Beomseok Suh

High liver fibrosis index FIB‐4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers

Screening for hepatocellular carcinoma (HCC) is clinically important given that its early detection has remarkable survival benefits. We investigated the possible role of FIB‐4, a recently developed noninvasive marker for liver fibrosis based on routine laboratory tests, as a clinical indicator for predicting future HCC among hepatitis B surface antigen (HBsAg) carriers. Our retrospective cohort study involved 986 Korean HBsAg carriers 40 years of age or older who visited Seoul National University Hospital for a health checkup. National medical service claims data were used to determine HCC incidence. Median follow‐up time was 5.4 years (interquartile range: 4.4 years). Adjusted for age, sex, body mass index, smoking, alcohol, and antiviral medication for hepatitis B, compared to subjects with FIB‐4 <1.25, subjects with 1.7≤ FIB‐4 <2.4 showed an adjusted hazard ratio (aHR) of 4.57 (95% confidence interval [CI]: 1.50‐13.92) and subjects with FIB‐4 ≥2.4 showed an aHR of 21.34 (95% CI: 7.73‐58.92) for HCC incidence. FIB‐4 was shown to have incremental predictive value to ultrasonographic liver cirrhosis for HCC incidence (C‐index: 0.701 vs. 0.831; P = 0.001). FIB‐4 was also better predictive of HCC incidence, compared to that of ultrasonographic liver cirrhosis (C‐index: 0.775 vs. 0.701; P = 0.040). Conclusion: High FIB‐4 is a highly predictive risk factor for HCC incidence among Korean HBsAg carriers. FIB‐4 is a promising, easily applicable, and cost‐effective clinical tool in identifying a subpopulation of HBsAg carriers who are at heightened risk. Our study needs to be replicated in larger future studies on various ethnic groups; nonetheless, our study suggests that FIB‐4 may play a valuable role in HCC screening among HBsAg carriers. (Hepatology 2015;61:1261–1268)

Treatment Gap in the National Health-screening Program in Korea: Claim-based Follow-up of Statin Use for Sustained Hypercholesterolemia

Participation in a screening program by itself may not improve clinical outcomes. Treatment gaps in the program may limit its full benefit. We evaluated statin prescription rates for subjects with sustained hypercholesterolemia to assess the treatment gaps in the National Health Screening Program (NHSP) in Korea. A retrospective, random cohort was established among National Health Insurance Corporation (NHIC) members. Finally, we examined 465,499 individuals who attended the NHSP from 2003 to 2010 without any history of dyslipidemia, statin prescription, or hospitalization for cardiovascular events until the end of 2002. The subsequent statin prescription rates were identified from the NHIC medical service claim database from 2003 to 2011. Descriptive data and odds ratio from multivariate logistic analyses on statin prescription rates and the corresponding correlations were evaluated. The NHSP detected 114,085 (24.5%) cases of newly diagnosed hypercholesterolemia. However, only 8.6% of these received statin prescription within 6 months of diagnosis. For cases of sustained hypercholesterolemia determined in the next screening visit by the NHSP, the statin prescription rate increased, but only to 12.2%. Statin prescriptions were more common among females, older individuals, and hypertension or diabetes patients. Furthermore, the statin prescription rates had increased over the study period. The NHSP exhibited low statin prescription rate which has been improving. For the NHSP to be effective, it would be worthwhile to decrease the gap between the diagnosis of hypercholesterolemia and the following treatment. Graphical Abstract

Elevated neutrophil to lymphocyte ratio and ischemic stroke risk in generally healthy adults

Elevated neutrophil to lymphocyte ratio (NLR) has been reported as a marker for chronic inflammation, associated with poor prognosis in ischemic stroke patients, but there has been no study that investigated its association with ischemic stroke risk. This study was conducted to investigate elevated NLR as an independent risk factor for ischemic stroke incidence. Our retrospective cohort study included 24,708 generally healthy subjects aged 30–75 who received self-referred health screening at Seoul National University Hospital. Data on ischemic stroke incidence was retrieved from national medical claims registry. Median follow-up time was 5.9 years (interquartile range 4.2 years). Adjusted for major cardiovascular risk factors, compared to subjects with NLR<1.5, subjects with 2.5≤NLR<3.0, 3.0≤NLR<3.5, and NLR≥3.5 had elevated risk for ischemic stroke incidence with aHR (95% CI) of 1.76 (1.09–2.84), 2.21 (1.21–4.04), and 2.96 (1.57–5.58), respectively. NLR showed significant improvement in discrimination for ischemic stroke incidence compared to traditional cardiovascular risk factors (C-index 0.748 vs. 0.739, P = 0.025). There was significant net improvement in reclassification in Framingham risk for ischemic stroke incidence after addition of NLR, with IDI 0.0035 (P<0.0001), and NRI 6.02% (P = 0.0015). This reclassification for ischemic stroke incidence by NLR was markedly pronounced among subjects with atrial fibrillation with CHA2DS2-VASc<2 (NRI 42.41%, P = 0.056). Our study suggests elevated NLR to be an independent risk factor for ischemic stroke incidence in generally healthy adults. Future studies are needed to validate our results and further assess how subjects with elevated NLR should be managed within current guidelines.

Trends in Cardiovascular Health Metrics among Korean Adults

Background American Heart Association (AHA) defined 7 cardiovascular health metrics for the general population to improve cardiovascular health in 2010: not smoking; having normal blood pressure; being physically active; normal body mass index, blood glucose, and total cholesterol levels; and eating a healthy diet. To investigate trends in cardiovascular health metrics in Korea, we used data from the third and fourth Korean National Health and Nutrition Examination Surveys. Methods We defined seven cardiovascular health metrics similar to the one defined by AHA but physical activity, body mass index, and healthy diet were properly redefined to be suited for the Korean population. We compared each cardiovascular health metric and calculated the sum of cardiovascular health metrics after dichotomizing each health metric to ideal (scored 1) and poor (scored 0). Results Health metric scores of smoking in males (P value for trend < 0.001), physical activity both in males and females (P-value for trend < 0.001 both), body mass index in females (P-value for trend = 0.030), and blood pressure both in males and females (P-value for trend < 0.001, both) were improved. On the other hand, health metric scores of healthy diet in males (P-value for trend = 0.002), and fasting blood glucose both in males and females (P-value for trend < 0.001 both) got worse. The total scores of seven health metrics were stationary. Conclusion Total scores were not changed but each metric showed various trends. A long-term study is necessary for analyzing exact trends.

Prediction of future hepatocellular carcinoma incidence in moderate to heavy alcohol drinkers with the FIB-4 liver fibrosis index

Although heavy alcoholics are at heightened risk for hepatocellular carcinoma (HCC), there are no guidelines that recommend HCC screening for heavy alcoholics. This study investigated FIB‐4, a noninvasive and easily applicable liver fibrosis index, as a risk factor for HCC incidence among alcohol drinkers without viral hepatitis.

The Prevalence of and Factors Associated with the Use of Smoking Cessation Medication in Korea: Trend between 2005–2011

Background In Korea, nicotine replacement therapy (NRT) has been widely used in government-led, public health center-based smoking cessation services since 2004 and varenicline has become available from 2007 but without reimbursement. In this study which used a series of nationwide cross-sectional surveys in Korea performed from 2005 to 2011, we examined the prevalence of smoking cessation medication use and factors associated with it. Methods We analyzed data from the third to fifth waves of Korean National Health and Nutrition Examination Survey (2005–2011). Prevalence of each smoking cessation method use was calculated for each year, and its secular trend was tested by multivariate logistic regression. Results Among smokers who made quit attempt during the previous year, 15.7% had used smoking cessation medications,15.3% had used NRT, and 0.7% had used prescription medication. There was a significant increasing trend for NRT use (P<0.001) during the study period, but use of prescription medication did not show any increase over time (P = 0.654) Education on smoking prevention and cessation was associated with smoking cessation medications use (OR 2.08, 95% CI 1.58–2.75). Conclusions While the use of NRT has increased over years through government-sponsored smoking cessation programs, use of prescription drugs remained very low and flat probably due to lack of reimbursement. Education of smokers about effective smoking cessation methods and change in reimbursement policy are suggested to stimulate evidence-based smoking cessation practice.

Mode of primary cancer detection as an indicator of screening practice for second primary cancer in cancer survivors: a nationwide survey in Korea

BackgroundWhile knowledge and risk perception have been associated with screening for second primary cancer (SPC), there are no clinically useful indicators to identify who is at risk of not being properly screened for SPC. We investigated whether the mode of primary cancer detection (i.e. screen-detected vs. non-screen-detected) is associated with subsequent completion of all appropriate SPC screening in cancer survivors.MethodsData were collected from cancer patients treated at the National Cancer Center and nine regional cancer centers across Korea. A total of 512 cancer survivors older than 40, time since diagnosis more than 2 years, and whose first primary cancer was not advanced or metastasized were selected. Multivariate logistic regression was used to examine factors, including mode of primary cancer detection, associated with completion of all appropriate SPC screening according to national cancer screening guidelines.ResultsBeing screen-detected for their first primary cancer was found to be significantly associated with completion of all appropriate SPC screening (adjusted odds ratio, 2.13; 95% confidence interval, 1.36–3.33), after controlling for demographic and clinical variables. Screen-detected cancer survivors were significantly more likely to have higher household income, have other comorbidities, and be within 5 years since diagnosis.ConclusionsThe mode of primary cancer detection, a readily available clinical information, can be used as an indicator for screening practice for SPC in cancer survivors. Education about the importance of SPC screening will be helpful particularly for cancer survivors whose primary cancer was not screen-detected.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations

Background/Aims Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. Methods A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. Results In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. Conclusions Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

Educational Disparities in Distribution of Cardiovascular Risk Factors and Quality of Care in Korean Adults: Korean National Health and Nutrition Survey IV.

Background The purpose of this study was to investigate how educational status influences cardiovascular risk factors and care of diabetes mellitus and hypertension. Methods From Korean National Health and Nutrition Survey IV, we obtained survey results of 6,835 men and 9,067 women more than 30 years old. We performed multivariate logistic regression to compare cardiovascular risk factors and care of hypertension and diabetes respective to educational status. Results There were disparities in cardiovascular risk factors by educational status. In men, impaired fasting glucose, high triglyceride, and smoking were less frequently found in the highest educated group than in the middle educated group. In women, the prevalence of abdominal obesity, impaired fasting glucose, high blood pressure, high triglyceride, and metabolic syndrome among the highest educated group were significantly lower. The proportion of those with proper physical activity in the highest educated group was found to be less than that of the middle educated group, regardless of gender. For care of diabetes mellitus and hypertension, disease recognition and treatment were lower among the lowest educated group in men, while these disparities were not shown in women. Instead, the lowest educated group in diabetic women received screening exams for eye and kidney complications less than the middle education group. In both genders, the high education group had a higher chance of receiving education about diabetes mellitus. Conclusion There were educational disparities in cardiovascular risk factors and care of hypertension and diabetes mellitus. The disparities were found to be different by gender.

KRAS G12C mutation as a poor prognostic marker of pemetrexed treatment in non-small cell lung cancer

Background/Aims The predictive and prognostic value of KRAS mutation and its type of mutations in non-small cell lung cancer (NSCLC) are controversial. This clinical study was designed to investigate the predictive value of KRAS mutations and its mutation types to pemetrexed and gemcitabine based treatment. Methods Advanced NSCLC patients tested for KRAS mutation (n = 334) were retrospectively reviewed and 252 patients with wild type epidermal growth factor receptor and no anaplastic lymphoma kinase fusion were enrolled for the analysis. KRAS mutations were observed in 45 subjects with mutation type as followed: G12C (n = 13), G12D (n = 12), G12V (n = 12), other (n = 8). Response rate (RR), progression-free survival (PFS), and overall survival (OS) of pemetrexed singlet and gemcitabine based chemotherapy were analysis. Results Age, sex, performance status were well balanced between subjects with or without KRAS mutations. No difference was observed in RR. Hazard ratio (HR) of PFS for pemetrexed treated subjects with G12C mutation compared to subjects with KRAS wild type was 1.96 (95% confidential interval [CI], 1.01 to 3.79; p = 0.045), but other mutations failed to show clinical significance. By analysis done by PFS, compared to the subjects with transition mutation, HR was 1.48 (95% CI, 0.64 to 3.40; p = 0.360) for subjects with transversion mutation on pemetrexed treatment and 0.41 (95% CI, 0.19 to 0.87; p = 0.020) for subjects treated with gemcitabine based chemotherapy. No difference was observed in OS. Conclusions In this study, different drug sensitivity was observed according to the type of KRAS mutation. NSCLC subpopulations with different KRAS mutation type should be considered as different subgroups and optimal chemotherapy regimens should be searched in further confirmative studies.