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1.
J Gastroenterol ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33948712

RESUMO

BACKGROUND: REFLECT was an open-label, phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). Based on phase 2 study (Study 202) results, body weight-based dosing for lenvatinib was used in REFLECT to minimize dose disruptions and modifications needed to address dose-related adverse events. This post hoc analysis of REFLECT data assessed lenvatinib efficacy and safety by body weight group. METHODS: The study randomly administered lenvatinib (n = 476) or sorafenib (n = 475) to patients with untreated (no prior systemic therapy) uHCC. Lenvatinib starting-dose data were stratified by body weight: patients weighing < 60 kg received 8 mg/day; patients weighing ≥ 60 kg received 12 mg/day. Overall survival (OS), progression-free survival (PFS), objective response rate, and safety were assessed. RESULTS: Survival outcomes and safety profiles appeared similar between the two body-weight-based lenvatinib starting-dose groups. Median OS for patients in the < 60 kg body weight group (n = 153) was 13.4 months [95% confidence interval (CI) 10.5-15.7] compared to 13.7 months (95% CI 12.0-15.6) in the ≥ 60 kg body weight group (n = 325). In both lenvatinib groups, PFS was 7.4 months (< 60 kg group: 95% CI 5.4-9.2; ≥ 60 kg group: 95% CI 6.9-9.0). Treatment-emergent adverse events (TEAEs) required dose modifications in 43.0% in the < 60 kg body weight group and 57.5% in the ≥ 60 kg body weight group. CONCLUSIONS: This exploratory analysis of data from REFLECT indicated that body weight-based lenvatinib dosing in patients with uHCC was successful in maintaining efficacy, with comparable rates of TEAEs and dose modifications in the two body weight groups. CLININCAL TRIAL: Trial registration ID: ClinicalTrials.gov # NCT01761266.

2.
Infect Chemother ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33538133

RESUMO

Viral hepatitis is the most important cause of acute and chronic liver disease in Korea. Particularly, hepatitis B virus (HBV) is the leading cause of liver-related mortality. Because of the nationwide vaccinations in the 1980s, hepatitis B surface antigen positive rates substantially decreased from 8% to 3%. Moreover, the introduction of potent nucleoside or nucleotide analogs led to the effective treatment of patients who had already been infected by HBV. The remaining issue has been to develop novel drugs that can cure HBV infection. Hepatitis C virus (HCV), on the other hand, is a hepatotropic virus that is parenterally transmitted. In Korea, the prevalence of HCV is estimated to be approximately 1%. Although no effective vaccine for HCV has been developed yet, highly effective and safe direct-acting antiviral therapy, which has a short treatment duration of 8-12 weeks, has made HCV eradication possible globally. Currently, the unsolved issue regarding HCV management is low disease awareness among patients and health care providers. Therefore, nationwide testing for anti-HCV would be a solution to identify patients infected with HCV but with no symptoms. Lastly, the Hepatitis A virus (HAV) is orally transmitted and results in acute hepatitis. In Korea, the young adult population is a high-risk group since this group is not vaccinated against HAV. More active vaccination and improved hygiene would be necessary to prevent HAV infection.

3.
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.

4.
Clin Transl Gastroenterol ; 12(1): e00290, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33433118

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) can develop among chronic hepatitis B patients after hepatitis B surface antigen (HBsAg) seroclearance. However, whether HCC risk after HBsAg seroclearance differs between antiviral therapy (AVT)-induced or spontaneous seroclearance cases and ways to identify at-risk populations remain unclear. METHODS: A retrospective cohort of 1,200 adult chronic hepatitis B patients who achieved HBsAg seroclearance (median age: 56 years; 824 men; 165 with cirrhosis; 216 AVT-induced cases) were analyzed. The risk of HCC after HBsAg seroclearance and the performance of 6 HCC prediction models were assessed. RESULTS: During a median of 4.8 years of follow-up (range: 0.5-17.8 years), HCC developed in 23 patients (1.9%). The HCC incidence rate was higher in the AVT-induced cases than that in the spontaneous cases (3.9% vs 0.9% at 5 years). AVT and cirrhosis were independent factors associated with HCC, with HCC incidence rates of 0.5%, 1.2%, 4.0%, and 10.5% at 5 years for spontaneous/no-cirrhosis, AVT-induced/no-cirrhosis, spontaneous/cirrhosis, and AVT-induced/cirrhosis patients, respectively. Among the 6 predictive HCC models tested, Chinese University-HCC score (0.82) showed the highest C-statistics, which was followed by guide with age, gender, HBV DNA, core promoter mutations and cirrhosis (0.81). DISCUSSION: AVT-induced HBsAg seroclearance was associated with higher HCC risk, especially for patients with cirrhosis, indicating that they need careful monitoring for HCC risk. The HCC risk models were able to stratify the HCC risk in patients with HBsAg seroclearance.

5.
Sci Rep ; 10(1): 21313, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277619

RESUMO

Fibronectin, a matrix glycoprotein aberrantly expressed in various tumor cells, is a known candidate biomarker for the early diagnosis of hepatocellular carcinoma (HCC). In this study, we investigated whether serum fibronectin levels could predict tumor recurrence in patients with early-stage HCC after curative treatment. A total of 83 patients who showed complete response after initial curative treatment were included. The levels of serum fibronectin at baseline and 4-6 weeks after initial treatment were analyzed with regard to their associations with recurrence. Multivariate logistic regression analyses were performed to construct a prognostic nomogram. Baseline fibronectin levels were not significantly correlated with tumor size, number, stage, and serum α-fetoprotein levels. However, decrease in serum fibronectin levels after treatment was significantly associated with reduced HCC recurrence in multivariate logistic regression (odds ratio, 0.009; p < 0.001). Furthermore, a nomogram consisting of gender and changes in serum fibronectin showed a good discriminatory capability for the prediction of HCC recurrence with an area under the receiver-operating curve of 0.87. In conclusion, changes in serum fibronectin levels may be a surrogate indicator for assessment of treatment response in patients with early HCC after curative treatment.

6.
Clin Cancer Res ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139266

RESUMO

PURPOSE: This study investigated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with advanced hepatocellular carcinoma previously treated with sorafenib (NCT03389126). EXPERIMENTAL DESIGN: This is a single-arm, single center, phase II trial. Patients with Child-Pugh A score who had at least one measurable lesion were enrolled. Intravenous avelumab 10 mg/kg every 2 weeks was given until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to RECIST v1.1. Secondary endpoints included time to progression (TTP), overall survival (OS), disease control rate (DCR), and safety. RESULTS: A total of 30 patients were enrolled. After a median follow-up of 13.9 months, 27 progression events and 20 death events occurred. There was no complete response, 3 (10.0%) partial response, and 19 (63.3%) stable disease. ORR was 10.0% and DCR was 73.3%. The median TTP and OS was 4.4 and 14.2 months, respectively. PD-L1 expression did not affect avelumab response. Prior duration of sorafenib treatment, when dichotomized by the median 2.7 months, was associated with treatment outcome. TTP (6.5 vs. 1.8 months, p = 0.007) and OS (19.0 vs. 7.8 months, p = 0.006) were superior in patients with longer sorafenib duration. There was tendency of higher ORR (20.0% vs. 0.0%, p = 0.22) in those with longer sorafenib duration. Avelumab was well tolerated with 7 grade 3 adverse events and no grade 4 adverse events. CONCLUSIONS: Avelumab showed moderate efficacy and was well tolerated in advanced hepatocellular carcinoma previously treated with sorafenib.

7.
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.

8.
Cancers (Basel) ; 12(10)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003306

RESUMO

Several models have been developed using conventional regression approaches to extend the criteria for liver transplantation (LT) in hepatocellular carcinoma (HCC) beyond the Milan criteria. We aimed to develop a novel model to predict tumor recurrence after LT by adopting artificial intelligence (MoRAL-AI). This study included 563 patients who underwent LT for HCC at three large LT centers in Korea. Derivation (n = 349) and validation (n = 214) cohorts were independently established. The primary outcome was time-to-recurrence after LT. A MoRAL-AI was derived from the derivation cohort with a residual block-based deep neural network. The median follow-up duration was 74.7 months (interquartile-range, 18.5-107.4); 204 patients (36.2%) had HCC beyond the Milan criteria. The optimal model consisted of seven layers including two residual blocks. In the validation cohort, the MoRAL-AI showed significantly better discrimination function (c-index = 0.75) than the Milan (c-index = 0.64), MoRAL (c-index = 0.69), University of California San Francisco (c-index = 0.62), up-to-seven (c-index = 0.50), and Kyoto (c-index = 0.50) criteria (all p < 0.001). The largest weighted parameter in the MoRAL-AI was tumor diameter, followed by alpha-fetoprotein, age, and protein induced by vitamin K absence-II. The MoRAL-AI had better predictability of tumor recurrence after LT than conventional models. The MoRAL-AI can also evolve with further data.

9.
Liver Cancer ; 9(5): 503-517, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33083277

RESUMO

Background and Aims: Biannual ultrasonography (US) is a current recommendation for hepatocellular carcinoma (HCC) surveillance in a high-risk group. The sensitivity of US, however, has been low in patients with a high risk of developing HCC. We aimed to compare sensitivity for HCC of biannual US and two-phase low-dose computed tomography (LDCT) in patients with a high risk of HCC. Methods: In this prospective single-arm study, participants with an annual risk of HCC greater than 5% (based on a risk index of ≥2.33) and who did not have a history of HCC were enrolled from November 2014 to July 2016. Participants underwent paired biannual US and two-phase LDCT 1-3 times. Two-phase LDCT included arterial and 3-min delayed phases. The sensitivity, specificity, and positive predictive value of HCC detection using US and two-phase LDCT were compared using a composite algorithm as a standard of reference. Results: Of the 139 enrolled participants, 137 underwent both the biannual US and two-phase LDCT at least once and had follow-up images. Among them, 27 cases of HCC (mean size: 14 ± 4 mm) developed in 24 participants over 1.5 years. Two-phase LDCT showed a significantly higher sensitivity (83.3% [20/24] vs. 29.2% [7/24], p < 0.001) and specificity (95.6% [108/113] vs. 87.7% [99/113], p =0.03) than US. A false-positive result was reported in 14 participants at US and 5 participants at two-phase LDCT, resulting in a significantly higher positive predictive value of two-phase LDCT (33.3% [7/21] vs. 80% [20/25], p < 0.001). Conclusions: Patients with a risk index ≥2.33 showed a high annual incidence of HCC development in our study, and two-phase LDCT showed significantly higher sensitivity and specificity for HCC detection than US.

10.
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.

11.
Cancers (Basel) ; 12(9)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967314

RESUMO

Aberrations of the human microbiome are associated with diverse liver diseases, including hepatocellular carcinoma (HCC). Even if we can associate specific microbes with particular diseases, it is difficult to know mechanistically how the microbe contributes to the pathophysiology. Here, we sought to reveal the functional potential of the HCC-associated microbiome with the human metabolome which is known to play a role in connecting host phenotype to microbiome function. To utilize both microbiome and metabolomic data sets, we propose an innovative, pathway-based analysis, Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome (HisCoM-MnM), for integrating microbiome and metabolomic data. In particular, we used pathway information to integrate these two omics data sets, thus providing insight into biological interactions between different biological layers, with regard to the host's phenotype. The application of HisCoM-MnM to data sets from 103 and 97 patients with HCC and liver cirrhosis (LC), respectively, showed that this approach could identify HCC-related pathways related to cancer metabolic reprogramming, in addition to the significant metabolome and metagenome that make up those pathways.

12.
PLoS One ; 15(9): e0239733, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32986758

RESUMO

OBJECTIVE: This study aimed to compare the efficacy between bipolar radiofrequency ablation (RFA), using twin internally cooled wet (TICW) electrodes, and switching monopolar RFA, using separable clustered (SC) electrodes, in the treatment of recurrent hepatocellular carcinoma (HCC) after locoregional treatment. MATERIALS AND METHODS: In this single-center, two-arm, parallel-group, randomized controlled study, we performed a 1:1 random allocation on eligible patients with recurrent HCC after locoregional treatment, to receive TICW-RFA or SC-RFA. The primary endpoint was the minimum diameter of the ablation zone per unit ablation time. Secondary endpoints included other technical parameters, complication rate, technical success and technique efficacy, and clinical outcomes. RESULTS: Enrolled patients were randomly assigned to the TICW-RFA group (n = 40) or SC-RFA group (n = 37). The two groups did not show significant differences in the primary endpoint, the minimum diameter of the ablation zone per unit ablation time was 2.71 ± 0.98 mm/min and 2.61 ± 0.96 mm/min in the TICW-RFA and SC-RFA groups, respectively (p = 0.577). Total RF energy delivery (11.75 ± 9.04 kcal vs. 22.61 ± 12.98 kcal, p < 0.001) and energy delivery per unit time (0.81 ± 0.49 kcal/min vs. 1.45 ± 0.42 kcal/min, p < 0.001) of the TICW-RFA group were less than those of the SC-RFA group. No procedure-related death or major complications occurred. Technical success was achieved in all patients in both groups, and technique efficacy rates were 100% (46/46) in the TICW-RFA group and 95.0% (38/40) in the SC-RFA group (p = 0.213). The 1-year and 2-year cumulative LTP rates were 11.8% and 24.2%, respectively, in the TICW-RFA group, and 8.6% and 18.1%, respectively, in the SC-RFA group (p = 0.661). CONCLUSION: In this single-center randomized controlled study from a Korean tertiary referral hospital, TICW-RFA demonstrated similar therapeutic efficacy and safety profile for recurrent HCC after locoregional treatment compared with SC-RFA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03806218).


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Eletrodos/classificação , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Idoso , Carcinoma Hepatocelular/patologia , Ablação por Cateter/instrumentação , Temperatura Baixa , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
13.
Dig Dis Sci ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856240

RESUMO

BACKGROUND AND AIMS: The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE). METHODS: This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison. RESULTS: A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p < 0.05), whereas, the DAA group (vs. IFN and control groups) independently predicted a reduced risk of progression (hazard ratio (HR) = 0.630, 95% confidence interval 0.411-0.966, p = 0.034). The cumulative incidence rate of HCC progression in the DAA group was significantly lower than that in the IFN and control groups (p = 0.033, log-rank test). In addition, the DAA group (vs. IFN and control groups) was independently associated with a reduced risk of mortality (p = 0.042). CONCLUSIONS: DAA treatment provided significantly prolonged progression-free survival in patients with CHC-related HCC treated with TACE compared to that in patients administered IFN or no treatment.

14.
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.

15.
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.

16.
Korean J Radiol ; 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32729269

RESUMO

OBJECTIVE: This study aimed to prospectively compare the efficacy, safety, and mid-term outcomes of dual-switching monopolar (DSM) radiofrequency ablation (RFA) to those of conventional single-switching monopolar (SSM) RFA in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center, two-arm, parallel-group, randomized controlled study was approved by the Institutional Review Board. Written informed consent was obtained from all patients upon enrollment. A total of 80 patients with 94 HCC nodules were randomized into either the DSM-RFA group or SSM-RFA group in a 1:1 ratio, using a blocked randomization method (block size 2). The primary endpoint was the minimum diameter of the ablation zone per unit time. The secondary endpoints included other technical parameters, complication rate, technique efficacy, and 2-year clinical outcomes. RESULTS: Significantly higher ablation energy per unit time was delivered to the DSM-RFA group than to the SSM-RFA group (1.7 ± 0.2 kcal/min vs. 1.2 ± 0.3 kcal/min; p < 0.001). However, no significant differences were observed between the two groups for the analyzed variables, including primary endpoint, regarding size of the ablation zone and ablation time. Major complication rates were 4.9% in the DSM-RFA group and 2.6% in the SSM-RFA group (p = 1.000). The 2-year local tumor progression (LTP) rates of the HCC nodules treated using DSM-RFA and SSM-RFA were 8.5% and 4.7%, respectively (p = 0.316). The 2-year LTP-free survival rates of patients in the DSM-RFA and SSM-RFA groups were 90.0% and 94.4%, respectively (p = 0.331), and the 2-year recurrence-free survival rates were 54.9% and 75.7%, respectively (p = 0.265). CONCLUSION: Although DSM-RFA using a separable clustered electrode delivers higher ablation energy than SSM-RFA, its effectiveness failed to show superiority over SSM-RFA in the treatment of HCC.

17.
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.

18.
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.

19.
BMC Cancer ; 20(1): 504, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487089

RESUMO

BACKGROUND: The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. METHODS: A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). RESULTS: Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system ("ASAR"). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570-0.871) in the derivation, 0.700 (95% CI = 0.445-0.905) in the internal validation, and 0.680 (95% CI = 0.652-0.707) in the external validation, respectively. Patients with ASAR< 4 showed significantly longer OS than patients with ASAR≥4 in all three datasets (all P < 0.001). Among Child-Pugh class B patients, a modified model without TACE response, i.e., "ASA(R)", discriminated OS with a c-index of 0.788 (95% CI, 0.703-0.876) in the derivation, and 0.745 (95% CI, 0.646-0.862) in the internal validation, and 0.670 (95% CI, 0.605-0.725) in the external validation, respectively. Child-Pugh B patients with ASA(R) < 4 showed significantly longer OS than patients with ASA(R) ≥ 4 in all three datasets (all P < 0.001). CONCLUSIONS: ASAR provides refined prognostication for repetition of TACE in patients with unresectable HCC. For Child-Pugh class B patients, a modified model with baseline factors might guide TACE initiation.

20.
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.

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