Purpose: This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Materials and Methods: We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method. Results: Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure. Conclusion Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

Background/Aims: Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. Methods: We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. Results: The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (p=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. Conclusions Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.

Background/Aims: With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance. Methods: Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-toplatelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR. Results: The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Timedependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC. Conclusions aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

Background: s/Aims: This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. Methods: We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Results: Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (P<0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS<0.05). Conclusions In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

Background: /Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. Methods: A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. Results: The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Conclusions Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Objective: To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). Materials and Methods: This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. Results: The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). Conclusion DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.

Objective: To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). Materials and Methods: This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. Results: The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). Conclusion DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Acyl-CoA Dehydrogenase ; Biomarkers ; Blotting, Western ; Carcinoma, Hepatocellular ; Humans ; Immunoblotting ; Liver ; Liver Cirrhosis ; Mass Spectrometry ; Methionine Adenosyltransferase ; Methionine ; Proteomics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Two-Dimensional Difference Gel Electrophoresis

BACKGROUND: Detection of anti-Kidd antibody is important because of its clinical significance. If detection is difficult due to weak serological reactivity or dosage effect, use of an enzyme method could be helpful. However, despite use of an enzyme method, we still observed weak reactivity of anti-Kidd antibody. METHODS: All identified anti-Kidd antibody cases from Jan 2012 to Aug 2015 in Asan Medical Center were reviewed. Antibody identification test was performed using the column agglutination technique using Bio-Rad ID-DiaPanel with LISS/Coombs card, Bio-Rad ID-DiaPanel-P with NaCl/Enzyme card, and ID-DiaPanel-P with LISS/Coombs card. The test results were compared. RESULTS: Sixty cases of anti-JK(a) or anti-Jk(b) were detected and tested by enzyme method. Among them, 34 (56.6%) cases showed strengthened reactivity using the ID-DiaPanel-P with NaCl/Enzyme card method. However, 26 (43.4%) cases showed weakened reactivity. Of these, 13 cases that could be tested by an additional method using ID-DiaPanel-P with LISS/Coombs card containing anti-IgG and anti-C3d showed successfully strengthened reactivity. CONCLUSION: The reactivity of anti-Kidd antibodies that was not strengthened using ID-DiaPanel-P with NaCl/Enzyme card method could be successfully strengthened by use of the ID-DiaPanel-P with LISS/Coombs card.
Agglutination ; Antibodies* ; Chungcheongnam-do