Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan.

BACKGROUND & AIMS: Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy. METHODS: Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases. RESULTS: Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications. CONCLUSIONS: Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR. IMPACT AND IMPLICATIONS: The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.

Steamed daylily flower (Hemerocallis fulva L.) protected cardiac and hepatic cells against ethanol induced apoptotic and oxidative damage.

Our previous study examined the phytochemical composition and bio-activities of raw daylily flower (Hemerocallis fulva L.). However, this plant food is usually served via heat process such as cooking in a soup. This study aimed to investigate the phytochemical profile and biofunctions of steamed daylily flower (SDF). The content of total phenolic acids, total flavonoids, total carotenoids, total anthocyanins and total triterpenoids in SDF aqueous extract was assessed. Normal cardiac and hepatic cells, H9c2 and L-02 cells, were used to evaluate the protective effects of SDF against ethanol. SDF concentrations of 0.25%, 0.5%, and 1% were applied to treat H9c2 or L-02 cells for 48 h at 37 °C initially, followed by exposure to ethanol at 150 mM for 24 h at 37 °C. Results showed that the content of assessed phytochemicals was in the range of 1019-2045 mg/100 g dry weight. Flavonoids and triterpenoids were two major detected phytochemicals in SDF. SDF treatments at 0.5% and 1% increased the viability of H9c2 cells, but at three concentrations enhanced the survival of L-02 cells. SDF at 0.5% and 1% up-regulated Bcl-2 messenger RNA (mRNA) expression and down-regulated Bax mRNA expression. Ethanol increased reactive oxygen species production, decreased glutathione content, as well as lowered glutathione peroxidase and catalase activities. SDF treatments reversed these changes. SDF at 0.5% and 1% reduced the activity of cytochrome P450 2E1 and nicotinamide adenine dinucleotide phosphate oxidase, limited p47phox mRNA expression, as well as enhanced factor E2-related factor 2 and heme oxygenase-1 mRNA expression. SDF at three concentrations decreased gp91phox mRNA expression. In conclusion, these novel findings indicated that SDF aqueous extract was rich in phytochemicals and provided anti-apoptotic and anti-oxidative actions to protect cardiac and hepatic cells against ethanol. Thus, SDF might be considered as a functional food with multiple bio-activities.

Elevated Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio after First Cycle of Chemotherapy and Better Survival in Esophageal Cancer Patients Receiving Concurrent Chemoradiotherapy.

Background: Prognostic factors for poor survival have been proposed in esophageal squamous cell carcinoma (SCC) patients receiving concurrent chemoradiotherapy (CCRT). We conducted a retrospective study on hematological profile after first cycle of chemotherapy for esophageal SCC patients receiving CCRT. Methods: From January 2008 to December 2017, a total of 420 patients with esophageal SCC were enrolled. All included patients had undergone CCRT. Complete blood count, differential count, NLR, and PLR before chemotherapy (CHT) and after first cycle of CHT were obtained. Univariate and multivariate Cox regression analyses were used to assess the association between survival and patient, disease, and treatment characteristics. Results: On univariate analysis, significant factors for overall survival (OS) and disease specific survival (DSS) included ECOG performance status, clinical staging, operation, cisplatin dose, prechemotherapy NLR and PLR, and elevated postchemotherapy NLR. On multivariate analysis, ECOG performance status 0-I, Clinical staging I-II, Operation, cisplatin dose >150 mg/m2, prechemotherapy PLR <375, and postchemotherapy platelet count ≥150 × 109/L were independent factors for predicting better OS. Independent factors for predicting better DSS included ECOG performance status 0-I, Clinical staging I-II, Operation, cisplatin dose >150 mg/m2, and prechemotherapy PLR <375. Conclusions: Our study showed that low levels of prechemotherapy PLR and NLR were associated with better OS and DSS. Elevated platelet count and NLR after first cycle of CHT were associated with better OS. Elevated PLR and NLR after first cycle of CHT were associated with better DSS.

Risk stratification of hepatocellular carcinoma incidence using a fibrosis-4-based prediction model in patients with chronic hepatitis C receiving antiviral therapy: a nationwide real-world Taiwanese cohort study.

A total of 1,589 patients who had received interferon-based treatment were enrolled and analyzed for the risk of hepatocellular carcinoma (HCC) in a real-world nationwide Taiwanese chronic hepatitis C cohort (T-COACH). We aimed to stratify HCC risk by non-invasive fibrosis index-based risk model. Of 1589 patients, 1363 (85.8%) patients achieved sustained virological response (SVR). Patients with SVR had 1, 3, 5 and 10-year cumulative HCC incidence rates of 0.55%, 1.87%, 3.48% and 8.35%, respectively. A Cox proportional hazards model revealed that non-SVR (adjusted hazard ratio [aHR]: 1.92, 95% confidence interval [CI]: 1.19-3.12, p = 0.008), diabetes mellitus (aHR: 2.11, 95% CI: 1.25-3.55, p = 0.005), and fibrosis (FIB)-4 at the end of follow-up (EOF; aHR: 5.60, 95% CI: 2.97-10.57, p < 0.0001) were independent predictors of HCC. Risk score models based on the three predictors were developed to predict HCC according to aHR. In model 1, the 10-year cumulative incidence rates of HCC were 43.35% in patients at high risk (score 9-10), 25.48% in those at intermediate risk (score 6-8), and 4.06% in those at low risk (score 3-5) of HCC. In model 2, the 10-year cumulative incidence rates of HCC were 39.64% in patients at high risk (at least two risk predictors), 19.12% in those at intermediate risk (with one risk predictor), and 2.52% in those at low risk (without any risk predictors) of HCC. The FIB-4-based prediction model at EOF could help stratify the risk of HCC in patients with chronic hepatitis C after antiviral treatment.

Postoperative Lifestyle of Patients with Liver Cancer: An Exploratory Study in a Single Center in Taiwan.

Various treatments are available for patients with liver cancer; however, complications after treatment affect their quality of life (QOL). To improve the QOL of patients with liver cancer, this study investigated the postoperative lifestyle of sixty patients at the Liouying District Hospital, Taiwan. A self-reported structured questionnaire and a modified Chinese version of the Health Enhancement Lifestyle Profile (HELP-C) were used to collect the demographic data and to assess patients' overall postoperative lifestyle, respectively. Significant differences were observed between the overall postoperative lifestyle and the demographic variables of age, ethnicity, education level, marital status, chronic diseases, and postoperative complications (p < 0.05). Significant differences (p < 0.05) were observed in the HELP-C domains of diet, leisure, and activities of daily living (ADL) between the sexes. The scores for diet (9.66 ± 4.21) and leisure (4.33 ± 2.03) in women were significantly lower (p < 0.05) than those in men (13.13 ± 4.98 and 6.17 ± 2.37, respectively), indicating that women with liver cancer should be more concerned about diet and leisure after surgery. However, the score for ADL was significantly higher (p < 0.05) in women (17.90 ± 5.15) than in men (13.48 ± 2.56), indicating that men should focus on improving ADL. This research provides reference clinical data on the postoperative lifestyle of patients with liver cancer to improve their QOL.

Self-Confidence, Not Self-Awareness, Is Negatively Associated With Areca Nut Dependence.

Areca nut is the fourth most commonly used addictive substance globally. Therefore, this study aimed to examine correlations among areca nut self-awareness, areca nut cessation self-confidence, and areca nut dependence in the Taiwanese population. This was a descriptive study in which 120 areca nut chewers who sought medical attention at a regional hospital and were residents of the Yunlin-Chiayi area, were recruited as study subjects. A structured questionnaire was used for data collection, which included demographic data, an areca nut self-awareness scale, an areca nut cessation self-confidence scale, and an areca nut dependence scale. A Pearson correlation analysis revealed that areca nut self-awareness and areca nut cessation self-confidence were not significantly correlated (r = 0.16, p = 0.069). Areca nut self-awareness and areca nut dependence also did not have a significant correlation (r = -0.06, p = 0.511). However, we found that areca nut cessation self-confidence and areca nut dependence were significantly negatively correlated (r = -0.37, p < 0.001), that is, the higher the areca nut cessation self-confidence, the lower the areca nut dependence. In addition, areca nut self-awareness showed significant correlations by age (r = 4.54, p = 0.005), occupation (r = 2.91, p = 0.02), and family support (r = 3.83, p = 0.03). Scheffe's post-hoc test revealed significant differences that subjects whose family members were extremely supportive of areca nut cessation had higher areca nut self-awareness. In conclusion, areca nut cessation self-confidence and areca nut dependence showed a significant negative correlation. Areca nut self-awareness revealed significant correlations by age, occupation, and family support. The results of this study can be used to provide a reference for implementing areca nut cessation policies in the future.

WITHDRAWN: Anti-apoptotic and Anti-oxidative Effects of Aqueous Ex-tract Prepared from Steamed Daylily Flower on Normal Cardiac and Hepatic Cells against Ethanol

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Long-term outcome of liver complications in patients with chronic HBV/HCV co-infection after antiviral therapy: a real-world nationwide study on Taiwanese Chronic Hepatitis C Cohort (T-COACH).

BACKGROUND AND AIM: The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. METHODS: A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44 years. RESULTS: Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65 year-old, BMI ≥ 27 kg/m2, FIB-4 ≥ 3.25, eGFR < 60 ml/min/1.73 m2, and non-HCV SVR, but not HBV co-infection. CONCLUSION: Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups.

Oridonin Attenuates the Effects of Chronic Alcohol Consumption Inducing Oxidative, Glycative and Inflammatory Injury in the Mouse Liver.

BACKGROUND/AIM: Oridonin (Ori) is a diterpenoid naturally present in medicinal plants with a potential as an antioxidant agent. This study aimed to evaluate the hepatic anti-oxidative, anti-glycative and anti-inflammatory properties of Ori at 0.125 and 0.25% against chronic ethanol intake in mice. MATERIALS AND METHODS: Mice were divided into five groups: i) normal diet group, ii) Ori group, iii) ethanol diet (Lieber-DeCarli liquid diet with ethanol) group, iv) ethanol diet plus 0.125% Ori and v) ethanol diet plus 0.25% Ori. After 8 weeks of Ori supplementation, blood and liver tissue were used for analyses. RESULTS: Ethanol increased the production of reactive oxygen species and nitric oxide, decreased glutathione content, and lowered the activity of glutathione peroxide, glutathione reductase and catalase. Ethanol suppressed the hepatic mRNA expression of nuclear factor E2-related factor 2. Ori supplements reversed these changes. Ethanol increased hepatic Ne-(carboxyethymethyl)-lysine (CML) and pentosidine levels, and enhanced aldose reductase (AR) activity and mRNA expression. Ori supplements at only 0.25% decreased CML and pentosidine levels, and lowered the AR activity as well as its mRNA expression. Ethanol increased the hepatic release of tumor necrosis factor-alpha, transforming growth factor-beta1, interleukin (IL)-1beta and IL-6. Histological data showed that ethanol induced necrosis and inflammatory cell infiltration, while Ori supplements alleviated these inflammatory responses. Ethanol up-regulated the hepatic mRNA expression of nuclear factor kappa B, myeloperoxidase and p38. Ori supplements reversed these changes. CONCLUSIONS: These novel findings suggest that Ori could be used as a potent agent against alcohol-induced hepatotoxicity.

Hepatitis C virus eradication decreases the risks of liver cirrhosis and cirrhosis-related complications (Taiwanese chronic hepatitis C cohort).

BACKGROUND AND AIM: It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new-onset liver cirrhosis (LC) in patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS: Taiwanese chronic hepatitis C cohort (T-COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new-onset LC and liver-related complications (DLD or HCC). RESULTS: Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow-up duration was 4.38 ± 2.79 years, with overall 46 798 person-years. The 10-year cumulative incidence rates of new-onset LC were 5.0% (95% confidence interval [CI]: 3.2-7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4-32.4) in those without SVR (hazard ratio [HR]: 0.22, P < 0.001). The 10-year cumulative incidence rates of liver-related complications were 21.4% (95% CI: 11.1-37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1-86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0.001). CONCLUSIONS: Hepatitis C virus eradication with PR therapy decreased the incidence of new-onset LC in noncirrhotic patients and the incidence of liver-related complications in cirrhotic patients with CHC.

Elimination of Hepatitis C Virus in a Dialysis Population: A Collaborative Care Model in Taiwan.

RATIONALE & OBJECTIVE: Hemodialysis facilities are high-risk environments for the spread of hepatitis C virus (HCV). Eliminating HCV from all dialysis facilities in a community may be achieved more effectively under a collaborative care model. STUDY DESIGN: Quality improvement study of multidisciplinary collaborative care teams including nephrologists, gastroenterologists, and public health practitioners. SETTING & PARTICIPANTS: All dialysis patients in Changhua County, Taiwan were treated using an interdisciplinary collaborative care model implemented within a broader Changhua-Integrated Program to Stop HCV Infection (CHIPS-C). QUALITY IMPROVEMENT ACTIVITIES: Provision of an HCV care cascade to fill 3 gaps, including screening and testing, diagnosis, and universal direct-acting antiviral (DAA) treatment implemented by collaborating teams of dialysis practitioners and gastroenterologists working under auspices of Changhua Public Health Bureau. OUTCOME: Outcome measures included quality indicators pertaining to 6 steps in HCV care ranging from HCV screening to treatment completion to cure. ANALYTICAL APPROACH: A descriptive analysis. RESULTS: A total of 3,657 patients from 31 dialysis facilities were enrolled. All patients completed HCV screening. The DAA treatment initiation rate and completion rate were 88.9% and 94.0%, respectively. The collaborative care model achieved a cure rate of 166 (96.0%) of 173 patients. No virologic failure occurred. The cumulative treatment ratios for patients with chronic HCV infection increased from 5.3% before interferon-based therapy (2017) to 25.6% after restricted provision of DAA (2017-2018), and then to 89.1% after universal access to DAA (2019). LIMITATIONS: Unclear impact of this collaborative care program on incident dialysis patients entering dialysis facilities each year and on patients with earlier stages of chronic kidney disease. CONCLUSIONS: A collaborative care model in Taiwan increased the rates of diagnosis and treatment for HCV in dialysis facilities to levels near those established by the World Health Organization.

Long-term risk of end-stage renal diseases with maintenance dialysis among chronic hepatitis C patients after antiviral therapy in Taiwan.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is associated with impaired renal function. The aim of this study is to explore the risk of and factors associated with end-stage renal diseases (ESRD) under maintenance dialysis among HCV patients after anti-HCV therapy. METHODS: A total of 12 696 HCV-infected patients with interferon-based therapy, including 9679 (76.2%) achieving sustained virological response (SVR), were enrolled from 23 hospitals in Taiwan. RESULTS: During a mean follow-up period of 5.3 years (67 554 person-years), the annual incidence of 4.1/10 000 person-years, 4.0/10 000 and 4.7/10 000 person-years among SVR patients and non-SVR patients, respectively. History of diabetes and baseline estimated glomerular filtration rate < 60 mL/min/m2 , instead of SVR, were the significant risk factors for developing ESRD with maintenance dialysis after anti-HCV therapy (adjusted hazard ratio 7.75 and 9.78). CONCLUSION: Diabetes and baseline impaired renal function were strongly associated with progression to ESRD with maintenance dialysis among chronic HCV-infected patients after antiviral therapy.

Successful Antiviral Therapy Reduces Risk of Schizophrenia Among Chronic Hepatitis C Patients: A Nationwide Real-World Taiwanese Cohort (T-COACH).

BACKGROUND: Chronic hepatitis C (CHC) has been associated with major psychoses, and interferon (IFN)-based therapy may cause psychiatric sequelae. We aimed to evaluate the effects of sustained virological response (SVR) on the incidence of major psychoses in a nationwide Taiwanese CHC cohort. METHODS: Fifteen thousand eight hundred thirty-six CHC Taiwanese who received IFN-based therapy were enrolled between 2003 and 2015. Of those, 12 723 patients were linked to the National Health Insurance Research Databases for the incidence of major psychoses. Death before major psychoses was considered a competing risk. RESULTS: Twenty-four patients developed new-onset major psychoses during 67 554 person-years (3.6 per 10 000 person-years), including 16 affective psychoses, 7 schizophrenia, and 1 organic psychotic condition. The incidence of major psychoses and affective psychoses did not differ between the SVR and non-SVR groups. The 10-year cumulative incidence of schizophrenia were significantly higher in the non-SVR than in SVR patients (0.14% vs 0.04%, P = .036). Cox subdistribution hazards showed that SVR and older age were associated with a significantly lower risk of schizophrenia (hazard ratio = 0.18 and 0.17). Sustained virological response was associated with decreased incidence of schizophrenia and majorly observed among patients with age <45 (P = .02). CONCLUSIONS: Successful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.

Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

Extrahepatic Malignancy Among Patients With Chronic Hepatitis C After Antiviral Therapy: A Real-World Nationwide Study on Taiwanese Chronic Hepatitis C Cohort (T-COACH).

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is associated with nonhepatocellular carcinoma malignancies. We aimed to evaluate whether achieving a sustained virological response (SVR, defined as HCV RNA seronegativity throughout posttreatment 24-week follow-up) could reduce the risk of non-hepatocellular carcinoma malignancy in a real-world nationwide Taiwanese Chronic Hepatitis C Cohort (T-COACH). METHODS: A total of 10,714 patients with chronic hepatitis C who had received interferon-based therapy (8,186 SVR and 2,528 non-SVR) enrolled in T-COACH and were linked to the National Cancer Registry database for the development of 12 extrahepatic malignancies, including those with potential associations with HCV and with the top-ranking incidence in Taiwan, over a median follow-up period was 3.79 years (range, 0-16.44 years). RESULTS: During the 44,354 person-years of follow-up, 324 (3.02%) patients developed extrahepatic malignancies, without a difference between patients with and without SVR (annual incidence: 0.69% vs 0.87%, respectively). Compared with patients with SVR, patients without SVR had a significantly higher risk of gastric cancer (0.10% vs 0.03% per person-year, P = 0.004) and non-Hodgkin lymphoma (NHL) (0.08% vs 0.03% per person-year, respectively, P = 0.03). When considering death as a competing risk, non-SVR was independently associated with gastric cancer (hazard ratio [HR]/95% confidence intervals [CIs]: 3.29/1.37-7.93, P = 0.008). When patients were stratified by age, the effect of SVR in reducing gastric cancer (HR/CI: 0.30/0.11-0.83) and NHL (HR/CI: 0.28/0.09-0.85) was noted only in patients aged <65 years but not those aged >65 years. DISCUSSION: HCV eradication reduced the risk of gastric cancer and NHL, in particular among younger patients, indicating that patients with chronic hepatitis C should be treated as early as possible.

Combination of carnosine and asiatic acid provided greater anti-inflammatory protection for HUVE cells and diabetic mice than individual treatments of carnosine or asiatic acid alone.

The purpose of present HUVE cells and mice study was to investigate the combined effects of carnosine and asiatic acid (AA) against diabetic progression. In HUVE cells, high glucose decreased cell viability, reduced Bcl-2 mRNA expression and increased Bax mRNA expression. The co-treatment of 0.5 µM carnosine plus 0.5 µM AA led to greater cell viability and Bcl-2 mRNA expression than 1 µM carnosine or 1 µM AA treatment alone. This combination more significantly decreased the production of DNA fragmentation, tumor necrosis factor (TNF)-alpha, reactive oxygen species (ROS), and nuclear factor kappa B binding activity than carnosine or AA treatment alone. In diabetic mice, the combination of 0.25% carnosine plus 0.25% AA in diet resulted in higher final body weight, and lower levels of plasma glucose and triglyceride than 0.5% carnosine or 0.5% AA treatment alone. Carnosine and AA combination caused more reduction in renal levels of leukin-6, TNF-alpha and ROS than carnosine or AA treatment alone. This combination also more significantly limited renal cyclooxygenase-2 activity and p-p38 phosphorylation than carnosine or AA treatment alone. These novel findings support that this combination is a more powerful remedy for diabetic control.

Hepatitis B reactivation in patients receiving targeted therapies.

OBJECTIVES: Hepatitis B virus (HBV) reactivation may occur spontaneously, during or after antiviral therapy, or when receiving immunosuppressive chemotherapy. HBV reactivation has also been reported in cancer patients receiving targeted therapies, such as monoclonal antibody and mammalian target of rapamycin (mTOR) inhibitor. This review article is aimed to discuss the issue regarding chronic HBV reactivation in patients receiving targeted therapies, with a special focus on tyrosine kinase inhibitors. METHODS: Using MEDLINE search, the literature relevant to hepatitis B reactivation, monoclonal antibody therapy and tyrosine kinase inhibitor was reviewed. RESULTS: HBV-infected patients receiving tyrosine kinase inhibitors (TKIs) may develop HBV reactivation even with resolved HBV infection status. Although the exact mechanism of TKI-induced HBV reactivation remains unclear, off-target immunological effects of TKI may play an important role in contributing to HBV reactivation. DISCUSSION: Further well-designed studies are necessary to find out the incidence and mechanism of HBV reactivation in patients receiving TKIs. Screening, monitoring and prophylaxis or pre-emptive antiviral therapy is mandatory in HBV patients who are going to receive immunosuppressive therapy or targeted therapy. CONCLUSION: HBV reactivation may occur in patients receiving monoclonal antibodies and TKIs, even with resolved HBV infection status. Although the exact mechanism of TKI-induced HBV reactivation remains unclear, off-target immunological effects of TKI may play an important role in contributing to HBV reactivation.

The Relationship between the Methylated Septin-9 DNA Blood Test and Stool Occult Blood Test for Diagnosing Colorectal Cancer in Taiwanese People.

BACKGROUND: Colorectal cancer (CRC) is a common and lethal disease in the world. There is an increasing number of cases in Taiwan and a higher rate at advanced stages. The immune fecal occult blood test (iFOBT) has been used as a screening method in Taiwan for years. A new novel diagnostic tool, the Methylated Septin-9 (MS-9) DNA blood test, had been reported to have high sensitivity and specificity for CRC detection. There are no available data in Taiwan, so we conducted this prospective randomized trial to investigate the relationship among the MS-9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people. METHODS: From July 1, 2012 to December 31, 2013, we prospectively selected 60 plasma samples from patients who were diagnosed with CRC and otherwise, the healthy group by colonoscopy in our hospital. Patients were divided into the CRC group and healthy group. CRC stages 0, I, II and stages III and IV were separately analyzed. We calculated the sensitivity and specificity of each group to determine the relationship among the MS-9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people. RESULTS: The results of the MS-9 DNA blood test for the 60 samples were divided into three groups, and the sensitivity as well as the specificity of the MS-9 DNA blood test to detect CRC were 47% and 89%, respectively. The results of iFOBT were also divided into three groups, and had higher sensitivity (84%) but lower specificity (55%) using iFOBT to detect CRC. Higher rates could be predicted to detect CRC if both the tests were positive. CONCLUSIONS: A combined MS-9 DNA blood test and iFOBT may help in a higher detection rate of CRC. It could be offered to individuals who are unwilling or unable to undergo colonoscopy. Further large prospective, randomized studies are needed in the future.