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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. 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. 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

Introduction We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. Methods Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). Results Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. Discussion Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.

To figure out the impact of national health insurance program and treatment modalities on the clinical outcomes of patients with retinoblastoma. Retrospective cohort study. Enrolled patients were classified into three groups according to the time period in which their initial diagnosis was performed: patients diagnosed before 1995 (group 1), patients diagnosed in the time period 1995–2010 (group 2), patients diagnosed after 2010 (group 3). Comparison was made of clinical features including presenting signs, tumor spreading, and treatment modes. Survival and globe salvage rates were analyzed within each group. There were 157 patients (202 eyes) enrolled from 1978 to 2015. The overall mortality rate was 24.2%. The overall 5-year survival rate was 63.4%, 73.8%, 89.1% in the three time periods respectively (P = 0.007). The 5-year survival improved continuously in both unilateral and bilateral disease (P = 0.057; P = 0.015). Patients without extraocular spreading or diagnosed before 2 years of age had a better 5- year survival of 97.4% and 81.1% respectively. The globe salvage rate improved from 8.2%, 14.5%, to 35.1% (P

Background/aims Direct‐acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)‐infected patients. The real‐world treatment outcome in Taiwanese patients on a nationwide basis is elusive. Methods The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end‐of‐treatment). Results A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype‐1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment‐naïve noncirrhotic, treatment‐naïve cirrhotic, treatment‐experienced noncirrhotic and treatment‐experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment‐experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment‐naïve noncirrhotic patients (94.8%) and treatment‐experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence

Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6–96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8–99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan.

Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. Methods Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg–IFN–α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). Results SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg–IFN–α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. Conclusion Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg–IFN–α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8–14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. Methods Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 μg (group 1), q2w 450 μg (group 2) or q1w PEG-IFN alfa-2a 180 μg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). Results The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA Conclusion In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B. Graphic abstract

Purpose:Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. Sleep problems are common in HCC patients and may be attributable to disturbances in the circadian rhythm. Research into the role of circadian rhythms in sleep quality among HCC patients is lacking, however. This study investigated the relationship between the diurnal cortisol profile and sleep quality among HCC patients. We aimed to identify alterations in the diurnal cortisol profile in patients with HCC compared to healthy controls and investigate whether they were associated with poor sleep quality among HCC patients.Methods:Participants comprised 75 HCC patients and 33 healthy individuals. The Taiwanese version of the Pittsburgh Sleep Quality Index (PSQI-T) was administered to assess sleep quality. Saliva samples were collected on 3 consecutive days at five time points daily to measure diurnal cortisol levels.Results:In the HCC group, 89.3% of individuals were poor sleepers (PSQI-T > 5), whereas among healthy individuals, 30.3% were poor sleepers. While the healthy participants’ diurnal cortisol profile followed a typical pattern that peaked 30 min after waking and declined gradually throughout the day, the cortisol level in the HCC patients rebounded at bedtime. Higher cortisol levels were marginally correlated with poor sleep quality ( OR = 1.00007, p < .05).Conclusions:Our study suggests a potential association between disturbed circadian rhythm and poor sleep quality in HCC patients. Further investigation of the causal relationship between sleep and circadian rhythm is warranted.

Oxidative stress is the major cause of atherosclerosis and cardiovascular diseases. This cross-sectional study is aimed at determining if parallel serum markers of oxidative stress are related to carotid intima-media thickness (IMT). We enrolled 134 participants with varied metabolic syndrome (Met-S) scores (zero, n=21; one, n=19; two, n=27; three, n=26; four, n=25; five, n=16). Biochemical profiles and potential oxidative stress biomarkers malondialdehyde (MDA) and uric acid were measured in fasting plasma. We found that carotid IMT positively correlated with both MDA and uric acid levels. Multivariate analysis revealed that both MDA (p<0.05) and uric acid (p<0.01) levels were significantly associated with carotid IMT in participants whose Met-S scores were ≥1 or ≥2. However, only uric acid (p<0.01) levels were positively associated with carotid IMT in patients with metabolic syndrome. Linear regression model analysis revealed that the prediction accuracies for carotid IMT from MDA combined with uric acid and from a combination of MDA, uric acid, and Met-S score were 0.176 and 0.237, respectively. These were better than the predication accuracies from MDA (r2=0.075) and uric acid (r2=0.148) individually. These results suggest that measuring uric acid levels along with MDA biomarkers and Met-S scores may be a promising step in the development of an effective model for monitoring the severity of carotid IMT and atherosclerosis in the patients with metabolic syndrome.

Background Tenofovir alafenamide (TAF) has good viral suppression efficacy and less adverse effect than tenofovir disoproxil fumarate (TDF). Real-world studies on the antiviral efficacy and safety of switching from TDF to TAF in patients with chronic hepatitis B (CHB) are limited. Methods This retrospective study included 167 nucleos(t)ide analogue (NA)-naive patients with CHB. All the patients received TDF at least 12 months before switching and TAF at least 12 months after switching at a single medical center. The Friedman test with Dunn–Bonferroni post hoc tests and repeated-measures analysis of variance was used to analyze the effect of complete viral suppression, alanine aminotransferase (ALT) level normalization, renal function changes, body weight, and body mass index in the periods before and after switching. Results The mean age and TDF treatment duration were 52 ± 11 years and 2.8 years (interquartile range, 1.51–5.15 years), respectively. The complete viral suppression rate was similar between the time of switching and 48 weeks after switching to TAF (77.8% vs 76%, P = 1.000). The percentage of alanine aminotransferase (ALT) normalization increased from 26.3% at TDF start to 81.4% (P < 0.001) at time of switching and 89.2% at 48 weeks after switching to TAF (P = 0.428). The median estimated glomerular filtration rate decreased from 100.09 mL/min/1.73 m² at TDF start to 91.97 mL/min/1.73 m² (P < 0.001) at the time of switching and stabilized at 48 weeks after switching to TAF (93.47 mL/min/1.73m², P = 1.000). The body weight decreased from 69.2 ± 12.2 kg at TDF start to 67.4 ± 12.1 kg (P < 0.001) at the time of switching to TAF and returned to 68.7 ± 12.7 kg (P < 0.001) 48 weeks thereafter. The body mass index (BMI) decreased from 25 ± 3.3 kg/m² at TDF start to 24.5 ± 3.3 kg/m² (P = 0.002) at the time of switching to TAF and returned to 25.1 ± 3.6 kg/m² (P < 0.001) 48 weeks thereafter. Conclusions Our study showed that switching to TAF from TDF had good antiviral effectiveness and stabilized renal function. The body weight and BMI decreased during TDF therapy and regained after switching to TAF.

Background/AimsThe study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan.MethodsThe Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3,144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). ResultsThe overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). ConclusionsThe results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

To evaluate the duration of topical brimonidine therapy before the onset of brimonidine-related allergic conjunctivitis and the clinical characteristics associated with the development of brimonidine allergy. We retrospectively enrolled patients who presented brimonidine allergy from December 1, 2008 to November 30, 2020. The duration of brimonidine treatment, concomitant medications, benzalkonium chloride (BAK) exposure, change in IOP, and season of onset were evaluated. 292 patients were included, among which 147 were female and 145 were male. The mean age was 58.3 ± 13.6 years old. The mean (median) duration of brimonidine therapy was 266.6 (196) days, with a peak at 60–120 days. The duration was similar whether the patients received brimonidine monotreatment or in combination with other glaucoma drugs, with or without BAK. The IOP increased by 5.6% after brimonidine allergy (P

Purpose. To evaluate Humphrey visual field (VF) progression rate before and after cataract surgery in patients with open-angle glaucoma (OAG) and angle-closure glaucoma (ACG). Methods. After reviewing all records in our Humphrey VF database from July 1, 2001, to December 31, 2018, eyes of OAG and ACG that had received uncomplicated phacoemulsification with intraocular lens implantation during the period and had been followed up regularly for more than one year with ≥3 reliable VF tests before and after cataract surgery, respectively, were enrolled. The VF progression rate, visual acuity, and intraocular pressure (IOP) before and after cataract surgery were compared. Results. Seventy-seven eyes (OAG: 51; ACG: 26) from 60 patients were enrolled. The mean preoperative and postoperative follow-up durations were 4.89 ± 2.70 and 5.48 ± 2.30 years in the OAG group and 5.14 ± 3.31 and 5.97 ± 2.35 years in the ACG group. IOP and visual acuity significantly improved postoperatively in both groups. In the OAG group, there was no significant change in the VF progression rate (pre-op: −0.39 ± 0.94 dB/year; post-op: −0.47 ± 0.72 dB/year) ( P = 0.619 ), whereas, in the ACG group, the rate significantly flattened after surgery from −1.39 ± 1.31 dB/year to −0.34 ± 0.64 dB/year ( P = 0.003 ). Conclusions. The VF progression rate did not differ between preoperative and postoperative eyes with OAG, but those with ACG exhibited rapid VF decline preoperatively, which was significantly flattened postoperatively.

PURPOSE To evaluate the 2-year efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) in Taiwanese patients with glaucoma. METHODS We included the patients who received standardized MP-TSCPC with follow-up examinations on a regular basis for 24 months. Treatment success was defined as the attainment of a postoperative intraocular pressure (IOP) between 6 and 21 mmHg or a ≥ 20% reduction in IOP from baseline without an increase in glaucoma medications. RESULTS A total of 60 eyes from 56 patients who underwent MP-TSCPC for refractory glaucoma were included. The median age at MP-TSCPC intervention was 58.9 ± 12.4 years. The percentage of treatment success was 88.3% at 3 months, 83.3% at 6 months, 78.3% at 12 months, and 75.0% at 24 months. The mean baseline IOP prior to MP-TSCPC was 34 ± 11.9 mmHg (range 14-56 mmHg). The mean postoperative IOP decreased to 20.9 ± 10.0 mmHg, 18.0 ± 7.8 mmHg, 17.5 ± 6.4 mmHg, and 18.2 ± 7.1 mmHg after 3 months, 6 months, 12 months, and 24 months, respectively, in successful cases. The mean number of glaucoma medications at baseline was 3.8 ± 0.2, and the mean numbers of glaucoma medications at postoperative months 3, 6, 12, and 24 were 2.6 ± 0.7, 2.8 ± 0.6, 2.5 ± 1.4 and 2.6 ± 1.4, respectively, in successful cases. Younger age and prior CW-TSCPC significantly contributed to surgical failure in the multivariate model. Complications after MP-TSCPC included mild anterior chamber inflammation, conjunctival hemorrhage, hypotony, and mydriasis, and all subsided after treatment. None of the eyes developed vitreous hemorrhage, cystoid macular edema, or phthisis bulbi in the late postoperative period. CONCLUSIONS This study demonstrated that younger age and prior CW-TSCPC were risk factors for MP-TSCPC failure within 2 years. MP-TSCPC might be safe and effective for refractory glaucoma patients with maximal antiglaucoma medications.

The incidence rates of type 2 diabetes mellitus (T2DM) and colorectal polyps have been increasing over the last decades. However, direct associations between T2DM and colorectal polyps have not been extensively reported. We will explore the relationship between T2DM and colorectal polyps. In the retrospective study, we classified DM and NonDM groups (control) from 993,516 people in Taiwan nationwide population insurance database from the period of 2000 to 2013. We collected data on income and comorbidities through the international classification of diseases, ninth revision—clinical modification (ICD-9-CM) codes. The T2DM group had a higher incidence rate of colorectal polyps (31.97%, 95% confidence interval [CI] = 30.97–33.28) than the control group (25.9%, 95% CI = 25.1–26.72), and the crude incidence ratio was 1.235 (95% CI = 1.174–1.300). In 13 years of follow-up (2000–2013), T2DM was linked to a significantly higher cumulative probability of colorectal polyps (log-rank test: P = .0001). Patients with T2DM had a 1.23-fold higher risk of new colorectal polyps than control patients in 13 years of follow-up. We explain the T2DM increases incidence for colorectal polyps in long term follow-up.

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

Background & Aims Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. Methods The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non–sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). Results The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P 90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (–1.98 mL/min/1.73 m2; 95% confidence interval, –2.24 to –1.72; P Conclusions Both sofosbuvir and non–sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

Background/Purpose: While direct-acting antiviral regimens have been approved for chronic hepatitis C (CHC) patients in Taiwan, reimbursement is limited to certain populations. Thus, pegylated interferon plus ribavirin (PEG-IFN/RBV) remains the standard of care for many patients. The aim of this study was to investigate the percentage of CHC patients who were recommended and willing to receive PEG-IFN/RBV, and to identify reasons why patients were not recommended or unwilling to receive treatment. Methods: 822 Taiwanese CHC patients were enrolled from May–August 2016 in this cross-sectional study. PEG-IFN/RBV recommendation and patient willingness to receive treatment were evaluated through surveys. Patient characteristics associated with treatment recommendation and willingness were assessed. Results: 311 (37.8%) patients were recommended PEG-IFN/RBV while 102 (12.4%) were willing to follow treatment recommendation. Rates of recommendation and willingness were lower in treatment-experienced, hepatitis C virus genotype 1 (GT1) and cirrhotic patients, and those treated in Northern Taiwan. Multivariate analyses found factors such as prior treatment experience, GT1, cirrhosis and low hemoglobin levels to be associated with lower recommendation rates while advanced age, GT1 and low baseline viral loads were associated with lower willingness rates. Physicians' top reasons for not recommending PEG-IFN/RBV included the wish to wait for better treatment options (60.3%), prior treatment failure (21.3%) and patients’ advanced age (20.9%). Patients were unwilling to receive treatment mainly due to concerns about side effects (91.4%), the wish to wait for better treatment options (71.3%) and inconvenience (25.4%). Conclusion: A minority of Taiwanese CHC patients were recommended PEG-IFN/RBV, of which few were willing to receive treatment. Keywords: Hepatitis C, Pegylated interferon, Ribavirin, Direct acting antiviral, Taiwan

Background While direct-acting antivirals have been approved for treating hepatitis C, the guidelines highlight the importance of considering potential drug-drug interactions between DAAs and concomitant medications. Aim To assess comorbidity prevalence, concomitant medication use and potential drug-drug interactions between DAAs and concomitant medications for hepatitis C patients in Taiwan. Methods This cross-sectional study enrolled 822 patients from May to August 2016 in Taiwan. Patient demographics, comorbidities and concomitant medications were evaluated by physician surveys. Results A total of 709 (86.3%) patients had ≥1 comorbidity; the most prevalent comorbidity categories were diseases of the digestive system (40.1%), circulatory system (38.7%) and endocrine/nutritional/metabolic diseases (35.2%). Elderly patients had more comorbidities. A total of 622 (75.7%) patients received ≥1 concomitant medication; the average number of concomitant medications was 3.2. The most common concomitant medication classes were cardiovascular (34.4%), gastrointestinal (25.7%) and central nervous system drugs (22.7%). Among patients without cirrhosis or with compensated cirrhosis, contraindications were most prevalent with paritaprevir/ritonavir/ombitasvir plus dasabuvir, daclatasvir/asunaprevir and glecaprevir/pibrentasvir (13.3%, 6.0% and 5.4% respectively), and least prevalent with sofosbuvir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir and sofosbuvir/velpatasvir (0.8%, 1.3%, 1.4% and 2.1% respectively). Sofosbuvir-based regimens had no contraindications in patients with decompensated cirrhosis. Conclusion Our population represented an elderly demographic, with a high prevalence of comorbidities and widespread use of concomitant medications. The potential drug-drug interactions between these concomitant medications and DAA regimens differed, with the fewest potential interactions with sofosbuvir-based regimens.

Background and Aim Ropeginterferon alfa‐2b (P1101) is a novel long‐acting mono‐PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N‐terminus, allowing every‐two‐week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia vera in 2019 and 2020, respectively. This phase 2 study aimed to evaluate the pharmacokinetics, safety, and preliminary efficacy of ropeginterferon alfa‐2b as compared with PEG‐IFN‐α2a in patients with chronic hepatitis C virus genotype 1 infection. Methods One hundred six treatment naive patients were enrolled in this phase 2 study and randomized to four treatment groups: subcutaneous weekly PEG‐IFN‐α2a 180 μg (group 1), weekly ropeginterferon alfa‐2b 180 μg (group 2), weekly ropeginterferon alfa‐2b 270 μg (group 3), or biweekly ropeginterferon alfa‐2b 450 μg (group 4) plus ribavirin for 48 weeks. Results After multiple weekly administration, serum exposure (AUC0‐τ) in ropeginterferon alfa‐2b 180 μg was approximately 41% greater and the accumulation ratio of 2‐fold greater than PEG‐IFN‐α2a 180 μg. The incidences of flu‐like symptoms were 66.7% (18/27), 53.3% (16/30), 55.0% (11/20), and 48.3% (14/29), anxiety were 14.8% (4/27), 6.7% (2/30), 0%, and 0%, and depression were 25.9% (7/27), 13.3% (4/30), 0%, and 3.4% (1/29), for groups 1–4, respectively. Two grade 2 of 3 depression were noted in PEG‐IFN‐α2a arm, but none in ropeginterferon arms. The SVR24 rates were 77.8% (21/27), 66.7% (20/30), 80% (16/20), and 69% (20/29), respectively. Conclusions Ropeginterferon alfa‐2b showed longer effective half‐life and superior safety profile than PEG‐IFN‐α2a. Biweekly injection of ropeginterferon alfa‐2b will be studied in larger viral hepatitis patient population., Ropeginterferon alfa‐2b (P1101) is a novel mono‐PEGylated recombinant proline‐interferon alfa‐2b with a 40 kDa branched polyethylene glycol (PEG) chain conjugated predominantly at its N‐terminus. Ropeginterferon alfa‐2b showed longer effective half‐life and superior safety profile than pegylated interferon alfa‐2a. Ropeginterferon alfa‐2b will be developed to fill the gap of the need for chronic hepatitis B treatment and is exceptionally needed for chronic hepatitis D.

In recent years, ultrasound attenuation imaging (ATI) has emerged as a new method to detect liver steatosis. However, thus far, no studies have confirmed the clinical utility of this technology. Using a retrospective database analysis of 28 patients with chronic liver disease who underwent ultrasound liver biopsy and ATI, we compared the presence and degree of steatosis measured by ATI with the results obtained through liver biopsy. The area under the receiver operating characteristic curve (AUROC) of the ATI for differentiating between normal and hepatic steatosis was 0.97 (95% confidence interval: 0.83–1.00). The AUROC of the ATI was 0.99 (95% confidence interval: 0.86–1.00) in grade ≥2 liver steatosis and 0.97 (95% confidence interval: 0.82–1.00) in grade 3. ATI showed good consistency and accuracy for the steatosis grading of liver biopsy. Therefore, ATI represents a novel diagnostic measurement to support the diagnosis of liver steatosis in non-invasive clinical practice.

Precis In patients with normal-tension glaucoma, topical dorzolamide might enhance the vessel density (VD), topical carteolol decreased the VD in the inferior-temporal peripapillary retina, whereas topical brimonidine did not change the VD. Purpose Topical anti-glaucoma medications may improve ocular perfusion pressure or micro-circulation in the optic nerve head. The study evaluated the responses of the retinal vessel density (VD) to topical carteolol, brimonidine, and dorzolamide in normal-tension glaucoma (NTG) using optical coherence tomography angiography (OCTA). Patents and methods This is a retrospective non-randomized, comparative study. The study included 131 individuals (77 men, 54 women) diagnosed with NTG, without systemic medication usage, who visited the glaucoma clinic of Chang Gung Memorial Hospital, Taiwan between January 2019 and May 2020. If both eyes were diagnosed with NTG, only the right eye was included. Of these, there were 80 carteolol-treated eyes, 27 brimonidine-treated eyes, and 24 dorzolamide-treated eyes. We studied the response of OCTA parameters and retinal nerve fiber layer (RNFL) thickness to drugs, six months after treatment. Results In dorzolamide-treated eyes, increases in the peripapillary superficial retinal VD, especially in the superior-nasal area, were significant; however, no RNFL thickness changes were observed. In contrast, the superficial retinal VD decreased at the inferior-temporal peripapillary area, and RNFL thickness decreased in the inferior-nasal paripapillary area of the carteolol-treated eyes. Finally, in brimonidine-treated eyes, changes in either VD parameters or RNFL thickness were not significant. Conclusions Topical dorzolamide possibly enhanced the VD of the peripapillary retina in NTG eyes. On the contrary, topical carteolol possibly decreased VD in the inferior-temporal peripapillary retina. Finally, in cases treated with topical brimonidine, the peripapillary microcirculation remained unchanged. The study shows preliminary results, future large-scaled studies are warranted to confirm the findings.

Background/Aims In a recent study, attenuation imaging (ATI) with ultrasound was used as a new approach for detecting liver steatosis. However, although there are many studies on ATI and controlled attenuation parameter (CAP) that prove their practicability, there are few studies comparing these two methods. As such, this study compared CAP and ATI for the detection and evaluation of liver steatosis. Methods A prospective analysis of 28 chronic liver disease patients who underwent liver biopsy, FibroScan® imaging, and ATI with ultrasound was conducted. The presence and degree of steatosis, as measured with the FibroScan® device and ATI, were compared with the pathological results obtained using liver biopsy. Results The areas under the receiver operating characteristic curve (AUROC) of ATI and CAP for differentiating between normal and hepatic steatosis were 0.97 (95% confidence interval [CI] 0.83–1.00) and 0.96 (95% CI 0.81–0.99), respectively. ATI has a higher AUROC than CAP does in liver steatosis, at 0.99 (95% CI, 0.86–1.00) versus 0.91 (95% CI, 0.74–0.98) in grade ≥ 2 and 0.97 (95% CI, 0.82–1.00) versus 0.88 (95% CI, 0.70–0.97) in grade = 3, respectively. Conclusion The ATI and CAP results showed good consistency and accuracy for the steatosis grading when compared with the liver biopsy results. Moreover, ATI is even better than CAP in patients with moderate or severe steatosis. Therefore, ATI represents a non-invasive and novel diagnostic tool with which to support the diagnosis of liver steatosis in clinical practice.

ObjectiveData regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5.Design191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR12) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed.ResultsThe SVR12 rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR12 rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR12 rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR12 were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations.ConclusionSOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.

OBJECTIVES Successful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. In this study, we attempted to compare 2-dimensional (2D) shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) with transient elastography (TE) and the controlled attenuation parameter (CAP) in patients under direct-acting antiviral (DAA) therapy. METHODS Patients with chronic hepatitis C infection undergoing DAA therapy from January 2017 to June 2020 were retrospectively examined. The results of 2D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy. RESULTS A total of 122 patients with a median age of 61 years were investigated; among them, 121 (99.2%) achieved a sustained virologic response at 12 weeks after DAA therapy. Fibrosis 4, the aspartate aminotransferase-to-platelet ratio index, 2D SWE, and TE were reduced after DAA therapy. The CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. Two-dimensional SWE and TE were strongly correlated (r = 0.885-0.897; P

Rationale & Objective Hemodialysis facilities are high-risk environments for 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 the Changhua county of Taiwan were treated using an inter-disciplinary 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 three 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. Outcomes Outcome measures included quality indicators pertaining to six steps in HCV care ranging from HCV screening to complete treatment and cure from treatment with DAA Analytical Approach A descriptive analysis. Results A total of 3657 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 96.0% (166/173). 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.

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 Conclusions Successful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.

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. 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.

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.

Purpose. To compare the effects of early phacoemulsification and intraocular lens implantation (phaco/IOL), delayed phaco/IOL after initial laser peripheral iridotomy (LPI), and conventional LPI alone in patients with acute primary angle-closure (PAC). Methods. Patients with acute PAC were included in the study, and those with secondary glaucoma, prior ocular trauma, or other ocular diseases and those who had undergone ocular surgeries previously were excluded. Patients were categorized into three groups: Group A, which underwent primary phaco/IOL after acute PAC; Group B, which underwent LPI initially after acute PAC, followed by phaco/IOL within 6 months; and Group C, which underwent LPI alone. The IOP control success at 12 months as well as changes in ocular characteristics and the number of antiglaucoma medications used after the treatment among the groups were evaluated. Results. Eighty-one eyes were included in the study: 24 eyes in Group A, 23 eyes in Group B, and 34 eyes in Group C. The linear mixed model analysis demonstrated considerable IOP control in Groups A and B. Visual acuity, anterior chamber depth (ACD), and angle width improved significantly in Groups A and B, but not in Group C. The number of antiglaucoma medications used was significantly higher in Group C than in Groups A and B. Conclusions. Patients who underwent phaco/IOL had better IOP control, improved vision, deeper ACD, and wider angle and required less antiglaucoma medications than those who underwent LPI alone. Performing phaco/IOL weeks to months after the initial LPI did not appear to adversely affect outcomes compared with those of early phaco/IOL.

Purpose: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by facial cutaneous venous dilatation (port-wine stain), leptomeningeal angioma, and ocular abnormalities. Here we report a case of SWS who experienced acute primary angle-closure in the same side of the nevus flammeus. Observations: A 64-years-old female patient with SWS port wine stain on the left side of her face was referred to our ER for acute primary angle-closure (PAC). The IOP was 64 mmHg in the left eye (12 mmHg in OD) and the visual acuity was 20/100. The acute PAC was aborted after medical treatment with intravenous Mannitol and oral Acetazolamide, but laser iridotomy (LI) was not performed because of the risk of bleeding. After the acute episode, her IOP remained stable in midteen under 3 topical medications. However, the patient reported several subacute attacks in the following month. We arranged phacoemulsification and intraocular lens (IOL) implantation two months after the initial PAC attack. The post-op condition was smooth with 20/20 visual acuity, and the angle opened dramatically on anterior segment optical coherence tomography (AS-OCT). Her IOP was around 13 mmHg without medication and there was no more acute PAC attack. Conclusions: SWS with ipsilateral acute PAC has seldom been reported. Lens extraction and IOL implantation can be an option in treating such patients since conventional laser iridotomy may cause bleeding. Keywords: Sturge-Weber syndrome, Acute primary angle-closure glaucoma, Phacoemulsification, Intra-ocular lens implantation, Laser iridotomy

OBJECTIVE This was a prospective study aiming to investigate whether levofloxacin plus bismuth-based quadruple therapy was more effective than levofloxacin-based triple therapy after failed first-line eradication therapies for Helicobacter pylori (H. pylori) infection. METHODS Sixty-seven patients infected with H. pylori were randomly assigned to two groups; the levofloxacin plus bismuth-based quadruple therapy group (RBAL [n = 33]; rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days) and the levofloxacin-based triple therapy group (RAL [n = 34]; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days). Endoscopy was performed 4–8 weeks after H. pylori eradication to assess treatment response. We followed up patient response and compliance and checked their resistance to antibiotics. RESULTS Intention-to-treat analysis revealed that both groups had similar eradication rates (RBAL vs RAL: 84.8% [95% confidence interval {CI} 72.6–97.1%] vs 67.6% [95% CI 51.9–83.4%], P = 0.0987). No significant differences in compliance or adverse events were found (P = 0.9829 and 0.0720). Epsilometer test showed that most eradication failure cases were levofloxacin-resistant. CONCLUSIONS Adding bismuth subcitrate to levofloxacin-based triple therapy was not more effective than not doing so, but no further side effects were noted. Both eradication therapies were equally safe and patients had the same tolerance to both regimens. Resistance rate to levofloxacin may be important when choosing second-line therapy.

Esophagus thermal injury is a rare case that can be easily overlooked by practitioners. We herein present a case of thermally induced diffuse corrosive esophagitis with complaints of dysphagia and retrosternal chest pain after having steamed pork. A thorough disease course was demonstrated by serials of endoscopy images and video. A comprehensive review of articles and a concise overview of esophageal thermal injury clinical manifestation, disease process, typical endoscopy features, pharmacomanagement option, and outcomes will be conducted in this article.

Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients.The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective-prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort.In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development.Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.

Background Age, obesity, and metabolic syndrome are known risk factors for gallstones; however, the combined impact of these different risk factors on gallstone formation has not yet been examined. Methods This retrospective, cross-sectional study involved 3190 participants, including 207 participants (6.5%) with gallstones and 986 (30.9%) with metabolic syndrome. Participants were divided into four phenotypes according to metabolic syndrome and obesity status: 1378 participants were metabolically healthy and non-obese (MHNO); 826 were metabolically healthy but obese (MHO); 185 were metabolically abnormal but not obese (MANO); and 801 participants were metabolically abnormal and obese (MAO). Results The MAO and MANO phenotypes had more gallstones than the MHO and MHNO phenotypes, regardless of age (

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.

Background Hepatitis B virus (HBV) relapse is a practical issue after nucleos(t)ide analogue (NA) therapy discontinuation in chronic hepatitis B (CHB). However a prospective multi-centre study remains lacking. The aim of this study was to prospectively investigate virological and clinical outcomes after NA therapy. Methods CHB patients, who discontinued tenofovir disoproxil fumarate (TDF) or entecavir (ETV) therapy based on the NA stopping guidelines, were prospectively recruited from January 2015 to January 2018. Patients with liver cirrhosis, active malignancies, hepatitis C virus, hepatitis D virus or human immunodeficiency virus coinfection, liver transplantation history, immune disorders, a history of NA therapy other than TDF or ETV, or a follow-up period of fewer than 4 weeks were excluded. Serum HBV DNA and quantitative hepatitis B surface antigen (qHBsAg) levels were measured every 3 months. Both cumulative incidences of and hazard ratios (HRs) for the predictors of HBV relapse were analysed. Results Totally, 178 patients (40 HBeAg-positive and 138 HBeAg-negative prior to NA therapy) were enrolled for this analysis (98 TDF and 80 ETV users), and the median follow-up period was 10.6 (interquartile range [IQR]: 5.6–7.2) months. The cumulative incidences of virological (VR) and clinical relapse (CR) in 2 years were 59.5% (95% confidence interval [CI]: 50.6%–68.3%) and 49.0% (95% CI: 34.0%–65.0%), respectively. Moreover, the cumulative incidences of severe hepatitis flare (ALT >500 IU/L) and liver decompensation were 11.8% (95% CI: 3.4%–19.6%) and 1.4% (95% CI: 0%–3.3%), respectively. No patient died of liver disease. In multivariable analysis, qHBsAg >100 IU/mL at the end of therapy was an independent risk factor of VR (HR 2.47, 95% CI: 1.30–4.70) and of CR (HR 3.16, 95% CI: 1.25–7.89), respectively. TDF users initially demonstrated a faster pattern of HBV relapse when compared to ETV users, but the relapse rates were not significantly different in 2 years. Conclusions In this study for non-cirrhotic patients, HBV relapse was common after cessation of NA therapy, and serum qHBsAg can be used as a predicting marker. A longer study period is essential for investigating long-term outcomes.

BACKGROUND Helicobacter pylori (H. pylori) infection causes elevation of lipid peroxidation product malondialdehyde (MDA) and this association may be due to the bacterium causing reactive oxygen species-mediated damage to DNA in the gastric epithelium. The aim of this study was to investigate the gastric juice MDA levels in relation to H. pylori infection and associated gastric diseases. METHODS Gastric juice samples were obtained from 117 patients undergoing endoscopy, and gastric juice MDA levels were determined by high-performance liquid chromatography (HPLC) system. We compared the MDA levels between patients with and without H. pylori infection and assessed the differences of MDA levels between chronic gastritis, gastric intestinal metaplasia, and gastric cancer postsurgical resection. RESULTS Malondialdehyde levels in gastric juice were significantly higher in chronic gastritis patients with H. pylori infection than in those without H. pylori infection (P

Stopping long-term nucleos(t)ide analogue therapy increases hepatitis B virus (HBV) surface antigen (HBsAg) loss rates in HBV e antigen (HBeAg)-negative patients. Viral rebound may induce immune responses facilitating functional cure. We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as an HBV DNA load of >2000 IU/mL until week 12, and relapse occurred earlier in patients treated with tenofovir versus those treated with entecavir (median time, 6 vs 24 weeks; P < .0001). This should be considered for future trials and monitoring of patients after treatment discontinuation.

Background: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. Methods: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. Results: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (−0.56 IU/mL, −0.60 IU/mL, and −0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Conclusion: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. Clinical trial ID: NCT: 00922207. Keywords: Chronic hepatitis B, Hepatitis B e antigen, Peginterferon alfa-2a, Adefovir, Entecavir

Low cost electric power generation using raw juice from culled papaya or fruit waste as feedstock was achieved in a sugar-air alkaline battery (SAAB) with about 37% coulombic efficiency at 0.7–0.8 mW cm−2 near peak power density. Such fruit waste, juice-based electrochemical energy could be poised as sustainable distributed energy resource for remote or underdeveloped regions that need cheap electricity without complicated infrastructure.

Purpose. To investigate visual field progression pattern and factors associated with progression in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and chronic angle-closure glaucoma (CACG). Methods. The raw data of the 30-2 Humphrey Field Analyzer from glaucoma patients with definite visual field progression were processed with pointwise linear regression (PLR) analysis. The rate of change of retinal threshold sensitivity in the ten glaucoma hemifield test (GHT) zones, the upper and the lower hemifields, and the whole field was evaluated and was correlated with patients’ basic demographic data. Results. An average follow-up of 6.94 ± 2.69 years that showed the rate of change of visual field threshold sensitivity was correlated with the peak posttreatment intraocular pressure (IOP) and the long-term IOP fluctuations in all GHT zones except in the inferior arcuate area. The baseline IOP, the trough posttreatment IOP, the refractive status, and the CCT were not correlated with VF progression. Conclusion. The rate of visual field progression was correlated with the peak posttreatment IOP and the long-term IOP fluctuation but with subfield differences.

Summary Background Endoscopic submucosal dissection (ESD) is an emerging technique for treating superficial neoplasms of the gastrointestinal tract. Clinical experience of ESD for superficial colorectal neoplasms remains limited in Taiwan. The aim of this study was to assess ESD performed in a series of patients at our hospital and report the results. Materials and methods Thirty-three patients who underwent ESD were retrospectively analyzed for tumor size, rate of en bloc resection, complete resection, curative resection, technical results, and complications. Results The tumors treated using ESD were situated in the cecum ( n = 6), ascending colon ( n = 2), transverse colon ( n = 2), descending colon ( n = 4), sigmoid colon ( n = 9), and rectum ( n = 10). The median size of the tumors was 30 mm (range, 10–55 mm). The en bloc resection rate was 72.7%, and the complete resection rate was 66.7%. In patients with en bloc resection, the curative resection rate was 87.5%. Histopathological analysis revealed adenoma with low-grade dysplasia ( n = 18), adenoma with high-grade dysplasia ( n = 7), and adenocarcinoma ( n = 8). Five patients experienced perforation, and the overall complication rate was 15.2%. None of these five patients received surgical treatment. Conclusion ESD is a challenging but relatively safe procedure to treat large superficial colorectal neoplasms. However, additional experience is required to achieve higher en bloc resection, complete resection, and curative resection rates.

Mass screening with abdominal ultrasonography (AUS) has been suggested as a tool to control adult hepatocellular carcinoma (HCC) in individuals, but its efficacy in reducing HCC mortality has never been demonstrated. This study aimed to assess the effectiveness of reducing HCC mortality by mass AUS screening for HCC based on a program designed and implemented in the Changhua Community-based Integrated Screening (CHCIS) program with an efficient invitation scheme guided by the risk score. We invited 11,114 (27.0%) of 41,219 eligible Taiwanese subjects between 45 and 69 years of age who resided in an HCC high-incidence area to attend a risk score-guided mass AUS screening between 2008 and 2010. The efficacy of reducing HCC mortality was estimated. Of the 8,962 AUS screening attendees (with an 80.6% attendance rate), a total of 16 confirmed HCC cases were identified through community-based ultrasonography screening. Among the 16 screen-detected HCC cases, only two died from HCC, indicating a favorable survival. The cumulative mortality due to HCC (per 100,000) was considerably lower in the invited AUS group (17.26) compared with the uninvited AUS group (42.87) and the historical control group (47.51), yielding age- and gender-adjusted relative mortality rates of 0.69 (95% confidence interval [CI]: 0.56-0.84) and 0.63 (95% CI: 0.52-0.77), respectively. Conclusion: The residents invited to community-based AUS screening for HCC, compared with those who were not invited, showed a reduction in HCC mortality by ∼31% among subjects aged 45-69 years who had not been included in the nationwide vaccination program against hepatitis B virus infection. (Hepatology 2014;59:1840–1849)