We aimed to determine the surveillance performance of alpha‐fetoprotein (AFP), lectin‐reactive AFP (AFP‐L3), des‐gamma‐carboxy prothrombin (DCP), and their combinations for the early detection of ...hepatocellular carcinoma (HCC) by using prospectively collected longitudinal samples in patients at risk. Among 689 patients with cirrhosis and/or chronic hepatitis B who participated in four prospective studies, 42 HCC cases were diagnosed, selected, and matched with 168 controls for age, sex, etiology, cirrhosis, and duration of follow‐up in a 1:4 ratio. Levels of AFP, AFP‐L3, and DCP at the time of HCC diagnosis, month −6, and month −12 were compared between cases and controls. Of 42 HCC cases, 39 (93%) had cirrhosis, 36 (85.7%) had normal alanine aminotransferase levels, and 31 (73.8%) had very early‐stage HCC (single <2 cm). AFP and AFP‐L3 began to increase from 6 months before diagnosis of HCC in cases (P < 0.05), while they remained unchanged in controls. At HCC diagnosis, the area under the receiver operator characteristic curves (AUROCs) for AFP, AFP‐L3, and DCP were 0.77, 0.73, and 0.71, respectively. Combining AFP and AFP‐L3 showed a higher AUROC (0.83), while adding DCP did not further improve the AUROC (0.86). With the optimal cutoff values (AFP, 5 ng/mL; AFP‐L3, 4%), the sensitivity and specificity of AFP and AFP‐L3 combination were 79% and 87%, respectively. The sensitivity of ultrasonography was 48.6%, which was increased to 88.6% and 94.3% by adding AFP and AFP + AFP‐L3, respectively. Conclusion: Among three biomarkers, AFP showed the best performance in discriminating HCC cases from controls; the AFP and AFP‐L3 combination, adopting cutoff values (5 ng/mL and 4%, respectively), significantly improved the sensitivity for detecting HCC at a very early stage.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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.
OBJECTIVE:To develop clinical predictive nomograms generating per-patient numerical probabilities of postoperative recurrence-free and overall survival at specific times.
BACKGROUND:The prognosis ...after surgical resection is diverse in patients with early-stage hepatocellular carcinoma (HCC).
METHODS:In a retrospective review, we evaluated data from 1085 mostly early-stage patients newly diagnosed with HCC who were subsequently treated by curative resection. We randomly divided the subjects into derivation (n = 760) and validation (n = 325) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of pre- and postoperative clinical and pathological covariates assessed for association with 2-year recurrence and 5-year HCC-specific death. The discriminatory accuracy of the models was compared with traditional tools by analyzing receiver operating characteristic curves.
RESULTS:The statistical nomograms built on the basis of sex, serum albumin, platelet count, microvascular invasion, and calculated tumor volume had good calibration and discriminatory abilities, with c-indices of 0.69 (2-year recurrence) and 0.66 (5-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the independent validation cohort (c-index, 0.66 for 2-year recurrence; and 0.67 for 5-year survival). The areas under the receiver operating characteristic curve using our methods were greater than those of conventional staging systems in the validation patients, indicating better discriminatory capability (corresponding c-indices, 0.55–0.56; and 0.55–0.61, respectively).
CONCLUSIONS:Our simple user-friendly calculators, which present graphically postsurgical prognostic models for recurrence and survival outcomes in patients with curatively resectable HCC, offer useful guidance to clinicians and patients for individually planning recurrence surveillance and adjuvant therapy.
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.
To investigate features of the anterior segment (AS) of the affected eye compared to the fellow eye within the same patient in acute primary angle closure (APAC).
Thirty-six patients with unilateral ...APAC were imaged with AS optical coherence tomography (OCT) before medical or laser treatment for the acute attack. Anterior chamber depth (ACD), iris curvature (IC), iris thickness at 750 μm from the scleral spur (IT750), lens vault (LV), anterior chamber area (ACA), and iris area were estimated by using ImageJ software (version 1.46). Conditional logistic regression analysis was performed to find the associated factors with the prediction of APAC.
When compared to fellow eyes, affected eyes showed significantly shallower ACD (1.90 ± 0.24 and 1.55 ± 0.30 mm, respectively; P < 0.001), smaller ACA (12.96 ± 2.38 and 10.41 ± 2.34 mm(2), respectively; P < 0.001), and greater LV (1.06 ± 0.31 and 1.26 ± 0.36 mm, respectively; P = 0.017). Less IC (odds ratio OR*100: 0.935 95% confidence interval: 0.894, 0.979, P = 0.004) and IT750 (OR*100: 0.904 0.8294, 0.987, P = 0.024), greater central corneal thickness (OR*100: 2.100 1.245, 3.542, P = 0.005), greater LV (OR: 66.7 2.529, 1761.3, P = 0.012), less ACA (OR: 0.386 0.193, 0.774, P = 0.007), and less ACD (OR*100: 0.912 0.855, 0.972, P = 0.005) were significantly associated with prediction of APAC.
Greater LV was the most prominent feature of affected eyes compared to fellow eyes in APAC patients when assessed by AS OCT. This may play a role in the development of acute attack in primary angle closure.
The risks and benefits of long-term dual antiplatelet therapy remain unclear.
This prospective, multicenter, open-label, randomized comparison trial was conducted in 24 clinical centers in Korea. In ...total, 5045 patients who received drug-eluting stents and were free of major adverse cardiovascular events and major bleeding for at least 12 months after stent placement were enrolled between July 2007 and July 2011. Patients were randomized to receive aspirin alone (n=2514) or clopidogrel plus aspirin (n=2531). The primary end point was a composite of death resulting from cardiac causes, myocardial infarction, or stroke 24 months after randomization. At 24 months, the primary end point occurred in 57 aspirin-alone group patients (2.4%) and 61 dual-therapy group patients (2.6%; hazard ratio, 0.94; 95% confidence interval, 0.66-1.35; P=0.75). The 2 groups did not differ significantly in terms of the individual risks of death resulting from any cause, myocardial infarction, stent thrombosis, or stroke. Major bleeding occurred in 24 (1.1%) and 34 (1.4%) of the aspirin-alone group and dual-therapy group patients, respectively (hazard ratio, 0.71; 95% confidence interval, 0.42-1.20; P=0.20).
Among patients who were on 12-month dual antiplatelet therapy without complications, an additional 24 months of dual antiplatelet therapy versus aspirin alone did not reduce the risk of the composite end point of death from cardiac causes, myocardial infarction, or stroke.
http://www.clinicaltrials.gov. Unique identifier: NCT01186146.
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
-transformed lower attenuation muscle area index (β = 0.140, p = 0.002) had an association with log
-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.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background:Although the prevalence of both atrial fibrillation (AF) and metabolic syndrome (MetS) has been increasing in East Asia, the association between them is uncertain.Methods and Results:A ...total of 24,741 middle-aged Korean men without baseline AF were enrolled in a health screening program from January 2003 to December 2008. Among them, 21,981 subjects were evaluated to determine the risk of AF based on baseline MetS status through December 2016. At every visit, the subjects were evaluated for AF using ECG. MetS was defined using the criteria of the International Diabetes Federation and was present in 2,529 subjects (11.5%). Mean (±standard deviation) age was 45.9±5.3 years. During a mean follow-up of 8.7 years, 168 subjects (0.8%) were diagnosed with AF. The age-adjusted and multivariate-adjusted hazard ratios (HR) for MetS with AF were 1.62 (P=0.02) and 1.57 (P=0.03), respectively. Among the components of MetS, central obesity (age-adjusted HR 1.62, P<0.01) and raised blood pressure (age-adjusted HR 1.43, P=0.02) were associated with an increased risk of AF.Conclusions:MetS is associated with an increased risk of AF in middle-aged East Asian men. Of the components of MetS, central obesity is the most potent risk factor for the development of AF in this population.
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.
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.
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.
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.
PDF
