Pau-Chung Chen

Statins and the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus Infection

PURPOSE Statins have potential protective effects against cancers, but no studies have focused on patients with chronic hepatitis B virus (HBV) infection. The purpose of this study was to investigate the association between the use of statins in HBV-infected patients and the risk of hepatocellular carcinoma (HCC). PATIENTS AND METHODS We conducted a population-based cohort study from the Taiwan National Health Insurance Research Database. A total of 33,413 HBV-infected patients were included as the study cohort. Each patient was individually tracked from 1997 to 2008 to identify incident cases of HCC since 1999. Subsequent use of statin, other lipid-lowering agents, aspirin, and angiotensin-converting enzyme inhibitors was identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% CIs for the association between the use of statins and the occurrence of HCC in the HBV-infected cohort. RESULTS There were 1,021 HCCs in the HBV cohort during the follow-up period of 328,946 person-years; the overall incidence rate was 310.4 HCCs per 100,000 person-years. There was a dose-response relationship between statin use and the risk of HCC in the HBV cohort. The adjusted HRs were 0.66 (95% CI, 0.44 to 0.99), 0.41 (95% CI, 0.27 to 0.61), and 0.34 (95% CI, 0.18 to 0.67) for statin use of 28 to 90, 91 to 365, and more than 365 cumulative defined daily doses (cDDDs), respectively, relative to no statin use (< 28 cDDDs). CONCLUSION Statin use may reduce the risk for HCC in HBV-infected patients in a dose-dependent manner. Further mechanistic research is needed.

Population-Based Case–Control Study of Chinese Herbal Products Containing Aristolochic Acid and Urinary Tract Cancer Risk

Background Consumption of Chinese herbs that contain aristolochic acid (eg, Mu Tong) has been associated with an increased risk of urinary tract cancer. Methods We conducted a population-based case–control study in Taiwan to examine the association between prescribed Chinese herbal products that contain aristolochic acid and urinary tract cancer. All patients newly diagnosed with urinary tract cancer (case subjects) from January 1, 2001, to December 31, 2002, and a random sample of the entire insured population from January 1, 1997, to December 31, 2002 (control subjects), were selected from the National Health Insurance reimbursement database. Subjects who were ever prescribed more than 500 pills of nonsteroidal anti-inflammatory drugs and/or acetaminophen were excluded, leaving 4594 case patients and 174 701 control subjects in the final analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariable logistic regression models for the association between prescribed Chinese herbs containing aristolochic acid and the occurrence of urinary tract cancer. Models were adjusted for age, sex, residence in a township where black foot disease was endemic (an indicator of chronic arsenic exposure from drinking water [a risk factor for urinary tract cancer]), and history of chronic urinary tract infection. Statistical tests were two-sided. Results Having been prescribed more than 60 g of Mu Tong and an estimated consumption of more than 150 mg of aristolochic acid were independently associated with an increased risk for urinary tract cancer in multivariable analyses (Mu Tong: at 61–100 g, OR = 1.6, 95% CI = 1.3 to 2.1, and at >200 g, OR = 2.1, 95% CI = 1.3 to 3.4; aristolochic acid: at 151–250 mg, OR = 1.4, 95% CI = 1.1 to 1.8, and at >500 mg, OR = 2.0, 95% CI = 1.4 to 2.9). A statistically significant linear dose–response relationship was observed between the prescribed dose of Mu Tong or the estimated cumulative dose of aristolochic acid and the risk of urinary tract cancer (P < .001 for both). Conclusions Consumption of aristolochic acid–containing Chinese herbal products is associated with an increased risk of cancer of the urinary tract in a dose-dependent manner that is independent of arsenic exposure.

Persistent Rotating Shift-Work Exposure Accelerates Development of Metabolic Syndrome among Middle-Aged Female Employees: A Five-Year Follow-Up

Limited follow-up studies are available as to whether special job-types, such as day-night rotating shift work, contribute to the progression of metabolic syndrome among female industrial employees. A retrospective cohort study on the development of metabolic syndrome was conducted by utilizing health examination records for a five-year interval. The records of 387 female employees without metabolic syndrome at baseline were used for the analysis. Data analyzed included age, metabolic syndrome components, insulin resistance status, lifestyle factors, and job-types. The initial mean age of subjects was 32.8 yrs. Abnormal rates at baseline, including metabolic syndrome components and insulin resistance, were all significantly higher among the 34 female workers with metabolic syndrome outcome. Also, the persistent rotating shift-work exposure rates and five-year change of metabolic syndrome component measurements were significantly unfavorable for subjects with metabolic syndrome outcome. After controlling for the potential confounders, significant raised risks were found in the female worker with persistent rotating shift-work exposure (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.3–9.0 vs. day workers) and in smokers (OR, 5.4; 95% CI, 1.1–25.8 vs. non-smokers). At the same time, the female workers initially with one or two metabolic syndrome components had a 4.6-fold (95% CI, 1.3–17.0) and 12.7-fold (95% CI, 3.2–50.1), respectively, increased risk of progressing to metabolic syndrome within five years. In conclusion, persistent day-night rotating shift work, smoking, and baseline metabolic syndrome components associate with the progression toward metabolic syndrome for middle-aged female workers. (Author correspondence: pchen@ntu.edu.tw, gphinx@gmail.com).

Statins and the Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection

PURPOSE Statins may have protective effects against cancer, but no studies have focused on their effects in patients with chronic hepatitis C virus (HCV) infection. The purpose of this study was to investigate the association between use of statins and risk of hepatocellular carcinoma (HCC) in HCV-infected patients. PATIENTS AND METHODS Ours was a population-based cohort study of 260,864 HCV-infected patients enrolled in the Taiwan National Health Insurance Research Database since January 1, 1999, and observed through December 31, 2010. Cox proportional hazards regression with time-dependent covariates for drug exposures was employed to evaluate the association between statin use and HCC risk. RESULTS There were 27,883 cases of HCC in the HCV cohort during a follow-up period of 2,792,016.6 person-years. Among the 35,023 patients using statins (defined as ≥ 28 cumulative defined daily doses [cDDDs]), 1,378 had HCC. Among the 225,841 patients not using statins (< 28 cDDDs), 26,505 were diagnosed with HCC. A dose-response relationship between statin use and HCC risk was observed. The adjusted hazard ratios were 0.66 (95% CI, 0.59 to 0.74), 0.47 (95% CI, 0.40 to 0.56), and 0.33 (95% CI, 0.25 to 0.42) for patients with 28 to 89, 90 to 180, and > 180 cDDDs per year, respectively, relative to nonusers. The reduction in risk also demonstrated a progressive duration-response relationship in patients with ≥ 28 cDDDs per year when compared with nonusers. CONCLUSION Among patients with HCV infection, statin use was associated with reduced risk of HCC. Further research is needed to elucidate the mechanism responsible for this effect.

Association among Serum Perfluoroalkyl Chemicals, Glucose Homeostasis and Metabolic Syndrome in Adolescents and Adults

OBJECTIVE Perfluoroalkyl chemicals (PFCs) have been used worldwide in a variety of consumer products. The effect of PFCs on glucose homeostasis is not known. RESEARCH DESIGN AND METHODS We examined 474 adolescents and 969 adults with reliable serum measures of metabolic syndrome profile from the National Health and Nutrition Examination Survey 1999–2000 and 2003–2004. RESULTS In adolescents, increased serum perfluorononanoic acid (PFNA) concentrations were associated with hyperglycemia (odds ratio [OR] 3.16 [95% CI 1.39–7.16], P < 0.05). Increased serum PFNA concentrations also have favorable associations with serum HDL cholesterol (0.67 [0.45–0.99], P < 0.05). Overall, increased serum PFNA concentrations were inversely correlated with the prevalence of the metabolic syndrome (0.37 [0.21–0.64], P < 0.005). In adults, increased serum perfluorooctanoic acid concentrations were significantly associated with increased β-cell function (β coefficient 0.07 ± 0.03, P < 0.05). Increased serum perfluorooctane sulfate (PFOS) concentrations were associated with increased blood insulin (0.14 ± 0.05, P < 0.01), homeostasis model assessment of insulin resistance (0.14 ± 0.05, P < 0.01), and β-cell function (0.15 ± 0.05, P < 0.01). Serum PFOS concentrations were also unfavorably correlated with serum HDL cholesterol (OR 1.61 [95% CI 1.15–2.26], P < 0.05). CONCLUSIONS Serum PFCs were associated with glucose homeostasis and indicators of metabolic syndrome. Further clinical and animal studies are warranted to clarify putative causal relationships.

Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial fibrillation-- a nation wide database analysis.

BACKGROUND Atrial fibrillation (AF) is a risk factor for ischemic stroke. Stroke-prevention strategies based on risk schemes have been developed but most of the data are from western people. Our goal is to investigate the risk factors of ischemic stroke in Taiwanese with AF in a nation-wide database. METHODS A universal national health insurance (NHI) program has been implemented in Taiwan since 1995. We used system sampling database from 1997 to 2008 with a total of 1,000,000 subjects. By using ambulatory and inpatient claim data, we included subjects with AF and were above 20 years old. We excluded those who had ever taken warfarin or aspirin or had valvular heart diseases. RESULT A total of 7920 patients (3633 women, 4287 men) were included in the final analyses. Cox regression analysis showed that the risk factors for ischemic stroke were age (OR=1.338 for age 65-74 years vs. age 20-64 years, P=0.014; OR=1.652 for age over 75 years vs. age 20-64 years, P<0.001), hypertension (HTN) (OR=2.656, P<0.001), diabetes mellitus (DM) (OR=1.341, P=0.005), heart failure (OR=1.611, P<0.001), previous ischemic stroke or transient ischemic accident (TIA) (OR=2.752, P<0.001) and peripheral arterial disease (PAD) (OR=1.814, P=0.006). The gender, coronary artery disease, history of myocardial infarction and chronic renal insufficiency were not associated with ischemic stroke. The rate of ischemic stroke was much lower in current cohort as compared with that in whites. Frequent used risk schemes including CHADS₂ and CHA₂DS₂-VASC had comparable but only limited ability to predict ischemic stroke in subjects with AF. CONCLUSION Compare with western people, hypertension plays a more important role in ischemic stroke in Taiwanese with AF and the incidence is lower. A substantial number of ischemic strokes cannot be accurately predicted by current risk schemes.

Perfluorinated Compounds in Umbilical Cord Blood and Adverse Birth Outcomes

Background Previous animal studies have shown that perfluorinated compounds (PFCs) have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) and birth outcomes. Methods In total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study (TBPS). Demographic data were obtained by interviewing mothers using a structured questionnaire and birth outcomes were extracted from medical records. Cord blood was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. Results The geometric mean (standard deviation) levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma were 1.84 (2.23), 5.94 (1.95), 2.36(4.74), and 10.26 (3.07) ng/mL, respectively. Only PFOS levels were found to be inversely associated with gestational age, birth weight, and head circumference [per ln unit: adjusted β (95% confidence interval, CI) = −0.37 (−0.60, −0.13) wks, −110.2 (−176.0, −44.5) gm and −0.25 (−0.46, −0.05) cm]. Additionally, the odds ratio of preterm birth, low birth weight, and small for gestational age increased with PFOS exposure [per ln unit: adjusted odds ratio (OR) (95%CI) = 2.45 (1.47, 4.08), 2.61(0.85, 8.03) and 2.27 (1.25, 4.15)]. When PFOS levels were divided into quartiles, a dose-response relation was observed. However, PFOA, PFNA, and PFUA were not observed to have any convincing impact on birth outcomes. Conclusions An adverse dose-dependent association was observed between prenatal PFOS exposure and birth outcomes. However, no associations were found for the other examined PFCs.

Does prenatal cadmium exposure affect fetal and child growth

Objectives Cadmium is known to be a significant health hazard, but most information comes from studies of adults. The effects of exposure to cadmium during fetal life on early growth and development remain uncertain. In this study we investigated the placental transport of cadmium and the effects of prenatal cadmium exposure on fetal and child growth in Taiwan. Methods The data in this study were from a birth cohort study in Taiwan which started in 2004. Pregnant women were recruited from four hospitals and interviewed after delivery to collect information on themselves and their infants. Children were followed up to obtain information on growth up to 3 years of age. Whole blood cadmium concentrations in maternal and cord blood samples were measured and the relationship with birth size and growth assessed using linear regression and mixed models. Results 321 maternal blood samples and 402 cord blood samples were eligible for analysis. Among 289 pairs with maternal and cord blood suitable for measurement, the median cadmium concentration in cord blood (0.31 μg/l) was less than that in maternal blood (1.05 μg/l), with low correlation between the two (r=0.04). An increase in cord blood cadmium was found to be associated with newborn decreased head circumference and to be significantly and consistently associated with a decrease in height, weight and head circumference up to 3 years of age. Conclusions Placental transport of cadmium is limited. However, prenatal cadmium exposure may have a detrimental effect on head circumference at birth and child growth in the first 3 years of life.

Parental Smoking During Pregnancy and Its Association with Low Birth Weight, Small for Gestational Age, and Preterm Birth Offspring: A Birth Cohort Study

BACKGROUND Intrauterine exposure to tobacco smoke has been discerned as an important risk factor for low birth weight (LBW), small for gestational age (SGA), and preterm birth infants. In this cohort study, we investigated the association of the amount of parental smoking during the different pregnancy stages with birth weight and the incidence of preterm delivery. METHODS Our study population was acquired from the Taiwan Birth Cohort Study. Between June 2005 and July 2006, 21,248 postpartum women were interviewed 6 months after their deliveries by a structured questionnaire. The parents were divided into four groups according to the amount of smoking during preconception, the first trimester, and the second and third trimesters. The relationships of parental smoking with gestational age and birth weight during the different pregnancy stages were assessed using multivariate linear regression. Multiple logistic regression analyses were performed to estimate the odds ratios and 95% confidence intervals of preterm delivery, LBW, and SGA infants during the different parental smoking status and the different pregnancy stages. RESULTS After adjusting for the physical and socioeconomic status of the parents and for paternal smoking during the same period, we found that maternal smoking decreased birth weight. Compared with the nonsmoking groups, all the maternal smoking groups had higher incidences of LBW, SGA, and preterm birth infants, especially when the mothers smoked >20 cigarettes/day. The association of paternal smoking with LBW, SGA, and preterm birth infants was insignificant. CONCLUSION Maternal smoking is responsible for increased incidences of LBW and preterm delivery of babies, and therefore, smoking cessation/reduction should be advised to pregnant women to reduce morbidities in their neonates. Further studies are needed to clarify the correlation of fetal health with passive smoking, including exposure to environmental tobacco smoke and to other smokers in the family.

The effect of prenatal perfluorinated chemicals exposures on pediatric atopy

BACKGROUND The role of perfluorinated compounds (PFCs) in the immune system and allergic diseases is not well-known. This study examined the effects of pre-natal exposure to PFCs on immunoglobulin E (IgE) levels and atopic dermatitis (AD). METHODS In Taiwan Birth Panel cohort study, newborns with cord blood and peri-natal factors (i.e. birth body weight, weeks of gestation, and type of delivery) gathered at birth were evaluated. At the age of 2 years, information on the development of AD, environmental exposures, and serum total IgE were collected. The AD and non-AD children were compared for the concentration of cord blood serum PFCs measured by Ultra-performance liquid chromatography/triple-quadrupole mass (UPLC-MS/MS). Correlations among cord blood IgE, serum total IgE at 2 years of age, and cord blood PFC levels were made. RESULTS Of 244 children who completed the follow-up and specimen collections, 43 (17.6%) developed AD. Concentrations of cord blood serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) were median (range) 1.71 (0.75-17.40), 5.50 (0.11-48.36), 2.30 (0.38-63.87), and 0.035 (0.035-0.420)ng/mL, respectively. PFOA and PFOS levels positively correlated with cord blood IgE levels (per ln-unit: β=0.134 KU/l, p=0.047 for PFOA; β=0.161 KU/l, p=0.017 for PFOS). Analyses stratified by gender revealed that PFOA and PFOS levels positively correlated with cord blood IgE levels only in boys (per ln-unit: β=0.206 KU/l, p=0.025 for PFOA; β=0.175 KU/l, p=0.053 for PFOS). When dividing cord blood serum PFCs into quartiles in the fully adjusted models, AD had no significant association with PFOS. CONCLUSIONS Pre-natal PFOA and PFOS exposures positively correlated with cord blood IgE levels.