1.A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease
Seung Joon CHOI ; Sungjin YOON ; Kyoung-Kon KIM ; Doojin KIM ; Hye Eun LEE ; Kwang Gi KIM ; Seung Kak SHIN ; Ie Byung PARK ; Seong Min KIM ; Dae Ho LEE
Diabetes & Metabolism Journal 2024;48(4):740-751
Background:
We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis).
Methods:
A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination.
Results:
A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH.
Conclusion
Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.
2.Local Ablation for Hepatocellular Carcinoma: 2024 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association
Seungchul HAN ; Pil Soo SUNG ; Soo Young PARK ; Jin Woong KIM ; Hyun Pyo HONG ; Jung-Hee YOON ; Dong Jin CHUNG ; Joon Ho KWON ; Sanghyeok LIM ; Jae Hyun KIM ; Seung Kak SHIN ; Tae Hyung KIM ; Dong Ho LEE ; Jong Young CHOI ; Research Committee of the Korean Liver Cancer Association
Gut and Liver 2024;18(5):789-802
Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements.Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, preprocedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.
3.Local ablation for hepatocellular carcinoma: 2024 expert consensus-based practical recommendation of the Korean Liver Cancer Association
Seungchul HAN ; Pil Soo SUNG ; Soo Young PARK ; Jin Woong KIM ; Hyun Pyo HONG ; Jung-Hee YOON ; Dong Jin CHUNG ; Joon Ho KWON ; Sanghyeok LIM ; Jae Hyun KIM ; Seung Kak SHIN ; Tae Hyung KIM ; Dong Ho LEE ; Jong Young CHOI ;
Journal of Liver Cancer 2024;24(2):131-144
Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.
4.Local Ablation for Hepatocellular Carcinoma: 2024Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association
Seungchul HAN ; Pil Soo SUNG ; Soo Young PARK ; Jin Woong KIM ; Hyun Pyo HONG ; Jung-Hee YOON ; Dong Jin CHUNG ; Joon Ho KWON ; Sanghyeok LIM ; Jae Hyun KIM ; Seung Kak SHIN ; Tae Hyung KIM ; Dong Ho LEE ; Jong Young CHOI ; Research Committee of the Korean Liver Cancer Association
Korean Journal of Radiology 2024;25(9):773-787
Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.
5.Surgery versus radiofrequency ablation in patients with Child- Pugh class-A/single small (≤3 cm) hepatocellular carcinoma
Jungnam LEE ; Young-Joo JIN ; Seung Kak SHIN ; Jung Hyun KWON ; Sang Gyune KIM ; Young Ju SUH ; Yujin JEONG ; Jung Hwan YU ; Jin-Woo LEE ; Oh Sang KWON ; Soon Woo NAHM ; Young Seok KIM
Clinical and Molecular Hepatology 2022;28(2):207-218
Background/Aims:
We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA).
Methods:
We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2–3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment.
Results:
The median follow-up period was 64.8 months (interquartile range, 0.1–162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396–1.232) (P=0.215) and 1.698 (1.777–2.448) (P=0.005), respectively.
Conclusions
SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.
6.Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease
Seung Joon CHOI ; Seong Min KIM ; Yun Soo KIM ; Oh Sang KWON ; Seung Kak SHIN ; Kyoung Kon KIM ; Kiyoung LEE ; Ie Byung PARK ; Cheol Soo CHOI ; Dong Hae CHUNG ; Jaehun JUNG ; MunYoung PAEK ; Dae Ho LEE
Diabetes & Metabolism Journal 2021;45(5):739-752
Background:
Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods.
Methods:
A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54).
Results:
MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa).
Conclusion
Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.
7.Partial Virological Response after 2 Years of Entecavir Therapy Increases the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Associated Cirrhosis
Seung Kak SHIN ; Hyung Joon YIM ; Jeong Han KIM ; Chan Uk LEE ; Jong Eun YEON ; Sang Jun SUH ; Young Kul JUNG ; Yun Soo KIM ; Ju Hyun KIM ; Oh Sang KWON
Gut and Liver 2021;15(3):430-439
Background/Aims:
The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients.
Methods:
A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk.
Results:
After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors.
Conclusions
PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.
8.Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease
Seung Joon CHOI ; Seong Min KIM ; Yun Soo KIM ; Oh Sang KWON ; Seung Kak SHIN ; Kyoung Kon KIM ; Kiyoung LEE ; Ie Byung PARK ; Cheol Soo CHOI ; Dong Hae CHUNG ; Jaehun JUNG ; MunYoung PAEK ; Dae Ho LEE
Diabetes & Metabolism Journal 2021;45(5):739-752
Background:
Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods.
Methods:
A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54).
Results:
MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa).
Conclusion
Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.
9.Partial Virological Response after 2 Years of Entecavir Therapy Increases the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Associated Cirrhosis
Seung Kak SHIN ; Hyung Joon YIM ; Jeong Han KIM ; Chan Uk LEE ; Jong Eun YEON ; Sang Jun SUH ; Young Kul JUNG ; Yun Soo KIM ; Ju Hyun KIM ; Oh Sang KWON
Gut and Liver 2021;15(3):430-439
Background/Aims:
The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients.
Methods:
A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk.
Results:
After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors.
Conclusions
PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.
10.Seroreversion and Acute Decompensation in Chronic Hepatitis B after Discontinuation of Oral Nucleotide Analog in the Patients Achieving HBsAg Loss
Hye Jeong CHO ; Seung Kak SHIN ; Oh Sang KWON ; Ju Hyun KIM ; Yun Soo KIM
The Korean Journal of Gastroenterology 2020;76(5):256-260
Although rare patients with chronic hepatitis B can achieve HBsAg loss on oral nucleos(t)ide analog (NA), the optimal timing of stopping oral NAs safely has been considered when HBsAg and HBV DNA are negative in the serum because HBsAg loss induced by nucleos(t)ide analogs (NAs) appears to be durable if immunosuppressive therapy or chemotherapy are not done. On the other hand, the author experienced a case of HBsAg seroreversion and acute decompensation after the discontinuation of NA in a patient with HBsAg loss. This rare case highlights the need for the close monitoring of patients who achieved HBsAg loss and stopped NA.

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