The epidemiology of pediatric psoriasis: A nationwide cohort study in Taiwan.

Psoriasis can affect individuals of all age groups. While the epidemiology of psoriasis in adults has been extensively studied, there is limited research specifically investigating pediatric cases. This study aimed to investigate the prevalence and incidence of skin psoriasis (PsO) and psoriatic arthritis (PsA) among pediatric patients in Taiwan. A nationwide cohort of 17 535 patients with psoriatic diseases under the age of 18 was enrolled from the National Health Insurance Research Database for the period 2000-2013, including 16 129 PsO patients and 2022 PsA patients. The age- and sex-standardized prevalence and incidence of pediatric PsO and PsA were calculated. The 2007 yearly reports of age- and sex-specific distribution of the general population was adopted as a standard. The results showed that between 2000 and 2013, the prevalence for pediatric PsO increased from 0.03% to 0.07%, and from 0.003% to 0.014% for pediatric PsA. During the same period, the incidence slightly decreased from 19.81 to 17.55 per 100 000 for pediatric PsO but increased from 1.02 to 5.06 per 100 000 for pediatric PsA. Adolescents (12 to <18 years) had higher prevalence and incidence rates of PsO and PsA than children (aged ≤ 12 years), with no sex difference observed in either age group. PsA preceding PsO was more common among children than adolescents (27.07% vs. 13.46%). This study provides important insights into the prevalence and incidence of psoriatic diseases in the pediatric population. Further research is needed to identify risk factors for pediatric psoriasis and to investigate its long-term health outcomes.

Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: a nationwide cohort study.

OBJECTIVES: To compare the risk of psoriatic arthritis (PsA) in psoriasis (PsO) patients treated with acitretin vs disease-modifying antirheumatic drugs (DMARDs). METHODS: This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan-Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and comorbidities. RESULTS: The study included 1,948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P=0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65-1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. CONCLUSION: Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients.

Daily aspirin associated with a reduced risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: a population-based cohort study.

Background: Emerging laboratory and animal studies suggest that aspirin may prevent non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), however clinical evidence remains lacking. Methods: Using Taiwan's National Health Insurance Research Database, we screened 145,212 NAFLD patients from 1997 through 2011. After excluding any confounding conditions, 33,484 patients who continuously received a daily dose of aspirin for 90 days or more (treated group), along with 55,543 patients who had not received antiplatelet therapy (untreated group), were respectively recruited. Inverse probability of treatment weighting using the propensity score was applied to balance the baseline characteristics. Cumulative incidence of, and hazard ratio (HR) for HCC occurrence were analyzed after adjusting competing events. The high-risk patients, who were defined as age ≥ 55 years & elevated serum alanine aminotransferase, were further analyzed. Findings: The 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (0.25% [95% CI, 0.19-0.32%] vs. 0.67% [95% CI, 0.54-0.81%]; P < 0.001). Aspirin therapy was significantly associated with a reduced HCC risk (adjusted HR [aHR] 0.48 [95% CI, 0.37-0.63]; P < 0.001). In the high-risk patients, the 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (3.59% [95% CI, 2.99-4.19%] vs. 6.54% [95% CI, 5.65-7.42%]; P < 0.001). Aspirin therapy remained associated with a reduced HCC risk (aHR 0.63 [95% CI, 0.53-0.76]; P < 0.001). Subgroup sensitivity analyses verified this significant association in nearly all subgroups. In the time-varying model amongst aspirin users, HCC risk was significantly lower through the use of aspirin for ≥ 3 years (aHR 0.64 [95% CI, 0.44-0.91]; P = 0.013), when compared with short-term use (< 1 year). Interpretation: Daily aspirin therapy is significantly associated with a reduced HCC risk in NAFLD patients. Funding: Ministry of Science and Technology, Ministry of Health and Welfare, and Taichung Veterans General Hospital, Taiwan.

Compositions of gut microbiota before and shortly after hepatitis C viral eradication by direct antiviral agents.

It is unclear whether dysbiosis in hepatitis C virus (HCV) infected patients results from the viral infection per se or develops as a result of hepatic dysfunction. We aimed to characterize compositions in gut microbiome before and shortly after HCV clearance. In this prospective cohort study, adult patients with confirmed HCV viremia were screened before receiving direct antiviral agents. Those with recent exposure to antibiotics or probiotics (within one month), prior abdominal surgery, or any malignancy were ineligible. Stool was collected before antiviral therapy started and at 12 weeks after the treatment completed. From the extracted bacterial DNA, 16 s rRNA gene was amplified and sequenced. Each patient was matched 1:2 in age and sex with uninfected controls. A total of 126 individuals were enrolled into analysis. The gut microbiome was significantly different between HCV-infected patients (n = 42), with or without cirrhosis, and their age-and sex-matched controls (n = 84) from the levels of phylum to amplicon sequence variant (all p values < 0.01 by principal coordinates analysis). All patients achieved viral eradication and exhibited no significant changes in the overall composition of gut microbiome following viral eradication (all p values > 0.5), also without significant difference in alpha diversity (all p values > 0.5). For the purpose of exploration, we also reported bacteria found differently abundant before and after HCV eradication, including Coriobacteriaceae, Peptostreptococcaceae, Staphylococcaceae, Morganellaceae, Pasteurellaceae, Succinivibrionaceae, and Moraxellaceae. Gut microbiota is altered in HCV-infected patients as compared with uninfected controls, but the overall microbial compositions do not significantly change shortly after HCV eradication.

Reduced risk of skin cancer and internal malignancies in vitiligo patients: a retrospective population-based cohort study in Taiwan.

The relationship between cancer and vitiligo has been explored but with inconsistent results. To examine the long-term cancer risk in vitiligo patients, we conducted a retrospective nationwide cohort study. From the National Health Insurance Research Database of Taiwan, a total of 13,824 vitiligo patients were identified and matched with 55,296 reference subjects without vitiligo by age, gender, and propensity score estimated by major comorbidities from 1997 to 2013. Demographic characteristics and comorbidities were compared between these two groups. Incidence rate ratios and hazard ratios (HRs) were calculated to examine cancer risks. The 16-year incidence rates of overall cancers were 621.06 (566.56-675.55) and 726.99 (697.24-756.74) per 100,000 person-years in the vitiligo and reference groups. Patients with vitiligo showed a significantly decreased risk of overall cancers [adjusted HR, 0.85; 95% confidence interval (CI), 0.77 to 0.93, p < 0.001] compared with reference subjects without vitiligo after adjusting for age, sex, comorbidities, and treatments. The risks of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were significantly reduced (adjusted HR 0.21, 95% CI 0.11-0.38, p < 0.001), as well as internal malignancies (adjusted HR 0.89, 95% CI 0.81-0.99, p = 0.026). The results were consistent across different subgroups of patients, including male gender, ages more than 40 years, and those receiving long-term systemic disease-modifying antirheumatic drugs and phototherapies. Information related to phenotype, disease duration, vitiligo lesion sites, family history of vitiligo or cancer, occupation, and personal lifestyle was not included in the database. Vitiligo is associated with reduced risks of BCC and SCC, as well as internal malignancies.

An altered fecal microbial profiling in rosacea patients compared to matched controls.

BACKGROUND/PURPOSE: Rosacea has been linked to inflammatory bowel disease and small bowel bacterial overgrowth. We aimed to investigate the fecal microbial profiling and the potential gene functions between rosacea and non-rosacea subjects. METHODS: A case-control study. Fecal microbiome and predicted genetic function inferred from high-throughput 16S ribosomal RNA sequencing were analyzed between rosacea (n = 11) and age-, gender- and body mass index-matched non-rosacea subjects (n=110). The correlation between altered microbiome as well as lifestyle and diet were also investigated. RESULTS: A significant reduction of fecal microbial richness was found in rosacea patients. A distinct fecal microbial community structure was demonstrated in rosacea patients. The discriminating enriched genera in rosacea patients included Rhabdochlamydia, CF231, Bifidobacterium, Sarcina, Ruminococcus, belonging to the phylum of Chlamydiae, Bacteroidetes, Actinobacteria, and Lentisphaerae. The discriminating reduced abundant genera included Lactobacillus, Megasphaerae, Acidaminococcus, Hemophilus, Roseburia, Clostridium, belong to the phylum of Firmicutes; and Citrobacter, belonging to the phylum of Proteobacteria. The distinct fecal microbial composition might be related to sulfur metabolism, cobalamin, and carbohydrate transport. CONCLUSION: An altered fecal microbial richness and composition were observed in rosacea patients. The distinct microbial composition might be related to sulfur metabolism, cobalamin and carbohydrate transport.

Association between inflammatory bowel disease and bullous pemphigoid: a population-based case-control study.

The coexistence of inflammatory bowel disease (IBD) and bullous pemphigoid (BP) has been reported. No large-scale study to date has explored the relationship between these diseases. This population-based case-control study examined the association between IBD and BP by using a nationwide database. A total of 5,263 BP patients and 21,052 age- and gender-, hospital visit number-matched controls were identified in the National Health Insurance Research Database of Taiwan (1997-2013). Demographic characteristics and comorbidities including IBD were compared. Logistic regression was conducted to examine the predicting factors for BP. The mean age at diagnosis was 74.88 years and 54.3% of subjects were male. BP patients tended to have more cardiovascular risk factors, autoimmune and neurologic comorbidities, and hematologic cancers than matched controls. There were 20 cases of IBD (0.38%), mostly ulcerative colitis (N = 17, 0.32%) among BP patients, compared to 33 IBD cases (0.16%) among controls (p < 0.001). Ulcerative colitis was found to be significantly associated with BP [adjusted odds ratio (OR) 3.60, 95% confidence interval (CI) 1.91-6.77, p < 0.001] on multivariate analysis. Treatment for IBD was not associated with BP development. Information about diet, lifestyle, alcohol consumption, and smoking habit was not available. We concluded that UC is independently associated with BP.

Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice.

Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.

Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B.

BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed at developing and validating a risk score to predict HCC in patients with CHB on entecavir or tenofovir treatment. METHODS: This study analysed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify patients with CHB continuously receiving entecavir or tenofovir. The development cohort included 23,851 patients from Taiwan; 596 (2.50%) of them developed HCC with a three-year cumulative incidence of 3.56% (95% CI 3.26-3.86%). The multivariable Cox proportional hazards model found that cirrhosis, age (cirrhosis and age interacted with each other), male sex, and diabetes mellitus were the risk determinants. These variables were weighted to develop the cirrhosis, age, male sex, and diabetes mellitus (CAMD) score ranging from 0 to 19 points. The score was externally validated in 19,321 patients from Hong Kong. RESULTS: The c indices for HCC in the development cohort were 0.83 (95% CI 0.81-0.84), 0.82 (95% CI 0.81-0.84), and 0.82 (95% CI 0.80-0.83) at the first, second, and third years of therapy, respectively. In the validation cohort, the c indices were 0.74 (95% CI 0.71-0.77), 0.75 (95% CI 0.73-0.78), and 0.75 (95% CI 0.72-0.77) during the first three years, and 0.76 (95% CI 0.74-0.78) and 0.76 (95% CI 0.74-0.77) in the extrapolated fourth and fifth years, respectively. The predicted and observed probabilities of HCC were calibrated in both cohorts. A score <8 and >13 points identified patients at distinctly low and high risks. CONCLUSIONS: The easily calculable CAMD score can predict HCC and may inform surveillance policy in patients with CHB during oral antiviral therapy. LAY SUMMARY: This study analyses population-wide data from the healthcare systems in Taiwan and Hong Kong to develop and validate a risk score that predicts hepatocellular carcinoma during oral antiviral therapy in patients with chronic hepatitis B. The easily calculable CAMD score requires only simple information (i.e. cirrhosis, age, male sex, and diabetes mellitus) at the baseline of treatment initiation. With a scoring range from 0 to 19 points, the CAMD score discriminates the risk of hepatocellular carcinoma with a concordance rate of around 75-80% during the first three years on therapy. The risk prediction can be extrapolated to five years on treatment with similar accuracy. Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.

Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir.

This study aimed to elucidate the temporal change and determinants for the risk of HCC in patients with chronic hepatitis B continuously receiving NUC. Through analysis of the national healthcare database in Taiwan, we screened a total of 65 426 infected patients receiving entecavir or tenofovir for at least 3 months and excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end-stage renal failure or a diagnosis of HCC within 3 months of starting treatment. Eligible patients (N = 27 820) were followed until HCC occurrence, completion of the allowed 3-year regimen or 31 December 2013. During a median follow-up of 25.1 (12.1-35.6) months, 802 patients developed HCC, with 1-, 2- and 3-year cumulative incidence of 1.82% (95% CI, 1.66-1.99%), 3.05% (95% CI, 2.82-3.28%) and 4.06% (95% CI, 3.77-4.36%), respectively. HCC annual incidence decreased with an adjusted IRR of 0.73 (95% CI, 0.66-0.80) per yearly interval and was associated with cirrhosis (IRR, 10.07; 95% CI, 6.00-16.90 in age <40 years; 4.69; 95% CI, 3.94-5.59 in age ≧40 years), age (IRR, 3.38; 95% CI, 2.10-5.47 for 40-50 years; 6.92; 95% CI, 4.27-11.21 for 50-60 years; 12.50; 95% CI, 7.71-20.25 for ≧60 years; <40 years as reference), male sex (IRR, 1.71; 95% CI, 1.44-2.04), HCV coinfection (IRR, 1.27; 95% CI, 1.02-1.58) and diabetes (IRR, 1.24; 95% CI, 1.05-1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B receiving entecavir or tenofovir declines over time and is determined by cirrhosis, age, male sex, HCV coinfection and diabetes.

Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort study.

BACKGROUND AND AIMS: The role of prior gastroscopy on the outcome of patients with gastric cancer remains unknown. This study determines the association between intervals of prior gastroscopy and mortality in patients with gastric cancer. METHODS: We identified 20,066 newly diagnosed patients with gastric cancer in the National Health Insurance Database of Taiwan between 2002 and 2007. After we excluded patients who had gastroscopies performed ≤6 months before the diagnosis of cancer, patients were matched into 3 cohorts according to the intervals of prior gastroscopy: 6 months to 2 years (<2 Y cohort), 2 to 5 years (2-5 Y cohort), and none within the previous 5 years (>5 Y cohort). The 3 cohorts were matched for age, curative treatment for gastric cancer, Helicobacter pylori therapy, and propensity scores comprised of sex, comorbidities, and concomitant medication usage. The primary outcome is the hazard ratio (HR) of all-cause mortality. RESULTS: After matching, we identified 1286, 1286, and 5144 patients for the <2 Y, 2 to 5 Y, and >5 Y cohorts. Compared with the >5 Y cohort, the HR of all-cause mortality for the <2 Y and 2 to 5 Y cohorts was 0.80 (95% confidence interval [CI], 0.72-0.89; P < .001) and 0.83 (95% CI, 0.76-0.91; P < .001), respectively. The HRs of gastric cancer-specific mortality were significantly lower in the <2 Y (0.80; 95% CI, 0.71-0.91; P < .001) and 2 to 5 Y cohorts (0.83; 95% CI, 0.75-0.93; P < .001). CONCLUSIONS: Patients with gastric cancer who had a gastroscopy performed within 5 years before the cancer diagnosis had significantly lower mortality. Our results may support the role of repeat endoscopic examination or surveillance endoscopy in selected patients.

Simvastatin-induced cell cycle arrest through inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21 accumulation in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and is one of the leading causes of cancer-related death worldwide. Simvastatin, an HMG-CoA reductase inhibitor, which decreases cholesterol synthesis by inhibiting mevalonate pathways and is widely used to treat cardiovascular diseases. Simvastatin exhibits anticancer effects against several malignancies. However, the molecular mechanisms underlying the anticancer effects of simvastatin on HCC are still not well understood. In this study, we demonstrated simvastatin-induced G0/G1 arrest by inducing p21 and p27 accumulation in HepG2 and Hep3B cells. Simvastatin also promoted AMP-activated protein kinase (AMPK) activation, which induced p21 upregulation by increasing its transcription. Consistent with this finding, we found genetic silencing of AMPK reduced p21 expression; however, AMPK silencing had no effect on p27 expression in HCC cells. Simvastatin decreased Skp2 expression at the transcriptional level, which resulted in p27 accumulation by preventing proteasomal degradation, an effect mediated by signal transducer and activator of transcription 3 (STAT3) inhibition. Constitutive STAT3 activation maintained high-level Skp2 expression and lower level p27 expression and significantly prevented G0/G1 arrest in simvastatin-treated HCC cells. Mevalonate decreased simvastatin-induced AMPK activation and rescued phospho-STAT3 and Skp2 expression in HCC cells, which resulted in the prevention of G0/G1 arrest through inhibition of p21 and p27 accumulation. Moreover, simvastatin significantly decreased tumor growth in HepG2 xenograft mice. Consistently, we found that simvastatin also increased p21 and p27 expression in tumor sections by reducing Skp2 expression and inducing AMPK activation and STAT3 suppression in the same tumor tissues. Taken together, these findings are demonstrative of the existence of a novel pathway in which simvastatin induces G0/G1 arrest by upregulating p21 and p27 by activating AMPK and inhibiting the STAT3-Skp2 axis, respectively. The results identify novel targets that explain the beneficial anticancer effects of simvastatin treatment on HCC in vitro and in vivo.

Gastric microbiota and predicted gene functions are altered after subtotal gastrectomy in patients with gastric cancer.

Subtotal gastrectomy (i.e., partial removal of the stomach), a surgical treatment for early-stage distal gastric cancer, is usually accompanied by highly selective vagotomy and Billroth II reconstruction, leading to dramatic changes in the gastric environment. Based on accumulating evidence of a strong link between human gut microbiota and host health, a 2-year follow-up study was conducted to characterize the effects of subtotal gastrectomy. Gastric microbiota and predicted gene functions inferred from 16S rRNA gene sequencing were analyzed before and after surgery. The results demonstrated that gastric microbiota is significantly more diverse after surgery. Ralstonia and Helicobacter were the top two genera of discriminant abundance in the cancerous stomach before surgery, while Streptococcus and Prevotella were the two most abundant genera after tumor excision. Furthermore, N-nitrosation genes were prevalent before surgery, whereas bile salt hydrolase, NO and N2O reductase were prevalent afterward. To our knowledge, this is the first report to document changes in gastric microbiota before and after surgical treatment of stomach cancer.

The Incidence of Gastric Adenocarcinoma Among Patients With Gastric Intestinal Metaplasia: A Long-term Cohort Study.

BACKGROUND AND AIMS: Gastric intestinal metaplasia (IM) has been known as a premalignant condition, but estimates of its cancer risk vary widely. We aimed to analyze cancer risk of gastric IM by a long-term cohort study. METHODS: We conducted a hospital-based study that included all patients with gastric IM between 1992 and 2010, and the development of gastric adenocarcinoma was evaluated until July 2011. Patients developing gastric cancer ≤180 days after the index diagnosis of IM were excluded. The incidence rate, the cumulative incidence, and the standardized incidence ratio (SIR) of gastric cancer were determined, and hazard ratios (HRs) of risk factors were calculated. RESULTS: We identified 7059 patients with a median follow-up duration of 5.1 years, and 81 patients developed gastric adenocarcinoma during the study period. The 5-, 10-, and 15-year cumulative incidences of gastric cancer were 0.9% [95% confidence interval (CI), 0.6-1.1), 2.0% (95% CI, 1.5-2.6), and 3.0% (95% CI, 2.0-4.0), respectively. On multivariate analysis, older age (eg, 75 y and above; HR=7.4; 95% CI, 2.8-19.6), low-grade dysplasia (HR=4.0; 95% CI, 2.1-7.9), and high-grade dysplasia (HR=18.8; 95% CI, 9.0-39.5) were independent risk factors. As compared with the risk in the general population, the SIR of gastric cancer among patients with gastric IM was 2.5 (95% CI, 2.0-3.1). However, the SIR was only 2.0 (95% CI, 1.5-2.6) in the nondysplasia subgroup, but was up to 35.2 (95% CI, 15.2-69.4) in the high-grade dysplasia subgroup. CONCLUSIONS: Gastric IM is an important risk factor for gastric cancer, but surveillance should be arranged only for those at an especially high risk.

Association between ultrasonography screening and mortality in patients with hepatocellular carcinoma: a nationwide cohort study.

OBJECTIVE: Current guidelines recommend screening for hepatocellular carcinoma (HCC) in high-risk populations. However, the effectiveness of screening in reducing mortality has been challenged. In addition, it is unclear which subgroups benefit most from HCC screening. DESIGN: This nationwide cohort study identified a total of 52,823 newly diagnosed HCC patients between 1 January 2002 and 31 December 2007. These HCC patients were classified into the following cohorts according to the time intervals in which they received ultrasonography screening: 0-6 months (6M), 7-12 months (12M), 13-24 months (24M), 25-36 months (36M) and not screened within 3 years (never screened). The chance to receive curative therapy and 5-year cumulative mortalities were calculated after adjusting for lead-time bias. RESULTS: Chances to receive curative therapy among the 6M, 12M, 24M, 36M and never screened cohorts were 24.3% (95% CI 23.7% to -24.9%), 26.9% (95% CI 25.7% to 28.2%), 22.9% (95% CI 21.8% to 24.1%), 21.3% (95% CI 19.9% to 22.8%) and 18.3% (95% CI 17.8% to 18.8%), respectively. Compared with the 6M cohort, adjusted HRs of mortality for the 12M, 24M, 36M and never screened cohorts were 1.11 (95% CI 1.07 to 1.15), 1.23 (95% CI 1.19 to 1.28), 1.31 (95% CI 1.26 to 1.37) and 1.47 (95% CI 1.43 to 1.51) (all p<0.001), respectively. On multivariable subgroup analyses, the associations between shorter screening intervals and better survival were observed in nearly all subgroups, especially in younger patients, patients without diabetes and patients with hepatitis B infection. CONCLUSIONS: Shorter ultrasonography screening intervals are associated with reduced overall mortality in HCC patients in a dose-dependent manner.

Evaluation of the Effect of Cumulative Operator Experience on Hepatocellular Carcinoma Recurrence after Primary Treatment with Radiofrequency Ablation.

PURPOSE: To investigate the association between cumulative operator volume and the risk of hepatocellular carcinoma (HCC) recurrence after potentially curative radiofrequency ablation (RFA). MATERIALS AND METHODS: This study was approved by the Research Ethics Committee. By using the Taiwan National Health Insurance Research Database, 52 096 patients with HCC were identified between July 1, 2004, and December 31, 2011. In total, 2827 patients were selected who underwent potentially curative RFA for newly diagnosed HCC. These patients were grouped into quintiles according to the cumulative operator volumes. Patients in the lowest or the highest quintiles were 1:1 matched according to their propensity scores. Finally, two separate groups, each containing 406 patients, were recruited in the high- and low-volume groups (cumulative operator volume of ≥79 cases and ≤10 cases, respectively). Cumulative incidences of and hazard ratios for HCC recurrence were analyzed after adjusting for competing mortality. RESULTS: The HCC recurrence rate of the high-volume group was significantly lower than that of the low-volume group (high-volume group 5-year recurrence rate of 65.8%, 95% confidence interval [CI]: 59.5%, 72.1%; low-volume group 5-year recurrence rate of 71.4%, 95% CI: 66.2%, 76.5%; P < .05). In modified Cox regression analysis, the highest cumulative operator volume was independently associated with a decreased risk of HCC recurrence (hazard ratio, 0.80; 95% CI: 0.67, 0.97; P < .05). Multivariable stratified analyses verified the association between the highest cumulative operator volume and decreased HCC recurrence in almost all subgroups. CONCLUSION: The risk of HCC recurrence could be significantly decreased by experienced RFA operators. Further studies based on cumulative operator volume may be helpful in improving the quality of RFA for HCC.

Nonsteroidal anti-inflammatory drugs are associated with reduced risk of early hepatocellular carcinoma recurrence after curative liver resection: a nationwide cohort study.

PURPOSE: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in reducing the risk of various de novo cancers has been reported; however, its role in reducing hepatocellular carcinoma (HCC) recurrence after liver resection still remains unknown. METHODS: We have conducted a nationwide cohort study by recruiting all patients with a newly diagnosed HCC who had received curative liver resection as their initial treatment. The use of NSAIDs and the risk of early HCC recurrence have been examined by multivariate and stratified analyses. To avoid immortal time bias, the use of NSAIDs has been treated as a time-dependent variable in Cox proportional hazard ratio models. RESULTS: Between January 1997 and December 2010, a total of 15,574 HCC patients who had received liver resection were enrolled in this study. The 1-, 3-, and 5-year overall survival rates were 90.4%, 73.2%, and 59.8%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 80.5%, 59.4%, and 50.2%, respectively. NSAID use (hazard ratio, 0.81; 95% confidence interval, 0.73-0.90) and minor liver resection (hazard ratio, 0.83; 95% confidence interval, 0.78-0.89) were independently associated with a reduced risk of early HCC recurrence after liver resection. In the stratified analyses, NSAID usage was universally associated with reduced risks in most subgroups, particularly for those aged younger than 65 years, male, with underlying diabetes mellitus and receiving major liver resection. CONCLUSIONS: The use of NSAIDs can be associated with a reduced risk of early HCC recurrence within 2 years after curative liver resection, regardless of patients' age, extent of liver resection, viral hepatitis status, underlying diabetes, and liver cirrhosis.