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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.

Background/Aims: Bile duct invasion (BDI) is rarely observed in patients with advanced hepatocellular carcinoma (HCC), leading to hyperbilirubinemia. However, the efficacy of pretreatment biliary drainage for HCC patients with BDI and obstructive jaundice is currently unclear. Thus, the aim of this study was to assess the effect of biliary drainage on the prognosis of these patients. Methods: We retrospectively enrolled a total of 200 HCC patients with BDI from multicenter cohorts. Patients without obstructive jaundice (n=99) and those who did not undergo HCC treatment (n=37) were excluded from further analysis. Finally, 64 patients with obstructive jaundice (43 subjected to drainage and 21 not subjected to drainage) were included. Propensity score matching was then conducted. Results: The biliary drainage group showed longer overall survival (median 10.13 months vs 4.43 months, p=0.004) and progression-free survival durations (median 7.00 months vs 1.97 months, p

Background/Aims: Young Korean men are obligated to serve in the military for 18 to 21 months. We investigated the effects of military service on steatotic liver disease (SLD) and other metabolic parameters. Methods: Pre-enlistment health check-up performed from 2019 to 2022 and in-service health check-up performed from 2020 to 2022 were merged as paired data. SLD was defined as a hepatic steatosis index of 36 or higher. Hypertension (HTN) and hypertriglyceridemia were also included in the analysis. Results: A total of 503,136 paired cases were included in the analysis. Comparing pre-enlistment and in-service health check-ups, the prevalence of SLD (22.2% vs 17.6%, p

Background/Aims Four high-genetic barrier nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB), namely entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and besifovir dipivoxil maleate (BSV), have been established. The aim of this study is to investigate the efficacy of four high-genetic barrier NAs using a network meta-analysis of randomized trials and propensity score-matched cohorts. Methods Systematic search was performed using PubMed, Cochrane library, and EMBASE and included randomized controlled trials and cohort studies that used propensity score matching. Studies on treatment-naïve CHB patients treated with ETV, TDF, TAF, or BSV were included. Outcomes included alanine aminotransferase normalization and hepatitis B e antigen seroclearance at week 48 and undetectable hepatitis B virus DNA at weeks 48 and 96. Network meta-analysis was performed to synthesize the results. Results In total, 15,000 patients from 16 studies were included. In terms of 48- and 96-week virologic response (VR), TDF outperformed ETV with statistical significance (48 weeks: odds ratio [OR], 1.38; p < 0.001; 96 weeks: OR, 1.57; p = 0.004). ETV was ranked first for 48-week biochemical response (BR) and outperformed TDF (OR, 0.76; p = 0.028). In the sensitivity analyses, 48-week VR from randomized-controlled trials were compiled, and the same trend toward the superiority of TDF over ETV was found (OR, 1.51; p = 0.030). Conclusions Four high-genetic barrier NAs were compared, and TDF was more likely to achieve a VR after 48 weeks, while ETV provided a superior BR after 48 weeks.

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is characterized by persistent inflammatory cascades, with macrophage activation playing a pivotal role. Chitinase 1 (CHIT1), produced by activated macrophages, is a key player in this cascade. In this study, we aimed to explore the role of CHIT1 in MASH with progressive liver fibrosis.MethodsFibrotic liver tissue and serum from distinct patient groups were analyzed using nCounter MAX, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. A MASH mouse model was constructed to evaluate the effectiveness of OATD-01, a chitinase inhibitor. Macrophage profiling was performed using single-nuclei RNA sequencing and flow cytometry.ResultsCHIT1 expression in fibrotic liver tissues was significantly correlated with the extent of liver fibrosis, macrophages, and inflammation. Single-nuclei RNA sequencing demonstrated a notable increase in macrophages numbers, particularly of lipid-associated macrophages, in MASH mice. Treatment with OATD-01 reduced non-alcoholic fatty liver disease activity score and Sirius red-positive area. Additionally, OATD-01-treated mice had lower CHIT1, F4/80, and α-smooth muscle actin positivity, as well as significantly lower levels of inflammatory markers, pro-fibrotic genes, and matrix remodeling-related mRNAs than vehicle-treated mice. Although the population of F4/80+CD11b+ intrahepatic mononuclear phagocytes remained unchanged, their infiltration and activation (CHIT1+MerTK+) significantly decreased in OATD-01-treated mice, compared with that observed in vehicle-treated mice.ConclusionsOur study underscores the pivotal role of CHIT1 in MASH. The observed significant improvement in inflammation and hepatic fibrosis, particularly at higher doses of the CHIT1 inhibitor, strongly suggests the potential of CHIT1 as a therapeutic target in MASH accompanied by progressive liver fibrosis.

Introduction: Despite its prognostic impact, nutritional status has not yet been integrated into the assessment of hepatocellular carcinoma (HCC). This study investigated the association between geriatric nutritional risk index (GNRI) and overall survival (OS) in patients with HCC using a nationwide registry. Methods: Data from the Korea Central Cancer Registry between 2008 and 2019 were analyzed. We explored the integration of the GNRI with the albumin-bilirubin (ALBI) grade for prognostic stratification. Restricted cubic spline regression was used to assess the association between GNRI and survival, stratified by ALBI grade. Results: Among the 16,416 treatment-naïve HCC patients, the ALBI grades were distributed as follows: grade 1, 7,409; grade 2, 7,445; and grade 3, 1,562. Patients were categorized according to Barcelona Clinic Liver Cancer (BCLC) stages: 5,132 stage 0/A, 2,608 stage B, 5,289 stage C, and 968 stage D. The median OS for all patients was 3.1 years (95% CI: 3.0–3.2) and significantly differed with the inclusion of ALBI grade and GNRI (p < 0.001). The effect of combining ALBI grade and GNRI was further evaluated for each BCLC stage. This risk stratification showed a significant correlation with OS for each BCLC stage (all p < 0.001), except for stage D (p = 0.082). Multivariate analysis revealed that a combination of favorable ALBI grade and high GNRI score was independently associated with decreased mortality risk. Conclusion: The GNRI was significantly correlated with OS across ALBI grades and BCLC stages. Integrating the GNRI into the ALBI grade may enhance risk stratification for patients with HCC.

Background/Aims: The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic diseases and assess clinical outcomes of such individuals. Methods: This was a retrospective study of 249 individuals who visited the Pancreatobiliary Diseases Center at Ewha Womans University Seoul Hospital due to the fear of pancreatic diseases between January 2019 and August 2021. Those referred from other departments or external medical facilities were excluded. Collected data included demographic details, comorbidities, causes of fear of pancreatic diseases, and the presence of pancreatic lesions in imaging studies. Results: The median age was 55 years (range, 22 to 82 years). One hundred eleven subjects (44.6%) were male. The causes of fear of pancreatic diseases were abdominal pain (n=144, 57.8%), back pain (n=114, 45.8%), body weight change (n=35, 14.1%), family history of pancreatic diseases (n=32, 12.9%), and others (n=39, 15.7%). Within the group with family history of pancreatic diseases, 25 subjects had a first-degree relative with PC. Of the 200 subjects who underwent imaging, there was no evidence of pancreatic diseases in 182 (91.0%). Pancreatic lesions identified were cystic lesions (n=15, 7.5%), non-specific calcification (n=1, 0.5%), lipoma (n=1, 0.5%), and solid tumor (n=1, 0.5%), later diagnosed as unresectable PC. Conclusion : s: Abdominal pain and back pain were the major causes of fear of pancreatic diseases. The prevalence of PC among those who underwent imaging was 0.5%. Such characteristics should be considered when consulting individuals with fear of pancreatic diseases.

Introduction: Variability in response to atezolizumab plus bevacizumab (AB) treatment of hepatocellular carcinoma (HCC) underscores the critical need for the development of effective biomarkers. We sought to identify peripheral blood biomarkers reflecting response to AB treatment. Methods: We analyzed dynamic changes in peripheral blood mononuclear cells from a prospective, multicenter cohort of 65 patients with HCC, using flow cytometry to evaluate the T-cell population before and 3 weeks after the first AB treatment. Results: We found a unique response of the CD8+ T cells in terms of both frequency and phenotype, in contrast to CD4+ T cells and regulatory T cells. Notably, CD8+ T cells showed significant changes in expression of Ki-67 and T-cell immunoreceptors with Ig and ITIM domains (TIGIT). These distinct responses were observed particularly in the programmed cell death receptor-1 (PD-1)+ subpopulation of CD8+ T cells. Interestingly, the baseline differentiation status of PD-1+CD8+ T cells, particularly the central memory T-cell subset, correlated positively with greater proliferation (higher Ki-67 expression) of PD-1+CD8+ T cells after treatment. Moreover, effector memory cells expressing CD45RA correlated negatively with the increase in TIGIT+/PD-1+CD8+ T cells. The increase in TIGIT+/CD8+ T cells was associated with the development of immune-related adverse events, whereas increase in Ki-67+/PD-1+CD8+ T cells was associated with the better objective response rate. Importantly, dynamic shifts of Ki-67+/PD-1+CD8+ T cells and TIGIT+/CD8+ T cells significantly predicted progression-free survival and overall survival, as confirmed by multivariate analysis. Conclusion: These findings highlight the potential of dynamic changes in CD8+ T cells as an on-treatment prognostic biomarker. Our study underscores the value of peripheral blood profiling as a noninvasive and practical method for predicting the clinical outcomes of AB treatment in patients with HCC.

Hepatic graft-versus-host disease (GVHD) significantly impacts morbidity and mortality among allogeneic hematopoietic stem cell transplant recipients. However, the relationship between clinical and immunopathological phenotypes and their influence on clinical outcomes in hepatic GVHD is not well understood. In this study, we aimed to study the implications of portal T-cell infiltration on the clinical outcomes in hepatic GHVD and its similarities to autoimmune liver disease. We analyzed 78 patients with biopsy-confirmed hepatic GVHD (n = 38) or autoimmune liver disease (n = 40) between 2016 and 2021. The cholestatic variant was defined by an R-value < 2.0, based on the ratio of alanine aminotransferase to alkaline phosphatase. The primary outcome was the biochemical response at 4 (early) and 8–12 (late) weeks after corticosteroid treatment. In hepatic GVHD patients, the hepatitic variant (n = 19) showed greater CD3+ T-cell infiltration than the cholestatic variant (n = 19; p < 0.001). No significant differences were observed in the infiltration of CD20+, CD38+, or CD68+ cells. The hepatitic variant had significantly better early and late responses and higher liver-related event-free survival than the cholestatic variants (p < 0.05). Concerning autoimmune liver diseases, the autoimmune hepatitis (AIH) group had significantly more portal T-cell infiltration and better treatment responses than the primary biliary cholangitis (PBC) group. In conclusion, higher portal T-cell infiltration may be associated with better clinical outcomes in patients with hepatic GVHD. Additionally, this study highlights similarities in portal T-cell infiltration and treatment response patterns between AIH and the hepatitic variant, as well as PBC and the cholestatic variant.

BackgroundAtezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial.Materials and methodsThis real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177).ResultsFirst, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments.ConclusionOur study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by persistent inflammatory cascades, with macrophage activation playing a pivotal role. Chitinase 1 (CHIT1), produced by activated macrophages, is a key player in this cascade. In this study, we aimed to explore the role of CHIT1 in MASH with progressive liver fibrosis. Methods: Fibrotic liver tissue and serum from distinct patient groups were analyzed using nCounter MAX, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. A MASH mouse model was constructed to evaluate the effectiveness of OATD-01, a chitinase inhibitor. Macrophage profiling was performed using single-nuclei RNA sequencing and flow cytometry. Results: CHIT1 expression in fibrotic liver tissues was significantly correlated with the extent of liver fibrosis, macrophages, and inflammation. Single-nuclei RNA sequencing demonstrated a notable increase in macrophages numbers, particularly of lipid-associated macrophages, in MASH mice. Treatment with OATD-01 reduced non-alcoholic fatty liver disease activity score and Sirius redpositive area. Additionally, OATD-01-treated mice had lower CHIT1, F4/80, and a-smooth muscle actin positivity, as well as significantly lower levels of inflammatory markers, pro-fibrotic genes, and matrix remodeling-related mRNAs than vehicle-treated mice. Although the population of F4/80+CD11b+ intrahepatic mononuclear phagocytes remained unchanged, their infiltration and activation (CHIT1+MerTK+) significantly decreased in OATD-01-treated mice, compared with that observed in vehicle-treated mice. Conclusions: Our study underscores the pivotal role of CHIT1 in MASH. The observed significant improvement in inflammation and hepatic fibrosis, particularly at higher doses of the CHIT1 inhibitor, strongly suggests the potential of CHIT1 as a therapeutic target in MASH accompanied by progressive liver fibrosis. [ABSTRACT FROM AUTHOR]

Background/Aims: Young Korean men are obligated to serve in the military for 18 to 21 months. We investigated the effects of military service on steatotic liver disease (SLD) and other metabolic parameters. Methods: Pre-enlistment health check-up performed from 2019 to 2022 and in-service health check-up performed from 2020 to 2022 were merged as paired data. SLD was defined as a hepatic steatosis index of 36 or higher. Hypertension (HTN) and hypertriglyceridemia were also included in the analysis. Results: A total of 503,136 paired cases were included in the analysis. Comparing pre-enlistment and in-service health check-ups, the prevalence of SLD (22.2% vs 17.6%, p<0.001), HTN (7.6% vs 4.3%, p<0.001), and hypertriglyceridemia (8.1% vs 2.9%, p<0.001) decreased during military service. In terms of body mass index, the proportion of underweight (8.2% vs 1.4%, p<0.001) and severely obese (6.1% vs 4.9%, p<0.001) individuals decreased over time. Regarding factors associated with SLD development and resolution, age was positively associated with SLD development (odds ratio, 1.146; p<0.001) and a health check-up interval of <450 days was a protective factor for SLD development (odds ratio, 0.746; p<0.001). Those serving in the marines were less likely to develop SLD, whereas those serving in the navy were more likely to develop SLD. Serving in the army or the navy was negatively associated with SLD resolution, whereas serving in the air force was positively associated with SLD resolution. Conclusions: The prevalence of SLD, HTN, and hypertriglyceridemia decreased substantially during Korean military service. [ABSTRACT FROM AUTHOR]

Background: Atezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial. Materials and methods: This real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177). Results: First, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments. Conclusion: Our study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies. [ABSTRACT FROM AUTHOR]

Background/Aims Despite its prognostic impact, nutritional status has not yet been integrated into the assessment ofhepatocellular carcinoma (HCC). This study investigated the association between geriatric nutritional risk index (GNRI) and overall survival (OS) in patientswith HCC using a nationwide registry. Methods Data from the Korea Central Cancer Registry between 2008 and 2019 were analyzed. We explored the integration of the GNRI with the albumin–bilirubin (ALBI) grade for prognostic stratification. Restricted cubic spline regression was used to assess the association between GNRI and survival, stratified by ALBI grade. Results Among the 16,416 treatment-naïve HCC patients, the ALBI grades were distributed as follows: grade 1, 7,409; grade 2,7,445; and grade 3, 1,562. Patients were categorized according to Barcelona Clinic Liver Cancer (BCLC) stages: 5,132 stage 0/A, 2,608 stage B, 5,289 stageC, and 968 stage D. The median OS for all patients was 3.1 years (95% CI:3.0–3.2) and significantly differed with the inclusion of ALBI grade and GNRI (Figure 1; p<0.001). The effect of combining ALBI grade and GNRI was further evaluated for each BCLC stage. This risk stratification showed a significant correlation with OS for each BCLC stage (all p<0.001), except for stage D (p=0.082). Multivariate analysis revealed that a combination of favorable ALBI grade and high GNRI score was independently associated with decreased mortality risk. Conclusion The GNRI was significantly correlated with OS across ALBI grades and BCLC stages. Integrating the GNRI into the ALBI grade may enhance risk stratification for patients with HCC. [ABSTRACT FROM AUTHOR]

Background/Aims PD-L1 expression is abundant not only in malignant cells but also in infiltrating cells within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). This study explored the association between PD-L1 expression in TME and outcomes in HCC patients treated with atezolizumab plus bevacizumab (AB), emphasizing the implications of PD-L1 expression in both malignant and tumor-infiltrating cells. Methods This retrospective study included 72 patients with HCC who underwent percutaneous core needle liver biopsy before AB treatment between September 2020 and December 2023. PD-L1 expression on tumor tissues was assessed using the combined positive score (CPS) with cutoff values of 1 and 10, utilizing antibody clone 22C3 (Dako). Results The distribution of PD-L1 CPS included 24 patients with CPS <1, 33 patients with CPS 1–10, and 15 patients with CPS ≥10. Significant differences in OS were observed across the three groups, with CPS ≥10 showing the highest survival rates (p=0.010). Patients with CPS ≥10 had better OS than those with CPS <10 (mOS 14.8 vs. 8.3 months, p=0.046), and CPS ≥1 had better OS than CPS <1 (p=0.021). For PFS, the CPS ≥10 group had the highest mPFS of 11.0 months among the three groups (p=0.044). Objective response rates (ORR) were higher in the PD-L1 CPS ≥10 group than in the 1-10 and <1 group (53.3%, 27.3%, and 16.7%, respectively; p=.047). Multivariate analysis identified that PD-L1 expression ≥10 and ≥1 were associated with favorable outcomes regarding OS (hazard ratio [HR] 0.283, p=.027 and HR 0.303, p=.006, respectively). Conclusion Higher PD-L1 expression in malignant and tumor-infiltrating cells was associated with better OS, PFS, and ORR in patients with HCC treated with AB. [ABSTRACT FROM AUTHOR]

Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health issue, with activated fibroblasts playing a key role in its progression. This study evaluated the potential of nintedanib, a drug used for idiopathic pulmonary fibrosis (IPF), in treating MASLD by targeting these fibroblasts. Additionally, the study explored how cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC) are influenced by Immunoglobulin A (IgA) complexes, which may alter immune responses and contribute to inflammation. Methods Fibroblasts from MASLD patients were treated with nintedanib and compared to sorafenib in vitro. A mouse model of fibrosis was used for in vivo analysis. Fibroblasts, including CAFs, were also isolated from HCC patients and treated with IgA dimers to assess their impact on CD71 and PD-L1 expression. The effects of nintedanib on these IgA-stimulated fibroblasts were evaluated. Single-cell sequencing identified HMGN3 as a key regulator of matrix CAFs, with subsequent experiments assessing nintedanib's effect on HMGN3 expression. Results Nintedanib significantly reduced activated fibroblast viability in vitro, outperforming sorafenib. In the mouse model, nintedanib selectively eliminated FAP+PD-L1+ fibroblasts, suggesting its therapeutic potential for MASLD. CAFs expressed higher levels of α-smooth muscle actin and fibroblast activation protein than non-tumor fibroblasts. IgA treatment increased PD-L1 expression on CAFs and reduced TNF-α levels in CD8+ T cells, indicating a possible suppression of antitumor immunity. Nintedanib effectively eliminated these IgA-stimulated fibroblasts. Additionally, nintedanib reduced HMGN3 expression in hepatic stellate cells. Conclusion Nintedanib shows promise as a treatment for MASLD by targeting and eliminating activated fibroblasts. Its ability to remove IgA-stimulated fibroblasts suggests it could also be beneficial in managing fibrosis in liver diseases like HCC. [ABSTRACT FROM AUTHOR]

Background/Aims It has been 4 years since the FDA approved the immunotherapybased regimen atezolizumab-bevacizumab as the first-line treatment of hepatocellular carcinoma. Hence, accurate biomarkers predicting prognosis of the relatively new treatment has not been discovered. In 2022, Scheiner et al suggested a scoring system named CRAFITY score, including CRP and AFP, that accurately predicted prognosis of HCC patients who were treated with atezolizumab-bevacizumab combination therapy. There have also been multiple studies suggesting PIVKA-II as an additionally accurate biomarker and NLR(neutrophil-lymphocyte ratio) as an accurate predictive factor for HCC patients. Naturally, we experimented in including PIVKA-II and NLR into the CRAFITY score system. Methods We included 146 patients diagnosed with HCC who were treated with atezolizumab-bevacizumab. We assigned 1 point for having an AFP ≥100 ng/ml and 1 point for having a CRP ≥1 mg/dl. As we added the PIVKA-II and NLR as new factors included in the scoring system (mCRAFITY), we assigned 1 point for having a PIVKA-II ≥40 mAU/ml and an additional 1 point for having NLR >2.5. We used the AUROC(area under the receiver operating characteristic) to evaluate the performance of our scoring system. Results The AUROC curve showed that the mCRAFITY score had better performance at 6 months and 12 months but worse performance at 18 months in predicting the prognosis of HCC patients. When OS and PFS was calculated, patients with mCRAFITY scores of less than 3 had significantly better prognosis than those with scores more than or equal to 3. (p value=0.0015 and 0.0391 respectively) Conclusion In conclusion, the mCRAFITY score that includes PIVKA-II and NLR may be more accurate than the previously announced CRAFITY score. Patients with mCRAFITY scores less than 3 had significantly better prognosis than whom at scores more than or equal to 3. [ABSTRACT FROM AUTHOR]

Background/Aims The CD69+ tissue-resident T-cell population comprises a considerable proportion of intrahepatic T cells and provides an early, rapid adaptive immune response. However, the characteristics of CD69- populations and their role need to be elucidated. Methods We collected background liver tissues, which were obtained during hepatectomy in patients with various etiologies of chronic liver disease. The patient cohort included n=28 with the following etiologies : hepatitis B virus (HBV, 46%), alcohol-related liver disease (21%), HBV combined with alcoho-related liver disease (HBV+Alc, 29%), and unknown etilogy (4%). Single-cell dissociation and flow cytometry were performed to analyze the liver-infiltrating T-cell population. Fatty changes and fibrosis grade were confirmed by histologic examinations. Results The CD69- subpopulation was more enriched in CD4+ T cells compared to CD8+ T cells. CD69- CD4+ /CD8+ T cells showed a similar activation phenotype but expressed PD-1 less, compared to the CD69+ subpopulation. Interestingly, the CD69- group exhibited higher ex vivo expression of perforin and granzyme B in CD4+ T cells. While perforin expression was lower in CD69- CD4+ T cells compared to CD69- /CD69+ CD8+ T cells, granzyme B levels were similar to those in CD69+ CD8+ T cells, with CD69+ CD8+ T cells having a greater granzyme B+ population. NKG2D+ and CD56+ populations among CD69- CD4+ T cells had more perforin or granzyme B, suggesting they might be activated in an innate-like manner. The frequency of cytotoxic CD69- CD4+ T cells was positively correlated with the serum ALT level but was negatively correlated with liver fibrosis. Conclusion We have identified for the first time that cytotoxic CD4+ T cells among liver-infiltrating T cells are mainly CD69- population, which can recirculate. This population might be associated with liver inflammation, which needs to be further validated. [ABSTRACT FROM AUTHOR]

Background/Aims Daratumumab, a monoclonal antibody targeting CD38, is currently used as a first-line therapy in patients with multiple myeloma. This study aims to investigate the risk of HBR in patients with the anti-HBc antibody and to evaluate the efficacy of prophylactic antiviral therapy in this population. Methods Data from 345 multiple myeloma patients treated with daratumumab between 2014 and 2024 were retrospectively collected. Patients with the anti-HBc antibody were included in the study, while those with positive HBsAg prior to daratumumab treatment were excluded. HBR was defined as HBsAg seroconversion or detection of HBV DNA until subsequent chemotherapy or 12 months after cessation of daratumumab if no subsequent chemotherapy was performed. Results Among the 345 patients, 109 had the anti-HBc antibody and were included in the analysis. The median duration of daratumumab treatment was 101 days, during which ten patients received prophylactic antiviral therapy (9 with entecavir and 1 with tenofovir alafenamide). Overall, 9 patients experienced HBR, with 3 suffering from severe hepatitis (ALT exceeding 200U/L) due to HBR. No patient who received prophylactic antiviral therapy experienced HBR. The cumulative incidence rates of HBR in the non-antiviral treatment group were 8.0% at 12 months after the start of daratumumab. When restricted mean survival time (RMST) was employed to compare the area under the Kaplan-Meier curve of HBR-free survival in both groups, the antiviral treatment group was significantly higher than the non-antiviral treatment group (Difference in RMST=2.00, p=0.002). HBsAb titers less than 100 IU/L (odds ratio 7.527, p=0.057) and anti-HBc antibody titer (odds ratio 1.234, p=0.156) showed a tendency towards an increased incidence of HBR. Conclusion There is a considerable risk of HBR in multiple myeloma patients with the anti-HBc antibody undergoing daratumumab treatment. The use of antiviral therapy may prevent HBR in these at-risk patients. [ABSTRACT FROM AUTHOR]

(1) Background: Despite numerous noninvasive methods for assessing liver fibrosis, effective ultrasound parameters remain limited. We aimed to identify easily measurable ultrasound parameters capable of predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and metabolic-dysfunction-associated steatotic liver disease (MASLD); (2) Methods: The data of 994 patients diagnosed with NAFLD via ultrasound at the Armed Forces Goyang Hospital were retrospectively collected from June 2022 to July 2023. A liver stiffness measurement (LSM) ≥ 8.2 kPa was classified as significant fibrosis. Liver steatosis with cardiometabolic risk factors was defined as MASLD. Two ultrasound variables, the portal venous pulsatility index (VPI) and main portal vein diameter (MPVD), were measured; (3) Results: Of 994 patients, 68 had significant fibrosis. Significant differences in VPI (0.27 vs. 0.34, p < 0.001) and MPVD (10.16 mm vs. 8.98 mm, p < 0.001) were observed between the fibrotic and non-fibrotic groups. A logistic analysis adjusted for age and body mass index (BMI) revealed that only VPI (OR of 0.955, p = 0.022, VPI on a 0.01 scale) and MPVD (OR of 1.501, p < 0.001) were significantly associated with significant liver fibrosis. In the MASLD cohort (n = 939), VPI and MPVD were associated with significant fibrosis. To achieve better accuracy in predicting liver fibrosis, we established a nomogram that incorporated MPVD and VPI. The established nomogram was validated in the test cohort, yielding an area under the receiver operating characteristic curve of 0.821 for detecting significant liver fibrosis; (4) Conclusions: VPI and MPVD, as possible surrogate markers, are useful in predicting significant fibrosis in patients with NAFLD and MASLD.