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Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20 years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20 years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79–1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden. [ABSTRACT FROM AUTHOR]

Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009–2013) and 151,810 controls were analyzed using Taiwan's National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants. [ABSTRACT FROM AUTHOR]

Air pollution triggers a tissue-specific inflammatory response. However, studies on the association between exposure to air pollutants and chronic rhinosinusitis (CRS) risk remain limited. Thus, we conducted this nationwide study to define the association between air pollution and CRS. We used the Longitudinal Health Insurance Database (LHID) and Taiwan Air Quality-Monitoring Database (TAQMD) to conduct a population-based cohort study. Study participants were recruited from the LHID, a data subset of the National Health Insurance Research Database that randomly sampled one million individuals. TAQMD has been an air pollutant database since 1998. In univariate and multivariate Cox proportional hazards regression models, adjusted hazard ratios (aHRs) and 95% CIs of CRS in five air pollutants were accounted. We adjusted for age, sex, urbanization level, insurance fee, comorbidities, and pollutant levels in the multivariate model. The total number of participants enrolled in this study was 160,504. The average age was 40.46 ± 14.62 years; males constituted 43.8% of the total participants. The percentages of alcoholism, tobacco dependence, and COPD were 1.5%, 2.8%, and 28.3%, respectively. After adjustment for age, sex, urbanization level, insurance fee, and comorbidities, the highest levels of air pollutants, including PM2.5 (aHR = 1.14, 95% CI = 1.06–1.22), NO2 (aHR = 1.07, 95% CI = 1.00–1.15), and PM10 (aHR = 1.13, 95% CI = 1.05–1.21) had a significantly greater CRS risk; we selected the lower concentration as the reference but did not correlate with CO. We found a significantly increased risk of CRS in residents with air pollutant exposure. [ABSTRACT FROM AUTHOR]

Objective: To compare the healing results between platelet-rich plasma (PRP) and platelet-derived patches versus traditional advanced wound dressings in patients with chronic wounds. Method: Patients with and without diabetes were divided into two groups, each of which received either PRP patch treatments or the advanced wound dressings. All wounds were cleaned, debrided and assessed by physicians. The data were analysed and represented as mean ± standard deviation (SD). Student's t-test was used to calculate the significance of differences between both groups. Values of p<0.05 were considered statistically significant. Results: Patients with and without diabetes receiving PRP patch treatments saw improvement in wound healing in two weeks (p=0.0083). Patients with diabetes who received platelet-derived patch treatment and PRP injection experienced wound size reduction to <25% of the original area by the fourth week of treatment, and >90% of the subjects had wounds of <10% their original size in the last three weeks of the trial. Conversely, the wound area in the control subjects receiving traditional advanced wound dressings remained at 25–50% of their original size from the fourth week of treatment to the end of the trial. The healing process of the PRP patch experimental group was statistically significant compared with the control group (p<0.0001). Conclusion: Combining treatments of PRP injections and platelet-derived patches significantly improved the healing outcomes of patients with chronic wounds, most notably in patients with diabetes, when compared with a traditional treatment of advanced wound dressings. [ABSTRACT FROM AUTHOR]

We determined the prevalence of asymptomatic peripheral arterial disease (PAD) and cardiovascular risk factors in Taiwan. Ambulatory participants (n = 1915) without symptoms of PAD were enrolled (mean age of 61.2 years). The ankle-brachial index (ABI) was used to detect the PAD (ABI < 0.90). The overall prevalence of asymptomatic PAD was 5.4% (2.8% in the younger participants [<65 years of age, n = 1021] and 8.4% in the elderly participants [≥65 years of age, n = 894]). Younger participants with asymptomatic PAD had a significantly higher rate of hypertension (55.2% vs 30%) and obesity (31% vs 13.3%) than those without asymptomatic PAD (P < .05). Elderly participants with asymptomatic PAD had a significantly higher rate of diabetes mellitus (36% vs 21.2%) and hypertension (69.3% vs 55.4%) than those without asymptomatic PAD (P < .05). Asymptomatic PAD is prevalent among elderly Taiwanese individuals. Overall, age was the strongest risk factor for the development of asymptomatic PAD. [ABSTRACT FROM PUBLISHER]

Aim: Chronic obstructive pulmonary disease (COPD) is an independent risk factor for cardiovascular morbidity and mortality. The aim of this study was to determine the prevalence of asymptomatic peripheral arterial disease (PAD) and the associated risk factors for patients with COPD. Methods: This prospective cross-sectional study enrolled 427 COPD patients (mean age: 70.0 years) without PAD symptoms consecutively. Demographic data, lung function and cardiovascular risk factors were recorded. The ankle-brachial index (ABI) was used to detect PAD (ABI<0.90). Results: The overall prevalence of asymptomatic PAD in the COPD patients was 8% (2.5% in the younger participants (<65 years of age, n = 118) and 10% in the elderly participants (≥65 years of age, n = 309). The COPD patients with asymptomatic PAD had a significantly higher rate of hyperlipidemia (47.1% vs. 10.4%) and hypertension (79.4% vs. 45.8%) than those without asymptomatic PAD (p<0.05). There was no significant difference in lung function (forced vital capacity and forced expiratory volume in one second) between the two groups. In multivariate logistic regression, hyperlipidemia was the strongest independent factor for PAD (odds ratio (OR): 6.89, p<0.005), followed by old age (OR: 4.80), hypertension (OR: 3.39) and smoking burden (pack-years, OR: 1.02). Conclusions: The prevalence of asymptomatic PAD among COPD patients in Taiwan is lower than in Western countries. Hyperlipidemia, old age, hypertension, and smoking burden were the associated cardiovascular risk factors. However, there was no association between lung function and PAD in the COPD patients. [ABSTRACT FROM AUTHOR]

Objective Psoriasis is associated with ischemic heart disease (IHD). Results of prior studies have suggested that methotrexate (MTX) may improve vascular disease in patients with psoriasis and rheumatoid arthritis. The aim of this study was to assess the risk of new-onset IHDs in psoriasis patients, comparing those taking MTX with those taking other nonbiologic antipsoriatic drugs. Methods In this retrospective cohort study, we utilized claims data from the National Health Insurance Research Database of Taiwan to identify 179,200 subjects who had received a diagnosis of psoriasis, with or without psoriatic arthritis, on at least 3 visits. The risk of hospitalization for new-onset IHD was compared between psoriasis patients taking MTX monotherapy (n = 6,578; MTX case cohort) and psoriasis patients taking other nonbiologic antipsoriatic drugs (n = 5,471; reference control cohort) between January 1996 and December 2008. Additional adjustments were made for cardiovascular risk factors, number of hospital visits, Charlson comorbidity score, and use of other antiinflammatory drugs. Results The incidence rates of IHD were 666 cases per 100,000 person-years in the MTX case cohort and 830 cases per 100,000 person-years in the reference control cohort (unadjusted P = 0.027). Increasing age, male sex, presence of hypertension, presence of diabetes, Charlson comorbidity score, and use of phototherapies were independent risk factors for hospitalization related to a new IHD in the study cohorts. However, the multivariate-adjusted hazard ratio for IHD-related hospitalizations among patients receiving MTX, in comparison with those receiving other nonbiologic antipsoriatic drugs, was 0.97 (95% confidence interval 0.79-1.19), after adjustment for age, sex, comorbidity score, number of hospital visits, and other antiinflammatory treatments for psoriasis. Conclusion In patients with psoriasis with or without coexisting psoriatic arthritis, the adjusted risk of hospitalization for an IHD among individuals receiving MTX was comparable with that among individuals receiving other nonbiologic antipsoriatic drugs. [ABSTRACT FROM AUTHOR]

Lung cancer remains a challenge in daily practice. Chemotherapy is first considered for advanced lung adenocarcinoma bearing no active driver mutations. Maintaining drug efficacy and overcoming drug resistance are essential. This study aimed to explore the real-world use of anti-diabetic agent metformin in combination with pemetrexed-based platinum doublets in a first-line setting. We retrospectively collected data during 2004~2013 from TaiwaN′s National Health Insurance Research Database to access the survival benefit of metformin combined with pemetrexed-based platinum doublets as a first-line therapy for diabetic patients with advanced lung adenocarcinoma. Demographic data and information regarding platinum reagents, diabetes medications, and metformin doses were gathered, and overall survival status regarding metformin use was analyzed. Overall survival status based on the daily dose and the calculated cumulative defined daily dose (DDD) of metformin prescribed during the first 3 months after lung cancer was diagnosed was also assessed. A total of 495 patients were enrolled with a mean age of 67 years old, and the majority of the patients were male. After adjusting for age, sex, diabetes medication, and platinum reagents used, the adjusted hazard ratio (HR) for the metformin-user group was 0.61 (95% confidence interval (CI); 0.46~0.79; p < 0.001). The metformin-user group had a survival benefit (log-rank p < 0.001). We analyzed metformin dosing during the first 3 months after lung cancer diagnosis, and for a daily dose ≥ 1500 mg, the adjusted hazard ratio (aHR) was 0.42 (95% CI; 0.27~0.65; p < 0.001). Regarding the cumulative DDD of metformin, a DDD equal to or exceeding 21 resulted in aHR of 0.48 (95% CI; 0.34~0.69; p < 0.001). In this study, we found that the combination of metformin and pemetrexed-based platinum doublets provides a robust survival benefit as a first-line therapy for diabetic patients with advanced lung adenocarcinoma. It is worth conducting a large and randomized clinical trial to further investigate the antitumor effects of metformin on advanced lung adenocarcinoma when used as a first-ling therapy, including in non-diabetic patients. [ABSTRACT FROM AUTHOR]

Background:Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear. Methodology/Principle Findings:Auto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of invivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice. Conclusion:The activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate whether adenotonsillectomy reduces upper respiratory tract infections (URIs) in the pediatric population. Methods and subjects: We identified 415 children, aged ≤18 years who had undergone adenoidectomy and/or tonsillectomy during the period from 1999 to 2006, from the Taiwan National Health Insurance Research Database. The comparison group consisted of 1630 children without the surgery randomly selected from the same database frequency matched with sex, age and the surgery date (index date). Changes in physician visits for URIs 2-year period before and 2-year period after the index date were compared between the two groups of children. Results: The number of outpatient visits for URIs decreased with time, children with tonsillectomy and/or adenoidectomy had a greater reduction than comparison children (mean changes, −14 times and −6 times, respectively) in the 2-year period after the index date. Multivariate analyses using generalized estimated equation revealed a significant effect in reducing URIs visits from the surgery (relative ratio=0.85, p <0.0001), strongest for children undergoing both tonsillectomy and adenoidectomy (relative ratio=0.76, p <0.0001). The association between surgery and the decrease in URIs was more pronounced for children aged 12 years and less. Conclusion: This population-based study suggests that tonsillectomy and/or adenoidectomy is associated with fewer physician visits for URIs. The association is weakened in old children. [Copyright &y& Elsevier]

Summary: The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF. [Copyright &y& Elsevier]

(1) Background: Recently, a growing number of studies have provided evidence to suggest a strong correlation between air pollution exposure and attention-deficit/hyperactivity disorder (ADHD). In this study, we assessed the relationship between early-life exposure to particulate matter (PM) 10 , PM 2 . 5 , and ADHD; (2) Methods: The National Health Insurance Research Database (NHIRD) contains the medical records, drug information, inspection data, etc., of the people of Taiwan, and, thus, could serve as an important research resource. Air pollution data were based on daily data from the Environmental Protection Administration Executive Yuan, R.O.C. (Taiwan). These included particulate matter (PM 2.5 and PM 10 ). The two databases were merged according to the living area of the insured and the location of the air quality monitoring station; (3) Results: The highest levels of air pollutants, including PM 2.5 (adjusted hazard ratio (aHR) = 1.79; 95% confidence interval (CI) = 1.58-2.02) and PM 10 (aHR = 1.53; 95% CI = 1.37-1.70), had a significantly higher risk of ADHD; (4) Conclusions: As such, measures for air quality control that meet the WHO air quality guidelines should be strictly and uniformly implemented by Taiwanese government authorities.

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-β1 - and IL-10 -specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-β1 SNPs (-509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-β1 SNP (-509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-β1 SNP (-509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-β1 SNP (-509 C/T) genotype in all subjects and TGF-β1 SNP (-509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-β1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-β1 (-509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.

Mounting evidence supports the notion that inflammatory processes play a role in carcinogenesis, and interleukin-10 (IL10) is an important inflammatory cytokine. This study aimed to evaluate the contribution of IL10 A-1082G (rs1800896), T-819C (rs3021097) and A-592C (rs1800872) genotypes to the risk of childhood acute lymphoblastic leukemia (ALL) in Taiwan. Associations of these IL10 polymorphic genotypes with ALL risk were analyzed in 266 patients with childhood ALL patients and 266 non-cancer healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The results showed that CC genotype carriers at IL10 T-819C were at lower risk for childhood ALL (odds ratio=0.33, 95% confidence interval=0.16-0.68). On the contrary, AC and CC genotype carriers at IL10 A-592C were at higher risk for childhood ALL (odds ratio=1.73 and 6.34, 95% confidence interval=1.19-2.51 and 3.16-12.72, respectively). There was no difference in the distribution of A-1082G genotypes between childhood ALL and control groups. The genotypes at IL10 T-819C and A-592C may serve as predictive biomarkers for childhood ALL in Taiwan., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Most epidemiological studies of acute respiratory distress syndrome (ARDS) have been conducted in western countries, and studies in Asia are limited. The aim of our study was to evaluate the incidence, in-hospital mortality, and 1-year mortality of ARDS in Taiwan.We conducted a nationwide inpatient cohort study based on the Taiwan National Health Insurance Research Database between 1997 and 2011. A total of 40,876 ARDS patients (68% male; mean age 66 years) were identified by International Classification of Diseases, 9th edition coding and further analyzed for clinical characteristics, medical costs, and mortality.The overall crude incidence of ARDS was 15.74 per 100,000 person-years, and increased from 2.53 to 19.26 per 100,000 person-years during the study period. The age-adjusted incidence of ARDS was 15.19 per 100,000 person-years. The overall in-hospital mortality was 57.8%. In-hospital mortality decreased from 59.7% in 1997 to 47.5% in 2011 (P < 0.001). The in-hospital mortality rate was lowest (33.5%) in the youngest patients (age 18-29 years) and highest (68.2%) in the oldest patients (>80 years, P < 0.001). The overall 1-year mortality rate was 72.1%, and decreased from 75.8% to 54.7% during the study period. Patients who died during hospitalization were older (69 ± 17 versus 62 ± 19, P < 0.001) and predominantly male (69.8% versus 65.3%, P < 0.001). In addition, patients who died during hospitalization had significantly higher medical costs (6421 versus 5825 US Dollars, P < 0.001) and shorter lengths of stay (13 versus 19 days, P < 0.001) than patients who survived.We provide the first large-scale epidemiological analysis of ARDS incidence and outcomes in Asia. Although the overall incidence was lower than has been reported in a prospective US study, this may reflect underdiagnosis by International Classification of Diseases, 9th edition code and identification of only patients with more severe ARDS in this analysis. Overall, there has been a decreasing trend in in-hospital and 1-year mortality rates in recent years, likely because of the implementation of lung-protective ventilation.

Many factors have been implicated in the onset of type 2 diabetes mellitus (T2DM). Recently, immune response and inflammation were suggested to play certain roles in the development and complications of T2DM. The aim of this study is to investigate the putative correlation between the promoter polymorphisms of interleukin-4 (IL-4), one of the immune-regulatory type 2 helper T-cell cytokines, and T2DM. Genomic DNA from 425 Taiwanese T2DM patients and 148 nondiabetic control study subjects were extracted, and their IL-4 promoter polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Both of the distribution of IL-4 C-589T (P = .013) and C-34T (P = .05) genotypes were significantly different between T2DM patients and control subjects. Significant association between IL-4 C-589T alleles (P = .002) and T2DM, as well as C-34T alleles and T2DM (P =.024), was also identified. In addition, a statistically significant association between homologous IL-4 -589 C/C genotype and lower circulatory high-density lipoprotein cholesterol levels was observed. Our results suggested that IL-4 promoter polymorphisms are associated with T2DM. A significant association between IL-4 -589 C/C genotype and lower circulatory high-density lipoprotein cholesterol level was observed as well. The above results suggested that IL-4 may participate in lipid metabolism and diabetic susceptibility., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Complex subtrochanteric fractures are uncommon injuries and challenging to manage. We elucidate the role of the Long Gamma AP Locking Nail (LGAPN) in the management of such fractures in the acute stage., Methods: Between 1992 and 2002, 64 consecutive cases with nonpathologic complex subtrochanteric fractures managed with the LGAPN were enrolled in this study. Associated injuries were present in 16 cases. The average follow-up period was 68 months., Results: Mean time to union was 14 weeks. There were two complications (one wound infection and one delayed union). The time to union and functional results were not statistically different between different ages (below 50 years old, or older than 50 years) and the number of distal locking screws used (one or two). Longer time to union is noted in patients with a longer operation time and a more comminuted fracture pattern by the AO classification., Conclusion: Closed reduction and internal fixation with the LGAPN were proven to be safe and effective in the treatment of complex traumatic subtrochanteric fractures in all age groups, and one distal locking screw is sufficient for distal fixation.

Swine are reservoirs of hepatitis E virus (HEV). In this study, a 2-year survey of HEV in feces and sera of swine was conducted to determine if: 1) HEV has circulated among pigs for some time in Taiwan; 2) the spread of HEV among different-aged pigs; and 3) there exists HEV strains possibly imported through trading. From 1998-2000, 521 serum samples and 54 fecal specimens from pigs were examined by reverse transcription polymerase chain reaction. None of the 11 pigs in suckling stage (< 2 months) were serum HEV RNA positive. The highest viremia rate (4.5%) was in pigs of 2 months age, followed by 1.2% and 1.8% in pigs of growing (3-4 months) and finishing stages (5-6 months), and none in pigs older than 6 months. Viremia showed little variation in different years and areas. None of the 20 fecal samples from pigs in suckling stage were HEV RNA positive, whereas 9% of the 34 samples from pigs in growing or finishing stages were positive. Most swine HEV isolates in Taiwan clustered within the genotype 4, whereas the three HEV isolates cloned from pigs imported recently from the U.S. belonged to the genotype 3 HEV in the U.S. The results suggest that HEV may infect pigs at an early growing stage and spread unnoticed among pigs and possibly across countries through trading., (Copyright 2002 Wiley‐Liss, Inc.)