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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<0.001) than the non-drainage group. Multivariate analysis showed that biliary drainage was a significantly favorable prognostic factor for overall survival (hazard ratio, 0.42; p=0.006) and progression-free survival (hazard ratio, 0.30; p<0.001). Furthermore, in the evaluation of first response after HCC treatment, biliary drainage was beneficial (p=0.005). Remarkably, the durations of overall survival (p=0.032) and progression-free survival (p=0.004) were similar after propensity score matching. Conclusions: Biliary drainage is an independent favorable prognostic factor for HCC patients with BDI and obstructive jaundice. Therefore, biliary drainage should be contemplated in the treatment of advanced HCC with BDI to improve survival outcomes [ABSTRACT FROM AUTHOR]

Background/Aims: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. Methods: We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. Results: A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (–0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. Conclusions: BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB. [ABSTRACT FROM AUTHOR]

Background/Aims: We studied the impact of socioeconomic status (SES) on mortality in hepatocellular carcinoma patients and analyzed the effect of SES on initial treatment allocation. Methods: A cohort study was conducted using data from the National Health Insurance ServiceNational Sample Cohort of Korea. A total of 3,032 hepatocellular carcinoma patients who were newly diagnosed between January 2003 and December 2013 were included. Income level was categorized as Medical Aid and ≤30th, 31st–70th, or >70th percentile as an SES indicator. Results: The proportion of Medical Aid was 4.3%. The highest risks of all-cause mortality associated with Medical Aid were evident in the transcatheter arterial chemoembolization group (fully adjusted hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.25 to 4.58), the other treatments group (fully adjusted HR, 2.86; 95% CI, 1.85 to 4.41), and the no treatment group (fully adjusted HR, 2.69; 95% CI, 1.79 to 4.04) but not in the curative treatment group. An association between the lower-income percentile and higher liver cancer-specific mortality was also observed, except in the curative treatment group. The association between income percentile and all-cause mortality was nonlinear, with a stronger association in the lower-income percentiles than in the higher income percentiles (p-value for nonlinear spline terms <0.05). Conclusions: Patients in the lower SES group, especially patients not eligible for curative treatment, had an increased risk of mortality. In addition, the association between SES and the risk for mortality was stronger in the lower-income percentile than in the moderate to higher income percentiles. [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 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]

Background/Aims Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for antiviral-naïve patients with chronic hepatitis B (CHB). However, it remains controversial which drug is more effective in preventing hepatocellular carcinoma (HCC). We aimed to compare the effects of TAF and TDF on HCC risk. Methods We included 1,628 treatment-naïve CHB patients who underwent antiviral therapy with either a TAF-based regimen (TAF group: n=335) or TDF only (TDF group: n=1,293) between 2007 and 2021. The TAF group consisted of patients who received TAF as a first-line treatment and those who switched from TDF to TAF. Propensity score (PS) matching was used to reduce the effects of confounding factors. Results After PS matching, we analyzed data from 334 patients in the TAF group (mean age: 48.0±11.7 years; 192 men [57.5%]) and 573 patients in the TDF group (mean age: 47.4±11.6 years; 326 men [56.9%]). During a 60-month follow-up, 8 patients in the TAF group (2.4%) and 46 patients in the TDF group (8.0%) developed HCC. TAF treatment was associated with a significantly lower risk of HCC compared to TDF (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.16-0.72; p<0.001). In multivariate analysis, factors independently associated with HCC development included age (adjusted HR [aHR], 1.07; p<0.001), liver cirrhosis (aHR, 2.02; p=0.045), diabetes (aHR, 4.78; p<0.001), alcohol use (aHR, 3.07; p=0.002), and TAF treatment (aHR, 0.22; p<0.001). Conclusion TAF treatment was associated with a 66% lower risk of HCC compared to TDF treatment. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background/Aims The combination of atezolizumab and bevacizumab is the leading treatment for advanced hepatocellular carcinoma (HCC), but finding a reliable biomarker to predict treatment outcomes remains challenging. This study sought to discover exosomal miRNA biomarkers that could predict favorable responses to this therapy. Methods Blood samples were collected from patients with advanced HCC before starting atezolizumab and bevacizumab treatment. Patients were divided into two groups: responders (those showing stable disease, partial, or complete response) and non-responders (those with disease progression). Serum was concentrated using a qEV isolation kit, and exosomal RNA was extracted for small RNA sequencing using next-generation sequencing (NGS). A decision tree analysis was used to identify miRNAs from the top 100 most expressed miRNAs that could differentiate between responders and non-responders. The findings were validated with a t-test. Results The study included eight patients in each group, mostly male, with the majority having viral-induced HCC. NGS identified 1076 miRNAs, with 12 showing significant differences in expression between responders and non-responders. Among these, three miRNAs were elevated, and nine were decreased in the responder group. Specifically, let7c-5p, miR-30a-5p, and miR192-5p were significantly higher in responders. Decision tree analysis highlighted 30 miRNAs from the top 100, with miR-30a-5p being significantly higher in responders (p=0.0047). Validation using quantitative reverse transcription PCR confirmed the increased expression of miR-30a-5p in responders. Additionally, transfecting miR-30a-5p into HepG2 cells led to reduced migration and proliferation. Conclusion Exosomal miRNAs show potential as biomarkers for predicting response to atezolizumab-bevacizumab therapy in HCC patients. [ABSTRACT FROM AUTHOR]

Background/Aims The combination of atezolizumab and bevacizumab is currently used as a first-line treatment for advanced hepatocellular carcinoma (HCC). Despite extensive research, accurately predicting the response to this therapy remains a challenge. Methods This study included patients with advanced HCC who were undergoing atezolizumab and bevacizumab therapy. Blood samples were collected on days 0 and 14 of the first treatment cycle. Peripheral blood mononuclear cells (PBMCs) were isolated from these samples. Eight patients were selected for further analysis: 4 had a complete or partial response, while 4 experienced disease progression. Single-cell RNA sequencing (scRNA-seq) was conducted on the PBMC samples. Results Before treatment, patients with a positive prognosis had higher frequencies of γδ T cells, CD4+ T cells, classical monocytes, CD8+ T cells, and non-classical monocytes in their PBMCs compared to those with a poor prognosis. After treatment, patients with favorable outcomes showed a significant increase in proliferating lymphocytes. In the CD8+ T cell group, a specific cluster (cluster 4) marked by high expression of the proliferation marker MKI67 and inhibitory checkpoint genes (PDCD1, HAVCR2, CTLA4) was more prevalent in patients with a positive prognosis prior to treatment. Furthermore, the frequency of this cluster increased post-treatment in those with better outcomes. Conclusion This study mapped the diverse circulating immune cells in patients with advanced HCC before and after treatment with atezolizumab and bevacizumab. A specific subgroup of CD8+ T cells emerged as a potential biomarker for predicting responses to this combination therapy. [ABSTRACT FROM AUTHOR]

Background/Aims: Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection. Methods: The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments. Results: The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) experienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%). Conclusions: G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P. [ABSTRACT FROM AUTHOR]

Background/Aims: Most prognostic prediction models for patients with liver cirrhosis include serum total bilirubin (TB) level as a component. This study investigated prognostic performance of serum direct bilirubin (DB) and developed new DB level-based prediction models for cirrhosis. Methods: A total of 983 hospitalized patients with liver cirrhosis were included. DB-Model for End-Stage Liver Disease (MELD) score was calculated using MELD score formula, with serum DB level replacing TB level. Results: Mean age of study population was 56.1 years. Alcoholic liver disease was the most frequent underlying condition (471 patients, 47.9%). Within 6 months, 144 patients (14.6%) died or received liver transplantation due to severe liver dysfunction. The area under the receiver operating characteristic curve (AUROC) for prediction of 6-month mortality with DB level was significantly higher than that with TB level (p<0.001). The AUROC of DB-MELD score for prediction of 6-month mortality was significantly higher than that of MELD score (p<0.001). Patients were randomly divided into training (n=492) and validation (n=491) cohorts. A new prognostic prediction model, “Direct Bilirubin, INR, and Creatinine” (DiBIC) score, was developed based on the most significant predictors of 6-month mortality. In training set, AUROC of DiBIC score for prediction of 6-month mortality was 0.892, which was significantly higher than that of the MELD score (0.875, p=0.017), but not different from that of DB-MELD score (0.886, p=0.272). Similar results were observed in validation set. Conclusions: New prognostic models, DB-MELD and DiBIC scores, have good prognostic performance in liver cirrhosis patients, outperforming other currently available models. [ABSTRACT FROM AUTHOR]

Background/Aims: We investigated changes in recurrence rates and significant recurrence predictors over time after complete cure of hepatocellular carcinoma (HCC). Methods: A total of 1,491 patients with first-time diagnosis of Barcelona Clinic Liver Cancer stage A HCC, completely cured by treatment between 2007 and 2016, were recruited from two Korean tertiary institutes. Results: The mean age of the population (1,144 men and 347 women) was 58.6 years. Of the total population, 914 patients (61.3%) had liver cirrhosis. Nine-hundred and forty-one (63.1%) and 550 (36.9%) patients were treated with surgical resection and radiofrequency ablation (RFA), respectively. One-year cumulative incidences of HCC recurrence were 14.3%, 9.9%, and 5.1% from the time of treatment, 3 years after treatment, and 5 years after treatment, respectively. Upon multivariate analysis, multiple tumors, maximal tumor size ≥3 cm, and high Model for End-Stage Liver Disease scores were independently associated with increased HCC recurrence risk from the time of treatment and 1 and 2 years after curative treatment (all p<0.05, except for maximal tumor size ≥3 cm for recurrence 2 years after treatment). Meanwhile, liver cirrhosis and RFA were independently associated with the increased HCC recurrence risk for almost all time points (liver cirrhosis: all p<0.05; RFA: all p<0.005 except for recurrence from 5 years after treatment). Conclusions: The recurrence rate of HCC after curative treatment gradually decreased over time. Two years after treatment, when tumor-related factors lose their prognostic implications, may be used as a cutoff to define the boundary between early and late recurrence of HCC. [ABSTRACT FROM AUTHOR]

Background/Aims: Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. Methods: Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). Results: Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). Conclusions: HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR. [ABSTRACT FROM AUTHOR]

Backgrounds/Aims: Rebleeding of gastric varices (GVs) after endoscopic variceal obturation (EVO) can be fatal. This study was performed to evaluate the usefulness of computed tomography (CT) for the prediction of rebleeding after EVO GV bleeding. Methods: Patients who were treated with EVO for GV bleeding and underwent CT before and after EVO were included. CT images of the portal phase showing pretreatment GVs and feeding vessels, and nonenhanced images showing posttreatment cyanoacrylate impaction were reviewed. Results: Fifty-three patients were included. Their mean age was 60.6±11.6 years, and 40 patients (75.5%) were men. Alcoholic liver disease was the most frequent underlying liver disease (45.3%). Complete impaction of cyanoacrylate in GVs and feeding vessels were achieved in 40 (75.5%) and 24 (45.3%) of patients, respectively. During the follow-up, GV rebleeding occurred in nine patients, and the cumulative incidences of GV rebleeding at 3, 6, and 12 months were 11.8%, 18.9%, and 18.9%, respectively. The GV rebleeding rate did not differ significantly according to the complete cyanoacrylate impaction in the GV, while it differed significantly according to complete cyanoacrylate impaction in the feeding vessels. The cumulative incidences of GV rebleeding at 3, 6, and 12 months were 22.3%, 35.2%, and 35.2%, respectively, in patients with incomplete impaction in feeding vessels, and there was no rebleeding during the follow-up period in patients with complete impaction in the feeding vessels (p=0.002). Conclusions: Abdominal CT is useful in the evaluation of the treatment response after EVO for GV bleeding. Incomplete cyanoacrylate impaction in feeding vessels is a risk factor for GV rebleeding. [ABSTRACT FROM AUTHOR]

Background/Aims: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. Methods: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. Results: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. Conclusions: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. [ABSTRACT FROM AUTHOR]

Background/Aims: In addition to the globally endorsed Barcelona Clinic Liver Cancer (BCLC) staging system, other algorithms or staging systems have been developed, including the Hong Kong Liver Cancer (HKLC) staging system. This study aimed to validate the HKLC staging system relative to the BCLC staging system for predicting survival for hepatocellular carcinoma (HCC) patients in Korea. Methods: From 2004 to 2013, 2,571 patients newly diagnosed with HCC were consecutively enrolled at three Korea University medical centers. Results: Both staging systems differentiated survival well (p<0.001). However, 1-year and 3-year survival were predicted better using the HKLC system than the BCLC system (area under the receiver operating characteristic curve: 0.869 vs 0.856 for 1 year, p=0.002; 0.841 vs 0.827 for 3 years, p=0.010). In hypothetical survival curves, the HKLC system exhibited better median overall survival than the BCLC system (33.1 months vs 19.2 months). In evaluations of prognosis according to either BCLC or HKLC treatment guidelines, risk of death was reduced in the group following only HKLC guidelines compared with the group following only BCLC guidelines (hazard ratio, 0.601; 95% confidence interval, 0.443 to 0.816; p=0.001). Conclusions: Although both staging systems predicted and discriminated HCC prognoses well, the HKLC system showed more encouraging survival benefits than the BCLC system. (Gut Liver 2018;12:94-101) [ABSTRACT FROM AUTHOR]

Background/Aims: Data are lacking regarding the management of chronic hepatitis B (CHB) with resistance to clevudine (CLV). This study evaluated the efficacy of different rescue therapies for CLV-resistant CHB. Methods: Patients with CLV-resistant CHB were enrolled in the cohort, and all patients developed virologic breakthrough during CLV therapy and had confirmed-genotypic resistance to CLV (rtM204I mutation) before enrollment. Results: Of the 107 patients, 12 received adefovir (ADV), 21 received a CLV plus ADV combination (CLV+ADV), 34 received a lamivudine plus ADV combination (LAM+ADV), and 40 received entecavir (ETV) therapy for 48 weeks. The CLV+ADV group had the lowest hepatitis B virus (HBV) DNA level (p<0.0001) and showed the greatest reduction of HBV DNA levels from baseline compared to all other groups (p=0.004) at week 48. HBV DNA was undetectable (<70 IU/mL) in 0%, 57.1%, 21.2%, and 27.5% (p=0.003) of the patients in each group, respectively, at week 48. At the end of the study, the mean alanine transaminase (ALT) level, rate of ALT normalization, and rate of hepatitis B envelope antigen loss or seroconversion did not differ between groups. Conclusions: CLV+ADV combination therapy in patients with CLV-resistant CHB more effectively suppresses HBV replication than ETV, ADV, or LAM+ADV therapy. [ABSTRACT FROM AUTHOR]

Background/Aims: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. Methods: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). Results: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and γ glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. Conclusions: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background/Aims: α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC. Methods: We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors. Conclusions: The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors. [ABSTRACT FROM AUTHOR]

Background/Aims: The use of self-expandable metallic stents (SEMS) is an established palliative treatment for malignant stenosis in the gastrointestinal tract; therefore, its application to benign stenosis is expected to be beneficial because of the more gradual and sustained dilatation in the stenotic portion. We aimed in this prospective observational study to evaluate the efficacy and safety of temporary SEMS placement in benign pyloric stenosis. Methods: Twenty-two patients with benign stenosis of the prepylorus, pylorus, and duodenal bulb were enrolled and underwent SEMS placement. We assessed symptom improvement, defined as an increase of at least 1 degree in the gastric-outlet-obstruction scoring system after stent insertion. Results: No major complications were observed during the procedures. After stent placement, early symptom improvement was achieved in 18 of 22 patients (81.8%). During the follow-up period (mean 10.2 months), the stents remained in place successfully for 6 to 8 weeks in seven patients (31.8%). Among the 15 patients (62.5%) with stent migration, seven (46.6%) showed continued symptomatic improvement without recurrence of obstructive symptoms. Conclusions: Despite the symptomatic improvement, temporary SEMS placement is premature as an effective therapeutic tool for benign pyloric stenosis unless a novel stent is developed to prevent migration. [ABSTRACT FROM AUTHOR]

Background/Aims The American Joint Committee on Cancer (AJCC) 8th edition staging manual introduced several significant changes to the staging system for hepatocellular carcinoma (HCC). Our study aimed to validate the latest staging system and compare the performance to the previous 7th edition. Methods We retrospectively reviewed database of 778 patients with pathologically confirmed stage I-III HCC between year 2003 and 2016 from three institutes. Overall and cancer- specific survival (OS, CSS) analysis were performed using Kaplan-Meier method and compared using log-rank tests. The Harrell concordance index (c index) and Akaike information criterion (AIC) were calculated to compare prognostic powers. Results A total 698 patients who had undergone hepatic resection were available for the analysis. The cohort were comprised of T1a (22.5%), T1b (38.4%), T2 (30.1%), T3 (4.2%), T4 (4.9%) stages according to AJCC 8th staging system while T1 (58.3%), T2 (32.7%), T3a (4.2%), T3b (2.9%), T4 (2%) stages according to AJCC 7th staging system. When the AJCC 8th staging system was applied for OS, p-values of pairwise comparisons among all T stages differed significantly (p<0.005) except for T3 and T4 (p=0.137). The AIC value of OS 8th edition staging system were lower than 7th edition (2,493.85 and 2,500.19, respectively) while c-indices were higher (0.63 and 0.66, respectively; p=0.005). The AJCC 8th system also performed better for CSS, the AIC value for the 8th edition was 1638.27 while it was 1651.96 for 7th edition and the c-indices were 0.7 and 0.65, respectively (p<0.001). Conclusions The latest prognostic stage provided more accurate prognostic information than the previous edition but further validation if required for the staging system between T3 and T4. [ABSTRACT FROM AUTHOR]

Background/Aims The combination of glecaprevir and pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral agent therapy approved in South Korea. It is estimated that there are 300 thousand individuals with hepatitis C virus (HCV) antibody- positive in South Korea. Among chronic hepatitis C (CHC) patients, virus genotype (GT) 1 and 2 combined account for the vast majority (~99%) of CHC. We evaluated the efficacy and safety of G/P in South Korean CHC GT1 or 2 patients with or without compensated cirrhosis. Methods We pooled the data from five Phase II/III trials for sub-analysis of patients from South Korea who received G/P for either 8 or 12 weeks. Efficacy was evaluated as the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Results The analysis included 265 patients (intention-to-treat population); 179 (67.5%) were HCV treatment-naïve, and 5 (1.9%) and 81 (30.6%) had previously received sofosbuvir or interferon-based treatment, respectively. A total of 262 of 265 patients (98.9%) achieved SVR12. There was one virologic failure (relapse at 12 weeks after treatment), one patient discontinued treatment due to adverse event (AE), which was assessed as not related to the treatment, and one patient had missing SVR12 result. G/P was safe and well-tolerated, with most of the AEs being grade 1 (mild) and eight of 265 patients (3.0%) reporting at least one AE of severity grade 3 or higher. Only two patients experienced grade 3 hepatic laboratory abnormalities; one hyperbilirubinemia and one alanine aminotransferase elevation. Conclusions G/P combination therapy for 8 or 12 weeks achieved a high efficacy with SVR12 rate of 98.9% among patients with CHC GT1 or 2 infection from South Korea. G/P was safe and had a favorable safety profile, comparable to that observed in the G/P global clinical trials. [ABSTRACT FROM AUTHOR]