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BACKGROUNDIt is unclear whether the level of serum hepatitis B virus (HBV) DNA at baseline affects the on-treatment risk of hepatocellular carcinoma (HCC) in hepatitis B e antigen-positive (HBeAg-positive), noncirrhotic patients with chronic hepatitis B (CHB).METHODSWe conducted a multicenter cohort study including 2073 entecavir- or tenofovir-treated, HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV DNA levels of 5.00 log10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV DNA levels.RESULTSDuring a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00-5.99 log10 IU/mL (P < 0.001). By multivariable analysis, the baseline HBV DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV DNA levels of 8.00 log10 IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00-7.99 log10 IU/mL, 6.00-6.99 log10 IU/mL, or 5.00-5.99 log10 IU/mL were 2.48 (P = 0.03), 3.69 (P = 0.002), and 6.10 (P < 0.001), respectively.CONCLUSIONOn-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log10 IU/mL or higher in HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of antiviral treatment when the viral load is high (≥8.00 log10 IU/mL) may maintain the lowest risk of HCC for those patients.FUNDINGPatient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for Cancer Control through the National Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea.

It was suggested that normalization of serum alanine aminotransferase (ALT) levels at 1 year of antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B (CHB). However, it remains unclear whether earlier ALT normalization is associated with lower hepatocellular carcinoma (HCC) risk, independent of fatty liver or cirrhosis and on-treatment virological response (VR), in patients with CHB. We analyzed 4,639 patients with CHB who initiated treatment with entecavir or tenofovir using landmark analysis and time-dependent Cox analysis. We defined normal ALT as ≤35 U/L (men) and ≤25 U/L (women) and VR as serum hepatitis B virus DNA <15 IU/mL. During a median 5.6 years of treatment, 509 (11.0%) patients developed HCC. ALT normalization occurred in 65.6% at 1 year and 81.9% at 2 years and was associated with a significantly lower HCC risk in landmark (P < 0.001) and time-dependent Cox analyses (adjusted hazard ratio [AHR] 0.57; P < 0.001). Compared with ALT normalization within 6 months, delayed ALT normalization at 6-12, 12-24, and >24 months was associated with incrementally increasing HCC risk (AHR 1.40, 1.74, and 2.45, respectively; P < 0.001), regardless of fatty liver or cirrhosis at baseline and VR during treatment. By contrast, neither earlier VR (AHR 0.93; P = 0.53) nor earlier hepatitis B e antigen seroclearance (AHR 0.91; P = 0.31) was associated with a significantly lower HCC risk. In patients with CHB treated with entecavir or tenofovir, earlier ALT normalization was independently associated with proportionally lower HCC risk, regardless of fatty liver or cirrhosis at baseline and on-treatment VR.

Previous population-based studies have demonstrated differences in cardiovascular events according to the new classification of steatotic liver disease (SLD). However, detailed data on coronary artery status have not been presented. We aimed to investigate the association between subtypes of SLD and coronary artery status using findings from coronary computed tomography angiography (CCTA). We analyzed 8622 asymptomatic individuals without coronary artery disease (CAD) who underwent both abdominal ultrasonography and CCTA. Study participants were divided into four groups: 934 in the no SLD without cardiometabolic (CM) criteria group, 4811 in the no SLD with CM criteria group, 2494 in the metabolic dysfunction-associated steatotic liver disease (MASLD) group, and 252 in the MASLD with increased alcohol intake (Met-ALD) group. Obstructive CAD was defined as coronary arterial stenosis ≥ 50%. Compared with the no SLD without CM group, the no SLD with CM, MASLD, and Met-ALD groups were significantly associated with any coronary plaque (multivariable-adjusted OR 2.05 [95% CI 1.67–2.52], 2.71 [2.18–3.35], and 2.36 [1.69–3.31], respectively); calcified plaques (1.97 [1.59–2.43], 2.54 [2.04–3.16], and 2.10 [1.49–2.96], respectively); non-calcified plaques (2.04 [1.28–3.25], 2.42 [1.51–3.89], and 3.26 [1.73–6.13], respectively); and obstructive CAD (2.57 [1.53–4.32], 3.64 [2.15–6.16], and 3.51 [1.73–7.10], respectively) ( p for all < 0.05). In addition, the inverse probability of treatment weighting (IPTW) analyses showed similar ORs for coronary plaques and obstructive CAD. Additionally, higher steatosis-associated fibrosis estimator (SAFE) was strongly associated with all atherosclerotic plaques and obstructive CAD. This association remained significant after multivariable adjustment and IPTW analyses. Subtypes of SLD had significant, yet different strengths of associations with subclinical coronary atherosclerosis. SAFE score classification effectively stratified the distinct associations with subclinical atherosclerosis in subjects with MASLD.

Background/Aims: There is no clear consensus on the relative ranking of interventional and radiation techniques with indications similar to those of radiofrequency ablation (RFA) for the treatment of early hepatocellular carcinoma (HCC). We used a network meta-analysis to compare the efficacy of non-surgical treatments for early HCC.Methods: We searched databases for randomized trials assessing the efficacy of loco-regional treatments for HCCs ≤5 cm with no extrahepatic spread or portal invasion. The primary outcome was the pooled hazard ratio (HR) for overall survival (OS), and secondary outcomes included overall and local progression-free survival (PFS). A frequentist network meta-analysis was performed, and the relative ranking of therapies was assessed with P-scores.Results: Nineteen studies comparing 11 different strategies in 2,793 patients were included. Chemoembolization plus RFA improved OS better than RFA alone (HR 0.52, 95% confidence interval [CI] 0.33–0.82; P-score=0.951). Cryoablation, microwave ablation, laser ablation, and proton beam therapy had similar effects on OS compared with RFA. For overall PFS, but not local PFS, only chemoembolization plus RFA performed significantly better than RFA (HR 0.61, 95% CI 0.42–0.88; P-score=0.964). Injection of percutaneous ethanol or acetic acid was significantly less effective than RFA for all measured outcomes, while no differences in progression outcomes were identified for other therapies included in the network.Conclusions: Our results suggest that chemoembolization combined with RFA is the best option for local treatment of early HCC. Cases with potential contraindications for RFA may benefit from a tailored approach using thermal or radiation modalities.

The aim of this study was to evaluate the association between serum testosterone and abdominal body composition based on abdominopelvic computed tomography (APCT) measurements after adjusting for individual metabolic syndrome components. We performed a cross-sectional study using male subjects (age range: 22–84 years) who underwent a general health examination with abdominopelvic computed tomography and testosterone measurements. Body composition was evaluated with APCT. To confirm an association between testosterone and abdominal body composition, we conducted linear regression analysis. The effect of abdominal body composition was adjusted for important clinical factors such as age, albumin, and metabolic components in the multivariable regression analysis. Overall, 1453 subjects were included in the primary analysis. After adjustment for age, individual metabolic components, albumin, hemoglobin A1c, and C-reactive protein, we found that subcutaneous fat area index (β = − 0.042, p  < 0.001), total abdominal muscle area index (β = 0.115, p  < 0.001), normal attenuation muscle area index (β = 0.070, p  < 0.001), and log e -transformed lower attenuation muscle area index (β = 0.140, p  = 0.002) had an association with log e -transformed testosterone level. After adjusting for individual metabolic syndrome components, testosterone was associated negatively with subcutaneous fat, but not visceral fat. In addition, testosterone was positively correlated with abdominal muscle regardless of qualitative features such as fat-rich and fat-free.

Background/Aims: Serum hepatitis B virus (HBV) DNA levels and non-invasive liver fibrosis scores are significantly associated with hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. Nonetheless, the relationship between HBV DNA levels and liver fibrosis scores is unclear.Methods: A historical cohort comprising 6,949 non-cirrhotic Korean CHB patients without significant alanine aminotransferase elevation was investigated. The association of HBV DNA levels with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (FIB)-4 score at baseline was analyzed using general linear models.Results: In HBeAg-negative patients (n=4,868), HBV DNA levels correlated linearly with both APRI and FIB-4 scores. In contrast, in HBeAg-positive patients (n=2,081), HBV DNA levels correlated inversely with both APRI and FIB-4 scores. Across the entire cohort, a significant non-linear parabolic relationship was identified between HBV DNA levels and fibrosis scores, independent of age and other covariates. Notably, moderate viral loads (6–7 log10 IU/mL) corresponded to the highest APRI and FIB-4 scores (p<0.001). Over a median 10-year follow-up, 435 patients (6.3%) developed HCC. Higher APRI scores ≥0.5 and FIB-4 scores ≥1.45 were significantly associated with elevated HCC risk (p<0.001 for both). HBV DNA level remained a significant predictive factor for HCC development, even after adjusting for APRI or FIB-4 scores.Conclusions: HBV viral load is significantly correlated with APRI and FIB-4 scores, and is also associated with HCC risk independent of those scores in CHB patients. These findings suggest that HBV DNA level is associated with hepatocarcinogenesis through both direct and indirect pathways.

The relationship between subclinical coronary atherosclerosis and lipoprotein(a) (Lp[a]) in asymptomatic people with and without diabetes mellitus (DM) is not well understood. We conducted a retrospective analysis of 7201 asymptomatic people (average age 54.4 ± 7.9 years; 65.3% male) who voluntarily had coronary computed tomography angiography (CCTA) as part of a general health evaluation and had no history of coronary artery disease (CAD). The severity and extent of subclinical coronary atherosclerosis were assessed using CCTA, with obstructive CAD defined as a diameter stenosis of at least 50%. Based on their Lp(a) levels, the study participants were divided into tertiles. To assess the relationship between Lp(a) levels and subclinical coronary atherosclerosis, logistic regression analysis was used. In participants without DM (n = 6252), after adjusting for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios (ORs) for calcified plaque, mixed plaque, non-calcified plaque, and obstructive CAD in the third Lp(a) tertile compared to the first tertile ( p  > 0.05 for all). On the other hand, in participants with DM (n = 949), there were no statistically significant differences in the ORs for calcified plaque (1.117, 95% confidence interval [CI] 0.794–1.572), mixed plaque (1.552, 95% CI 0.888–2.714), or non-calcified plaque (1.735, 95% CI 0.980–3.072) between the first and third Lp(a) tertiles. However, the adjusted ORs for obstructive CAD (2.051, 95% CI 1.248–3.372) were significantly higher in the third Lp(a) tertile compared to the first Lp(a) tertile. In asymptomatic individuals with DM, higher Lp(a) levels were associated with obstructive CAD, which may be linked to an increased risk of cardiac events.

Beta-adrenergic receptor blockers are used in patients with coronary artery disease (CAD) to reduce the harmful effects of excessive adrenergic activation on the heart. However, there is limited evidence regarding the benefit of beta-blockers in the context of contemporary management following percutaneous coronary intervention (PCI). We used the nationwide South Korea National Health Insurance database to identify 87,980 patients with a diagnosis of either acute myocardial infarction (AMI; n = 38,246) or angina pectoris (n = 49,734) who underwent PCI between 2013 and 2017, and survived to be discharged from hospital. Beta-blockers were used in a higher proportion of patients with AMI (80.6%) than those with angina (58.9%). Over a median follow-up of 2.2 years (interquartile range 1.2–3.3 years) with the propensity-score matching analysis, the mortality risk was significantly lower in patients treated with a beta-blocker in the AMI group (HR: 0.78; 95% CI 0.69–0.87; p  < 0.001). However, the mortality risk was comparable regardless of beta-blocker use (HR: 1.07; 95% CI 0.98–1.16; p  = 0.10) in the angina group. The survival benefit associated with beta-blocker therapy was most significant in the first year after the AMI event.

The impact of pre-existing depression on mortality in individuals with established coronary artery disease (CAD) remains unclear. We evaluate the clinical implications of pre-existing depression in patients who underwent percutaneous coronary intervention (PCI). Based on National Health Insurance claims data in Korea, patients without a known history of CAD who underwent PCI between 2013 and 2017 were enrolled. The study population was divided into patients with angina (n = 50,256) or acute myocardial infarction (AMI; n = 40,049). The primary endpoint, defined as all-cause death, was compared between the non-depression and depression groups using propensity score matching analysis. After propensity score matching, there were 4262 and 2346 matched pairs of patients with angina and AMI, respectively. During the follow-up period, there was no significant difference in the incidence of all-cause death in the angina (hazard ratio [HR] of depression, 1.013; 95% confidence interval [CI] 0.893–1.151) and AMI (HR, 0.991; 95% CI 0.865–1.136) groups. However, angina patients less than 65 years of age with depression had higher all-cause mortality (HR, 1.769; 95% CI 1.240–2.525). In Korean patients undergoing PCI, pre-existing depression is not associated with poorer clinical outcomes. However, in younger patients with angina, depression is associated with higher all-cause mortality.

Prior epidemiological evidences suggest that hepatitis B virus (HBV) infection is linked to cancers other than hepatocellular carcinoma. This prospective hospital registry-based case-control study aimed to investigate the sero-epidemiological association between chronic HBV infection and various types of cancer. 95,034 patients with first-diagnosed non-hepatocellular malignancy in a tertiary hospital between 2007 and 2014; and 118,891 non-cancer individuals as controls from a health promotion center were included. Cases and controls were compared for HBV surface antigen (HBsAg) positivity by conditional regression with adjustment for age, hypertension, diabetes, body mass index, alcohol consumption, smoking status and cholesterol level in both genders. An analysis of matched data indicated significant associations of HBV infection with lymphoma (adjusted odds ratio[AOR] 1.53 [95% CI 1.12-2.09] in men and 3.04 [1.92-4.82] in women) and biliary cancer (2.59[1.98-3.39] in men and 1.71[1.16-2.51] in women). Cervical (1.49[1.11-2.00]), uterine (1.69[1.09-2.61]), breast (1.16[1.02-1.32]), thyroid (1.49[1.28-1.74]), and lung cancers (1.79[1.32-2.44]) in women; and skin cancer (5.33[1.55-18.30]) in men were also significantly related to HBV infection. Chronic HBV infection is associated with several malignant disorders including lymphoma, and biliary, cervical, uterine, breast, thyroid, lung, and skin cancers. Our findings may offer additional insights into the development of these neoplasms and may suggest the need to consider HBV screening in cancer patients and cancer surveillance in HBV-infected subjects.