RESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with impaired renal function, and both diseases often occur alongside other metabolic disorders. However, the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear. The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients. METHODS: All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation. RESULTS: Among 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05). CONCLUSIONS: Agile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.
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Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Adulto , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios Prospectivos , Prevalencia , Factores de Riesgo , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Cirrosis Hepática/complicaciones , RiñónRESUMEN
We aimed to compare the severity of liver disease, metabolic profile and cardiovascular disease (CVD) risk of chronic hepatitis B (CHB) patients with and without hepatic steatosis and patients with non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD and CHB were prospectively enrolled from 10 Asian centres. Fibroscan was performed for all patients and hepatic steatosis was defined based on controlled attenuation parameter >248 dB/m. CVD risk was assessed using the Framingham risk score. The data for 1080 patients were analysed (67% NAFLD, 33% CHB). A high proportion (59%) of CHB patients had hepatic steatosis. There was a significant stepwise increase in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, controlled attenuation parameter and liver stiffness measurement, from CHB patients without hepatic steatosis to CHB patients with hepatic steatosis to NAFLD patients (p < 0.001 for all comparisons). There was a significant stepwise increase in the proportion of patients with metabolic syndrome and in CVD risk, with very high or extreme CVD risk seen in 20%, 48% and 61%, across the groups (p < 0.001 between CHB patients with and without hepatic steatosis and p < 0.05 between CHB patients with hepatic steatosis and NAFLD patients). In conclusion, there was a high proportion of CHB patients with hepatic steatosis, which should be diagnosed, as they may have more severe liver disease, so that this and their metabolic risk factors can be assessed and managed accordingly for a better long-term outcome.
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Enfermedades Cardiovasculares , Diagnóstico por Imagen de Elasticidad , Hepatitis B Crónica , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Estudios Prospectivos , Índice de Masa Corporal , Factores de Riesgo , AsiaRESUMEN
BACKGROUND: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver-related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non-invasive tests (NITs) including FIB-4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. AIM: To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. METHODOLOGY: This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. RESULTS: 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62-0.69) for FIB-4 and 0.63 (95% CI 0.60-0.66) for APRI. The specificities were 0.94 for FIB-4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63-0.71) for FIB-4, 0.60 (95% CI 0.56-0.64) for APRI and 0.65 (95% CI 0.61-0.69) for NFS. The specificities were 0.95 for FIB-4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. CONCLUSION: The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB-4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects.
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Hígado Graso , Hepatitis B Crónica , Masculino , Humanos , Adulto , Femenino , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/patología , Hígado Graso/diagnóstico , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Valor Predictivo de las Pruebas , Biopsia , Aspartato Aminotransferasas , Índice de Severidad de la Enfermedad , Biomarcadores , Curva ROCRESUMEN
OBJECTIVE: To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. METHODS: A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). RESULTS: There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. CONCLUSIONS: We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.
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Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Gastroscopía , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Humanos , Metaplasia , Lesiones Precancerosas/epidemiología , Estudios Prospectivos , Factores de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/etiologíaRESUMEN
BACKGROUND AND AIMS: HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection. APPROACH AND RESULTS: We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF). Immunosuppressive Drug Resistant Armored TCR-T cells of desired specificity (HBV or Epstein-Barr virus) were then engineered by concomitantly electroporating mRNA encoding specific TCRs and mutated variants of calcineurin B (CnB) and inosine-5'-monophosphate dehydrogenase (IMPDH), and their function was assessed through intracellular cytokine staining and cytotoxicity assays in the presence of TAC and MMF. Liver transplanted HBV-HCC patients receiving different immunosuppressant drugs exhibited varying levels of activated (CD39+ Ki67+ ) peripheral blood mononuclear cells after HBV-TCR T-cell infusions that positively correlate with clinical efficacy. In vitro experiments with TAC and MMF showed a potent inhibition of TCR-T cell polyfunctionality. This inhibition can be effectively negated by the transient overexpression of mutated variants of CnB and IMPDH. Importantly, the resistance only lasted for 3-5 days, after which sensitivity was restored. CONCLUSIONS: We engineered TCR-T cells of desired specificities that transiently escape the immunosuppressive effects of TAC and MMF. This finding has important clinical applications for the treatment of HBV-HCC relapses and other pathologies occurring in organ transplanted patients.
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Carcinoma Hepatocelular/cirugía , Rechazo de Injerto/prevención & control , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/terapia , Linfocitos T/trasplante , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Técnicas de Cocultivo , Resistencia a Medicamentos/genética , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Células Hep G2 , Hepatitis B/patología , Hepatitis B/cirugía , Hepatitis B/virología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/metabolismo , Humanos , Inmunoterapia Adoptiva/métodos , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/patología , Hígado/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Trasplante de Hígado/efectos adversos , Ácido Micofenólico/farmacología , Ácido Micofenólico/uso terapéutico , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Ingeniería de Proteínas , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Tacrolimus/farmacología , Tacrolimus/uso terapéuticoRESUMEN
Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti-hepatitis C virus antibody (anti-HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at-risk population, such as immunocompromised hosts and end-stage renal failure patients on hemodialysis. HCV antigen (Ag) could be useful in identifying the ongoing infection in such clinical scenarios. Hence, we aimed to study the utility of HCV Ag testing for the diagnosis of acute and chronic hepatitis C. Of 89 samples studied, 19 were from acute hepatitis C patients who were immunocompromised or were on hemodialysis, 43 were from active chronic hepatitis C patients and 27 were from patients treated for chronic hepatitis C. All samples were tested for HCV Ag using the Abbott ARCHITECT HCV Ag assay. HCV Ag was reactive in 19/19 samples from acute hepatitis C patients and 42/43 samples from active chronic hepatitis C patients. It was nonreactive in all samples from treated patients. The test showed a sensitivity and specificity of 98.4% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 96.4%, respectively. The HCV antigen test has high clinical sensitivity and specificity and is useful for the diagnosis of acute and chronic hepatitis C infection in at-risk and immunocompromised patients. Its short turnaround time and relatively low cost are advantageous for use in patients on hemodialysis and other at-risk patients who require monitoring of HCV infection and reinfection.
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Hepacivirus/genética , Antígenos de la Hepatitis C/análisis , Hepatitis C Crónica/diagnóstico , Hepatitis C/diagnóstico , Huésped Inmunocomprometido , Pruebas Inmunológicas/métodos , Adulto , Diagnóstico Precoz , Femenino , Hepacivirus/química , Hepatitis C/sangre , Hepatitis C/prevención & control , Antígenos de la Hepatitis C/sangre , Antígenos de la Hepatitis C/inmunología , Hepatitis C Crónica/sangre , Hepatitis C Crónica/prevención & control , Humanos , Pruebas Inmunológicas/economía , Pruebas Inmunológicas/normas , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Valor Predictivo de las Pruebas , ARN Viral/sangre , ARN Viral/genética , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear. OBJECTIVES: We aim to describe the prescription pattern of PGx drugs among adult medical outpatients. METHODS: We estimated the 5-year cumulative incidence (CI) for receiving three groups of PGx drugs using competing risks analysis: (i) all PGx drugs, (ii) PGx drugs with guidelines and (iii) PGx drugs with serious clinical effects. Comparisons of CIs were also done by patient characteristics using Gray's test. RESULTS: The 5-year CIs of receiving any new PGx drug, PGx drug with guidelines and serious clinical effects were 42.6%, 37.3% and 13.7%, respectively. The 5-year CI of receiving any new PGx drug was higher for patients >40 years old (43.6% vs ≤40 years old 36.0%, P < 2.2 × 10-22 ), Malays and Indians (50.3% and 49.8% vs Chinese 31.1%, P < 2.2 × 10-22 ), those who attended one of the following four specialties at the index visit compared to other specialties (infectious diseases [46.2% vs 42.6%, P = 2.9 × 10-4 ], psychiatry [48.3% vs 42.3%, P = 7.4 × 10-13 ], renal [49.8% vs 40.9%, P < 2.2 × 10-22 ], and rheumatology and immunology [54.8% vs 41.7%, P < 2.2 × 10-22 ]) and those prescribed ≥5 drugs at index visit (51.7% vs 0-4 drugs 41.7%, P < 2.2 × 10-22 ). CONCLUSIONS: Medical outpatients have a substantial probability of benefiting from pre-emptive PGx testing and this is higher in certain subgroups of patients.
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Pruebas de Farmacogenómica , Psiquiatría , Adulto , Humanos , Pacientes Ambulatorios , Farmacogenética , PrescripcionesRESUMEN
BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome. Worryingly, it has been increasingly reported among nonobese patients. This study aims to analyse patient characteristics of biopsy-proven NAFLD in an Asian cohort and explore differences stratified by body mass index (BMI). METHODS: Clinical, laboratory, and histological data were collected from 263 adults with biopsy-proven NAFLD. Patients with and without obesity (BMI cut-off 25) were compared. The ability to predict advanced liver fibrosis with three non-invasive scores, the NAFLD Fibrosis score (NFS), Fibrosis-4 (FIB4), and the aspartate aminotransferase to platelet ratio index (APRI), was compared. RESULTS: Obese subjects had a lower mean age (49.5 ± 12.5 vs 54.0 ± 12.9 years, P = 0.017), a higher prevalence of diabetes (52.4% vs 36.8%, P = 0.037), and a higher waist circumference (113.9 ± 16.0 cm vs 87.0 ± 18.4 cm, P = 0.022). The prevalence of dyslipidaemia (68.0% vs 61.4%, P = 0.353) and hypertension (61.7% vs 49.1%, P = 0.190) was comparable between the two groups. The distribution of non-alcoholic steatohepatitis (NASH) (63.1% versus 61.4%, P = 0.710) and advanced fibrosis (31.6% versus 26.3%, P = 0.447) were also similar in both groups. All three non-invasive scores (NFS, FIB4, and APRI) performed poorly in predicting advanced fibrosis in nonobese patients with NAFLD. The FIB4 was the most accurate non-invasive score in predicting advanced fibrosis in the obese group. CONCLUSIONS: Obese and nonobese patients are equally at risk of NASH and advanced fibrosis. While the FIB4 is the most accurate non-invasive score in predicting advanced fibrosis among obese individuals, further research is warranted to develop a nonobese specific score to correctly identify nonobese NAFLD patients with advanced fibrosis.
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Enfermedad del Hígado Graso no Alcohólico , Obesidad , Adulto , Anciano , Pueblo Asiatico , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/etiología , Puntuaciones en la Disfunción de Órganos , Recuento de Plaquetas , RiesgoRESUMEN
BACKGROUND: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria. AIM: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection. METHODS: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included. The expanded Baveno-VI criteria were applied to evaluate the sensitivity (SS), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the presence of high-risk varices (HRV). RESULTS: Among 165 cACLD patients included, 17 (10.3%) had HRV. The commonest etiology of cACLD was chronic hepatitis B (36.4%) followed by NAFLD (20.0%). Application of expanded Baveno-VI criteria avoided more screening gastroscopy (43.6%) as compared to the original Baveno-VI criteria (18.8%) without missing more HRV (1 with both criteria). The overall SS, SP, PPV and NPV of the expanded Baveno-VI criteria in predicting HRV were 94.1%, 48.0%, 17.2% and 98.6%, respectively. CONCLUSION: Application of the expanded Baveno-VI criteria can safely avoid screening gastroscopy in 43.6% of cACLD patients with an excellent ability to exclude HRV.
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Pueblo Asiatico , Enfermedad Hepática en Estado Terminal/diagnóstico por imagen , Enfermedad Hepática en Estado Terminal/etnología , Gastroscopía/normas , Tamizaje Masivo/normas , Anciano , Estudios de Cohortes , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Gastroscopía/métodos , Hepatitis B Crónica/diagnóstico por imagen , Hepatitis B Crónica/etnología , Hepatitis B Crónica/cirugía , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is often associated with hepatitis B virus (HBV) infection. Cells of most HBV-related HCCs contain HBV-DNA fragments that do not encode entire HBV antigens. We investigated whether these integrated HBV-DNA fragments encode epitopes that are recognized by T cells and whether their presence in HCCs can be used to select HBV-specific T-cell receptors (TCRs) for immunotherapy. METHODS: HCC cells negative for HBV antigens, based on immunohistochemistry, were analyzed for the presence of HBV messenger RNAs (mRNAs) by real-time polymerase chain reaction, sequencing, and Nanostring approaches. We tested the ability of HBV mRNA-positive HCC cells to generate epitopes that are recognized by T cells using HBV-specific T cells and TCR-like antibodies. We then analyzed HBV gene expression profiles of primary HCCs and metastases from 2 patients with HCC recurrence after liver transplantation. Using the HBV-transcript profiles, we selected, from a library of TCRs previously characterized from patients with self-limited HBV infection, the TCR specific for the HBV epitope encoded by the detected HBV mRNA. Autologous T cells were engineered to express the selected TCRs, through electroporation of mRNA into cells, and these TCR T cells were adoptively transferred to the patients in increasing numbers (1 × 104-10 × 106 TCR+ T cells/kg) weekly for 112 days or 1 year. We monitored patients' liver function, serum levels of cytokines, and standard blood parameters. Antitumor efficacy was assessed based on serum levels of alpha fetoprotein and computed tomography of metastases. RESULTS: HCC cells that did not express whole HBV antigens contained short HBV mRNAs, which encode epitopes that are recognized by and activate HBV-specific T cells. Autologous T cells engineered to express TCRs specific for epitopes expressed from HBV-DNA in patients' metastases were given to 2 patients without notable adverse events. The cells did not affect liver function over a 1-year period. In 1 patient, 5 of 6 pulmonary metastases decreased in volume during the 1-year period of T-cell administration. CONCLUSIONS: HCC cells contain short segments of integrated HBV-DNA that encodes epitopes that are recognized by and activate T cells. HBV transcriptomes of these cells could be used to engineer T cells for personalized immunotherapy. This approach might be used to treat a wider population of patients with HBV-associated HCC.
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Carcinoma Hepatocelular/terapia , ADN Viral , Virus de la Hepatitis B/genética , Inmunoterapia Adoptiva/métodos , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Recurrencia Local de Neoplasia/genética , Linfocitos T/inmunología , Transcriptoma/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Electroporación , Epítopos de Linfocito T/biosíntesis , Epítopos de Linfocito T/genética , Epítopos de Linfocito T/inmunología , Antígenos de la Hepatitis B/genética , Antígenos de la Hepatitis B/inmunología , Humanos , Inmunoterapia Adoptiva/efectos adversos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Trasplante de Hígado , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Biosíntesis de Proteínas , ARN Viral/genética , Receptores de Antígenos de Linfocitos T , Integración Viral , alfa-Fetoproteínas/metabolismoRESUMEN
BACKGROUND & AIMS: Lifestyle modification is the cornerstone for the management of non-alcoholic fatty liver disease (NAFLD). We aim to understand lifestyle habits of NAFLD patients, compare across Asian regions and identify area of deficiency. METHODS: In the multi-centre controlled attenuation parameter (CAP)-Asia study, we collected clinical data and lifestyle habit data of NAFLD patients from Singapore, mainland China, Hong Kong, Taiwan and Malaysia. Physical activity was assessed using the International Physical Activity Questionnaire. RESULTS: A total of 555 patients were included in the final analysis (mean age 54.5 ± 11.2 years, 54.1% men and median liver stiffness 6.7 kPa). More patients from mainland China (27.4%) and Taipei (25.0%) were smokers. Modest drinking was more common in Taiwan (25.0%) and Hong Kong (18.2%); only 1.3% had binge drinking. Majority of patients drank coffee (64.0%) and tea (80.2%), with varying amounts and durations in different regions. Soft drinks consumption was most common in Singapore (62.2%) and Malaysia (57.7%). Only 29.7% of patients met the Physical Activity Guidelines Recommendations, with no major differences across regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity, and sitting time was an independent factor associated with high CAP. Tea and coffee consumption were independently associated with high CAP and liver stiffness, respectively. CONCLUSIONS: Despite some heterogeneity, unhealthy lifestyle and physical inactivity are common across Asian regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity. Healthcare providers may use the comparative data to identify areas of deficiency.
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Enfermedad del Hígado Graso no Alcohólico , Adulto , Anciano , China , Femenino , Hábitos , Hong Kong/epidemiología , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Conducta Sedentaria , Singapur/epidemiología , Taiwán/epidemiologíaRESUMEN
BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) patients often have dyslipidemia, and optimal treatment of dyslipidemia lowers the risk of cardiovascular disease and mortality. Our aim was to study the prescription of statin and low-density lipoprotein cholesterol treatment targets in NAFLD patients. METHODS: Consecutive NAFLD patients attending five clinics in Asia were included in this study. The 10-year cardiovascular disease risk was calculated based on the Framingham Heart Study, and patients were categorized as moderate, high, or very high risk for cardiovascular disease on the basis of the American Association of Clinical Endocrinologist 2017 Guidelines. The low-density lipoprotein cholesterol treatment goal for each of the risk groups was 2.6, 2.6, and 1.8 mmol/L, respectively. RESULTS: The data for 428 patients were analyzed (mean age 54.4 ± 11.1 years, 52.1% male). Dyslipidemia was seen in 60.5% (259/428), but only 43.2% (185/428) were on a statin. The percentage of patients who were at moderate, high, and very high risk for cardiovascular disease was 36.7% (157/428), 27.3% (117/428), and 36.0% (154/428), respectively. Among patients who were on a statin, 58.9% (109/185) did not achieve the treatment target. Among patients who were not on a statin, 74.1% (180/243) should be receiving statin therapy. The percentage of patients who were not treated to target or who should be on statin was highest among patients at very high risk for cardiovascular disease at 79.6% (78/98) or 94.6% (53/56), respectively. CONCLUSION: This study highlights the suboptimal treatment of dyslipidemia and calls for action to improve the treatment of dyslipidemia in NAFLD patients.
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Dislipidemias/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Dislipidemias/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
Hepatitis B is leading cause of liver related morbidity in Asia with predominant genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with advanced fibrosis (Ishak ≥ 4). Sixty-three treatment-naïve patients identified with advanced fibrosis on liver-biopsy performed between 1998 and 2000 at Singapore General Hospital. FFPE tissue was available for 59 patients and serum for 42 patients. HBV-DNA was quantified in serum and liver while qHBsAg quantified in serum. Patients were followed-up till December 2015. The median age was 47 ± 16 years, with 77.7% males. About 19 were GT-B, 43 patients were GT-C, and 1 had both GT-B and C. Mean follow-up was 13.5 years. The median serum HBV-DNA was 6.25 ± 2.17 and 6.58 ± 1.85 log IU/ml, serum HBsAg was 3.29 ± 0.80 and 3.45 ± 1.85 log IU/ml, and intrahepatic HBV-DNA was 0.52 ± 3.73 copies/cell and 0.4 ± 1.37 copies/cell in the GT-B and C, respectively (P > 0.1 in all). Complete cirrhosis (Ishak-6) was present in 47.6%, Ishak-5 fibrosis in 33.3%, and Ishak-4 fibrosis in 19% at recruitment. On follow-up HCC developed in 8/43 in GT-C and in 3/19 GT-B (P = 0.86). Advanced age and cirrhosis were significant factors for development of HCC. No difference in serum HBV-DNA, qHBsAg or intrahepatic HBV-DNA was seen in the two genotypes. HCC development seen over long-term follow-up was independent of genotypes in patients with advanced fibrosis. J. Med. Virol. 89:845-848, 2017. © 2016 Wiley Periodicals, Inc.
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Carcinoma Hepatocelular/epidemiología , Genotipo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Cirrosis Hepática/complicaciones , Adulto , Anciano , Asia , Biopsia , ADN Viral/sangre , Femenino , Estudios de Seguimiento , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Singapur/epidemiologíaRESUMEN
BACKGROUND & AIM: Diabetes mellitus has been linked to cirrhosis-related mortality in Western populations, but less is known about this relationship in Asian populations. We studied the impact of diabetes on the risk of cirrhosis mortality in a population-based cohort among Chinese in Singapore. METHODS: We used data collected and analysed from the Singapore Chinese Health Study, a prospective community-based cohort of 63 275 subjects aged 45-74 years during enrolment between 1993 and 1998. Information on diet, lifestyle and medical history was collected via structured questionnaire. Mortality cases from cirrhosis in the cohort were identified via linkage with nationwide death registry up to 31 December 2014. Cox proportional regression models were used to estimate the associations with adjustment for risk factors of cirrhosis. RESULTS: After a mean follow-up of 16.9 years, there were 133 deaths from cirrhosis. Diabetes was associated with an increased risk of cirrhosis mortality (hazard ratio [HR]: 2.80; 95% confidence interval [CI]: 2.04-3.83), and for both viral (HR: 2.20; 95% CI: 1.18-4.11) and non-viral hepatitis-related cirrhosis mortality (HR: 3.06; 95% CI: 2.13-4.41). The association between diabetes and non-viral hepatitis-related cirrhosis mortality was stronger among participants of body mass index (BMI) less than 23 kg/m2 (HR: 7.11; 95% CI: 3.42-14.79) compared to heavier individuals (HR: 2.28; 95% CI: 1.20-4.35) (Pinteraction =0.02). CONCLUSION: Diabetes is a risk factor for cirrhosis mortality, especially for non-viral hepatitis-related cirrhosis in population with BMI considered low or normal in Asia.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Cirrosis Hepática/etiología , Cirrosis Hepática/mortalidad , Anciano , Pueblo Asiatico/estadística & datos numéricos , Dieta , Femenino , Estudios de Seguimiento , Humanos , Estilo de Vida , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Singapur/epidemiología , Análisis de SupervivenciaRESUMEN
UNLABELLED: Limited experimental and epidemiologic data suggest that coffee may reduce hepatic damage in chronic liver disease. The association between consumption of coffee and other beverages and risk of cirrhosis mortality was evaluated in the Singapore Chinese Health Study. This is a prospective population-based cohort of 63,275 middle-aged and older Chinese subjects who provided data on diet, lifestyle, and medical histories through in-person interviews using a structured questionnaire at enrollment between 1993 and 1998. Mortality from cirrhosis in the cohort was ascertained through linkage analysis with nationwide death registry. After a mean follow-up of 14.7 years, 114 subjects died from cirrhosis; 33 of them from viral hepatitis B (29%), two from hepatitis C (2%), and 14 from alcohol-related cirrhosis (12%). Compared to nondrinkers, daily alcohol drinkers had a strong dose-dependent positive association between amount of alcohol and risk of cirrhosis mortality. Conversely, there was a strong dose-dependent inverse association between coffee intake and risk of nonviral hepatitis-related cirrhosis mortality (P for trend = 0.014). Compared to non-daily coffee drinkers, those who drank two or more cups per day had a 66% reduction in mortality risk (hazard ratio [HR] = 0.34, 95% confidence interval [CI] = 0.14-0.81). However, coffee intake was not associated with hepatitis B-related cirrhosis mortality. The inverse relationship between caffeine intake and nonviral hepatitis-related cirrhosis mortality became null after adjustment for coffee drinking. The consumption of black tea, green tea, fruit juices, or soft drinks was not associated with risk of cirrhosis death. CONCLUSION: This study demonstrates the protective effect of coffee on nonviral hepatitis-related cirrhosis mortality, and provides further impetus to evaluate coffee as a potential therapeutic agent in patients with cirrhosis.
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Consumo de Bebidas Alcohólicas/mortalidad , Bebidas , Café , Cirrosis Hepática/mortalidad , Pueblo Asiatico/estadística & datos numéricos , Bebidas Gaseosas , Conducta Alimentaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Singapur/epidemiología , TéRESUMEN
BACKGROUND: Liver stiffness measurement (LSM) by transient elastography is a popular noninvasive test of fibrosis. Traditional LSM cutoffs dichotomize patients and do not clearly indicate the confidence of diagnosis. AIM: We derived and validated probability functions of fibrosis and cirrhosis based on LSM and determined the effect of alanine aminotransferase (ALT) on the scores. METHODS: Consecutive chronic hepatitis B patients who underwent liver function tests, LSM, and liver biopsies at six European and Asian centers (2/3 in the training cohort and 1/3 in the validation cohort) were recruited. Binary logistic regression was performed to predict the probabilities of different fibrosis stages based on LSM and/or ALT. RESULTS: A total of 1,051 patients were included in the final analysis (53 % with ALT ≥ 60 IU/L, 32 % F2, 20 % F3, and 24 % F4). The probability functions (LiFA-HBV score) with and without ALT adjustment closely mirrored the proportion with different fibrosis stages in both the training and validation cohorts. For a range of up to 300 IU/L, ALT maintained a weak linear relationship with LSM for each fibrosis stage (r (2) = 0.018-0.13). Based on relative integrated discrimination improvement, the addition of ALT to the LiFA-HBV score increased the correct reclassification of F3-4 and F4 by 5 and 17 %, respectively. CONCLUSIONS: ALT increases LSM in a linear fashion in chronic hepatitis B patients at any fibrosis stage. The LiFA-HBV score accurately predicts the probability of fibrosis. ALT adjustment increases the rate of reclassification modestly and is not essential.
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Diagnóstico por Imagen de Elasticidad , Hepatitis B Crónica/diagnóstico , Cirrosis Hepática/diagnóstico , Hígado/patología , Adulto , Alanina Transaminasa/sangre , Asia , Biomarcadores/sangre , Biopsia , Distribución de Chi-Cuadrado , Pruebas Enzimáticas Clínicas , Europa (Continente) , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Humanos , Modelos Lineales , Hígado/virología , Cirrosis Hepática/sangre , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Pruebas de Función Hepática , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Probabilidad , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND & AIMS: The interaction between HBV replication and immune modulatory effects mediated by IFNα therapy is not well understood. We characterized the impact of HBV DNA replication on the early IFNα-induced immunomodulatory mechanisms. METHODS: We interrogated the transcriptional, serum cytokine/chemokine and cellular immune profiles of 28 patients with HBeAg+ chronic HBV infection (CHB) randomly assigned to one of 4 treatment cohorts (untreated n=5, weekly dosing of 360 µg Pegasys [PegIFNα] n=11, daily dose of 300 mg Viread [tenofovir disoproxil fumarate, TDF] n=6, or a combination of both n=6). Samples were characterized at multiple early time points through day 14 of therapy, after which all patients were given standard of care (180 µg Pegasys injected subcutaneously, weekly). RESULTS: PegIFNα induced a distinct and rapid up-regulation of IFN signaling pathway that coincided with increase detection of distinct serum cytokines/chemokines (IL-15, IL-6, and CXCL-10) and the up-regulation of the frequency of proliferating NK and activated total CD8+ T cells. IFNα treatment alone did not result in rapid decay of HBV replication and was not able to restore the defective HBV-specific T cell response present in CHB patients. In addition, the IFNα immune-stimulatory effects diminished after the first dose, but this refractory effect was reduced in patients where HBV replication was simultaneously inhibited with TDF. CONCLUSIONS: We present here the first comprehensive description of the early effects of IFNα treatment on immune and viral biomarkers in HBeAg+ CHB patients. Our results show that PegIFNα-induced innate immune activation directly benefits from the suppression of HBV replication.
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Antivirales/uso terapéutico , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Replicación Viral/efectos de los fármacos , Adolescente , Adulto , Estudios de Cohortes , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Recombinantes/uso terapéutico , Linfocitos T/inmunologíaRESUMEN
INTRODUCTION: Chronic hepatitis B (CHB) remains common in endemic regions, causing significant healthcare burden. Patients with CHB may need to be adherent to nucleoside analogue (NA) for a long period of time to prevent complications. This study aims to investigate the safety, efficacy and patient experience of a virtual monitoring clinic (VMC) in monitoring stable patients taking NA for CHB. METHODS: Patients on NA and regular follow-up were randomised to either VMC alternating with doctors' clinic visit or to a control group in which they continued standard follow-up by doctors. Therapy adherence was measured by medication possession ratio (MPR) for NA therapy, incidence of virological breakthrough and hepatocellular carcinoma (HCC) development at two years of follow-up. Patient acceptance was measured on a Likert scale of 1-10. RESULTS: A total 192 patients completed follow-up: 94 and 98 patients in the VMC and control groups, respectively. Mean age was 60.6 ± 10.8 years, with 95.3% Chinese ethnicity and 64.1% males. Age, gender, race, educational, employment and financial status were similar in both groups. Upon study completion, the majority of patients - 76 (80.9%) in VMC group and 74 (75.5%) in control group - had MPR ≥0.8; 88.8% were satisfied and rated VMC better than a traditional follow-up clinic with doctors only. More than 85% of patients rated ≥8/10 on the Likert scale for VMC, and preferred VMC over traditional clinic visits. Clinical outcomes observed were HCC development in one (1.1%) in the VMC group and four (4.1%) in the control group (p = 0.369). Two (2.1%) and one (1.0%) virological breakthroughs were observed in the VMC and control groups, respectively (p = 0.615). No incidence of HCC or abnormal blood tests were missed in the VMC arm. DISCUSSION: VMC is a viable and safe clinical model for monitoring stable CHB patients on NA therapy without compromising patients' adherence to medications and is preferred by patients.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Antivirales/uso terapéutico , IncidenciaRESUMEN
STUDY OBJECTIVE: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. DESIGN: Prospective, single-arm study. SETTING: National Cancer Centre, Singapore. PATIENTS: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment. INTERVENTION: Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment. MEASUREMENTS: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. MAIN RESULTS: A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. CONCLUSIONS: The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.