The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased among the general population and chronic hepatitis B (CHB) patients worldwide. Although fatty liver disease is a well-known risk factor for adverse liver outcomes like cirrhosis and hepatocellular carcinoma, its interactions with the hepatitis B virus (HBV) and clinical impacts seem complex. The presence of hepatic steatosis may suppress HBV viral activity, potentially leading to attenuated liver injury. In contrast, the associated co-morbidities like diabetes mellitus or obesity may increase the risk of developing adverse liver outcomes. These findings implicate that components of MAFLD may have diverse effects on the clinical manifestations of CHB. To this end, a clinical strategy is proposed for managing patients with concurrent CHB and MAFLD. This review article discusses the updated evidence regarding disease prevalence, interactions between steatosis and HBV, clinical impacts, and management strategies, aiming at optimizing holistic health care in the CHB population.

OBJECTIVE: The objective was to identify risk factors that were associated with the progression from endometriosis to ovarian cancer based on medical insurance data. METHODS: The study was performed on a dataset obtained from the National Health Insurance Research Database, which covered all the inpatient claim data from 2000 to 2013 in Taiwan. The International Classification of Diseases (ICD) code 617 was used to screen the dataset for the patients who were admitted to hospital due to endometriosis. They were then tracked for subsequent diagnosis of ovarian cancer, and available biological, socioeconomic and clinical information was also collected. Univariate and multivariate analyses were then performed based on the Cox regression model to identify risk factors. C-index was calculated and cross validated. RESULTS: A total of 229,617 patients who were admitted to hospital due to endometriosis from 2000 to 2013 were included in the study, out of whom 1,473 developed ovarian cancer by the end of 2013. A variety of factors, including age, residence, hospital stratification, premium range, and various comorbidities had significant impact on the progression (p < 0.05). Among them, age, urbanization of residence, hospital stratification, premium range, post-endometriosis childbearing, pelvic inflammation, and depression all had independent, significant impact (p < 0.05). The validated C-index was 0.69. CONCLUSION: For a woman diagnosed with endometriosis, increased age, residing in a highly urbanized area, low or high income, depression, pelvic inflammation, and absence of childbearing post-endometriosis all put her at high-risk to develop ovarian cancer. The findings may be of help to gynecologists to identify high-risk patients.
Cohort Studies* ; Comorbidity ; Dataset ; Depression ; Diagnosis ; Endometriosis* ; Female ; Humans ; Inflammation ; Inpatients ; Insurance* ; International Classification of Diseases ; Multivariate Analysis ; National Health Programs ; Ovarian Neoplasms* ; Risk Factors* ; Taiwan ; Urbanization

Background/Aims: Fatty liver disease is defined as a cluster of diseases with heterogeneous etiologies, and its definition continues to evolve. The novel conceptional criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) were proposed in 2020 to avoid the exclusion of a certain subpopulation, but their evaluations have been limited. We aimed to examine and compare the clinical as well as histologic features of MAFLD versus nonalcoholic fatty liver disease (NAFLD) in patients with biopsy-proven hepatic steatosis. Methods: From January 2009 to December 2019, 175 patients with histology-proven hepatic steatosis and 10 with cryptogenic cirrhosis who were treated at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. Patients were classified into different groups according to the diagnostic criteria of MAFLD and NAFLD. The clinical and histologic features were then analyzed and compared. Results: In total, 76 patients (41.1%) were diagnosed with both MAFLD and NAFLD, 81 patients (43.8%) were diagnosed with MAFLD alone, nine patients (4.9%) were diagnosed with NAFLD alone, and 19 patients (10.3%) were diagnosed with neither. Those with MAFLD alone exhibited a higher degree of disease severity regarding histology and laboratory data than those with NAFLD alone. Advanced fibrosis was associated with the presences of hepatitis B virus infection and metabolic diseases. Conclusions The novel diagnostic criteria for MAFLD include an additional 38.9% of patients with hepatic steatosis and can better help identify those with a high degree of disease severity for early intervention than can the previous NAFLD criteria.

Background/Aims: Fatty liver disease is defined as a cluster of diseases with heterogeneous etiologies, and its definition continues to evolve. The novel conceptional criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) were proposed in 2020 to avoid the exclusion of a certain subpopulation, but their evaluations have been limited. We aimed to examine and compare the clinical as well as histologic features of MAFLD versus nonalcoholic fatty liver disease (NAFLD) in patients with biopsy-proven hepatic steatosis. Methods: From January 2009 to December 2019, 175 patients with histology-proven hepatic steatosis and 10 with cryptogenic cirrhosis who were treated at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. Patients were classified into different groups according to the diagnostic criteria of MAFLD and NAFLD. The clinical and histologic features were then analyzed and compared. Results: In total, 76 patients (41.1%) were diagnosed with both MAFLD and NAFLD, 81 patients (43.8%) were diagnosed with MAFLD alone, nine patients (4.9%) were diagnosed with NAFLD alone, and 19 patients (10.3%) were diagnosed with neither. Those with MAFLD alone exhibited a higher degree of disease severity regarding histology and laboratory data than those with NAFLD alone. Advanced fibrosis was associated with the presences of hepatitis B virus infection and metabolic diseases. Conclusions The novel diagnostic criteria for MAFLD include an additional 38.9% of patients with hepatic steatosis and can better help identify those with a high degree of disease severity for early intervention than can the previous NAFLD criteria.

OBJECTIVE: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. METHODS: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. RESULTS: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p < 0.001), recurrent urinary tract infections (p = 0.013), and leg lymphedema (p = 0.038). Age over 50-year (HR = 9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR = 7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR = 5.13; 95% CI, 1.38–19.1) and DSS (HR = 5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p = 0.046), but no impact on survival. CONCLUSION: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.
Cohort Studies* ; Endometrial Neoplasms* ; European Union ; Female ; Gynecology ; Humans ; Hysterectomy ; Leg ; Lymphedema ; Neoplasm Grading ; Obstetrics ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies* ; Urinary Tract Infections ; Uterine Neoplasms

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 µM and 17.8 µM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.
Acetylcysteine ; Antineoplastic Agents ; Apoptosis Regulatory Proteins ; Apoptosis* ; Arthritis, Rheumatoid ; Cell Line ; Elaeagnaceae ; Fibroblasts ; Humans ; Lung ; Membrane Potential, Mitochondrial ; Mouth Neoplasms* ; Plants, Medicinal ; Reactive Oxygen Species

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

OBJECTIVE: The study investigated to compare health care utilization and expenditures between diabetic patients with and without depression in Taiwan. METHODS: Health care utilization and expenditure among diabetic patients with and without depression disorder during 2000 and 2004 were examined using Taiwan's population-based National Health Insurance claims database. Health care utilization included outpatient visits and the use of inpatient services, and health expenditures were outpatient, inpatient, and total medical expenditures. Moreover, general estimation equation models were used for analyzing the factors associated with outpatient visits and expenditures. Multiple logistic regression analysis was applied for identifying the factors associated with hospitalization. RESULTS: The average annual outpatient visits and annual total medical expenditures in the study period were 44.23–52.20; NT$87,496–133,077 and 30.75–32.92; NT$64,411–80,955 for diabetic patients with and without depression. After adjustment for covariates, our results revealed that gender and complication were associated with out-patient visits. Moreover, the time factor was associated with the total medical expenditure, and residential urbanization and complication factors were associated with hospitalization. CONCLUSION: Health care utilization and expenditures for diabetic patients with depression were significantly higher than those without depression. Sex, complications, time, and urbanization are the factors associated with health care utilization and expenditures.
Cohort Studies* ; Delivery of Health Care* ; Depression* ; Health Expenditures* ; Hospitalization ; Humans ; Inpatients ; Logistic Models ; National Health Programs ; Outpatients ; Patient Acceptance of Health Care* ; Taiwan ; Time Factors ; Urbanization

Objective: The relationship of antipsychotics and the risk of refracture in treated patients is unclear. The aim of this study is to evaluate the association between prolonged antipsychotic and the incidences of bone fractures and refractures in schizophrenia. Methods: This is a retrospective nested case-control study using Taiwan National Health Insurance Research Database recorded from 2000 to 2005, with cases followed up to end of 2011. Total of 7,842 schizophrenic patients, 3,955 had developed bone fractures were compared with 3,887 control subjects matched in age, sex, and index date.Antipsychotic drug exposure was classified based on the drug type and medication duration. Conditional logistic regression analyses were performed. Odds ratio (OR) and confidence interval (CI) were calculated. Results: We found (after adjustments) higher risks of developing fractures under continued use of typical (OR = 1.70; 95% CI, 1.51−1.91) or atypical antipsychotics (OR = 1.43; 95% CI, 1.28−1.60) were found. Additionally, continued use typical (OR = 1.84; 95% CI, 1.35−2.50) or atypical antipsychotics (OR = 1.44; 95% CI, 1.06−1.95) was positively associated with refracture risks. Moreover, refractures were associated with continuous use of chlorpromazine (one typical antipsychotics, OR = 2.45; 95% CI, 1.14−5.25), and risperidone (OR = 1.48; 95% CI, 1.01−2.16) or zotepine (OR = 2.15; 95% CI, 1.06−4.36) (two atypical antipsychotics). Conclusion Higher risks of bone fracture and refracture were found in schizophrenia under prolonged medication with typical or atypical antipsychotics. We therefore recommend that clinicians should pay more attention on bone density monitoring for patients using long-term antipsychotics.