RESUMEN
BACKGROUND & AIMS: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk. METHODS: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development. RESULTS: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up. CONCLUSIONS: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir. LAY SUMMARY: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.
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Inteligencia Artificial/normas , Carcinoma Hepatocelular/fisiopatología , Hepatitis B Crónica/complicaciones , Adulto , Antivirales/farmacología , Antivirales/uso terapéutico , Inteligencia Artificial/estadística & datos numéricos , Pueblo Asiatico/etnología , Pueblo Asiatico/estadística & datos numéricos , Carcinoma Hepatocelular/etiología , Estudios de Cohortes , Simulación por Computador/normas , Simulación por Computador/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Guanina/análogos & derivados , Guanina/farmacología , Guanina/uso terapéutico , Hepatitis B Crónica/fisiopatología , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/fisiopatología , Masculino , Persona de Mediana Edad , República de Corea/etnología , Tenofovir/farmacología , Tenofovir/uso terapéutico , Población Blanca/etnología , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND AND AIM: This study aimed to investigate the clinical benefits of locoregional radiation therapy (RT) before, after, and concurrent with sorafenib therapy for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. METHODS: Patients treated with sorafenib for BCLC stage C HCC between January 2015 and December 2017 were retrospectively reviewed. In this study, only RT to locoregional sites, including the primary HCC, tumor thrombosis, or lymph node metastasis, was analyzed. Propensity score matching was used to adjust important baseline characteristics between groups. RESULTS: Among 398 patients treated with sorafenib, 68 (17.1%) patients were treated with locoregional RT. Median progression-free survival and overall survival (OS) were 2.2 and 9.5 months, respectively. In the multivariate analysis, locoregional RT (P < 0.001) was associated with a favorable OS. After 1:1 propensity score matching, patients who did not receive locoregional RT showed a worse OS than those who received RT (median 9.6 vs 15.7 months, P = 0.017). Whereas locoregional RT before/concurrent with sorafenib did not result in prolonged OS, locoregional RT after sorafenib showed significantly prolonged OS compared with sorafenib without locoregional RT (P = 0.003). Moreover, patients treated with ≥ 12 weeks of sorafenib significantly benefited from locoregional RT (15.3 vs 23.6 months, P = 0.046). CONCLUSION: Locoregional RT was associated with significantly longer survival in BCLC stage C HCC patients who were treated with sorafenib. Therefore, incorporating locoregional RT could improve the dismal prognosis for these patients.
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Carcinoma Hepatocelular , Quimioradioterapia , Neoplasias Hepáticas , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioradioterapia/métodos , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estadificación de Neoplasias , Estudios Retrospectivos , Sorafenib/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: There is insufficient research on digestive symptoms and outcomes following coronavirus disease (COVID-19) vaccination. We aimed to investigate digestive symptoms and related complications among South Koreans who were administered COVID-19 vaccines. METHODS: Forty-six patients (men: 22, women: 24) with a median age of 68 years (interquartile range:55.5, 73.8 years) who experienced digestive symptoms following COVID-19 vaccination between March 1 and July 30, 2021, were included. This retrospective single-center study collected information on clinical symptoms, laboratory tests, imaging results, comorbidities, complications, treatment type, and prognosis. RESULTS: Thirty-three (71.7%), nine (19.6%), and three (6.5%) patients were administered AZD1222 (AstraZeneca), BNT162b2 (Pfizer/BioNTech), and JNJ-78436735 (Johnson and Johnson) vaccines, respectively. Patients were classified with mild (25 patients, 54.3%), moderate (five patients, 10.9%), and severe (16 patients, 34.8%) based on disease severity. Digestive symptoms included abdominal pain, diarrhea, dyspepsia, and nausea, which usually developed within 1 day (78.3%) following the first vaccination. In total, 14 (30.4%) patients experienced only gastrointestinal symptoms, whereas 32 (69.6%) experienced non-gastrointestinal symptoms. Complications included enterocolitis (76%), acute kidney injury (9%), anaphylactoid reaction (2%), and duodenal perforation (2%). CONCLUSIONS: COVID-19 vaccines caused digestive symptoms and other complications that ranged from mild to severe. While further validation is required, our results suggest that monitoring digestive symptoms following COVID-19 vaccination can help detect rather severe complications that require medical intervention.
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Vacunas contra la COVID-19 , COVID-19 , Enfermedades del Sistema Digestivo , Ad26COVS1 , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , ChAdOx1 nCoV-19 , Enfermedades del Sistema Digestivo/etiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , VacunaciónRESUMEN
BACKGROUND: Muscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH. RESULTS: This study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5-10) per week in the pregabalin group and 6.5 (4.0-10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (-36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy. CONCLUSION: With multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01271660.
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Calambre Muscular , Calidad de Vida , Analgésicos/efectos adversos , Método Doble Ciego , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Calambre Muscular/inducido químicamente , Calambre Muscular/etiología , Pregabalina/efectos adversos , Resultado del Tratamiento , Ácido gamma-Aminobutírico/efectos adversosRESUMEN
BACKGROUND & AIMS: Third-generation cephalosporins (TGCs) are recommended as first-line antibiotics for treatment of spontaneous bacterial peritonitis (SBP). However, antibiotics against multidrug-resistant organisms (such as carbapenems) might be necessary. We aimed to evaluate whether carbapenems are superior to TGC for treatment of SBP. METHODS: We performed a retrospective study of 865 consecutive patients with a first presentation of SBP (275 culture positive; 103 with TGC-resistant bacterial infections) treated at 7 referral centers in Korea, from September 2013 through January 2018. The primary outcome was in-hospital mortality. We made all comparisons using data from patients whose baseline characteristics were balanced by inverse probability of treatment weighting. RESULTS: Of patients who initially received empirical treatment with antibiotics, 95 (11.0%) received carbapenems and 655 (75.7%) received TGCs. Among the entire study cohort, there was no significant difference in in-hospital mortality between the carbapenem (25.8%) and TGC (25.3%) groups (adjusted odds ratio [aOR], 0.97; 95% CI, 0.85-1.11; P = .66). In the subgroup of patients with high chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores (score of 7 or greater, n = 314), carbapenem treatment was associated with lower in-hospital mortality (23.1%) than in the TGC group (38.8%) (aOR, 0.84; 95% CI, 0.75-0.94; P=.002). In contrast, among patients with lower CLIF-SOFA scores (n = 436), in-hospital mortality did not differ significantly between the carbapenem group (24.7%) and the TGC group (16.0%) (aOR, 1.06; 95% CI, 0.85-1.32; P = .58). CONCLUSIONS: For patients with a first presentation of SBP, empirical treatment with carbapenem does not reduce in-hospital mortality compared to treatment with TGCs. However, among critically ill patients (CLIF-SOFA scores ≥7), empirical carbapenem treatment was significantly associated with lower in-hospital mortality than TGCs.
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Carbapenémicos , Peritonitis , Antibacterianos/uso terapéutico , Carbapenémicos/uso terapéutico , Cefalosporinas/uso terapéutico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Peritonitis/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Bile acid (BA) dysregulation is related to not only metabolic diseases but also nonalcoholic fatty liver disease (NAFLD). We investigated whether circulating BA levels are altered according to the histological severity of NAFLD independent of metabolic derangements. METHODS: Global metabolic profiling and targeted BA analysis using sera collected from biopsy-proven no-NAFLD (n = 67), nonalcoholic fatty liver (NAFL) (n = 99), and nonalcoholic steatohepatitis (NASH, n = 75) subjects were performed sequentially. Circulating metabolome analysis integrated with the hepatic transcriptome was performed to elucidate the mechanistic basis of altered circulating BA profiles after stratification by obesity (body mass index ≤ 25 kg/m2 ). Circulating BA alterations were also validated in an independent validation cohort (29 no-NAFLD, 70 NAFL and 37 NASH). RESULTS: Global profiling analysis showed that BA was the metabolite significantly altered in NASH compared to NAFL. Targeted BA analysis demonstrated that glyco-/tauro-conjugated primary BAs were commonly increased in nonobese and obese NASH, while unconjugated primary BAs increased only in nonobese NASH. These characteristic primary BA level changes were maintained even after stratification according to diabetes status and were replicated in the independent validation cohort. Compared to nonobese NAFL patients, nonobese NASH patients exhibited upregulated hepatic expression of CYP8B1. CONCLUSIONS: BA metabolism is dysregulated as the histological severity of NAFLD worsens, independent of obesity and diabetes status; dysregulation is more prominent in nonobese NAFLD patients. Metabolome-driven omics approach provides new insight into our understanding of altered BA metabolism associated with individual phenotypes of NAFLD.
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Diabetes Mellitus , Enfermedad del Hígado Graso no Alcohólico , Ácidos y Sales Biliares/metabolismo , Humanos , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad/complicaciones , Obesidad/metabolismoRESUMEN
BACKGROUND & AIMS: The association between nonalcoholic fatty liver disease (NAFLD) and pulmonary function remains elusive because of the heterogeneous spectrum and inaccurate diagnostic methods of NAFLD, and insufficient pulmonary function data. We conducted this study to identify the association between histological severity of NAFLD and pulmonary function. METHODS: This study included patients ≥18 years old with baseline pulmonary function data between August 2014 and July 2019 within a biopsy-evaluated prospective NAFLD cohort. Cross-sectionally, pre-/post-bronchodilator spirometric data with diffusing capacity (DLCO ) were compared according to histological severity of NAFLD in the various demographic and metabolic subgroups. Multivariable-adjusted analysis revealed specific histological features associated with reduced pulmonary function. RESULTS: In a total of 420 patients with biopsy-proven NAFLD, pre-/post-bronchodilator forced vital capacities (FVCs; a percentage of the predictive value) were inversely correlated with histological severity of NAFLD. Conversely, pre-bronchodilator forced expiratory volume in 1 second (FEV1 )/FVC was positively correlated with NAFLD severity. Post-bronchodilator FVC (%) decreased and DLCO /alveolar volume (VA ) increased linearly with worsening histological severity of NAFLD in multivariable analysis. In particular, fibrosis stage remained a significant independent predictor of decreased post-bronchodilator FVC (%) (ß-coefficient, 4.41; 95% confidence interval [-8.39, -0.43]; P = .031) even after adjusted for clinical variables, exclusively in age <65 years, female, never-smoker and nonchronic obstructive pulmonary disease subgroups. CONCLUSIONS: Pulmonary function deteriorates with worsening histological severity of NAFLD, especially at the fibrosis stage. The common pathogenesis of reduced pulmonary function and NAFLD fibrosis progression should be further explored.
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Enfermedad del Hígado Graso no Alcohólico , Adolescente , Anciano , Biopsia , Femenino , Fibrosis , Humanos , Hígado/patología , Cirrosis Hepática/patología , Pulmón , Enfermedad del Hígado Graso no Alcohólico/patología , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND & AIMS: Non-selective beta-blockers (NSBBs) are the mainstay of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. We investigated whether non-invasive markers of portal hypertension correlate with hemodynamic responses to NSBBs in cirrhotic patients with esophageal varices. METHODS: In this prospective cohort study, 106 cirrhotic patients with high-risk esophageal varices in the derivation cohort received carvedilol prophylaxis, and completed paired measurements of hepatic venous pressure gradient, liver stiffness (LS), and spleen stiffness (SS) at the beginning and end of dose titration. LS and SS were measured using acoustic radiation force impulse imaging. A prediction model for hemodynamic response was derived, and subject to an external validation in the validation cohort (63 patients). RESULTS: Hemodynamic response occurred in 59 patients (55.7%) in the derivation cohort, and in 33 patients (52.4%) in the validation cohort, respectively. Multivariate logistic regression analysis identified that ΔSS was the only significant predictor of hemodynamic response (odds ratio 0.039; 95% confidence interval 0.008-0.135; pâ¯<0.0001). The response prediction model (ModelΔSSâ¯=â¯0.0490-2.8345â¯×â¯ΔSS; scoreâ¯=â¯(exp[ModelΔSS])/(1â¯+â¯exp[ModelΔSS]) showed good predictive performance (area under the receiver-operating characteristic curve [AUC]â¯=â¯0.803) using 0.530 as the threshold value. The predictive performance of the ModelΔSS in the validation set improved using the same threshold value (AUCâ¯=â¯0.848). CONCLUSION: A new model based on dynamic changes in SS exhibited good performance in predicting hemodynamic response to NSBB prophylaxis in patients with high-risk esophageal varices. LAY SUMMARY: Non-selective beta-blockers are the mainstay of primary prophylaxis to prevent variceal bleeding in patients with cirrhosis and high-risk esophageal varices. This prospective study showed that a prediction model based on changes in spleen stiffness before vs. after dose titration might be a non-invasive marker for response to prophylactic non-selective beta-blocker (carvedilol) therapy in patients with cirrhosis and high-risk esophageal varices. ClinicalTrials.gov Identifier: NCT01943318.
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Carvedilol/administración & dosificación , Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Hipertensión Portal , Cirrosis Hepática , Bazo/patología , Antagonistas Adrenérgicos beta/administración & dosificación , Quimioprevención/métodos , Reglas de Decisión Clínica , Diagnóstico por Imagen de Elasticidad/métodos , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/prevención & control , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión Portal/diagnóstico , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Hígado/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is known to increase the risk of adenomatous colonic polyps. However, the role of screening colonoscopy in patients with biopsy-proven NAFLD in detecting advanced colorectal neoplasm is not clearly evidence-based. Therefore, we investigated whether the histological severity of NAFLD is associated with advanced colorectal neoplasm. METHODS: This study included patients ≥18 years old who underwent screening colonoscopy between 2013 and 2018 within a biopsy-evaluated prospective NAFLD cohort. Advanced colorectal neoplasm was defined as an adenomatous polyp greater than 10 mm in diameter and/or with villous histology and/or with high-grade dysplasia or adenocarcinoma. RESULTS: Among the 476 patients with clinically suspected NAFLD, 379 patients were diagnosed with biopsy-proven NAFLD and 97 patients had no evidence of NAFLD histologically, who were analyzed as healthy controls. The prevalence of advanced colorectal neoplasm was 11.1% (n = 53). Patients with advanced colorectal neoplasm had higher grade of steatosis (P = 0.004) and higher stage of hepatic fibrosis (P = 0.044) than those with normal colonoscopic findings or low-grade adenomatous polyp. Multivariable logistic regression analysis revealed that the presence of nonalcoholic steatohepatitis (NASH) was an independent risk factor for both colorectal polyp (odds ratio [OR], 2.08; 95% confidential interval [CI], 1.12-3.86; P = 0.020) and advanced colorectal neoplasm (OR, 2.81; 95% CI, 1.01-7.87; P = 0.049). CONCLUSIONS: The presence of biopsy-proven NASH was significantly associated with an increased risk of advanced colorectal neoplasm among patients with NAFLD. This finding may alert physicians to conduct screening colonoscopy in patients with NASH to detect advanced colorectal neoplasm early.
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Neoplasias Colorrectales/epidemiología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Adulto , Anciano , Biopsia , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/diagnóstico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Prevalencia , Estudios Prospectivos , Sistema de Registros , República de Corea/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: Alcoholic hepatitis (AH) ranks among the most costly diseases in South Korea. However, accurate hospitalization incidence rates, mortality rates, and contributing factors have not been investigated in South Korea. This study aimed to provide the nationwide incidence of hospitalization, inhospital mortality, and readmission rates for South Korean patients with AH. METHODS: Using the Korean Health Insurance Review and Assessment service database, a total of 39 800 inpatient cases from 2008 to 2012 were identified based on the International Classification of Diseases, 10th Revision diagnosis code for AH (K70.1). Standardized hospitalization incidence and mortality rates were calculated, and logistic regression analysis was performed to identify risk factors for inhospital mortality and readmission. Follow-up data for those admitted in 2008 were collected to assess readmissions. RESULTS: The standardized incidence rate for AH hospitalization per 105 person/year decreased from 19 in 2008 to 14 in 2012 (P = 0.001). The annual inhospital mortality rate ranged from 0.2% to 0.5%. Inhospital mortality was significantly higher in older patients (odds ratio [OR], 1.36) and those with cirrhosis (OR, 4.40). The readmission rate for patients admitted in 2008 was 34.0%. Male sex (OR, 1.21) and low economic status (OR, 2.35) were significantly associated with readmission, whereas older age (OR, 0.96), cirrhosis (OR, 0.77), and urban residency (OR, 0.68) were inversely associated with readmission. CONCLUSIONS: This study captured a 5-year epidemiologic period in South Korea of patients with AH to reflect the real burden of AH and to provide valuable information to policy-makers assessing public health priorities.
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Hepatitis Alcohólica/epidemiología , Hepatitis Alcohólica/mortalidad , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Factores de Edad , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Factores Sexuales , Clase Social , Factores de TiempoRESUMEN
Prophylactic antiviral therapy is recommended for hepatitis B virus (HBV)-infected patients with malignancies who are undergoing systemic chemotherapy. In the current study, we aimed to develop a risk scoring system to guide the selection of prophylactic antiviral agents. In this retrospective analysis, we included consecutive chronic hepatitis B patients who received antiviral prophylaxis for chemotherapy of solid or hematologic malignancies at three large-volume hospitals in Korea. The primary endpoint was HBV reactivation. The inverse probability treatment weighting method was used to minimize selection bias in terms of antiviral assignments. A total of 419 patients were enrolled: 129 patients received lamivudine (LAM), 216 received telbivudine (LdT), and 74 received entecavir (ETV), respectively. Of these, 36 patients developed on-treatment HBV reactivation (LAM, 17; LdT, 18; ETV, 1). Multivariate analysis identified three independent predictors for reactivation: hepatitis B e-antigen positivity, HBV DNA level, and type of malignancy. Accordingly, a risk scoring system was developed wherein one point was assigned for each of the risk factors. HBV reactivation occurred more frequently in the high-risk group (score ≥ 2) than in the low-risk group (hazards ratio, 14.17; P < 0.001). ETV exhibited superior prophylactic efficacy over LdT or LAM in the high-risk group, whereas no significant difference was noted in the low-risk group. The prognostic scoring system was useful for risk stratification of chemotherapy-related HBV reactivation. High genetic barrier agents appear to be vital for high-risk patients, whereas cost-effectiveness may be more relevant for low-risk patients.
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Antineoplásicos/uso terapéutico , Antivirales/administración & dosificación , Técnicas de Apoyo para la Decisión , Hepatitis B Crónica/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Activación Viral , Adulto , Anciano , Pueblo Asiatico , Quimioprevención/métodos , ADN Viral/sangre , Quimioterapia , Femenino , Antígenos e de la Hepatitis B/sangre , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , República de Corea , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of heterogeneous metabolic subtypes. This study compared the diagnostic performances of noninvasive fibrosis tests in predicting advanced fibrosis among patients with NAFLD and examined the effects of the subgroups on their diagnostic performances. METHODS: Three hundred fifteen patients with biopsy-proven NAFLD were prospectively enrolled. Acoustic radiation force impulse imaging (ARFI) was performed to obtain liver stiffness measurements (LSMs). The aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis 4 index (FIB-4), NAFLD fibrosis score (NFS) and BARD score were calculated. The diagnostic performances of noninvasive fibrosis tests were evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: Fibrosis 4 index (FIB-4) showed the highest AUROC for advanced fibrosis (0.866; 95% CI, 0.811-0.922). AUROC subgroup analyses were performed to assess the effects of the subgroups on diagnostic performance. For patients with advanced fibrosis, the APRI, BARD, FIB-4 and NFS AUROCs were significantly different among the radiological steatosis grades. Additionally, the AUROC of ARFI tended to decrease with increasing radiological steatosis severity. FIB-4 and NFS showed significantly lower AUROCs for advanced fibrosis in obese NAFLD than in nonobese NAFLD (P = .002 and P < .001 respectively). However, only radiological steatosis severity was independently associated with advanced fibrosis in multivariable analysis. CONCLUSIONS: Steatosis severity may affect the diagnostic performances of noninvasive fibrosis tests in patients with NAFLD. The application of different tools should be tailored for various NAFLD subgroups to optimize noninvasive fibrosis assessments.
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Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Adulto , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Biopsia , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Radiofrequency ablation (RFA) is effective for early-stage hepatocellular carcinoma but recurrence is problem. GOALS: To identify prognostic factors including alpha-fetoprotein (AFP) for overall survival and intrahepatic recurrence after RFA. PATIENTS AND METHODS: Not only naïve but also previously treated patients with solitary hepatitis B virus-related hepatocellular carcinoma <5 cm were prospectively enrolled and a ≥50% decrease from baseline to 1 month after RFA was defined as an initial AFP response. Tumor responses were assessed by the modified response evaluation criteria in solid tumors. RESULTS: Among 255 patients, 156 patients (61.2%) developed intrahepatic recurrence. Radiologic progression occurred in 54.8% (86/157) in the AFP responders and 71.4% (70/98) in the AFP nonresponders. In multivariate analysis, a history of previous treatment [hazard ratio (HR), 2.037; P=0.015 for percutaneous ethanol injection vs. none; and HR, 2.642; P<0.001 for transarterial chemoembolization vs. none] and an initial AFP nonresponse (HR, 1.899; P<0.001) were independent predictors of accelerated progression after RFA. Moreover, those who had a history of previous treatment and did not achieve an initial AFP response had significantly unfavorable overall survival (HR, 3.581; P<0.001) and the increased risk of intrahepatic remote recurrence (HR, 5.385; P<0.001) compared with those with an initial AFP response and no history of previous treatment. CONCLUSIONS: Biological response evaluation by the measurement of serial AFP levels is a useful predictor of overall survival and intrahepatic remote recurrence after RFA. Therefore, an initial AFP response may aid in determining the need of closer follow-up as a therapeutic response indicator of RFA.
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Carcinoma Hepatocelular/fisiopatología , Neoplasias Hepáticas/patología , Ablación por Radiofrecuencia/métodos , alfa-Fetoproteínas/metabolismo , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Quimioembolización Terapéutica/métodos , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Hepatitis B/complicaciones , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: In patients with early-stage hepatocellular carcinoma (HCC), selection of candidates for liver transplantation (LT) requires refinement based on tumor biology to maximize the outcome. We aimed to prognosticate LT candidates with HCC using a risk prediction model for post-LT recurrence. PATIENTS AND METHODS: A total of 197 consecutive patients were included who underwent LT for hepatitis B-related HCC within the Milan criteria. A risk prediction model was developed for post-LT recurrence using the Cox model and was internally validated. RESULTS: Among those undergoing LT as their first HCC treatment (n=70, initial LT group), poor prognosis was associated with maximal tumor size and multinodularity. The remaining 127 patients (deferred LT group) received radiofrequency ablation (n=69) and/or transarterial chemoembolization (n=98) before LT. Multinodularity, maximal tumor size, posttransarterial chemoembolization progressive disease, baseline alpha-fetoprotein, and alpha-fetoprotein difference (between baseline and pre-LT) were incorporated into a risk prediction model for the deferred LT group, which was thereby stratified into low-risk (score<5), intermediate-risk, and high-risk (score≥8) subgroups. Recurrence-free survival was significantly different among the deferred LT prognostic subgroups (P<0.001). CONCLUSIONS: This risk prediction model may help refinement of "ablate-and-wait" strategy for LT candidates by avoiding LT in those with either high risk score at baseline or increasing score under repeated locoregional therapies.
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Carcinoma Hepatocelular/cirugía , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Ablación por Radiofrecuencia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Selección de Paciente , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Ablación por Radiofrecuencia/efectos adversos , Ablación por Radiofrecuencia/mortalidad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Little information is available regarding the relationship between alcoholic liver diseases (ALD) and the development of gastric neoplasia. AIM: The aim of this study was to examine whether ALD is associated with the increased risk of gastric neoplasia. METHODS: We reviewed the medical records 514 patients diagnosed with ALD at Seoul Metropolitan Government Boramae Hospital between January 2000 and December 2011. Control subjects were selected by using propensity score matching (age, sex, and body mass index) from 8190 members of the general population who underwent EGD for screening for gastric neoplasia at Boramae Health Promotion Center during the study period. We compared the frequency of gastric neoplasia between the two groups and evaluated the risk factors for the development of gastric cancer in patients with ALD. In addition, we compared the frequency of gastric cancer between patients with ALD and those with nonalcoholic steatohepatitis (NASH). RESULTS: Of the 514 patients with ALD, 16 patients (3.1 %) had gastric neoplasia, including 14 gastric cancers (2.7 %). The odds of detecting a gastric cancer in ALD patients were approximately 4.77 times greater than in healthy controls [odds ratio (OR) 4.77; 95 % confidence interval (CI) 1.36-16.69; P = 0.007]. ALD (OR 5.32, 95 % CI 1.51-18.68, P = 0.009) was found to be an independent risk factor by multivariate logistic analysis. However, there were no significant differences in the prevalence of gastric adenoma and gastric cancer between patients with ALD and those with NASH. CONCLUSIONS: The rate of gastric cancer was significantly higher in patients with ALD than in healthy controls, suggesting that strict endoscopic surveillance is warranted in patients with ALD.
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Adenoma/epidemiología , Carcinoma/epidemiología , Hepatopatías Alcohólicas/epidemiología , Neoplasias Gástricas/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Endoscopía del Sistema Digestivo , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Oportunidad Relativa , Factores de Riesgo , Seúl/epidemiologíaRESUMEN
AIMS: The aim of this study was to develop a population pharmacokinetic (PK) model of udenafil and its active metabolite, DA-8164, in healthy subjects and patients with hepatic impairment (HI) and to estimate the optimal dosing recommendations for patients with HI. METHODS: An open label, three parallel group, age and weight matched control study was conducted in 18 volunteers, six healthy subjects (n = 6) and patients with mild (Child-Pugh class A, n = 6) and moderate HI (Child-Pugh class B, n = 6). Serial blood samples were collected for up to 72 h after a single administration of udenafil 100 mg. A population PK model was developed using non-linear mixed effects modelling (nonmem, ver. 7.2). The simulated data from the final PK model and original data of healthy subjects were compared to identify the optimal dose for patients with HI. RESULTS: A two compartment model for both udenafil and DA-8164 best described the data. Prothrombin time on metabolic clearance of udenafil to DA-8164 was included in the final model as a covariate. Compared with the AUC(0,tlast ) value after administration of udenafil 100 mg to healthy subjects, the geometric mean ratios (95% confidence interval) after 100 mg and 75 mg udenafil administration were 1.21 (1.10, 1.32) and 0.74 (0.67, 0.81) in patients with mild HI, respectively. Meanwhile, those were 1.55 (1.43, 1.67) and 1.02 (0.92, 1.12) in patients with moderate HI, respectively. CONCLUSIONS: This study suggests that the recommended doses of udenafil are 100 mg and 75 mg in patients with mild and moderate HI, respectively.
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Hepatopatías/complicaciones , Inhibidores de Fosfodiesterasa 5/farmacocinética , Pirimidinas/administración & dosificación , Pirimidinas/farmacocinética , Sulfonamidas/administración & dosificación , Adulto , Área Bajo la Curva , Estudios de Casos y Controles , Relación Dosis-Respuesta a Droga , Humanos , Hepatopatías/fisiopatología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Dinámicas no Lineales , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Índice de Severidad de la Enfermedad , Sulfonamidas/farmacocinéticaRESUMEN
BACKGROUND AND AIM: Gastrointestinal bleeding (GIB) often accompanies alcoholic hepatitis (AH). The study aimed to investigate clinical characteristics of GIB in AH patients and to identify risk factors for mortality in AH patients with GIB. METHODS: Data from 329 patients hospitalized with AH in a single center during 1999-2014 were retrospectively analyzed. Patients with AH were dichotomized into GIB and non-GIB groups. The GIB group was further divided into portal hypertensive bleeding (PHB) and non-PHB groups. Clinical characteristics and survival outcomes were compared between the groups. Risk factors for mortality were analyzed using Cox regression. RESULTS: Among the 329 AH patients, 132 experienced GIB at admission or during hospitalization. The most common cause of GIB was an esophageal varix. The GIB group had worse survival outcomes than the non-GIB group (log-rank test, P = 0.034). The PHB group had worse survival outcomes than the non-PHB group (log-rank test, P = 0.001). On multivariate analysis, alcohol consumption, ascites, encephalopathy, infection, Maddrey's discriminant function, and the model for end-stage liver disease (MELD) score independently predicted mortality in the entire AH cohort. The MELD score (hazard ratio, 1.085; 95% confidence interval, 1.052-1.120; P < 0.001) and PHB (hazard ratio, 2.162; 95% confidence interval, 1.021-4.577; P = 0.044) were significant prognosticators for patients with AH and GIB. CONCLUSIONS: The presence of PHB and a higher MELD score adversely affected survival in AH patients with GIB. Accordingly, prompt endoscopic examination for exploring the etiologies of GIB may alert physicians to predict the risk of death in AH patients with GIB.
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Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/mortalidad , Adulto , Pueblo Asiatico , Estudios de Cohortes , Enfermedad Hepática en Estado Terminal/complicaciones , Várices Esofágicas y Gástricas/complicaciones , Femenino , Predicción , Humanos , Hipertensión Portal/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prohibitinas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND AND AIMS: Alcoholic liver diseases often evolve to acute-on-chronic liver failure (ACLF), which increases the risk of (multi-)organ failure and death. We investigated the development and characteristics of alcohol-related ACLF and evaluated prognostic scores for prediction of mortality in Asian patients with active alcoholism. METHODS: A total of 205 patients who were hospitalized with severe alcoholic liver disease were included in this retrospective cohort study, after excluding those with serious cardiovascular diseases, malignancy, or co-existing viral hepatitis. The Chronic Liver Failure (CLIF) Consortium Organ Failure score was used in the diagnosis and grading of ACLF, and the CLIF Consortium ACLF score (CLIF-C ACLFs) was used to predict mortality. RESULTS: Patients with ACLF had higher Maddrey discriminant function, model for end-stage liver disease (MELD), and MELD-sodium scores than those without ACLF. Infections were more frequently documented in patients with ACLF (33.3% vs 53.0%; P = 0.004). Predictive factors for ACLF development were systemic inflammatory response syndrome (odds ratio [OR], 2.239; P < 0.001), serum sodium level (OR, 0.939; P = 0.029), and neutrophil count (OR, 1.000; P = 0.021). For prediction of mortality at predefined time points (28-day and 90-day) in patients with ACLF, areas under the receiver-operating characteristic were significantly greater for the CLIF-C ACLFs than for Child-Pugh, MELD, and MELD-sodium scores. CONCLUSIONS: Infection and systemic inflammatory response syndrome play an important role in the development of alcohol-related ACLF in Asian patients with active alcoholism. The CLIF-C ACLFs may be more useful for predicting mortality in ACLF cases than liver-specific scoring systems.
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Insuficiencia Hepática Crónica Agudizada/etiología , Alcoholismo/complicaciones , Hepatopatías Alcohólicas/etiología , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Pueblo Asiatico , Estudios de Cohortes , Femenino , Predicción , Humanos , Hepatopatías Alcohólicas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
GOALS AND BACKGROUND: The diagnostic role of noninvasive fibrosis assessment, which can obviate liver biopsy in Asian patients with hepatitis C, remains controversial. This study aimed to evaluate the diagnostic accuracy of noninvasive fibrosis assessment to predict advanced fibrosis or cirrhosis in Asian patients with hepatitis C. STUDY: A total of 101 antiviral treatment-naive patients with hepatitis C were prospectively enrolled between March 2011 and March 2013. Liver stiffness was measured by acoustic radiation force impulse (ARFI) elastography. At the same time, liver biopsy was performed to obtain histologic data of hepatic fibrosis. Diagnostic measurements of serum fibrosis indices and ARFI imaging were compared with predicted advanced fibrosis or cirrhosis by analyzing the area under the receiver operating characteristic (AUROC) curve. RESULTS: The median age of the study population was 59 years (range, 25 to 82 y). Aspartate aminotransferase to alanine aminotransferase ratio (AAR), Fib-4, Forns index, aspartate aminotransferase to platelet ratio index (APRI), and Lok index showed significant, positive correlations with METAVIR stages (P<0.001). Fib-4 had the greatest AUROC for advanced fibrosis (≥F3) (0.864; 95% CI, 0.793-0.934), and the Lok index had the highest AUROC for predicting cirrhosis (F4) (0.847; 95% CI, 0.767-0.927). A tendency toward increasing liver stiffness existed in a graded manner across METAVIR stages (P<0.001). CONCLUSIONS: Fib-4 and Lok index were useful noninvasive fibrosis indices for predicting advanced fibrosis and cirrhosis in Asian patients with hepatitis C. In addition, ARFI elastography exhibited acceptable diagnostic performance in the assessment of hepatic fibrosis in patients with hepatitis C.
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Diagnóstico por Imagen de Elasticidad/métodos , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Pueblo Asiatico , Aspartato Aminotransferasas/sangre , Biopsia/métodos , Femenino , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios ProspectivosRESUMEN
OBJECTIVE: This study is a pilot study to assess the clinical outcomes of percutaneous disc decompression using the L'DISQ in patients with lumbar discogenic pain. STUDY DESIGN: An institutional, prospective clinical data analysis. METHODS: We ablated the torn annulus using L'DISQ on 20 patients with axial low back pain for at least 3 months (average 29 months) unresponsive to conservative management. Before the therapeutic procedure, all the patients had been diagnosed with lumbar discogenic pain through provocation discography, which had confirmed the level of painful discs. The torn annulus was identified through lumbosacral magnetic resonance image and computed tomographic discogram. Baseline data were prospectively gathered before the procedure and at 1, 4, 12, 24, and 48 weeks post-procedure. Data included pain intensity (visual analog scale [VAS]), measure of disability (Oswestry Disability Index [ODI] and Rolando-Morris Disability Questionnaire [RM]), and health-related quality of life (Bodily Pain Scale of Short Form-36 version 2 [SF-36 BP]). RESULTS: At 48 weeks, the VAS fell from 7.55 ± 1.28 to 3.60 ± 2.28 scores, the ODI and RM had decreased significantly, and the SF-36 BP showed significant improvement (P < 0.05). The success rates of procedure were 55.0% at 48 weeks. There were no complications with the exception of a minor venous bleeding at the site of needle puncture. CONCLUSIONS: The L'DISQ device is specifically designed to ablate adjacent disc tissue using a wand that can be navigated into a torn annulus. Following ablation, we measured clinically significant pain improvement and decreased disability for patients with axial low back pain.