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  • MDPI AG  (8)
  • Kim, Yoon Jun  (8)
  • 1
    In: Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-07-06), p. 1805-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 2
    In: Cancers, MDPI AG, Vol. 13, No. 23 ( 2021-11-29), p. 6009-
    Abstract: It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage. A total of 761 patients (RFA, n = 194; resection, n = 567) from Seoul National University Hospital (Seoul, South Korea) and 1277 patients (RFA, n = 352; resection, n = 925) from the Korean Primary Liver Cancer Registry were included in the hospital and nationwide cohorts, respectively. Primary and secondary endpoints were OS and recurrence-free survival (RFS), respectively. Additional analysis was performed when the history of the antiviral treatment and the type of prescribed nucleos(t)ide analogue were confirmed. The rate of complications was compared between the two treatment groups in the hospital cohort. Baseline characteristics were balanced, using inverse probability of treatment weighting (IPTW). In the hospital cohort, the RFA group had a smaller mean tumor size (1.7 vs. 3.9 cm) but a higher proportion of cirrhotic patients than the resection group (85.6% vs. 63.1%) (both p 〈 0.01). During 81.0 (interquartile range, 62.3–107.1) months of follow-up, there was no difference in OS (adjusted hazard ratio (aHR) = 0.870, 95% confidence interval (CI) = 0.400–1.897, p = 0.73) and RFA was associated with shorter RFS (aHR = 1.562, 95% CI = 1.099–2.219, p = 0.01) after employing IPTW. Antiviral treatment was independently associated with longer OS (aHR = 0.444, 95% CI = 0.251–0.786, p = 0.01) as well as RFS (aHR = 0.544, 95% CI = 0.391–0.757, p 〈 0.01) in the hospital cohort. In the nationwide cohort, there was no difference in OS (aHR = 0.981, 95% CI = 0.661–1.456, p = 0.92) between the two treatment groups when adjusted for antiviral treatment, which was a negative independent risk factor for mortality (aHR = 0.655, 95% CI = 0.451–0.952, p = 0.03) after IPTW. Among patients treated with tenofovir (n = 96) or entecavir (n = 184) in the hospital cohort, there was no difference in either OS (aHR = 0.522, 95% CI = 0.058–4.724, p = 0.56) or RFS (aHR = 1.116, 95% CI = 0.738–1.688, p = 0.60). The overall incidence of complications was higher in the resection group (26.3%) than in the RFA group (13.9%) (p 〈 0.01). RFA may provide comparable OS to resection in the treatment of very early or early HCC with a lower rate of complications, although RFS is marginally shorter than in the resection group after adjusting for antiviral treatment. Regardless of the type of NA, antiviral treatment in patients with HBV-related HCC is strongly associated with both OS and RFS.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 3
    In: Cancers, MDPI AG, Vol. 11, No. 9 ( 2019-09-03), p. 1295-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
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  • 4
    In: Cancers, MDPI AG, Vol. 11, No. 11 ( 2019-11-04), p. 1721-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
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  • 5
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 9 ( 2023-05-08), p. 3336-
    Abstract: The association of smoking with hepatocellular carcinoma (HCC) or cardiovascular disease (CVD) has been reported, but the study of its relationship with metabolic-associated fatty liver disease (MAFLD) is limited. We aimed to investigate the effect of smoking on the incidence of HCC or CVD in MAFLD patients. Using the Korean nationwide health screening database, we analyzed subjects between 2001 and 2015. A total of 283,088 subjects including 110,863 MAFLD patients and 172,225 controls were analyzed. Smoking status was divided by non-smoker, ex-smoker, or current smoker. In the follow-up period, a total of 2903 (1.0%) subjects developed HCC, and the MAFLD group (1723, 1.6%) had a significantly higher incidence than the control group (1180, 0.7%). In the MAFLD group, current smokers showed significantly higher risk of HCC compared to non-smokers (adjusted HR 1.24, 95% CI 1.08–1.41), whereas the control group did not (adjusted HR 1.07, 95% CI 0.89–1.30). A total of 18,984 (6.7%) patients developed CVD, and the incidence was significantly higher in the MAFLD group (8688, 7.8%) than in the control group (10,296, 6.0%), similar to HCC. The risk of CVD in current smokers increased by 22% compared to non-smokers in the MAFLD group (adjusted HR 1.22, 95% CI 1.15–1.30) and by 21% (adjusted HR 1.21, 95% CI 1.13–1.29) in the control group. Based on sex stratification, men showed increased incidence of both HCC and CVD by smoking, whereas women had only increased risk of CVD. Smoking significantly increases the incidence of HCC and CVD in MAFLD patients; thus, it is highly recommended to quit smoking completely in the population with MAFLD.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 6
    In: Diagnostics, MDPI AG, Vol. 12, No. 7 ( 2022-07-20), p. 1757-
    Abstract: Background: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). Methods: We retrospectively included 284 samples with HBV DNA 〈 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, n = 239 and HBeAg-positive, n = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. Results: There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co] 1.323; adjusted R2 = 0.8445; p 〈 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg 〈 1000 IU/mL or ≥1000 IU/mL and found a significant positive linear correlation between sqHBsAg S/Co and qHBsAg (qHBsAg [IU/mL] = 0.072 × sqHBsAg [S/Co] 1.331; adjusted R2 = 0.7878; p 〈 0.001) in HBeAg-positive patients with qHBsAg titers of 〈 1000 IU/mL and a significant negative correlation in HBeAg-positive patients with qHBsAg titers of ≥1000 IU/mL (qHBsAg [IU/mL] = 8.987 × 1014 × sqHBsAg [S/Co] −3.175; adjusted R2 = 0.6350; p 〈 0.001). Conclusions: There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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  • 7
    In: Biomedicines, MDPI AG, Vol. 11, No. 2 ( 2023-01-27), p. 382-
    Abstract: Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can detect early stages of hepatocellular carcinoma (HCC). However, the survival benefit of Gd-EOB-DTPA-enhanced MRI in the surveillance of patients with cirrhosis has not yet been determined. We explored whether the intermittent replacement of ultrasonography (USG) with Gd-EOB-DTPA-enhanced MRI during HCC surveillance improved the clinical outcomes of patients with cirrhosis. We performed a retrospective cohort study of 421 HCC patients who were newly diagnosed during surveillance. Of these patients, 126 (29.9%) underwent surveillance based on Gd-EOB-DTPA-enhanced MRI and USG (USG+MRI group). The patients (295, 70.1%) who did not undergo MRI during surveillance were referred to as the USG group. In the USG+MRI group, 120 (95.2%) of 126 patients were diagnosed with early-stage HCC, whereas 247 (83.7%) of 295 patients were diagnosed with early-stage HCC in the USG group (P = 0.009). The significantly longer overall survival and time to progression in patients in the USG+MRI group compared to the unmatched cohort USG group was consistently observed by inverse probability weighting and propensity score-matched analysis. Gd-EOB-DTPA-enhanced MRI combined surveillance improved the detection of early-stage HCC and clinical outcomes such as overall survival and the time to progression in patients with cirrhosis.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 8
    In: Diagnostics, MDPI AG, Vol. 12, No. 5 ( 2022-05-07), p. 1170-
    Abstract: Background: Inflammation is a key feature shaping the microenvironment of hepatocellular carcinoma (HCC), and liver fibrosis is associated with the prognosis of patients with HCC. In this study, we investigated whether baseline inflammation-based scores and serum fibrosis markers can help in predicting the prognosis of HCC patients treated with transarterial chemoembolization (TACE). Methods: A total of 605 consecutive patients with HCC treated by TACE were included. The systemic immune-inflammation index (SII), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), FIB-4 index, and aspartate aminotransferase-to-platelet ratio index (APRI) were analyzed regarding their associations with disease progression and survival. Results: All tested inflammation-based scores and fibrosis markers were significantly associated with tumor progression and overall survival in the univariate analyses. In the multivariate analysis, NLR (hazard ratio [HR] , 1.06; p = 0.007) and FIB-4 (HR = 1.02, p = 0.008) were independent risk factors for disease progression, along with α-fetoprotein (AFP) levels, maximum tumor size and number, and presence of vascular invasion. Furthermore, NLR (HR, 1.09; p 〈 0.001) and FIB-4 (HR, 1.02; p = 0.02) were independent prognostic factors for survival. Conclusions: High baseline NLR and FIB-4 levels might help the prediction of disease progression and death in patients with HCC after TACE.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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