 males, 3 females). Positive CXR and HRCT findings were found in 14/21 (66.7%) and 19/21 (90.5%) respectively. Commonest abnormalities observed were bilateral consolidation and ground glass opacities (9/21, 42.9% each). Mid zone distribution was seen in 15/21(71.4%). Underlying CLD was seen in 14/21 (66.7%) with positive findings in 11/14 (78.6%) on CXR and 13/14 (92.9%) on HRCT. Presence of pleural effusion (PE)(57.1%) and lymphadenopathy(50%) were statistically significant (p<0.05). Median length of hospital stay was longer: 12 days (IQR 1-30) with significant mortality rate in this group. CONCLUSIONS: Imaging profile of patients with H1N1 influenza revealed that patients with underlying CLD were more likely to have imaging findings, pleural effusion, lymphadenopathy, receive intensive care and longer hospital stay with increased risk for mortality.
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Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Adulto , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Systemic inflammatory response syndrome (SIRS) is associated with an increased risk of hepatic encephalopathy, renal failure, and poor outcome in patients with cirrhosis; however, there is a paucity of studies on this entity for severe alcoholic hepatitis (SAH). AIM: To evaluate SIRS at baseline as a predictor of development of acute kidney injury (AKI) and mortality in patients with SAH. METHODS: Consecutive in-patients with SAH (discriminant function ≥ 32) without AKI at baseline were followed up for the development and progression of AKI (AKIN criteria). RESULTS: Of the 365 patients (mean age 45.5 ± 9.5, 356 males), SIRS at baseline was present in 236 (64.6%). AKI developed in 122 (33.4%), of which 50 (40.9%) had progression of AKI. SIRS was associated with bacterial infections in 96 (40.6%) and in 140 (59.3%) occurred in the absence of proven infection microbiologically. The presence of SIRS predicted both AKI development (p < 0.001, OR 2.9, 95% CI 1.7-4.8) and AKI progression (p = 0.002, OR 3.27, 95% CI 1.48-7.21). Resolution of AKI also had a significant inverse association with SIRS (p = 0.001). High MELD score (p = 0.002, HR 1.1, 95% CI 1.02-1.09), in-hospital progression of AKI (p = 0.04, HR 1.54, 95% CI 1.003-2.38), and SIRS (p = 0.004, HR 1.98, 95% CI 1.25-3.1) were significant predictors of 90-day mortality (model 1), while high MELD score (p < 0.001, HR 1.1, 95% CI 1.04-1.12) and bacterial infections (p = 0.001, HR 1.8, 95% CI 1.27-2.6) were independent predictors of mortality in the second multivariate model (model 2). CONCLUSION: SIRS at admission predicts both the development of AKI and 90-day mortality in patients with SAH. This could definitely have a therapeutic and prognostic implication.
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Injúria Renal Aguda/epidemiologia , Infecções Bacterianas/epidemiologia , Hepatite Alcoólica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Injúria Renal Aguda/mortalidade , Adulto , Estudos de Coortes , Progressão da Doença , Doença Hepática Terminal , Feminino , Encefalopatia Hepática/epidemiologia , Hepatite Alcoólica/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Peritonite/epidemiologia , Pneumonia Bacteriana/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Infecções Urinárias/epidemiologiaRESUMO
Strongyloidiosis is usually an asymptomatic chronic nematodal disease. The term hyperinfection is used to denote autoinfection, a phenomenon in which the number of worms increases enormously. Development or exacerbation of gastrointestinal and pulmonary symptoms is seen, (A) and the detection of increased numbers of larvae in stool and or sputum is the hallmark. It is known to occur with a change in immune status of the host; this can occur due to immunosuppressants. Cytomegalovirus (CMV) is also known to suppress host immunity. Due to the nonspecific presentation, the diagnosis is frequently missed, and the outcome remains poor with 15-87% mortality despite therapy. We report here a case of Strongyloides stercoralis hyperinfection following immunosuppressive therapy for autoimmune hepatitis and concomitant CMV infection with purpura fulminance and frank sepsis, with fatal outcome.
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BACKGROUND & AIMS: Serum ferritin is a known marker of hepatic necro-inflammation and has been studied to predict 1 year mortality and post-transplant survival in decompensated cirrhotics. However, there are no studies evaluating ferritin as a predictor of early mortality. We investigated whether serum ferritin levels could predict 15 day and 30 day mortality in patients with decompensated cirrhosis. METHODS: 318 patients with decompensated cirrhosis were included. RESULTS: Patients of decompensated cirrhosis [257 males, mean age of 51 [±13]years, were followed for a median of 31 days. Serum ferritin levels were significantly different between survivors and non-survivors [p<0.001] and showed significant correlation with MELD score [p<0.001], CTP score [p<0.001], leucocyte counts [TLC] [p<0.001], serum sodium [p<0.001], ACLF grades [p=0.005], spontaneous bacterial peritonitis [SBP] [p=0.02], hepatic encephalopathy [HE] [p<0.001] and hepatorenal syndrome [HRS] [p=0.012]. Serum ferritin, etiology, MELD, HE, CTP score, sodium, TLC, and ACLF grades were significant predictors of mortality on univariate analysis. Ferritin [p=0.04, HR 1.66 95% CI (1.02-2.73)] was a significant predictor of early mortality on multivariate analysis along with HE [p=0.006, HR 3.47 95% CI (2.13-8.41)] (Model 1), TLC [p=0.02, HR 1.81 95% CI (1.06-3.07)] (Model 2), ACLF grades [p=0.018, HR 2.013,95% CI (1.126-3.60)], and CTP score [p<0.0001, HR 1.36 95% CI (1.17-1.59)] (Model 3). CONCLUSION: Serum ferritin levels correlate with severity of hepatic decompensation and are associated with early liver related death independent of the MELD score in hospitalized patients with decompensated cirrhosis. This could also have a potential therapeutic implication.
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Ferritinas/sangue , Cirrose Hepática/sangue , Cirrose Hepática/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBsAg response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of ≥ 1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg-positive and HBeAg-negative patients, respectively. Early decline in HBsAg levels at week 4 was predictive of subsequent significant HBsAg level decline. HBeAg seroconversion occurred in 29.9% of HBeAg-positive patients. On multinomial logistic regression, HBsAg level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBeAg seroconversion and HBV DNA level decline from baseline at week 4 and week 12 (OR = 3.704; 95% CI = 1.511-9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032-2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV-infected patients treated with tenofovir exhibit a significant (≥ 1.0 log) decline in HBsAg levels. Early decline in HBsAg levels at week 4 was predictive of subsequent and significant HBsAg level decline. The HBsAg decline did not correlate with HBeAg seroconversion in HBeAg-positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion.
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Adenina/análogos & derivados , Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Adolescente , Adulto , Idoso , DNA Viral/sangue , Monitoramento de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir , Fatores de Tempo , Adulto JovemRESUMO
Paraduodenal pancreatitis is a distinct clinicopathological entity involving the duodenum and the pancreatic tissue in the vicinity of the minor papilla. Most afflicted patients are young alcoholic males who present clinically with upper abdominal pain, weight loss, nausea, and vomiting. Pancreatic tissue elements in the duodenal wall and impedance to exocrine pancreatic secretions at the minor papilla are key factors in the pathogenesis of this condition. On imaging, the condition may manifest as a solid fibrotic mass around the minor papilla or as cysts in the duodenum and the pancreaticoduodenal groove. Duodenal stenosis, biliary strictures, chronic calcifying pancreatitis, and pancreatic ductal dilatation are also often observed.
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Diagnóstico por Imagem , Duodenopatias/diagnóstico , Duodenopatias/terapia , Pancreatite Crônica/diagnóstico , Meios de Contraste , Duodenopatias/patologia , Humanos , Pancreatite Crônica/patologia , Pancreatite Crônica/terapiaRESUMO
BACKGROUND: Nosocomial urinary tract infections (UTIs) are common in catheterized patients. Fungal UTI has become an important nosocomial problem over the past decade. The microbiology of candiduria is rapidly evolving and new trends are being reported. AIMS: To study the microbiological trends and antifungal resistance profile of Candida in urine of catheterized chronic liver disease (CLD) patients at a super specialty hepatobiliary tertiary-care center. MATERIALS AND METHODS: urine samples were collected by sterile technique, processed by semi-quantitative method as per the standard protocols. Direct microscopic examination of urine sample was also done to look for the presence of pus cells, red blood cells, casts, crystals or any bacterial or fungal element. RESULT: A total of 337 yeast isolates were obtained from catheterized patients, non-albicans Candida spp. emerged as the predominant pathogen and was responsible for 67.06% of nosocomial fungal UTI. Candida tropicalis accounted for 34.71% of the cases, whereas Candida albicans grew in 32.93%, Candida glabrata 16.32%, rare Candida spp. Nearly 11.5% (Candida hemolunii to be confirmed by molecular methods). Antifungal sensitivity varied non-albicans species except C. tropicalis, Candida parapsilosis were more often resistant to antifungal drugs. CONCLUSION: Nosocomial Candida UTIs in CLD patients is common, due to the cumulative pressure of contributing factors such as urinary instrumentation and prolonged use of broad-spectrum antibiotics. Non-albicans Candida were found to outnumber C. albicans in catherized CLD patients. Risk of strain persistence is also higher with non-albicans Candida. Thus, species identification and susceptibility testing is a must for appropriate management of such patients.
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OBJECTIVES: Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE. METHODS: In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay. RESULTS: A total of 120 patients (mean age 39.4±9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7±2.8 and the MELD (model for end-stage liver disease) score was 24.6±4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8±3.4 vs. 8.2±4.6 days, P=0.001). CONCLUSION: Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.
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Fármacos Gastrointestinais/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Lactulose/uso terapêutico , Rifamicinas/uso terapêutico , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fármacos Gastrointestinais/administração & dosagem , Encefalopatia Hepática/mortalidade , Humanos , Lactulose/administração & dosagem , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Rifamicinas/administração & dosagem , Rifaximina , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN-γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCRζ-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection.
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Linfócitos T CD8-Positivos/imunologia , Hepatite B/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/análise , Antígenos de Superfície da Hepatite B/sangue , Humanos , Recém-Nascido , Interferon gama/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/análise , Gravidez , Adulto JovemRESUMO
Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end-point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n=128) or placebo (n=131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow-up, only 62/222 (28%) reached primary end-point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P=0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P=0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end-point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV infection with good immune response 28%. Women who were anti-HBe positive were a low-risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg-positive status and negativity for anti-HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg-positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother-to-baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother-to-child transmission of HBV infection.
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Anticorpos Anti-Hepatite B/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Imunoglobulinas Intravenosas/administração & dosagem , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adulto , Feminino , Seguimentos , Humanos , Masculino , Placebos/administração & dosagem , Gravidez , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 µg q4wk or Peg-IFNα-2a 180 µg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 µg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research.
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Albuminas/efeitos adversos , Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Pulmão/efeitos dos fármacos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Adulto , Albuminas/administração & dosagem , Antivirais/administração & dosagem , Feminino , Humanos , Interferon-alfa/administração & dosagem , Pulmão/diagnóstico por imagem , Pulmão/fisiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Capacidade de Difusão Pulmonar , Radiografia Torácica , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Ribavirina/administração & dosagem , EspirometriaRESUMO
Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.
Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Cirrose Hepática/complicações , Falência Hepática , Nucleosídeos/administração & dosagem , Pirimidinonas/administração & dosagem , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/efeitos adversos , DNA Viral/sangue , Método Duplo-Cego , Feminino , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Nucleosídeos/efeitos adversos , Estudos Prospectivos , Pirimidinonas/efeitos adversos , Índice de Gravidade de Doença , Telbivudina , Timidina/análogos & derivados , Resultado do Tratamento , Adulto JovemRESUMO
Albinterferon alfa-2b (albIFN) is a fusion protein of recombinant human albumin/recombinant interferon (IFN)-α-2b, with â¼200-h half-life. Safety/efficacy of albIFN q4wk was evaluated in 391 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to one of four open-label treatment groups: pegylated IFN (Peg-IFN)-α-2a 180 µg qwk or albIFN 900, 1200 or 1500 µg q4wk, plus oral ribavirin 800 mg/day, for 24 weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <20 IU/mL 24 weeks post-treatment). SVR rates were as follows: 85%, 76%, 76% and 78% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 µg, respectively (P = NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4) were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not influenced by interleukin 28B genotype, although rapid virologic response rates were greater with interleukin 28B CC (P = NS). Serious adverse event rates were as follows: 4%, 11%, 3% and 3% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 µg, respectively. No increase in serious/severe respiratory events was noted with albIFN. Fewer absolute neutrophil count reductions <750/mm(3) occurred with albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions <10 g/dL were less frequent with albIFN 900 and 1200 µg vs 1500 µg and Peg-IFNα-2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN administered q4wk produced fewer haematologic reductions than Peg-IFNα-2a, but had numerically lower SVR rates (P = NS) in patients with chronic HCV genotype 2/3.