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Backgrounds/Aims Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. Methods This study analyzed 248 consecutive patients with HCC and EHM (median age, 58.5 years; male, 83.5%; Child-Pugh A, 88.7%) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. Results Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI], 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR], 1.97; P

Background/Aims: Atezolizumab and bevacizumab have shown promising results for the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials. In this study, the real-world efficacy and safety of atezolizumab and bevacizumab in treating advanced HCC were evaluated. Methods: In this retrospective study of patients at a Korean tertiary cancer center, 111 patients with Barcelona Clinic Liver Cancer stage B or C HCC received atezolizumab and bevacizumab as first-line therapy from May 2022 to June 2023. We assessed the progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. Results: Patients with Barcelona Clinic Liver Cancer stage C HCC and Child-Pugh class A liver function were included in the study. The median PFS was 6.5 months, with an ORR of 27% and a DCR of 63%. Several factors, including the albumin-bilirubin grade, age, C-reactive protein and α-fetoprotein in immunotherapy score, macrovascular invasion, lung metastases, and combined radiotherapy, were found to significantly influence PFS (p

Abstract International liver societies recommend hepatocellular carcinoma (HCC) surveillance for those at high-risk of developing HCC. While previous studies have shown the benefits of surveillance for middle-aged patients, but its necessity for elderly patients is unclear. This study aimed to assess the benefits of HCC surveillance in the elderly by comparing diagnosis mode of HCC. Consecutive, elderly patients aged 75 years or older who were newly diagnosed with HCC were screened at our institution between January 2009 and December 2021. Patients were grouped into those who were diagnosed with HCC during surveillance (n = 235, surveillance group) and those who were diagnosed with HCC due to symptoms (n = 184, symptomatic group). The study outcome was overall survival. It was compared in the overall cohort and a propensity score (PS)-matched cohort. Early-stage diagnosis was more frequent in the surveillance group than in the symptomatic group (mUICC stage I/II: 72.3% vs. 39.1%, p

Introduction: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with treatment outcomes closely tied to liver function. This study evaluates the prognostic utility of the albumin-bilirubin (ALBI) score compared to the traditional Child-Pugh (CP) grading, leveraging real-world evidence from a large-scale, multi-center database. Methods: The Liver Cancer IN Korea (LINK) research network, a multi-center initiative, retrospectively collected electronic health records from three academic hospitals in South Korea, encompassing HCC patients diagnosed between 2015 and 2020. Inclusion criteria mandated at least one HCC treatment and excluded patients with other primary cancer diagnoses. The study followed patients until death, the last visit, or June 2021, employing standardized data processing and rule-based algorithms for data consistency. The prognostic efficacy of ALBI scores and CP scores was compared through time-dependent receiver operating characteristic (ROC) curves and the inverse probability censoring weighting method. Results: From 25,248 newly diagnosed patients, 10,297 were included, with 65.82% having hepatitis B etiology and a mean follow-up of 27.49 months. Patients’ classification by modified ALBI (mALBI) grade at diagnosis revealed: grade 1 (48.87%), 2a (20.50%), 2b (24.54%), and 3 (5.17%), with a minimal percentage missing (0.92%). Transarterial therapy (54.07%) and tyrosine kinase inhibitors (84.14% as the first-line systemic therapy) were predominant treatments. The ALBI score demonstrated greater prognostic efficacy than the CP score in long-term outcomes, with time-dependent area under the ROC curve analysis showing a score of 0.71 for ALBI versus 0.67 for CP at 60 months. Furthermore, higher mALBI grades were significantly associated with poorer survival outcomes, as indicated by both univariate and multivariate Cox proportional regression model analyses (p < 0.001). Conclusions: The study confirmed the ALBI score’s superior prognostic ability over the CP score, especially evident in long-term outcomes, suggesting a shift toward more nuanced liver function assessment tools in real-world clinical practice.

Background/Aims Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. Methods This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. Results The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24–9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). Conclusions More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

Management of hepatocellular carcinoma (HCC) is challenging due to the complex relationship between underlying liver disease, tumor burden, and liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor. Liver transplantation can substantially alter patient prognosis, but donor availability varies by each patient which further complicates treatment decision. Recent advancements in HCC treatments have introduced numerous potentially efficacious treatment modalities. However, high level evidence comparing the risks and benefits of these options is limited. In this complex situation, multidisciplinary approach or multidisciplinary team care has been suggested as a valuable strategy to help cope with escalating complexity in HCC management. Multidisciplinary approach involves collaboration among medical and health care professionals from various academic disciplines to provide comprehensive care. Although evidence suggests that multidisciplinary care can enhance outcomes of HCC patients, robust data from randomized controlled trials are currently lacking. Moreover, the implementation of a multidisciplinary approach necessitates increased medical resources compared to conventional cancer care. This review summarizes the current evidence on the role of multidisciplinary approach in HCC management and explores potential future directions.

Introduction: Steatotic liver disease (SLD) is a new overarching term proposed to replace nonalcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease. Subclassification includes metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. This study aimed to investigate whether SLD and its subclassification could stratify hepatocellular carcinoma (HCC) risk. Methods: A cohort of 85,119 adults without viral hepatitis or heavy alcohol intake was analyzed for the risk of HCC according to SLD and its subclassification. The fibrosis-4 (FIB-4) index was used to estimate the degree of liver fibrosis. Results: During a median follow-up of 11.9 years, HCC was diagnosed in 123 individuals. The incidence rate of HCC per 1,000 person-years was higher in individuals with SLD than in those without SLD (0.197 vs. 0.071, p < 0.001), with an adjusted hazard ratio of 2.02 (95% confidence interval: 1.40–2.92). The HCC incidence rate per 1,000 person-years was 0, 0.180, and 0.648 for cryptogenic SLD, MASLD, and MetALD, respectively. When participants with SLD was further stratified by the FIB-4 index, the HCC incidence rate per 1,000 person-years was 0.074 for SLD with FIB-4 < 1.3 and 0.673 for SLD with FIB-4 ≥ 1.3. Of note, HCC risk was substantially high (HCC incidence rate: 1.847 per 1,000 person-years) for MetALD with FIB-4 ≥ 1.3. Conclusions: HCC risk was different by SLD and its subclassification. The utilization of SLD and its subclassification can aid in stratifying HCC risk and facilitate the identification of individuals requiring interventions to mitigate the risk of HCC.

Abstract The treatment decisions for patients with hepatocellular carcinoma are determined by a wide range of factors, and there is a significant difference between the recommendations of widely used staging systems and the actual initial treatment choices. Herein, we propose a machine learning-based clinical decision support system suitable for use in multi-center settings. We collected data from nine institutions in South Korea for training and validation datasets. The internal and external datasets included 935 and 1750 patients, respectively. We developed a model with 20 clinical variables consisting of two stages: the first stage which recommends initial treatment using an ensemble voting machine, and the second stage, which predicts post-treatment survival using a random survival forest algorithm. We derived the first and second treatment options from the results with the highest and the second-highest probabilities given by the ensemble model and predicted their post-treatment survival. When only the first treatment option was accepted, the mean accuracy of treatment recommendation in the internal and external datasets was 67.27% and 55.34%, respectively. The accuracy increased to 87.27% and 86.06%, respectively, when the second option was included as the correct answer. Harrell’s C index, integrated time-dependent AUC curve, and integrated Brier score of survival prediction in the internal and external datasets were 0.8381 and 0.7767, 91.89 and 86.48, 0.12, and 0.14, respectively. The proposed system can assist physicians by providing data-driven predictions for reference from other larger institutions or other physicians within the same institution when making treatment decisions.

Background and Aims: Nivolumab was the first immune checkpoint inhibitor approved for hepatocellular carcinoma (HCC). External beam radiation therapy (EBRT) is locally effective and may enhance the effectiveness of immunotherapy. This study investigated the efficacy and safety of concurrent nivolumab and EBRT in HCC with macrovascular invasion. Methods: In this phase II multicenter trial, patients with HCC and macrovascular invasion were concurrently treated with intravenous nivolumab (3 mg/kg every 2 weeks) and EBRT, followed by maintenance nivolumab until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) and safety, and secondary endpoints were overall survival, time-to-progression, objective response rate, and disease control rate. Results: Between January 2020 and June 2021, 50 patients (male 84%, median age 62.5) were enrolled; 47 (94.0%) and 13 (26.0%) with portal (Vp1/2, n = 21; Vp3, n = 23; Vp4, n = 3) and hepatic vein invasion, respectively. Patients received EBRT (median dose: 50 [IQR 43–50] Gy) after the first nivolumab dose. The median number of nivolumab doses was 8.5. Median PFS was 5.6 (90% CI 3.6–9.9) months. Median overall survival and time-to-progression were 15.2 (90% CI 10.8–19.6) and 5.6 (90% CI 3.6–9.9) months, respectively. The objective response rate and disease control rate were 36.0% and 74.0%, respectively. The median duration of response was 9.9 months. Of 35 patients with follow-up data, 23 received subsequent systemic treatment, including atezolizumab-bevacizumab, sorafenib, lenvatinib, and regorafenib. Treatment-related any grade adverse events (AEs) and grade 3/4 AEs occurred in 40 (80.0%) and 6 (12.0%) patients, respectively. Common treatment-related AEs included pruritus (38.0%) and rash (16.0%), with no treatment-related deaths. Conclusion: Concurrent nivolumab therapy and EBRT showed encouraging PFS with acceptable safety in patients with advanced HCC and macrovascular invasion. Impact and implications: Immune checkpoint inhibitors, the standard care for advanced hepatocellular carcinoma (HCC), show relatively poor therapeutic effects in patients with advanced HCC and macrovascular invasion. In this investigator-initiated phase II study, we, for the first time, show that concurrent external beam radiation therapy with nivolumab, an immune checkpoint inhibitor, led to encouraging progression-free survival in patients with HCC and macrovascular invasion. The concurrent treatment was tolerable without significant safety concerns. Further randomized studies investigating the combination of immunotherapy and external beam radiation therapy are required. ClinicalTrials.gov identifier: NCT04611165

Abstract Background No randomized controlled trials have been completed to see whether statin can decrease hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. We used large-scale, population-based, observational data to emulate a target trial with two groups, statin user and statin non-user. Methods Among 1,379,708 nonunique individuals from the Korean National Health Insurance Service data, 2,915 CHB patients with serum cholesterol level of 200 mg/dL or higher who started statin therapy and 8,525 propensity-score matched CHB patients with serum cholesterol level of 200 mg/dL or higher who did not start statin therapy were analyzed for the development of HCC. In addition, liver cancer or liver-related mortality and all-cause mortality were assessed. Results During follow-up, 207 participants developed HCC. Incidence rate of HCC was 0.2 per 1,000 person-years in the statin user group and 0.3 per 1,000 person-years in the statin non-user group. Fully adjusted hazard ratio (HR) for incident HCC comparing statin user group to statin nonuser group was 0.56 (95% confidence interval [CI]: 0.39 to 0.80). The association between statin use and decreased HCC risk was consistent in all subgroups analyzed. Fully adjusted HR comparing statin user to statin nonuser was 0.59 (95% CI: 0.35 to 0.99) for liver cancer or liver-related mortality and 0.93 (95% CI: 0.78 to 1.11) for all-cause mortality. Conclusions Statin might have a benefit for preventing HCC in CHB patients with elevated cholesterol levels. Statin should be actively considered for CHB patients with dyslipidemia.

Background/Aims: This study aimed to investigate whether pretransplant frailty can predict postoperative morbidity and mortality after liver transplantation (LT) in patients with cirrhosis.Methods: We retrospectively reviewed 242 patients who underwent LT between 2018 and 2020 at a tertiary hospital in Korea.Results: Among them, 189 patients (78.1%) received LT from a living donor. Physical frailty at baseline was assessed by the Short Physical Performance Battery (SPPB), by which patients were categorized into two groups: frail (SPPB

Background/Aims: Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission. Methods: Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models. Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively. Results: In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46–2.32]; p

Background/Aims: The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. Methods: A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. Results: After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCA response rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS

Background/Aims Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. Methods This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). Results In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (P

Abstract Normalization of serum alanine aminotransferase (ALT) levels is one of the goals of hepatitis B treatment. However, ALT levels in cirrhosis patients might be normal or mildly elevated regardless of ongoing inflammation. Therefore, we examined whether on-treatment ALT and other potential on-treatment indicators could be clinical surrogates of antiviral therapy in HBV-related cirrhosis. A total of 911 patients with HBV-related liver cirrhosis who started treatment with entecavir or tenofovir were analyzed. At 1 year of antiviral therapy, we evaluated ‘ALT normalization’, ‘undetectable serum HBV DNA’, ‘fibrosis-4 (FIB-4) index improvement’, and ‘serum HBeAg loss’ as potential biomarkers for HCC development. During 6.6 (3.8–10.2) years of follow-up, 222 patients (24.3%) newly developed HCC. Undetectable HBV DNA levels at 1 year were observed in 667 patients (73.2%), and the HCC incidence was significantly lower in this population (adjusted hazard ratio (HR) 0.66, 95% CI 0.50–0.87). Improvement of the FIB-4 index (

Background & aimsA new nomenclature, Steatotic Liver Disease (SLD), has been proposed by consensus with sub-classifications and requires evidence-based validation. We assessed whether the presence and severity of SLD, as well as its sub-classifications, are associated with the progression of coronary atherosclerosis.MethodsThis longitudinal cohort study included 13,811 adults who participated in repeated regular health screening examinations between January 1, 2004 and December 31, 2021 that included assessments of their coronary artery calcium (CAC) scores. SLD was defined using abdominal ultrasonography and classified as metabolic dysfunction associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. SLD severity was assessed using fibrosis-4 (FIB-4) scores. The progression of CAC scores was measured using multidetector CT scans.ResultsThe average duration of follow-up was 5.8 years. During follow-up, the annual rate of CAC progression in participants with and without SLD was 18% (95% CI 17%-19%) and 14% (95% CI 13%-14%) (p < 0.01), respectively. The multivariable ratios of progression rates when we compared participants with cryptogenic SLD, MASLD, or MetALD with those without SLD were 0.98 (95% CI 0.95-1.01), 1.03 (95% CI 1.03-1.04), and 1.07 (95% CI 1.04-1.09), respectively. The multivariable ratios of progression rates when we compared participants with SLD with FIB-4 score ConclusionsSLD was associated with a higher risk of coronary atherosclerosis, and the risk differed by sub-classifications and severity. These findings suggest that the newly proposed definition has clinical relevance in terms of stratifying cardiovascular disease risk.

Hepatocellular carcinoma (HCC) is a major cause of death in many countries, including South Korea. To provide useful and sensible advice for clinical management of patients with HCC, the Korean Liver Cancer Association and National Cancer Center Korea Practice Guideline Revision Committee have recently revised the practice guidelines for HCC management. However, there are some differences between practice guidelines and real-life clinical practice. In this review, we describe some key recommendations of the 2022 version of practice guidelines and the real-life clinical situation in South Korea, together with discussion about efforts needed to reduce the difference between guidelines and real-life clinical practice.

Abstract It is unclear if various types and domains of exercise have an identical effect on non-alcoholic fatty liver disease (NAFLD). Thus, this study aimed to investigate associations of different physical activity domains and muscle strength exercise with NAFLD using a nation-wide cohort database. Adults aged 20–79 years who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2018 were analyzed. Hepatic steatosis index was used to identify NAFLD. Physical activity was assessed with the Global Physical Activity Questionnaire. Of 21,015 participants, 4942 (23.5%) had NAFLD. Participants with ≥ 150 min/week of total physical activity had a lower risk of NAFLD than those with

Background & Aims: The metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults. Methods: A cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992). Results: Participants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92–1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09–3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01–2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria. Conclusions: In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC. Impact and Implications: This study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.

Abstract Background The importance of insulin resistance is gaining increasing attention as it plays an important role in carcinogenesis in hepatocellular carcinoma (HCC). Although exercise is the most important intervention for lowering insulin resistance, it is not easy for HCC patients to maintain high compliance and do appropriate exercise. Mobile health (mHealth) with wearable devices can be the solution to carry out an adjusted and supervised exercise that can normalize insulin resistance in patients with HCC. We developed an HCC-specific application equipped with patient-centered exercise. In this paper, we present a randomized controlled trial protocol comparing an intervention group with a control group to determine whether mHealth-based exercise is effective in normalizing insulin sensitivity in HCC patients with insulin resistance after anticancer treatment. Methods An assessor unblinded open label randomized controlled trial (RCT) will be conducted for 80 participants with treatment-naïve or recurrent HCC who have received treatment and achieved complete response at the time of screening. They will be randomly assigned (1:1) to one of two groups: an intervention group (n = 40) and a control group (n = 40). The intervention group will carry out mHealth-based exercise for 6 months from baseline, whereas the control group will receive the usual follow-up care for the first 3 months and mHealth-based exercise for the next 3 months. Both groups will be assessed at baseline, 3 months, and 6 months from baseline. The primary outcome is the normalized rate of insulin resistance in each group at 3 months. Insulin resistance is estimated by calculating homeostatic model assessment for insulin resistance (HOMA-IR). The secondary outcomes are body composition, physical fitness level, physical activity, and quality of life at 3 months. Discussion This study is the first RCT to investigate the effect of mHealth-based home exercise with a wrist-wearable device on insulin sensitivity, physical fitness, and quality of life for HCC patients with insulin resistance. The result of this RCT will confirm not only safety and functional improvement but also biological effect when exercising using mHealth in HCC patients. Trial registration ClinicalTrials.gov NCT04649671 . Registered on 2 December 2020. The World Health Organization Trial Registration Data Set is not registered.

Changes in the prevalence of disease over time provide valuable information from a public health perspective. We used data from Korea Military Manpower Administration medical examinations for conscription between 2003 and 2019 (n = 5,355,941), which involved young men aged 19 years, to observe changes in liver disease over time at a population level. Trends in the prevalence of hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) levels, the fibrosis-4 (FIB-4) index, obesity, and hypertension were assessed. The prevalence of HBsAg steadily decreased from 3.19% for men born in 1984 to 0.18% for men born in 2000. Among HBsAg-negative subjects, the prevalence of elevated ALT levels increased from 13.15% for men born in 1986 to 16.48% for men born in 2000. The prevalence of obesity, hypertension and the proportion with high FIB-4 scores (≥ 1.45) also increased. This population-based nationwide analysis showed a decreasing trend of HBsAg and increasing trends of possible non-alcoholic fatty liver disease.

Background: The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. Method: The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. Result: A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. Conclusion: Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.

It is well known that renal dysfunction has a devastating effect on the prognosis of liver cirrhosis. In this study, the aim was to assess whether the incorporation of the kidney dysfunction type into the MELD-Na score enhances its predictive capacity for outcomes in patients awaiting liver transplantation (LT), compared to utilizing the MELD 3.0 score with albumin. In total, 2080 patients awaiting the LT were enrolled at two tertiary care institutions in Korea. Discrimination abilities were analyzed by using Harrell’s c-index and iAUC values between MELD-Na-kidney dysfunction type (MELD-Na-KT) and MELD 3.0 with albumin. Clinical endpoints encompassed 3-month survival, 3-month transplant-free survival (TFS), overall survival (OS), and total TFS. Out of the total of 2080 individuals, 669 (32.16%) were male. Regarding the types of renal function impairment, 1614 (77.6%) were in the normal group, 112 (5.38%) in the AKD group, 320 (15.35%) in the CKD group, and 34 (1.63%) were in the AKD on CKD group. MELD 3.0 with albumin showed better discrimination (c-index = 0.714) compared to MELD-Na-KT (c-index = 0.708) in predicting 3-month survival. Similar results were observed for OS, 3-month TFS, and total TFS as well. When divided by sex, MELD 3.0 with albumin showed the comparable prediction of 3-month survival to MELD-Na-KT (c-index 0.675 vs. 0.671, p-value 0.221) in males. However, in the female group, MELD 3.0 with albumin demonstrated better results compared to MELD-Na-KT (c-index 0.733 vs. 0.723, p-value 0.001). The integration of kidney dysfunction types into the MELD-Na did not yield superior prognostic results compared to the MELD 3.0 score with albumin. Rather, in the female group, the MELD 3.0 score with albumin was better able to predict survival. These findings suggest that laboratory values pertaining to liver dysfunction or creatinine levels may be more significant than the type of kidney dysfunction when predicting the short-term prognosis of LT candidates.

Purpose This study investigated the utility of second-line contrast-enhanced ultrasonography (CEUS) using Sonazoid in Liver Imaging Reporting and Data System category 3 (LR-3) and 4 (LR-4) observations on gadoxetate-enhanced magnetic resonance imaging (MRI). Methods This retrospective study included LR-3 or LR-4 observations on gadoxetate-enhanced MRI subsequently evaluated with CEUS from 2013 to 2017. The presence of MRI features, CEUS-arterial phase hyperenhancement (CEUS-APHE), and Kupffer phase defect (KPD) was evaluated. Multivariable logistic regression analysis was performed to identify significant imaging features associated with the diagnosis of hepatocellular carcinoma (HCC). The optimal diagnostic criteria were investigated using the McNemar test. Results In total, 104 patients with 104 observations (63 HCCs) were included. The presence of both CEUS-APHE and KPD on CEUS enabled the additional detection of 42.3% (11/26) of LR-3 HCCs and 78.4% (29/37) of LR-4 HCCs. Transitional phase (TP) hypointensity (adjusted odds ratio [OR], 10.59; P

Preclinical studies highlighted potential therapeutic applications of aspirin and statins as anticancer agents based on their pleiotropic effects. Epidemiologic studies suggested the role of aspirin and statins in the chemoprevention of hepatocellular carcinoma (HCC). However, observational data is prone to bias, and no prospective randomized trials are currently available to assess the risks and benefits of statin or aspirin therapy for chemoprevention of HCC. It is therefore important for clinicians and researchers to be aware of the quality of current evidence regarding this issue. In this review, we summarize currently available evidence to assist clinicians with their decision to use statin or aspirin and provide information for further clinical investigations.

Abstract Cancer cachexia affects quality of life, response to chemotherapy, and survival in many advanced cancer patients. The aim of this study was to evaluate the prognostic value of pretreatment cachexia index (CXI) in patients with advanced hepatocellular carcinoma (HCC) treated with systematic chemotherapy. Patients with advanced HCC treated with lenvatinib therapy between October 2018 and October 2020 were retrospectively studied. The CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil-to-lymphocyte ratio). The association with treatment response and early adverse events within the first two months of lenvatinib therapy was investigated. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method with log-rank test. Multivariable Cox regression was used to identify the predictors of survival. A total of 116 patients (median age: 60, male: 84.5% ) with calculated CXI. They divided into two groups: high CXI (≥ 53, n = 82) and low CXI (

Background 2018 American Heart Association/American College of Cardiology cholesterol guideline recommends statin in patients with chronic and/or stable liver disease for secondary prevention of atherosclerotic cardiovascular disease yet remains equivocal on the adequate intensity of statin for patients with chronic liver disease (CLD). We aimed to assess the association between statin intensity and mortality among patients with CLD with atherosclerotic cardiovascular disease. Methods and Results We conducted a population‐based cohort study in South Korea. We assessed the risk of survival and clinical outcomes using inverse probability of treatment‐weighted Cox proportional hazards regression. We also estimated the absolute risk difference between treatment groups based on the Poisson distribution. During an average of 2.35 person‐years, 10 442 patients with CLD with atherosclerotic cardiovascular disease were identified. Among those patients, 5515 (52.8%) received high‐intensity statin, and 4927 (47.2%) received low/moderate‐intensity statin. High‐intensity statin was associated with lower risk for all‐cause mortality (hazard ratio [HR], 0.83 [95% CI, 0.75–0.92]), cardiovascular‐cause mortality (HR, 0.85 [0.71–1.01]), liver‐cause mortality (HR, 0.72 [0.54–0.97]) compared with low/moderate‐intensity statin. Although both hospitalizations for recurrent myocardial infarction and stroke were shown to be increased among high‐intensity statin users, effect estimate was homogeneous in the absolute scale (myocardial infarction: HR, 1.12 [1.04–1.19], risk difference, 7.57 [−0.69 to 15.84] per 1000 person‐years; stroke: HR, 1.11 [0.97 to 1.27]; risk difference, −1.70 [−5.19 to 1.78]). Conclusions Among patients with CLD with atherosclerotic cardiovascular disease, high‐intensity statin was significantly associated with a lower risk of mortality. These findings herein support the guidelines for statin use in patients with CLD while demonstrating potential benefit of optimal intensity use.

Introduction: We aimed to investigate whether concurrent use of intrahepatic external beam radiotherapy (EBRT) is a viable option for patients with advanced hepatocellular carcinoma (HCC) undergoing tyrosine kinase inhibitor (TKI) therapy. Methods: A total of 453 patients with Barcelona Clinic Liver Cancer-stage C (BCLC-C) HCC, who started first-line treatment with TKI with intrahepatic EBRT (TKI + RT, n = 97) or TKI without intrahepatic EBRT (TKI, n = 356) were analyzed. The overall survival (OS) and progression-free survival (PFS) were compared in the overall cohort, patients who received at least 8 weeks of TKI treatment, and a propensity score-matched cohort. Results: OS and PFS was better in those treated with TKI + RT than TKI (8.6 vs. 4.4 months and 4.5 vs. 2.3 months, respectively, with p < 0.001). Of note, the TKI + RT group demonstrated significant longer time-to-intrahepatic tumor progression. In subgroup analysis, TKI + RT led to better OS than TKI in all subgroups and PFS was significantly improved in patients without extrahepatic metastasis, and those with portal vein invasion. There was no significant difference in treatment discontinuation due to adverse events between the TKI + RT and TKI groups (32.0% vs. 37.9%, p = 0.34). Furthermore, patients treated with TKI + RT showed better liver function preservation over time compared to TKI without intrahepatic EBRT. Comparable treatment outcomes were observed between patients who received at least 8 weeks of TKI treatment and the propensity-score matched cohort. Discussion/Conclusion: Concurrent intrahepatic EBRT targeting liver and/or macrovascular invasion can be a viable option to improve outcomes of BCLC-stage C patients receiving TKI therapy with an aim to control intrahepatic progression and preserving liver function.

Abstract Background A limited number of studies have characterized genomic properties of hepatocellular carcinoma (HCC) patients in response to anti-PD-1 immunotherapy. Methods Herein, we performed comprehensive molecular characterization of immediate (D-42 to D-1) pre-treatment tumor biopsy specimens from 60 patients with sorafenib-failed HCC in a single-arm prospective phase II trial of pembrolizumab. Objective response rate was the primary efficacy endpoint. We used whole-exome sequencing, RNA sequencing, and correlative analysis. In addition, we performed single-cell RNA sequencing using peripheral blood mononuclear cells. Results The overall response rate of pembrolizumab in sorafenib-failed HCC patients was 10% ([6/60] 95% CI, 2.4–17.6). In a univariate analysis using clinicopathological features, female gender, PD-L1 positivity, and low neutrophil-to-lymphocyte ratio (NLR) were identified as contributing factors to pembrolizumab response. Somatic mutations in CTNNB1 and genomic amplifications in MET were found only in non-responders. Transcriptional profiles through RNA sequencing identified that pembrolizumab responders demonstrated T cell receptor (TCR) signaling activation with expressions of MHC genes, indicating increased levels of T cell cytotoxicity. In single-cell sequencing from 10 pre- and post-treatment peripheral blood mononuclear cells (PBMCs), patients who achieved a partial response or stable disease exhibited immunological shifts toward cytotoxic CD8+ T cells. Conversely, patients with progressive disease showed an increased number of both CD14+ and CD16+ monocytes and activation of neutrophil-associated pathways. Conclusions Taken together, HCC patients with infiltration of cytotoxic T cells, along with increased active circulating CD8+ T cells during pembrolizumab treatment and down-regulation of neutrophil-associated markers, significantly benefited from pembrolizumab treatment. Trial registration NCT#03163992 (first posted: May 23, 2017)

Abstract Background Alanine aminotransferase (ALT) levels are widely used to screen liver disease, and many asymptomatic individuals show elevated ALT levels. As elevated ALT level indicates liver injury, even a small amount of alcohol intake may be harmful in subjects with elevated ALT levels, but there is limited evidence of the effect of light to moderate amount of alcohol intake in this subgroup. Methods A cohort of 367,612 men and women without established liver diseases (including chronic viral hepatitis, alcohol-associated liver disease, cirrhosis, liver transplantation, or rare forms of liver disease) who underwent at least 1 health screening exam between 2009 and 2015 were assessed for liver-related and all-cause mortality. Elevated ALT levels were defined as ≥ 34 U/L for men and 25 U/L for women. Results In participants with normal ALT levels, the fully-adjusted hazard ratios (95% CI) for liver-related mortality comparing light and moderate drinkers to non-drinkers were 0.73 (0.51–1.05), and 1.06 (0.73–1.52), respectively. In participants with elevated ALT levels, the corresponding hazard ratios were 1.57 (1.08–2.28), and 2.09 (CI 1.46–2.99), respectively (p value for alcohol intake by ALT interaction

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is potentially reversible. However, whether improvement of NAFLD leads to clinical benefits remains uncertain. We investigated the association between regression of NAFLD and the risk of incident diabetes in a longitudinal way.MethodsA cohort of 11,260 adults who had NAFLD at in an initial exam, had the second evaluation for NAFLD status at 1~2 years from an initial exam were followed up for incident diabetes from 2001 and 2016. NAFLD was diagnosed with abdominal ultrasound.ResultsAt baseline, NAFLD was regressed in 2,559 participants (22.7%). During 51,388 person-years of follow-up (median 4 years), 1,768 participants developed diabetes. The fully adjusted hazard ratio (HR) for incident diabetes in participants with regressed NAFLD compared to those with persistent NAFLD was 0.81 [95% confidence interval (CI) 0.72-0.92]. When assessed by NAFLD severity, among participants with a low NAFLD fibrosis score (NFS) (< -1.455), participants with regressed NAFLD had a lower risk of incident diabetes than those with persistent NAFLD (HR 0.77, 95% CI 0.68-0.88). However, in participants with an intermediate to high NFS (≥ -1.455), the risk of incident diabetes was not different between NAFLD regression and persistence groups (HR 1.12, 95% CI 0.82-1.51).ConclusionsRegression of NAFLD was associated with decreased risk of incident diabetes compared to persistent NAFLD. However, the benefit was evident only for NAFLD patients with low NFS. This suggests that early intervention for NAFLD, before advanced fibrosis is present, may maximize the metabolic benefit from NAFLD regression.

Purpose The aim of this study was to develop and validate a fully-automatic quantification of the hepatorenal index (HRI) calculated by a deep convolutional neural network (DCNN) comparable to the interpretations of radiologists experienced in ultrasound (US) imaging. Methods In this retrospective analysis, DCNN-based organ segmentation with Gaussian mixture modeling for automated quantification of the HRI was developed using abdominal US images from a previous study. For validation, 294 patients who underwent abdominal US examination before living-donor liver transplantation were selected. Interobserver agreement for the measured brightness of the liver and kidney and the calculated HRI were analyzed between two board-certified radiologists and DCNN using intraclass correlation coefficients (ICCs). Results Most patients had normal (n=95) or mild (n=198) fatty liver. The ICCs of hepatic and renal brightness measurements and the calculated HRI between the two radiologists were 0.892 (95% confidence interval [CI], 0.866 to 0.913), 0.898 (95% CI, 0.873 to 0.918), and 0.681 (95% CI, 0.615 to 0.738) for the first session and 0.920 (95% CI, 0.901 to 0.936), 0.874 (95% CI, 0.844 to 0.898), and 0.579 (95% CI, 0.497 to 0.650) for the second session, respectively; the results ranged from moderate to excellent agreement. Using the same task, the ICCs of the hepatic and renal measurements and the calculated HRI between the average values of the two radiologists and DCNN were 0.919 (95% CI, 0.899 to 0.935), 0.916 (95% CI, 0.895 to 0.932), and 0.734 (95% CI, 0.676 to 0.782), respectively, showing high to excellent agreement. Conclusion Automated quantification of HRI using DCNN can yield HRI measurements similar to those obtained by experienced radiologists in patients with normal or mild fatty liver.

Abstract Aims/Introduction We aimed to determine whether mean and visit‐to‐visit glycated hemoglobin (HbA1c) variability independently increase the incidence of non‐alcoholic fatty liver disease (NAFLD) across the diabetic continuum from normal glucose tolerance (NGT) to established diabetes. Materials and Methods In a longitudinal cohort study, 21,123 participants underwent five or more annual health screening checkups. Participants were categorized into diabetes (n = 1,635), prediabetes (n = 6,650) and NGT (n = 12,838) groups. Mean, standard deviation (SD) and coefficient of variation data on HbA1c were obtained from three consecutive measurements. The associations between those data and incident NAFLD were analyzed using Cox regressions. Results Over a median follow‐up period of 57 months, 3,860 (18.3%) participants developed NAFLD. The risk of NAFLD increased continuously, with the mean HbA1c beginning at 4.9%, even in the NGT group. We found a significant association between increasing HbA1c variability and incident NAFLD (coefficient of variation, adjusted hazard ratio 1.14, 95% confidence interval 1.01–1.29; standard deviation, adjusted hazard ratio 1.19, 95% confidence interval 1.05–1.36) in the diabetes group, but not in the NGT or prediabetes group. Consistent findings were observed when NAFLD patients with a low possibility of fibrosis were excluded. The association between the coefficient of variation of HbA1c and incident NAFLD in the diabetes group was significant only in those with an increasing trend of post‐baseline HbA1c (adjusted hazard ratio 1.24, 95% confidence interval 1.01–1.52). Conclusions Increased mean HbA1c levels elevated the risk of incident NAFLD, even with NGT. Increases in visit‐to‐visit variability of HbA1c independently elevated the risk of incident NAFLD, but only in the diabetes group.

PurposeTo present the trends in radiotherapy for the management of hepatocellular carcinoma (HCC) at a single tertiary referral hospital in South Korea.Materials and MethodsWe retrospectively reviewed prospectively collected registry data of patients newly diagnosed with HCC between January 2005 and December 2017 at the Samsung Medical Center. Trends in radiotherapy, delivery techniques, tumor stage, and age were evaluated.ResultsDuring the study period, 9,132 patients were newly diagnosed with HCC at our institution. Of these, 2,445 patients (26.8%) received radiotherapy for all lesions, including extrahepatic metastases; 1,865 patients (20.4%) received radiotherapy for intrahepatic lesions alone, and 469 patients (5.1%) received radiotherapy as initial management. Although the proportion of patients receiving radiotherapy increased slightly over the study period (24.2% vs. 26.6%), the proportions of patients receiving radiotherapy for intrahepatic lesions (16.8% vs. 21.9%) and as initial management (0.1% vs. 12.5%) increased dramatically. The majority of patients treated between 2005 and 2008 received three-dimensional conformal radiotherapy (56.3%), whereas the majority of patients treated between 2018 and 2021 received proton beam therapy (43.6%). With the technical developments, the overall survival (OS) of patients who received radiotherapy as initial management increased significantly (5-year OS: from 5.4% to 30.1%), and the OS difference between patients who did and did not receive radiotherapy as initial management significantly decreased (ratio of restricted mean survival time: from 0.383 to 0.544).ConclusionThis registry-based, retrospective study indicated an increasing trend in the utilization of radiotherapy, adoption of advanced radiotherapy techniques, and OS improvements in patients with HCC.

BackgroundThis study aimed to compare the clinical outcomes of patients with hepatocellular carcinoma (HCC) and macroscopic tumor thrombosis who were treated with lenvatinib with or without combined liver-directed radiotherapy (LRT).MethodsFrom the institutional registry, we enrolled 82 patients diagnosed with HCC involving macroscopic tumor thrombosis and treated with lenvatinib monotherapy (non-LRT group, n = 54, 65.9%) or lenvatinib in combination with LRT (LRT group, n = 28, 34.1%). Patients were classified into the LRT group if LRT was performed within 8 weeks of lenvatinib initiation.ResultsDuring the median follow-up period of 5.4 (range 1.4 to 17.5) months, there was no significant difference between the two groups in terms of overall adverse events. Although there was no statistical difference between the two groups in terms of overall response rate (32.1% vs. 20.4%, p = 0.15), a significantly higher treatment response was observed in the LRT group in terms of intrahepatic tumor response (67.9% vs. 20.4%, p < 0.001). In the LRT group, there was a slight difference in overall survival compared to the non-LRT group (64.1% in the LRT group vs. 37.7% in the non-LRT group at 12 months, hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.28–1.03; p = .06), although it did not reach a statistically significant level. However, progression-free survival (PFS, 67.2% in the LRT group vs. 35.0% in the non-LRT group at 6 months, HR 0.47; 95% CI 0.27–0.82; p = 0.008) and intrahepatic progression-free survival (IHPFS, 74.3% in the LRT group vs. 43.3% in the non-LRT group at 6 months, HR 0.45; 95% CI 0.25–0.81; p = 0.008) were significantly superior in the LRT group. This result was also reproduced in the multivariate analysis adjusted for α-fetoprotein, another significant prognostic factor in this study, and the well-known prognostic factors, namely the presence of main portal vein tumor thrombosis and albumin-bilirubin grade.ConclusionsThe combination of lenvatinib and LRT is relatively safe and effective in increasing the intrahepatic tumor response and improving PFS and IHPFS in patients with HCC and macroscopic tumor thrombosis.

Background : The Model for End-Stage Liver Disease (MELD)-based allocation system was implemented in Korea in July 2016 without a mandatory abstinence period for liver transplantation (LT) listing. However, the impact of the allocation policy has not been evaluated in patients with severe alcoholic hepatitis (AH). Methods : A total of 81 consecutive patients with severe AH between January 2014 and December 2018 were analyzed. The clinical course of patients before and after the implementation of the MELD-based allocation system was assessed. Results : More patients received LT (25%–65%) after the MELD allocation system was implemented. The increase in patients receiving deceased donor LT was dramatic (17%–51%, P=0.001) compared to patients receiving living donor LT (7%–14%, P=0.30). The overall survival was better for those who received LT (88% vs. 44% at 1 year, P

Background: Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. Methods: A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. Results: A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. Conclusion: Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

Clinical practice guidelines are important for guiding the management of specific diseases by medical practitioners, trainees, and nurses. In some cases, the guidelines are utilized as a reference for health policymakers in controlling diseases with a large public impact. With this in mind, practice guidelines for the management of chronic hepatitis B (CHB) have been developed in the United States, Europe, and Asian-Pacific regions to suggest the best-fit recommendations for each social and medical circumstance. Recently, the Korean Association for the Study of the Liver published a revised version of its clinical practice guidelines for the management of CHB. The guidelines included updated information based on newly available antiviral agents, the most recent opinion on the initiation and cessation of treatment, and updates for the management of drug resistance, partial virological response, and side effects. Additionally, CHB management in specific situations was comprehensively revised. This review compares the similarities and differences among the various practice guidelines to identify unmet needs and improve future recommendations.

Background/Aims Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown. Methods A total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed. Results During a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years. Conclusions The HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.

Abstract Background The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. Methods A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). Results Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system (“ASAR”). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570–0.871) in the derivation, 0.700 (95% CI = 0.445–0.905) in the internal validation, and 0.680 (95% CI = 0.652–0.707) in the external validation, respectively. Patients with ASAR

Background : The diagnosis of latent tuberculosis infection (LTBI) in solid organ transplantation (SOT) patients under lifelong immunosuppression has profound effects on preoperative and postoperative management. Interferon-gamma release assay (IGRA) is widely used to screen LTBI before or after transplantation. Methods : We evaluated the effect of posttransplantation immunosuppression on IGRA and influencing factors by measuring interval change of QuantiFERON-TB Gold Plus (QFT-Plus) between pretransplantation (pre-QFT-Plus) and posttransplantation (post-QFT-Plus) state in 20 patients who previously had reactive IGRA but not taken LTBI treatment. Results : Eleven (55%) out of 20 pre-QFT-Plus reactive patients became nonreactive state in repeated QFT-Plus (post-QFT-Plus) at 194-413 days (median, 257 days) after transplantation (discordant group). Even in persistently reactive group (concordant group), interferon-gamma (IFN-γ) levels after transplantation were decreased about 34% and 36% of their pretransplantation levels for TB1 and TB2, respectively. The only significant factors that affect interval change of QFT-Plus between pre- and post-SOT status were the concentrations of IFN-γ in pre-QFT-Plus (6.93 vs. 0.44 IU/mL in TB1 and 7.33 vs. 0.71 IU/mL in TB2). Conclusions: The reactivity of QFT-Plus is significantly compromised by immunosuppressive therapy, which increase the risk of false negative, particularly in patients with low level of IGRA reactivity. Therefore, interpretation of IGRA under immunosuppressive treatment require a caution and eventually, more sensitive tuberculosis-specific cytokine markers might be needed.

Background/Aims Real-world data about the treatment outcomes of patients receiving rituximab-containing immunochemotherapy followed by rituximab maintenance are required to understand better the treatment for follicular lymphoma (FL). Methods A cross-sectional study analyzed FL patients who were treated with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab maintenance. Results Of 139 patients, 85 patients received R-CVP and 54 received R-CHOP. The characteristics did not differ significantly between the groups. Only grade 3 of FL was more common in R-CHOP. The complete response rate did not differ significantly between R-CHOP (50/54, 92.6%) and R-CVP (77/85, 90.6%). The number of disease relapses during rituximab maintenance did not differ significantly between the groups (p = 0.798). Therefore, the comparison of progression-free survival (PFS) showed no significant difference: the 3-year PFS rates for R-CVP and R-CHOP were 77% and 85%, respectively (p = 0.567). Although five of 56 hepatitis B virus (HBV) core antibody (anti-HBc)-positive patients experienced HBV reactivation, all cases of HBV reactivation were identified during regular monitoring for HBV DNA in blood, and were successfully managed with antiviral treatment. Conclusions The survival outcomes of FL patients on rituximab maintenance after responding to R-CVP or R-CHOP were similar. Rituximab-containing immunochemotherapy followed by rituximab maintenance can be safely used for anti-HBc-positive patients if HBV DNA titer in blood can be regularly monitored.

Background/Aims We systematically evaluated the clinical characteristics, prevalence of cirrhosis, and mode of detection in virus-unrelated (non-B non-C, NBNC) hepatocellular carcinoma (HCC) patients in Korea. Methods A total of 447 consecutive treatment-naïve NBNC-HCC adult patients who were registered at the Samsung Medical Center HCC registry in Korea from 2010 to 2013 were analyzed. NBNC was defined as negative hepatitis B surface antigen and negative anti-hepatitis C virus antibody. Presence of cirrhosis was determined based on histological, radiological, endoscopic, and serologic results. Mode of detection was classified as either under surveillance, incidental, or symptomatic. Results Heavy alcohol use was the most common potential etiology in NBNCHCC (NBNC-A, alcohol) (59.7%). Ten patients had other identifiable causes (NBNC-O, other identifiable cause) such as autoimmune hepatitis. The rest (38.0%) had no-identifiable cause (NBNC-NA-NO, non-alcohol, no-other identifiable cause). In NBNC-NA-NO group, 83.5% (96/115) of patients with available hepatitis B core immunoglobulin G antibody (HBcIgG) showed HBcIgG positivity, and 80.6% (137/170) had metabolic risk factors (diabetes, obesity, hypertension, and/ or dyslipidemia). Cirrhosis was present in 90.0%, 70.4%, and 60.0% of NBNC-O, NBNC-A, and NBNC-NA-NO patients, respectively. The proportion of patients diagnosed under surveillance was 25.5% across all patients, with specific proportions being 80.0%, 27.7%, and 18.8% for NBNC-O, NBNC-A, and NBNC-NA-NO, respectively. Conclusions Among NBNC-HCC patients, heavy alcohol use or any other identifiable cause was not found in 38.0%. These NBNC-NA-NO HCC patients showed a high prevalence of HBcIgG positivity and metabolic risk factors, suggesting that prior hepatitis B virus infection and metabolic risk factors may be major contributing factors in the hepatocarcinogenesis in NBNC-NA-NO patients.

PurposeHepatocellular carcinoma (HCC) patients usually achieve a complete response after treatment. This study was aimed to assess the clinical outcome of HCC patients who had achieved a complete response but later presented with elevated tumor marker levels without an identifiable recurrent tumor on gadoxetic acid-enhanced magnetic resonance imaging (MRI).MethodsWe retrospectively reviewed the clinical outcome of 58 HCC treated patients who had achieved a complete response but later was referred to our institution's multidisciplinary tumor board for a clinically suspected hidden HCC recurrence based on elevated tumor marker levels but negative gadoxetic acid-enhanced MRI. The imaging studies, tumor markers, and clinical information were reviewed. The total follow-up period was at least 15 months after the initial negative gadoxetic acid-enhanced MRI.ResultsFollow-up imaging studies detected an HCC lesion in 89.7% (n = 52/58) of the patients within the study period, and approximately half of the tumors (46.2%, n = 24/52) developed within 3 months. The most frequent site of recurrence was the liver (86.5%; n = 45/52), but extra-hepatic metastasis was also common (19.2%; n = 10/52). In 5.8% (n = 3/52), HCC reoccurred in the combined form of intra-hepatic and extra-hepatic recurrence. Extra-hepatic metastasis alone occurred in 13.5% (n = 7/52) of patients.ConclusionsHCC frequently recurred within a short interval in patients who achieved a complete response to treatment in the presence of increased tumor marker levels, even if gadoxetic acid-enhanced MRI was negative. Under such circumstances, we suggest a short-term follow-up including, but not limited to, gadoxetic acid-enhanced MRI along with systemic evaluation.