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1.
Hepatology ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811378

RESUMO

We thank Dr. Liu et al for their interest and the comments about our article.(1) In our current study, we validated an association of the burden of metabolic risk factors with risks of hepatocellular carcinoma (HCC) using a large nationwide population-based cohort of patients with chronic hepatitis B virus (HBV) infection. The criteria for metabolic risk factors (obesity, high blood pressure, hypercholesterolemia, and diabetes) were adopted and modified from a previous Taiwanese study including 1,690 men with chronic HBV infection.

2.
Dig Dis Sci ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538921

RESUMO

BACKGROUND: Prognosis prediction in patient with hepatocellular carcinoma (HCC) after transarterial radioembolization (TARE) remains difficult. The aim of this study was to develop a prognostic model to aid in the decision to use TARE. METHODS: A total of 174 patients in Korea who underwent TARE for HCC as the initial treatment were included. We developed a prediction model for overall survival (OS) based on independent risk factors for OS and validated the model by bootstrap method. RESULTS: The median maximal size of the tumors was 8.2 cm, the median number of tumors was 2, and the median albumin level was 4.0 g/dL. Portal vein tumor thrombosis was found in 46.0% (Vp1-3 [39.7%] and Vp4 [6.3%]). Four independent risk factors associated with OS (maximal tumor size, tumor number, albumin, and portal vein tumor thrombosis) were used to develop the SNAP-HCC score. Bootstrap validation of the scoring index determined that the Harrell's c-index for OS was 0.756 (95% confidence interval: 0.729-0.783). Patients grouped based on their SNAP-HCC (scores 0-5) were well discriminated, with significant differences between the groups (all P < 0.05). Patients with SNAP-HCC < 3 showed significantly longer OS than patients with SNAP-HCC ≥ 3 (P < 0.001). The respective survival probabilities at years 1 and 3 were 0.81 and 0.73 in the low-risk (SNAP-HCC < 3) and 0.32 and 0.14 in the high-risk (SNAP-HCC ≥ 3) patients. CONCLUSIONS: The SNAP-HCC scoring system predicted the outcome of HCC patients undergoing TARE as an initial treatment. This model could be helpful for initial planning the treatment of HCC patients.

3.
Hepatology ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33140415

RESUMO

BACKGROUND AND AIMS: Long-term antiviral therapy can effectively suppress viral replication and improve clinical outcomes in patients with chronic hepatitis B (CHB), but it cannot eliminate risk of hepatocellular carcinoma (HCC). We investigated the association of metabolic risk factors with the risks of cancer and all-cause mortality in CHB patients. APPROACH AND RESULTS: This nationwide population-based study from the Korean National Health Insurance Service database consisted of adults with CHB who underwent health examinations from 2007 through 2012. We collected baseline data on metabolic risk factors, including obesity, high blood pressure, hypercholesterolemia, and diabetes. The risks of developing HCC, non-HCC cancer, and overall death were analyzed according to the metabolic risk profile. The study population comprised of 317,856 patients (median age, 46 years [interquartile range, 37-54 years]; 219,418 men [69.0%]) had 2,609,523.8 person-years of follow-up. A total of 18,850 HCCs, 22,164 non-HCC cancers, and 15,768 deaths were observed during a median follow-up period of 8.5 years. The metabolic risk factor burden was positively associated with the risks of HCC, non-HCC cancer, and all-cause mortality (all P<.0001 for trend). Patients with ≥3 metabolic risk factors, compared to those without metabolic risk factors, showed adjusted hazard ratios of 1.23 (95% confidence interval [CI], 1.16-1.31) for HCC, 1.34 (95% CI, 1.27-1.41) for non-HCC cancer, and 1.31 (95% CI, 1.23-1.39) for all-cause mortality. Among patients receiving antiviral therapy for over 5 years, the risk-increasing association of the sum of metabolic risk factors with the risks of HCC and overall death was consistent. CONCLUSION: The metabolic risk factor burden was associated with increased risks of HCC, non-HCC cancer, and all-cause mortality in patients with CHB.

4.
BMC Cancer ; 20(1): 1001, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059615

RESUMO

BACKGROUND: Histone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib. METHODS: The anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate the mechanism of cell death, which was also evaluated by small interfering RNA (siRNA) transfection and subsequent immunoblot assays. In vivo experiments were conducted using two different murine HCC models. C3H mice implanted with MH134 cells and C57BL/6 mice implanted with RIL-175 cells were treated with weekly CKD-5 with and without sorafenib for 2 weeks. RESULTS: CKD-5 treatment significantly suppressed human HCC cell growth in both normoxic and hypoxic conditions. Microarray analysis and real-time PCR showed that CKD-5 treatment significantly increased peripherin expression in HCC cells and that downregulation of peripherin by siRNA decreased CKD-5-induced apoptosis. The combination of CKD-5 and sorafenib decreased cell viability more effectively than sorafenib or CKD-5 monotherapy in human and murine HCC cells. The effectiveness of the combination therapy was consistently demonstrated in the animal models. Histological and biochemical analyses demonstrated good tolerance of CKD-5 plus sorafenib in vivo. CONCLUSION: CKD-5 may enhance sorafenib efficacy through epigenetic regulation. The combination of CKD-5 and sorafenib might be a novel therapeutic option for the treatment of HCC.

5.
Clin Mol Hepatol ; 26(4): 529-539, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32829570

RESUMO

BACKGROUND/AIMS: Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis due to the lack of effective systemic therapies. Epithelial-to-mesenchymal transition (EMT) is a pivotal event in tumor progression, during which cancer cells acquire invasive properties. In this study, we investigated the effects of phosphatidylinositol 3-kinase (PI3K) inhibitors, including LY294002 and idelalisib, on the EMT features of HCC cells in vitro. METHODS: Human HCC cell lines, including Huh-BAT and HepG2, were used in this study. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and cell cycle distributions were evaluated using a flow cytometer by propidium iodide staining. Immunofluorescence staining, quantitative real-time polymerase chain reaction, and immunoblotting were performed to detect EMT-associated changes. RESULTS: PI3K inhibitors suppressed the proliferation and invasion of HCC cells and deregulated the expression of EMT markers, as indicated by increased expression of E-cadherin, an epithelial marker, and decreased expression of N-cadherin, a mesenchymal marker, and Snail, a transcription factor implicated in EMT regulation. Furthermore, LY294002 and idelalisib inhibited the phosphorylation of GSK-3ß and induced the nuclear translocation of GSK-3ß, which corresponded to the downregulation of Snail and ß-catenin expressions in Huh-BAT and HepG2 cells. CONCLUSION: The inhibition of PI3K/Akt signaling decreases Snail expression by enhancing the nuclear translocation of GSK-3ß, which suppresses EMT in HCC cells, suggesting the potential clinical application of PI3K inhibitors for HCC treatment.

6.
Cancers (Basel) ; 12(7)2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640555

RESUMO

Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32623007

RESUMO

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.

8.
Clin Infect Dis ; 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32556157

RESUMO

BACKGROUND: HBsAg seroclearance is considered a functional cure for patients with chronic hepatitis B, but is rarely achievable with oral nucleos(t)ide analogs alone. We conducted a randomized controlled proof-of-concept trial to evaluate the impact of adding pegylated interferon (Peg-IFN) alfa-2a plus sequential or concomitant hepatitis B virus (HBV) vaccination. METHODS: A total of 111 patients who achieved serum HBV DNA <20 IU/mL and quantitated HBsAg (qHBsAg) <3,000 IU/mL with entecavir were randomly assigned (1:1:1) to the E+sVIP group (entecavir + Peg-IFN alfa-2a [180 µg every week over 48 weeks] + sequential HBV vaccination [20 µg of HBsAg on weeks 52, 56, 60, and 76]), E+cVIP group (entecavir + Peg-IFN alfa-2a + concomitant HBV vaccination [weeks 4, 8, 12, and 28]), or the control group (entecavir only). The primary endpoint was HBsAg seroclearance at week 100 and secondary endpoints included safety. RESULTS: No differences in baseline qHBsAg were observed among the groups. The E+sVIP group in the intention-to-treat analysis showed a significantly higher chance of HBsAg seroclearance during week 100 than the control group (16.2% vs. 0%, P=0.025), but the E+cVIP group (5.4%) failed to reach a significant difference (P=0.54). Adverse events were significantly more frequent in the E+sVIP (81.1%) or E+cVIP group (70.3%) than the control group (2.7%) (both P<0.0001). However, the frequency of serious adverse events did not differ significantly among three groups (2.7%, 5.4%, and 2.7%, respectively; P=1.00). CONCLUSIONS: Entecavir plus an additional Peg-IFN alfa-2a treatment followed by sequential HBV vaccination under an intensified schedule significantly increases the chance of HBsAg seroclearance compared to entecavir alone.

9.
Clin Mol Hepatol ; 26(3): 328-339, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460459

RESUMO

BACKGROUND/AIMS: Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients. METHODS: Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias. RESULTS: Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0-10.8) months for regorafenib and 5.9 (95% CI, 3.7-8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30-0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51-1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04). CONCLUSION: After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.

10.
J Cardiovasc Magn Reson ; 22(1): 25, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32321533

RESUMO

BACKGROUND: Cardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation. METHODS: This study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19). RESULTS: CMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: - 24.2 ± 2.7% in cirrhosis vs - 18.6 ± 2.2% in healthy controls, P < 0.001). No significant differences in LV size, wall thickness, mass index, and diastolic function between cirrhosis patients and healthy controls were seen (all P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P < 0.001) than healthy controls. ECV showed a positive correlation with Child-Pugh score (r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P < 0.001). One-year post-transplantation, echocardiographic LV-GLS (from - 24.9 ± 2.4% to - 20.6 ± 3.4%, P < 0.001) and ECV (from 30.9 ± 4.5% to 25.4 ± 2.6%, P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001). CONCLUSIONS: Myocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Ecocardiografia Doppler , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Cirrose Hepática/cirurgia , Transplante de Fígado , Imagem Cinética por Ressonância Magnética , Disfunção Ventricular Esquerda/diagnóstico por imagem , Listas de Espera , Idoso , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular
11.
Ultraschall Med ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323278

RESUMO

PURPOSE: To assess the diagnostic performance of the normalized local variance (NLV) ultrasound technique in the detection of the fatty liver using histopathology as a reference standard. MATERIALS AND METHODS: We prospectively enrolled 194 consecutive patients with clinical suspicion of diffuse liver disease or history of liver transplantation. Conventional grayscale ultrasound and NLV examinations were performed and immediately followed by liver biopsies. The degrees of fatty liver, necroinflammatory activity, and fibrosis stage were evaluated by histopathological assessment. The diagnostic performance of the NLV values in detecting each grade of fatty liver was determined using receiver operating characteristics analyses, and multivariate linear regression analyses were performed to identify variables significantly associated with the NLV values. RESULTS: The number of patients in each degree of fatty liver and hepatic fibrosis was 118/37/26/13 and 81/68/24/6/14 for none/mild/moderate/severe steatosis and F0 / F1/F2 / F3/F4 fibrosis on histopathological examinations, respectively. The area under the receiver operating characteristics curve and optimal cut-off NLV value for detecting fatty liver of varying degrees were 0.911 and 1.095 for ≥ S1, 0.974 and 1.055 for ≥ S2, and 0.954 and 1.025 for ≥ S3, respectively. Multivariate analyses revealed that not fibrosis or inflammation but rather the degree of steatosis was associated with the NLV value. CONCLUSION: The NLV value demonstrated excellent diagnostic performance for detecting varying degrees of fatty liver, and the degree of steatosis on histopathological examinations was the only significant factor affecting the NLV value.

12.
J Gastroenterol Hepatol ; 35(11): 1960-1968, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32128882

RESUMO

BACKGROUND AND AIM: As the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing globally, patients with both NAFLD and chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is also frequently found. This study aimed to investigate the clinical impact of concurrent NAFLD on the prognosis of patients with CHB-related HCC. METHODS: Patients with CHB-related HCC who underwent surgical resection were consecutively selected from August 2009 to December 2013. The association between histologically proven concurrent NAFLD and clinical outcomes were analyzed. Propensity score (PS) matching was adapted to adjust for baseline characteristics. We also investigated the presence of nonalcoholic steatohepatitis (NASH) among patients with NAFLD and its association with clinical outcomes. RESULTS: Among 338 CHB-related HCC patients selected, 196 patients (58.0%) were diagnosed with concurrent NAFLD. The median follow-up duration was 74.9 months. The patients with NAFLD tended to have better recurrence-free survival (RFS; log-rank, P = 0.16) and had significantly better overall survival (OS; log-rank, P = 0.004) than those without NAFLD. However, the survival benefit of the concurrent NAFLD was not significant in a multivariable Cox analysis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73, P = 0.84) or an analysis after PS matching (log-rank, P = 0.57). Regarding the presence or absence of NASH, no differences in the RFS (log-rank, P = 0.61) and OS (log-rank, P = 0.26) were found. CONCLUSIONS: Concurrent NAFLD was not associated with both RFS and OS in patients with CHB-related HCC after adjusting for baseline characteristics. Moreover, NAFLD patients with NASH did not have significantly different clinical outcomes compared with NAFLD patients without NASH.

13.
Eur J Gastroenterol Hepatol ; 32(3): 378-385, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011388

RESUMO

OBJECTIVES: Hepatocellular carcinoma can develop after hepatitis C virus eradication. We developed a new hepatocellular carcinoma risk score (HCC-SVR score) based on independent predictors for chronic hepatitis C after sustained virological response. METHODS: Between 2003 and 2016, a total of 1193 patients with chronic hepatitis C who achieved sustained virological response through antiviral therapy were included (669 for training cohort and 524 for validation cohort). The HCC-SVR score was developed using multivariate Cox proportional hazards regression modelling. RESULTS: Hepatocellular carcinoma (n = 19) occurred more frequently in older, male patients and was associated with liver cirrhosis; hypertension; diabetes; lower platelet count; higher alpha-fetoprotein, aspartate, and alanine aminotransferase; lower total cholesterol; and higher fibrosis-4 index (FIB-4) (all P < 0.05). FIB-4 (hazard ratio = 1.080), male gender (hazard ratio = 8.189), and higher alpha-fetoprotein (hazard ratio = 1.060) independently predicted hepatocellular carcinoma (all P < 0.05). HCC-SVR score successfully predicted hepatocellular carcinoma development risk [area under receiver operating characteristic curve (AUC) = 0.771, 0.857, and 0.911 at 2, 4, and 6 years, respectively]. The cumulative incidence rate of hepatocellular carcinoma differed significantly among groups stratified by HCC-SVR risk score (0-2 points, low; 3-7 points, intermediate; 8-9 points, high risk) (all P < 0.05 by log-rank test). HCC-SVR score was maintained in a validation cohort (n = 524) (AUC = 0.728 at 2 years, 0.737 at 4 years, and 0.809 at 6 years). CONCLUSION: The HCC-SVR score enables risk stratification for hepatocellular carcinoma development at sustained virological response in patients with chronic hepatitis C.

14.
Gut Liver ; 14(6): 755-764, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31816672

RESUMO

Background/Aims: The risk for colonoscopic postpolypectomy bleeding (PPB) in patients with chronic liver disease (CLD) remains unclear. We determined the incidence and risk factors for colonoscopic PPB in patients with CLD, especially those with liver cirrhosis. Methods: We retrospectively reviewed the medical records of patients with CLD who underwent colonoscopic polypectomy at Seoul National University Hospital between 2011 and 2014. The study endpoints were immediate and delayed PPB. Results: A total of 1,267 consecutive patients with CLD were included in the study. Immediate PPB occurred significantly more often in the Child- Pugh (CP) B or C cirrhosis group (17.5%) than in the CP-A (6.3%) and chronic hepatitis (4.6%) groups (p<0.001). Moreover, the incidence of delayed PPB in the CP-B or C cirrhosis group (4.4%) was significantly higher than that in the CP-A (0.7%) and chronic hepatitis (0.2%) groups (p<0.001). The independent risk factors for immediate PPB were CP-B or C cirrhosis (p=0.011), a platelet count <50,000/µL (p<0.001), 3 or more polyps (p=0.017), endoscopic mucosal resection or submucosal dissection (p<0.001), and polypectomy performed by trainees (p<0.001). The independent risk factors for delayed PPB were CP-B or C cirrhosis (p=0.009), and polyps >10 mm in size (p=0.010). Conclusions: Patients with CP-B or C cirrhosis had an increased risk for bleeding following colonoscopic polypectomy.

15.
J Clin Gastroenterol ; 54(7): 633-641, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31033805

RESUMO

BACKGROUND AND GOALS: Although nonalcoholic fatty liver disease (NAFLD) is a risk factor of hepatocellular carcinoma (HCC), it is unclear whether NAFLD additionally increases the risk of HCC among chronic hepatitis B (CHB) patients. This study evaluated the association between NAFLD and the risk of HCC in patients whose hepatitis B virus (HBV) was well controlled. STUDY: This study included consecutive CHB patients whose serum HBV DNA levels were continuously suppressed <2000 IU/mL with antiviral treatment. Fatty liver was radiologically diagnosed. Patients with concomitant hepatitis C infection, autoimmune hepatitis, or excessive alcohol use were excluded. RESULTS: Among 826 patients, 86 patients (10.4%) developed HCC during the study period (median, 43.1 mo). The patients with NAFLD (N=260) had a significantly higher risk for HCC compared with patients without NAFLD (N=566) (adjusted hazard ratio, 1.67; 95% confidence interval, 1.05-2.63; P=0.03) after adjustment for age, the presence of cirrhosis, hepatitis B envelop antigen positivity, low-level viremia and hypertension. There was significant association between incomplete biochemical response (IBR) (alanine aminotransferase levels ≥40 IU/L) and the presence of NAFLD (P<0.001 by χ test). IBR at the time of virological response was associated with a significantly higher risk of HCC development (adjusted hazard ratio, 1.63; 95% confidence interval, 1.06-2.54; P=0.03). CONCLUSIONS: NAFLD increases the risk of HCC in patients with CHB in whom HBV is effectively suppressed by antivirals. Patients with IBR should be suspected of concurrent NAFLD. Further study is warranted to evaluate whether improvement of NAFLD might decrease the risk of HCC development.

16.
Cancers (Basel) ; 11(11)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689972

RESUMO

BACKGROUND: For patients with hepatocellular carcinoma (HCC), the definition of refractoriness to transarterial chemoembolization (TACE), which might make them a candidate for systemic therapy, is still controversial. We aimed to derive and validate a tumor marker-based algorithm to define the refractoriness to TACE in patients with intermediate-stage HCC. METHODS: This multi-cohort study was comprised of patients who underwent TACE for treatment-naïve intermediate-stage HCC. We derived a prediction model for overall survival (OS) using the pre- and post-TACE model to predict tumor recurrence after living donor liver transplantation (MoRAL) (i.e., MoRAL score = 11×√protein induced by vitamin K absence-II + 2×√alpha-fetoprotein), which was proven to reflect both tumor burden and biologic aggressiveness of HCC in the explant liver, from a training cohort (n = 193). These results were externally validated in both an independent hospital cohort (from two large-volume centers, n = 140) and a Korean National Cancer Registry sample cohort (n = 149). RESULTS: The changes in MoRAL score (ΔMoRAL) after initial TACE was an independent predictor of OS (MoRAL-increase vs. MoRAL-non-increase: adjusted hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.37-3.46, p = 0.001; median OS = 18.8 vs. 37.8 months). In a subgroup of patients with a high baseline MoRAL score (≥89.5, 25th percentile and higher), the prognostic impact of ΔMoRAL was more pronounced (MoRAL-increase vs. MoRAL-non-increase: HR = 3.68, 95% CI = 1.54-8.76, p < 0.001; median OS = 9.9 vs. 37.4 months). These results were reproduced in the external validation cohorts. CONCLUSION: The ΔMoRAL after the first TACE, a simple and objective index, provides refined prognostication for patients with intermediate-stage HCC. Proceeding to a second TACE may not provide additional survival benefits in cases of a MoRAL-increase after the first TACE in patients with a high baseline MoRAL score (≥89.5), who might be candidates for systemic therapy.

17.
Cancers (Basel) ; 11(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484287

RESUMO

BACKGROUND AND AIMS: Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries. METHODS: This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea. The primary and secondary endpoints were time-to-recurrence, and overall survival (OS), respectively. The performance of the MoRAL score was compared with those of other various Liver transplantation (LT) criteria, including the Milan criteria, University of California San Francisco (UCSF) criteria, up-to-seven criteria, Kyoto criteria, AFP model, total tumor volume/AFP criteria, Metroticket 2.0 model, and Weill Cornell Medical College group model. RESULTS: The median follow-up duration was 78.1 months. Among all models assessed, the MoRAL score showed the best discrimination function for predicting the risk of tumor recurrence after LT, with c-index of 0.78, compared to other models (all p < 0.001). The MoRAL score also represented the best calibration function by Hosmer-Lemeshow test (p = 0.15). Especially in the beyond-MC sub-cohort, the MoRAL score predicted tumor recurrence (c-index, 0.80) and overall survival (OS) (c-index, 0.70) significantly better than any other models (all p < 0.001). When the MoRAL score was low (<314.8), the five-year cumulative risks of tumor recurrence and death were excellent in beyond-MC (27.8%, and 20.5%, respectively) and within-MC (16.3%, and 21.1%, respectively) sub-cohorts. CONCLUSIONS: The MoRAL score provides the most refined prognostication for predicting HCC recurrence after LDLT.

18.
Ther Adv Med Oncol ; 11: 1758835919866072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447948

RESUMO

Background: This study aimed to compare the therapeutic effectiveness including progression-free survival (PFS), overall survival (OS), and safety of conventional transarterial chemoembolization (cTACE) and drug-eluting bead transarterial chemoembolization (DEB-TACE) in a superselective fashion for the patients with nodular hepatocellular carcinoma (HCC) (n ⩽ 5) and Child-Pugh class A. Methods: A total of 198 consecutive patients with nodular HCCs (n ⩽ 5) and Child-Pugh class A liver function who were initially treated with cTACE (n = 125) or DEB-TACE (n = 57) were included retrospectively. The primary endpoint was PFS. Secondary endpoints included time-to-target lesion progression (TTTLP), OS, and safety. Results: The median follow up was 62 months (range, 1-87 months). The PFS was significantly longer in the cTACE group than in the DEB-TACE group (median, 18 months versus 7 months; hazard ratio [HR] = 0.658, log-rank p = 0.031), whereas OS was comparable (log-rank p = 0.299). TTTLP was significantly longer in the cTACE group than in the DEB-TACE group (median, 34 months versus 11 months; log-rank p < 0.001). In the stratification analysis based on tumor size, the cTACE group showed significantly longer TTTLP than the DEB-TACE group in the 1.0-2.0 cm and 2.1-3.0 cm subgroups (HR = 0.188, log-rank p < 0.001 and HR = 0.410, p = 0.015, respectively) but not in the 3.1-5.0 cm and 5.1-10.0 cm subgroups (all p > 0.05). Postembolization syndrome occurred more frequently in the cTACE group than in the DEB-TACE group (p = 0.006). Conclusions: DEB-TACE is followed by significantly shorter PFS than cTACE in patients with nodular HCCs (n ⩽ 5) and Child-Pugh class A, although OS is comparable. Postembolization syndrome occurs more frequently in cTACE than in DEB-TACE.

20.
Eur Radiol ; 29(12): 6499-6507, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31175413

RESUMO

OBJECTIVES: To evaluate the diagnostic performance of attenuation imaging (ATI) in the detection of hepatic steatosis compared with a histopathology gold standard. METHODS: We prospectively enrolled 108 consecutive patients (35 males; median age, 54.0 years) who underwent percutaneous liver biopsy for evaluation of diffuse liver disease between January 2018 and November 2018 in a tertiary academic center. Grayscale ultrasound examination with ATI was performed just before biopsy, and an attenuation coefficient (AC) was obtained from each patient. The degree of hepatic steatosis, fibrosis stage, and necroinflammatory activity were assessed on histopathologic examination. The significant factor associated with the AC was found by a linear regression analysis, and the diagnostic performance of the AC for the classification into each hepatic steatosis stage was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The distribution of hepatic steatosis grade on histopathology was 53/11/22/16/6 for none/mild (< 10%)/mild (≥ 10%)/moderate/severe steatosis, respectively. The area under the ROC curve, sensitivity, specificity, and optimal cutoff AC value for detection of hepatic steatosis ranged from 0.843-0.926, 74.5-100.0%, 77.4-82.8%, and 0.635-0.745, respectively. Multivariate analysis revealed that the degree of steatosis was the only significant determinant factor for the AC. CONCLUSIONS: The AC from ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis. The degree of steatosis was the only significant factor affecting the AC, whereas fibrosis and inflammation were not. KEY POINTS: • Attenuation imaging (ATI) is based on two-dimensional grayscale ultrasound images that can incorporate into routine ultrasound examinations with less than 2 min of acquisition time. • ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with an area under the ROC curves ranging from 0.843 to 0.926, and there was no technical failure in this study indicating high applicability of this technique. • The degree of hepatic steatosis was the only significant factor affecting the result of ATI examination.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Ultrassonografia/métodos , Adulto , Biópsia , Biópsia por Agulha , Estudos de Avaliação como Assunto , Fígado Gorduroso/patologia , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença
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