Park, Sang Min

Background Antibiotic use may alter gut microbiota, which could be associated with various diseases, including cardiovascular disease (CVD). Accordingly, further epidemiological evidence is needed to clarify the potential risk of CVD associated with antibiotic exposure. We evaluated the association between long‐term antibiotic exposure and CVD risk in South Korea. Methods and Results This nationwide retrospective cohort study used data from the Korean National Health Insurance Service database. A total of 2 159 965 individuals aged 40 to 79 years who had no history of antibiotic prescriptions from 2004 to 2005 were included and followed through December 31, 2021. Antibiotic exposure was defined as the cumulative days of antibiotic prescriptions from 2006 to 2010. The primary end point was incident CVD with 2 or more days of hospitalization from 2011 to 2021. Adjusted hazard ratios (aHR) and 95% CIs for CVD according to antibiotic exposure were estimated using multivariable Cox proportional hazards models, adjusting for a range of covariates. Longer cumulative antibiotic prescription days were associated with an increased risk of CVD. The aHRs for CVD associated with 1 to 14, 15 to 90, 91 to 180, 181 to 364, and ≥365 days of antibiotic exposure were 0.98 (95% CI, 0.96–1.01), 1.01 (95% CI, 0.99–1.03), 1.05 (95% CI, 1.03–1.08), 1.06 (95% CI, 1.04–1.09), and 1.10 (95% CI, 1.07–1.13) compared with those with no antibiotic prescriptions. Conclusions In this large population‐based cohort study of Korean adults, long‐term antibiotic exposure may be associated with a higher risk of CVD. Further research is warranted to establish causality and elucidate the underlying mechanisms for this association.

Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for the development of cardiovascular disease. However, the association between changes in NAFLD status and the risk of cardiovascular disease (CVD) remains uncertain. Starting January 1, 2013, participants were followed until the occurrence of CVD event, death, or December 31, 2020. This was a population-based cohort study that included data from adults aged ≥ 20, who underwent 2 consecutive health screenings from 2009 to 2012. NAFLD was defined as a Fatty Liver Index ≥ 60 at each screening. The primary endpoint was a CVD event, which encompassed ischemic heart disease and cerebrovascular disease. The association between changes in NAFLD status and the risk of CVD was determined using multivariable Cox proportional hazards regression. This cohort comprised 4656,305 adults with a median age of 53 years. During 36,396,968 person-years of follow-up, 238,933 (5.1%) CVD events were observed. Compared to patients with no NAFLD at both screenings, patients who developed NAFLD at the second screening exhibited an increased risk of CVD (adjusted hazard ratio, 1.15; 95% confidence interval, 1.13–1.17). In contrast, individuals who recovered from NAFLD at the second screening demonstrated a reduced CVD risk compared to those with persistent NAFLD (adjusted hazard ratio, 0.91; 95% confidence interval, 0.90–0.92). The reversal of NAFLD is associated with a reduced risk of CVD. Therefore, focusing on NAFLD treatment could serve as a clinical target for lowering CVD risk.

(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91–1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73–1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63–1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings.

Abstract Background : Studies have proposed an inverse association between allergic diseases and cancer risk, but few studies to date have specifically investigated the risk of primary liver cancer (hepatocellular carcinoma, HCC; intrahepatic cholangiocarcinoma, ICC) in patients with or without allergic diseases. Objective : The aim of this study was to evaluate the association between allergic diseases and risk of developing liver cancer.Methods: A retrospective cohort study of the Korean National Health Insurance Service database was performed to study 405,512 South Korean adults ages 40 and above who underwent routine health screening after January 1st, 2005. All participants were followed for liver cancer diagnosis or death until December 31st, 2013. Those who died before the index date, had pre-diagnosed cancer, or did not undergo health screening were excluded. Cox proportional hazards regression was performed to determine the adjusted hazard ratios(aHRs) and 95% confidence intervals (CIs) for risk of developing liver cancer according presence or absence of atopic dermatitis, asthma and allergic rhinitis.Results: The aHR (95% CI) for overall liver cancer among allergic patients was 0.72 (0.64-0.81). Allergic patients had significantly reduced risk of HCC (aHR: 0.70, 95% CI: 0.61-0.81) but not ICC (aHR: 0.99, 95% CI: 0.71-1.08). Presence of allergic diseases was associated with significantly lower risk of liver cancer in both patients with (aHR: 0.61, 95% CI: 0.47-0.8) or without (aHR: 0.74, 95% CI: 0.65-0.85) chronic Hepatitis B/C infections. Presence of allergic diseases was associated with significantly lower risk of liver cancer in patients without cirrhosis (aHR: 0.72, 95% CI 0.63-0.82), but not in those with cirrhosis (aHR: 0.98, 95% CI 0.68-1.41). Patients with multiple allergies had even lower risk of liver cancer compared to patients with single allergy. Conclusion: Patients with allergic diseases have significantly lower risk of developing liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment of liver cancer.

Introduction Despite extensive studies on the relationship between diabetes mellitus (DM) and depression, the associations of depressive symptom severity with prevalence, awareness, treatment, and control of diabetes remain unclear. We aimed to investigate changes in these outcomes of diabetes as depressive symptoms aggravate. Research design and methods We conducted a cross-sectional analysis of 14 328 participants in the 2011–2016 National Health and Nutrition Examination Survey. Participants were classified into depressive symptom groups of none, mild, moderate, moderately severe, and severe depending on their Patient Health Questionnaire-9 scores. Multivariate logistic regression analyses were conducted in three models adjusted for expanding confounders to evaluate the associations between severity of depressive symptoms and prevalence, awareness, treatment, and control of DM. Results As depressive symptom severity worsened, both prevalence and awareness of DM increased regardless of models (p value for trend <0.01 in all models for prevalence and awareness; adjusted OR (aOR) 2.14, 95% CI 1.29 to 3.56 for prevalence in the severe group, model 1; aOR 2.43, 95% CI 1.27 to 4.64 for awareness in the moderately severe group, model 1). Notwithstanding higher awareness of diabetes in the moderately severe and severe groups (84.5% and 86.2%, respectively, vs 71.3% in the none group), these groups were treated less (aOR 0.25, 95% CI 0.11 to 0.55 in the severe group, model 3) or inadequately controlled (aOR 0.51, 95% CI 0.27 to 0.98 in the moderately severe group, model 3). Conclusions The gap between patients’ higher awareness and lower treatment rate or control of diabetes among individuals with severe depressive symptoms highlights the unmet needs for postdiagnostic multidisciplinary care for patients with comorbid depression and DM.