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    Transarterial Chemoembolization in Treatment-Naïve and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome Analysis
    (Springer Science and Business Media LLC, 2019-12)
    Kim, David Sooik
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    Lim, Tae Seop
    ;
    Jeon, Mi Young
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    Kim, Beom Kyung
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    Park, Jun Yong
    OBJECTIVES: Transarterial chemoembolization (TACE) improves the survival of patients with hepatocellular carcinoma (HCC); however, TACE treatment outcomes of patients with treatment-naïve HCC (TN-HCC) and those with recurrent HCC after curative resection (R-HCC) have not yet been compared. METHODS: We recruited 448 patients with TN-HCC, and 275 patients with R-HCC treated with TACE as first-line anti-cancer treatment. RESULTS: At first TACE, patients with TN-HCC showed a significantly lower proportion of male gender (74.9% vs. 84.3%), higher proportion of liver cirrhosis (61.9% vs. 49.3%), higher aspartate aminotransferase (median 48 vs. 31 IU/L), alanine aminotransferase (median 38 vs. 26 IU/L), alpha-fetoprotein (AFP) (median 96.6 vs. 7.7 ng/mL), and total bilirubin (mean 1.0 vs. 0.8 mg/dL) levels, longer prothrombin time (median 1.05 vs. 1.01 international normalized ratio), higher tumor number (mean 2.1 vs. 1.7), larger tumor size (median 3.1 vs. 1.6 cm), and lower proportion of Barcelona Clinic Liver Cancer stage 0-A (55.6% vs. 71.9%) than patients with R-HCC (all P < 0.05). Multivariate analysis showed that TACE for TN-HCC (vs. R-HCC) was an independent predictor of mortality (hazard ratio, 1.328; P = 0.024) with AFP level and tumor number (all P < 0.05). However, treatment outcomes between TN-HCC and R-HCC became statistically similar after propensity score-matched (PSM) analysis using liver cirrhosis, tumor size, and multiple tumors (P < 0.05). CONCLUSIONS: Based on the similar TACE treatment outcomes observed with the PSM analysis, the current TACE treatment guideline for patients with TN-HCC might similarly be applied for patients with R-HCC.
    Scopus© Citations 9
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    Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B
    (The Korean Association for the Study of the Liver, 2013)
    Park, Mi Sung
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    Kim, Beom Kyung
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    Kim, Kyung Sik
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    Kim, Ja Kyung
    ;
    Kim, Seung Up
    Scopus© Citations 10
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    Author Correction: Comparison between chronic hepatitis B patients with untreated immune-tolerant phase vs. those with virological response by antivirals
    (2019-11)
    Lee, Hye Won
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    Kim, Seung Up
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    ;
    Park, Jun Yong
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    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Scopus© Citations 2
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    Scopus© Citations 38
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    Comparison between chronic hepatitis B patients with untreated immune-tolerant phase vs. those with virological response by antivirals
    (Springer Science and Business Media LLC, 2019-02)
    Lee, Hye Won
    ;
    Kim, Seung Up
    ;
    ;
    Park, Jun Yong
    ;
    Routine nucleos(t)ide analogs (NUCs) have not yet been recommended for patients with immune-tolerant (IT) phase in chronic hepatitis B virus (HBV) infection. We aimed to evaluate prognosis of patients in untreated IT-phase (UIT group), compared to those in immune-active phase who achieved virological response by NUCs according to guidelines (VR group). Between 2006 and 2012, patients in UIT or VR groups were included. Cumulative risks of HCC and liver-related events (LREs) development were assessed. Furthermore, propensity-score was calculated based upon age, gender, diabetes and liver stiffness. UIT group (n = 126) showed younger age, lower proportion of male gender and lower LS than VR group (n = 641). UIT group had similar 10-year cumulative risks of HCC (2.7% vs. 2.9%, p = 0.704) and LRE (4.6% vs. 6.1%, p = 0.903) development, compared to VR group. When we re-defined UIT group by the lower ALT cut-offs, 10-year cumulative risks of HCC and LRE development were 2.9% and 4.8%, respectively. Using propensity-score matching and inverse probability treatment weighting analysis, similar results were reproduced. UIT group consistently had similar prognosis compared to VR group. Therefore, further large-scale prospective studies in order to verify rationales of routine NUCs in UIT group are still required.
    Scopus© Citations 31
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    Prognosis of Untreated Minimally Active Chronic Hepatitis B Patients in Comparison With Virological Responders by Antivirals
    (Ovid Technologies (Wolters Kluwer Health), 2019-06)
    Lee, Hye Won
    ;
    Kim, Seung Up
    ;
    Park, Jun Yong
    ;
    ;
    OBJECTIVES: Serum hepatitis B virus (HBV)-DNA > 2,000 IU/mL is associated with higher risk of disease progression. However, without hepatocellular carcinoma (HCC) or cirrhosis, nucleos(t)ide analogs (NUCs) are recommended only for patients with elevated serum HBV-DNA and alanine aminotransferase ≥2 × upper normal limit. METHODS: We evaluated prognosis of untreated minimally active (MA) hepatitis patients (defined as HBV-DNA > 2,000 IU/mL, but never fulfilling current criteria for NUCs during follow-up) (untreated MA group), compared to virological responders by NUCs (NUC-VR group). Eligible patients undergoing transient elastography were consecutively enrolled. Patients with an immune-tolerant or inactive phase and with cirrhosis or HCC at enrollment were excluded. Cumulative risks of disease progression were assessed using the Kaplan-Meier method. RESULTS: The untreated MA group (n = 152) had higher HBV-DNA, alanine aminotransferase, and total bilirubin levels, and lower proportions of male and positive hepatitis B e antigen, compared to the NUC-VR group (n = 641). The untreated MA group had higher risks of HCC (adjusted hazard ratio [HR] 3.485, 95% confidence interval [CI] 1.234-9.846; P = 0.018), but similar risks of cirrhotic complications (adjusted HR 0.649, 95% CI 0.227-1.854; P = 0.420), compared to the NUC-VR group. Inverse probability of treatment weighting analysis using propensity score showed that the untreated MA group had higher risks of HCC (HR 4.464, 95% CI 2.008-9.901; P < 0.001), but similar risks of cirrhotic complications (HR 1.171, 95% CI 0.594-2.309; P = 0.649), compared to the NUC-VR group. DISCUSSION: Through appropriate adjustment of potential prognostic factors, the untreated MA group consistently showed higher risks of HCC, but similar risks of cirrhotic complications, compared to the NUC-VR group. HCC risk might be reduced through earlier NUCs for the untreated MA group.
    Scopus© Citations 21
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    Progression of Untreated Minimally Active Chronic HBV Infection Compared to Inactive Infection
    (Elsevier BV, 2019-12)
    Lee, Hye Won
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    Kim, Seung Up
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    Park, Jun Yong
    ;
    Nucleos(t)ide analogs (NUCs) are recommended when both are fulfilled in the absence of hepatocellular carcinoma (HCC) or cirrhosis; (1) elevated serum hepatitis B virus (HBV)-DNA (≥20,000 IU/mL for hepatitis B e antigen-positive chronic hepatitis B [CHB] or ≥2000 IU/mL for hepatitis B e antigen-negative CHB) and (2) serum alanine aminotransferase ≥2× upper limit of normal.1 Therefore, many patients still remain untreated. Such untreated patients have so called "minimally active CHB," where serum HBV-DNA is persistently >2000 IU/mL and other parameters for NUCs are below the criteria.2 There have been little data concerning their prognosis.
    Scopus© Citations 18
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    Association Between Level of Fibrosis, Rather Than Antiviral Regimen, and Outcomes of Patients With Chronic Hepatitis B
    (Elsevier BV, 2016-11)
    Kim, Hye Soo
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    Kim, Beom Kyung
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    Kim, Seung Up
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    Park, Jun Yong
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    BACKGROUND & AIMS: We performed a propensity-score matched analysis to investigate whether entecavir, compared with lamivudine, can reduce risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B after adjusting for level of fibrosis. METHODS: We performed a retrospective study of 1079 patients with chronic hepatitis B who received first-line therapy with lamivudine (n = 435) or entecavir (n = 644) from 2006 through 2013. Only patients with available liver stiffness value measured by transient elastography were recruited. Liver cirrhosis was diagnosed by ultrasonography. To adjust for the imbalance of patients treated with lamivudine versus entecavir, we performed propensity-score matching (PSM), at a ratio of 1:1, using 7 factors (age, sex, hepatitis B e antigen, alanine aminotransferase, serum albumin, platelet count, and liver stiffness; PSM1) or 8 factors (variables of PSM1 plus ultrasonography measurements of cirrhosis; PSM2). Patients with virologic breakthrough or resistance mutations received rescue therapy. RESULTS: Over the 7-year period, 91 patients developed HCC and 104 had liver-related events in the entire cohort. In multivariate analyses, level of fibrosis, but not antiviral regimen, was independently associated with risk of HCC (P < .05). The PSM1 group included 342 pairs of patients and the PSM2 group included 338 pairs. Similar proportions of patients given lamivudine versus entecavir developed HCC in each model (10.5% given lamivudine vs 9.9% given entecavir in PSM1 and 11.9% vs 12.6% in PSM2; all P > .05). When PSM was applied to patients with liver stiffness value ≤13 kPa or >13 kPa, patients given lamivudine versus entecavir still had similar cumulative rates of HCC development (all P > .05). CONCLUSIONS: In a PSM analysis, we associated level of fibrosis, rather than antiviral regimen, with risk of HCC, when patients received appropriate rescue therapy in case of virologic breakthrough or resistance mutations.
    Scopus© Citations 38
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    Fibrosis-matched outcomes between chronic hepatitis B patients with drug-induced virological response and inactive carriers
    (Wiley, 2019-01)
    Kim, Hye Soo
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    Lee, Hye Won
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    Park, Jun Yong
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    BACKGROUND & AIMS: We compared the risk of hepatocellular carcinoma (HCC) development between patients with chronic hepatitis B (CHB) who achieved virological response (VR; HBV-DNA < 2000 IU/mL) with nucleos(t)ide analogues (NUCs) treatment (NUC-VR group) and patients with inactive CHB phase (ICHBP group). METHODS: To adjust for imbalances between NUC-VR and ICHBP groups, propensity score matching (PSM) models with 1:1 ratios were performed. RESULTS: This study included 2032 patients (n = 1291 in NUC-VR group and n = 741 in ICHBP group). Before PSM, NUC-VR group was at higher risk of HCC development than ICHBP group at 7 years (9.4% in NUC-VR group vs 3.3% in ICHBP group; P < 0.001). However, after PSM, the cumulative HCC development rates at 7 years were similar in NUC-VR and ICHBP groups using the three PSM models [2.0% vs 4.3%, PSM model-1 (612 pairs); 3.7% vs 4.4%, PSM model-2 (618 pairs); and 2.4% vs 4.3%, PSM model-3 (610 pairs)] (all P > 0.05). CONCLUSIONS: After adjusting heavier hepatic fibrosis burden in NUC-VR group, overall clinical outcomes between 2 groups had become comparable. Therefore, if appropriate, NUCs to prevent viral replication and hepatic inflammation are required for achieving better prognosis.
    Scopus© Citations 5