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Background Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment-induced sustained virologic response (SVR) in patients on haemodialysis. Aims To assess the risk of HCV reinfection among patients on haemodialysis with treatment-induced SVR. Methods Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct-acting antiviral (DAA)-based treatment received follow-up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12 . The low-risk general population who achieved SVR12 and who underwent the same post-SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person-years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups. Results We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post-SVR12 follow-up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24 . The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09-0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10-0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44-4.38, P = 0.57). Conclusions The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low-risk general population. HCV microelimination in this special population is feasible once universal screening and scaled-up treatment are implemented.

Background: In patients with unresectable hepatocellular carcinoma (HCC), the advances in direct-acting antiviral (DAA) therapy for chronic hepatitis C remain unclear. We aimed to investigate the characteristics of DAA therapy, when compared to interferon (IFN) therapy. Methods: In this hospital-based study, all HCC patients in Barcelona Clinic Liver Cancer (BCLC) stage B or C, who received pegylated IFN or DAA, were retrospectively screened from 2009 to 2020. Patients without viremia, without HCC, or with HCC in BCLC stage 0, A, or D prior to antiviral therapy were excluded. Rates of and odds ratio (OR) for sustained virological response (SVR) achievement were analyzed. Results: Nineteen and 78 patients were recruited into the IFN and DAA groups, respectively. The median age was significantly older in the DAA group (DAA vs. IFN: 69.5 [25–75% IQR: 62.8–77.3] vs. 64.0 [25–75% IQR: 61.0–68.0]; p < 0.05). The SVR rates were higher in the DAA group as per protocol (DAA vs. IFN: 94.5% vs. 76.5%; p < 0.05) and in BCLC stage B (DAA vs. IFN: 95.2% vs. 76.5%; p < 0.05). All patients in BCLC stage C received DAA therapy, with the SVR rate being 90.9%. In multivariable regression analysis, the 4-week virological response (OR 5.6, 95% CI: 1.3–25.4) and HCC within the up-to-7 criteria (OR 3.7, 95% CI: 1.1–12.9) were independent factors associated with SVR (all p < 0.05). Conclusions: Compared to IFN therapy, more elderly patients with unresectable HCCs were able to receive DAA therapy, while achieving a significantly higher SVR rate.

BACKGROUND AND AIM Pancreatic elastase-1 (PE-1) has been investigated in pancreatic disorders. However, the reference interval (RI) of PE-1 in blood remains unconfirmed. We aimed to establish the blood RI of PE-1 in an adult population. METHODS In this prospective cross-sectional study, we enrolled 400 adults who had received the whole-body physical check-up program between May 1, 2019 and November 20, 2019. The serum and plasma PE-1 levels were measured by latex turbidimetric immunoassay in different storage conditions (fresh, refrigerated, and frozen). The 95% and 99% RI of PE-1 were calculated according to the Clinical & Laboratory Standards Institute guidelines. The correlations between PE-1 and other parameters were analyzed using multivariable regression models. Ultimately, 38 patients with acute pancreatitis were prospectively recruited as the validation cohort. RESULTS The PE-1 levels in fresh serum were highly correlated with those in refrigerated (R2 = 0.998) or frozen (R2 = 0.942) samples; however, plasma should not be suggested in frozen conditions (plasma vs serum: R2 = 0.185). In the RI study population (202 male & 198 female participants), the median age was 52.6 (25-75% interquartile range: 43.1-61.0). The 95% and 99% RIs of PE-1 were 30.0-221.0 and 22.0-359.0 ng/dL, respectively. Triglycerides (β = 0.106, P = 0.033), lipase (β = 0.154, P = 0.007), and CA19-9 (β = 0.130, P = 0.008) were independent factors associated with PE-1. In the pancreatitis validation cohort, with a cut-off value of 359.0 ng/dL, the sensitivity and specificity were 100% and 99.8%, respectively. CONCLUSION The RI of PE-1 established in this study can be used for further applications. Serum is the suggested form for frozen sample storage.

Background: The benefits of hepatitis C virus (HCV)eradication for hepatocellular carcinoma (HCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B/C remain uncertain. Methods: In this hospital-based cohort study, all HCV-infected patients with BCLC stage B/C HCC during the period January 2017 to March 2021 were retrospectively screened, with 97 patients who had completed direct-acting antiviral (DAA) therapy being enrolled for final analysis. Results: In total, the sustained virological response (SVR) rate was 90.7%. In logistic regression analysis, progressive disease (PD) to prior tumor treatments was significantly associated with SVR failure (odds ratio 5.59, 95% CI 1.30–24.06, p = 0.021). Furthermore, the overall survival (OS) rate was significantly higher in the SVR group than that in the non-SVR group (1-year OS: 87.5% vs. 57.1%, p = 0.001). SVR was found to be an independent factor related to OS (hazard ratio 8.42, 95% CI 2.93–24.19, p = 0.001). However, even upon achieving SVR, the OS rates in BCLC stage C or Child–Pugh stage B patients remained poor. Conclusions: In BCLC stage B/C HCC, DAA could achieve a high SVR rate except in those patients with PD to prior HCC treatments. SVR was related to improvements in OS; therefore, DAA therapy should be encouraged for patients diagnosed without a short life expectancy.

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

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.

Data regarding the efficacy and tolerability of elbasvir/grazoprevir (EBR/GZR) for East-Asian hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. We prospectively recruited 40 HCV GT1b hemodialysis patients who received EBR/GZR for 12 weeks at 6 academic centers in Taiwan. The efficacy endpoints were sustained virologic response 12 weeks off-therapy (SVR12) by intention-to-treat (ITT) modified ITT (mITT) analyses. Patients’ baseline characteristics, early viral kinetics and HCV resistance-associated substitutions (RASs) at HCV non-structural 3 and 5 A (NS3 and NS5A) regions potentially affecting SVR12 were analyzed. The tolerability for EBR/GZR was also assessed. The SVR12 rates by ITT and mITT analyses were 95% (38 of 40 patients; 95% confidence interval (CI): 83.5–98.6%) and 100% (38 of 38 patients; 95% CI: 90.8–100%), respectively. Patients’ baseline characteristics, on-treatment viral decline, and baseline HCV RASs did not affect SVR12. All patients tolerated treatment well. Among 5 patients who had serious adverse events (AEs) including one death due to on-treatment suicide and the other death due to off-therapy acute myocardial infarction, none of these events were judged related to EBR/GZR. The common AEs included upper respiratory tract infection (7.5%), fatigue (5.0%) and anorexia (5.0%). Nine (22.5%) and 8 (20.0%) patients had on-treatment hemoglobin levels of 9.0–10.0 g/dL and 7.0–9.0 g/dL. Three (7.5%) patients had on-treatment elevated alanine aminotransferase (ALT) quotient > 2.5, in whom one (2.5%) had EBR/GZR-induced late ALT elevation. No patients developed hyperbilirubinemia or hepatic decompensation. In conclusion, treatment with EBR/GZR is effective and well-tolerated for East-Asian HCV GT1b patients receiving hemodialysis.

Background Prophylaxis with nucleos(t)ide analogue (NA) is recommended to prevent hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–positive patients receiving rituximab-based B-cell depletion therapy. However, little is known about the risk of clinical relapse after withdrawal of NA. Methods We retrospectively analyzed 77 noncirrhotic HBsAg carriers with hematological cancer who received rituximab-containing chemotherapy. All of them received either prophylactic entecavir or tenofovir therapy. The risk of clinical relapse and hepatic decompensation after cessation of NA was explored. Results Clinical relapse and hepatic decompensation developed in 25 (32.5 %) and 11 (14.3 %) of the patients, respectively, and 2 patients died of hepatic decompensation. Most of the hepatic events occurred within 1 year (20 of 25; 80.0%) after stopping NA. A higher pretreatment viral load (≥2000 vs Conclusions Pretreatment HBV DNA ≥2000 IU/mL is associated with increased risk of liver-related disease after cessation of prophylactic NA therapy in patients who received rituximab-containing chemotherapy.

Objective Systemic therapy, such as sorafenib, has been used clinically to treat patients with advanced stage or Barcelona Clinic Liver Cancer staging system (BCLC) stage C hepatocellular carcinoma (HCC). The aim of the study was to evaluate the therapeutic benefit of combined sorafenib and transarterial chemoembolization (TACE) in this group of patients. Methods Data on patients with HCC at BCLC stage C from August 2012 to September 2017 were collected. Patients who were given sorafenib alone were classified as the monotherapy group and those taking sorafenib and TACE were classed as the combined therapy group. Results A total of 118 patients were enrolled. There were 65 and 53 patients in the monotherapy and the combined therapy group, respectively. The groups' general characteristics were similar. Compared with the monotherapy group the combined therapy group experienced prolonged time-to-progression (TTP) (mean 6.42 mo vs 3.63 mo, P = 0.003) and overall survival (OS) (mean 11.21 mo vs 5.98 mo, P = 0.001). A subgroup analysis found that patients with macroscopic vascular invasion (MVI) also had prolonged TTP and OS in the combined therapy group than the monotherapy group (mean TTP, 7.93 mo vs 3.43 mo, P = 0.007; mean OS, 13.41 mo vs 5.50 mo, P = 0.001), however, these significant differences did not exist for those with extrahepatic spread (EHS). Conclusion Combined sorafenib and TACE therapy has significant better outcomes than sorafenib alone in patients with stage C HCC, particularly those with MVI.

More options regarding the choice of direct-acting antivirals (DAAs) are helpful for avoiding individual limitations in treating hepatitis C virus (HCV) infection. We aimed to assess the efficacy and tolerability of grazoprevir (GZR)/elbasvir (EBR) treatment in genotype-1b (GT-1b) HCV-infected liver or kidney transplant recipients. In this phase 4, single-arm, open-label, multicenter trial, patients received GZR 100 mg/EBR 50 mg daily for 12 weeks. Patients with any HCV infection other than GT-1b, liver decompensation, human immunodeficiency virus, or hepatitis B virus co-infection, a history of NS5A inhibitor exposure, or any severe drug–drug interactions (DDIs), was excluded. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Of the 14 patients (10 kidney and 4 liver transplant subjects) enrolled in this study, 9 (64%) were females; the median age was 64.0 (range: 43–73) years. The regularly used immunosuppressants were tacrolimus (93%), everolimus (29%), and sirolimus (7%), with patient blood levels easily managed and generally stable (all P > 0.05 in quantile regression analysis). The rate of SVR12 was 100% in intent-to-treat analysis. Only one patient discontinued GZR/EBR therapy at 6 weeks posttreatment, due to a treatment-unrelated adverse event (AE); however, this patient remained, achieving SVR12. Most AEs were mild in severity and deemed to be not treatment-related. No organ rejection episodes or deaths occurred during the study period. The single-tablet regimen of GZR/EBR for 12 weeks is highly effective and well tolerated in GT-1b HCV-infected liver or kidney transplant recipients, and its DDIs are generally easy to manage. (This study has been registered at ClinicalTrials.gov under identifier NCT03723824.)

There are large gaps in understanding the molecular machinery accounting for the association of hepatitis C virus (HCV) infection with autoimmunity. Mixed cryoglobulinemia (MC) is the most common HCV-associated extrahepatic manifestation, which is characterized by B-cell lymphoproliferation and autoantibody production. B-cell activating factor (BAFF) is a member of the tumor necrosis factor family and plays an important role in B-cell proliferation. We explored the roles of hepatocyte-derived exosomal microRNAs (exo-miRNAs) and BAFF in the extrahepatic diseases of HCV infection. The exo-miRNA profiles were explored using a next-generation sequencing approach, followed by quantitative reverse transcription-PCR validation. The Toll-like receptor 7 (TLR7) polymorphism were analyzed using quantitative PCR. The biological function of exo-miRNAs and TLR7 polymorphism in BAFF expression was evaluated by using immunoblotting and enzyme-linked immunosorbent assay. Significantly increased levels of BAFF, exosomes, and TLR7 were found in HCV patients, particularly in those with MC (P

The 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. The 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 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The 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). The 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.

Data are limited regarding the real-world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI). We aimed to evaluate the performance of GLE/PIB in patients with chronic kidney disease (CKD) stage 4 or 5 in Taiwan. 108 chronic HCV patients with CKD stage 4 (n = 32) or 5 (n = 76) receiving GLE/PIB for 8-12 weeks were retrospectively recruited at 4 academic centres in Taiwan. The effectiveness was determined by sustained virologic response at off-therapy week 12 (SVR12 ) for evaluable (EP) and per-protocol populations (PP). The safety profiles were also assessed. By EP and PP analyses, the SVR12 rate was 99.1% (107 of 108 patients; 95% confidence interval (CI): 94.9%-99.8%) and 100% (107 of 107 patients; 95% CI: 96.5%-100%). The SVR12 rates were 100% (95% CI: 89.3%-100%) and 98.7% (95% CI: 92.9%-99.8%) in patients with CKD stage 4 and 5, respectively. One patient, who declined off-therapy follow-up after permanently discontinuing GLE/PIB at on-treatment week 9 due to scheduled cardiac surgery, had nonvirologic failure. Sixteen (14.8%) patients had serious adverse events (AEs), which were judged not related to GLE/PIB. The three most common AEs were pruritus (19.4%), fatigue (15.7%) and nausea (13.9%). None had ≥3-fold upper limit of normal for total bilirubin and alanine aminotransferase levels. None of the 9 patients with hepatitis B virus (HBV) coinfection developed HBV-associated hepatitis. In conclusion, GLE/PIB for 8-12 weeks is effective and well-tolerated in HCV patients with severe RI.

Although interferon (IFN)-based therapy has been shown to reduce hepatocellular carcinoma (HCC) development once patients with chronic hepatitis C virus (HCV) infection achieve sustained virologic response (SVR), IFN-based therapy is limited by its multiple adverse effects, non-oral administration, and unsatisfactory SVR rate. In recent years, IFN-free all-oral direct-acting antivirals (DAAs) have replaced IFN-based therapy as the standard of care for HCV infection worldwide because of the higher SVR rate and lower incidence of adverse effects. By using currently approved DAA regimens, HCV can be eradicated in more than 95% of infected hosts, regardless of their disease severity. Since 2016, the risk of de novo occurrence or recurrence of HCC in hepatitis C patients receiving DAAs has been debatable because of a report addressing an unexpected high early tumor recurrence rate. To solve this important, interesting, yet controversial issue, we thus reviewed the latest and most relevant articles on this subject and proposed recommendations to manage such patients for healthcare providers. Keywords: Direct-acting antivirals, Hepatitis C virus, Hepatocellular carcinoma

BACKGROUND AND AIM Data regarding the efficacy and safety of paritaprevir/ritonavir, ombitasvir plus dasabuvir (PrOD) for East Asian non-cirrhotic hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. METHODS Forty-six HCV GT1b non-cirrhotic patients receiving hemodialysis who received PrOD for 12 weeks were prospectively enrolled in seven academic centers in Taiwan. The primary efficacy endpoint was sustained virologic response 12 weeks off-therapy (SVR12 ). Patients' baseline characteristics, early virokinetics, and HCV resistance-associated substitutions (RASs) potentially related to SVR12 were analyzed. The safety profiles were also assessed. RESULTS The SVR12 rate was 100% (46 of 46 patients). Patients' baseline characteristics, on-treatment viral decline, and baseline HCV resistance-associated substitutions did not affect SVR12 . All patients tolerated treatment well. One patient with folliculitis temporarily discontinued treatment, and another two patients had serious adverse events (SAEs), which were considered not related to PrOD treatment. The common adverse events were pruritus (19.6%), fatigue (15.2%), and upper respiratory tract infection (6.5%). Twelve (19.6%) and one (2.2%) patients had hemoglobin levels

Thrombocytopenia may be associated with increased bleeding risk impacting timing and outcome of invasive procedures in patients with chronic liver disease (CLD). Lusutrombopag, a small-molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures. L-PLUS 2 was a global, phase 3, randomized, double-blind, placebo-controlled study. Adults with CLD and baseline PCs < 50 × 109 /L were randomized to receive once-daily lusutrombopag 3 mg or placebo ≤ 7 days before an invasive procedure scheduled 2-7 days after the last dose. The primary endpoint was avoidance of preprocedure platelet transfusion and avoidance of rescue therapy for bleeding. A key secondary endpoint was number of days PCs were ≥ 50 × 109 /L throughout the study. Safety analysis was performed on patients who received at least one dose of study drug. This study occurred between June 15, 2015, and April 19, 2017, with a total of 215 randomized patients (lusutrombopag, 108; placebo, 107); 64.8% (70/108) of patients in the lusutrombopag group versus 29.0% (31/107) in the placebo group met the primary endpoint (P < 0.0001; difference of proportion 95% confidence interval [CI], 36.7 [24.9, 48.5]). The median duration of PCs ≥ 50 × 109 /L was 19.2 days with lusutrombopag (without platelet transfusion) compared with 0.0 in the placebo group (with platelet transfusion) (P = 0.0001). Most adverse events were mild or moderate in severity, and rates were similar in the lusutrombopag and placebo groups (47.7% and 48.6%, respectively). Conclusion: Lusutrombopag was superior to placebo for reducing the need for platelet transfusions and achieved durable PC response in patients with thrombocytopenia and CLD undergoing invasive procedures, with a safety profile similar to placebo.

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08-5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.

The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR.Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12).5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common.LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.

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 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. Methods Between July 2019 and March 2020, 1,880 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. Results The SVR12 rates by EP and PP analyses were 95.6% (1,798 of 1,880 patients; 95% confidence interval (CI): 94.6%-96.5%) and 99.3% (1,798 of 1,811 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 1,859 (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. Conclusions SOF/VEL for 12 weeks is efficacious and well-tolerated chronic HCV-infected patients with compensated liver disease in Taiwan.

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.

To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of

About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were still 2–3% of patients that failed to clear HCV. To understand the causes of DAA failure in Taiwan, we conducted a multi-center, clinical, and virologic study. A total of 147 DAA-failure patients were recruited, and we searched HCV NS3/4A, NS5A and NS5B for known resistance-associated substitutions (RASs) by population sequencing, and conducted whole genome sequencing (WGS) for those without known RASs. A total of 107 patients received genotype-specific DAAs while 40 had pangenotype DAAs. Clinically, the important cause of failure is poor adherence. Virologically, common RASs in genotype-specific DAAs were NS5A-L31, NS5A-Y93, and NS5B-C316, while common RASs in pangenotype DAAs were NS5A-L31, NS5A-A/Q/R30, and NS5A-Y93. Additionally, new amino acid changes were found by WGS. Finally, we identified 12 cases with inconsistent baseline and post-treatment HCV genotypes, which is suggestive of re-infection rather than treatment failure. Our study described the drug resistance profile for DAA failure in Taiwan, showing differences from other countries.

Background: Lack of nucleos(t)ide analogue (NA) prophylaxis prior to chemotherapy is a common problem worldwide. The efficacy of newer-generation NAs in the rescue for the hepatitis B virus (HBV) reactivation has not been confirmed. We aimed to compare lamivudine (LVD) and entecavir (ETV) in the rescue of chemotherapy-induced HBV flare-up. Methods: In this retrospective cohort study, we screened all HBV carriers who received therapeutic LVD or ETV for hepatitis flare-up after chemotherapy between January 1, 2004 and December 31, 2015. Patients who had other concurrent primary liver diseases such as chronic hepatitis C, who had baseline HBV viral load 4 s (HR: 10.78, 95% confidence interval [CI]: 1.55–74.93) and HBV viral load L (HR: 3.40 per 1 log IU/ml, 95% CI: 1.39–8.40) were independent prognostic factors for liver-related mortality. There was no drug resistance to LVD or ETV over the course of 1 year. Conclusion: Clinical outcomes were not different between LVD and ETV users. Delayed detection of hepatitis flare-up with coagulopathy and a high viral load could result in a poor prognosis.

Background Non-alcoholic fatty liver disease (NAFLD) is associated with features of metabolic syndrome. The aim of this study was to investigate the association between NAFLD and metabolic syndrome in a Chinese population. Methods Data from subjects were retrospectively collected from 2006 to 2009. The exclusion criteria included significant consumption of alcohol and chronic hepatitis B and C. The patients were assigned to two groups according to ultrasound findings: normal group and fatty liver group. The liver function of patients was determined by assessing serum alanine aminotransferase (ALT). Metabolic syndrome was diagnosed based on the 2005 International Diabetes Federation criteria. Results A total of 7568 subjects were enrolled and 5736 (75.8%) and 1832 (24.2%) patients were assigned to the normal and fatty liver groups, respectively. The fatty liver group had significant male predominance (69.7% vs 56.0%), higher body mass index (mean, 26.67 vs 23.55 kg/m2) compared with the normal group. There were 441 (7.7%) and 377 (20.6%) cases with metabolic syndrome in the normal and fatty liver groups, respectively, with significant difference (P=0.001), and the subgroup of 385 cases with fatty liver and elevated ALT had higher prevalence (28.8%) of metabolic syndrome. The strongest association of an individual component of metabolic syndrome with NAFLD was hyperlipidemia (adjusted OR=2.55, 95% CI: 2.22-2.94). Conclusion The individuals with NAFLD had a higher ratio of metabolic syndrome. Hyperlipidemia had the strongest positive association with NAFLD.

Sorafenib is of proven efficacy in treating patients of hepatocellular carcinoma (HCC). Our study was aimed to determine the factors influence the sorafenib efficacy. We evaluated data of HCC patients receiving sorafenib from June 2012 to October 2016. All HCC cases were of the Barcelona Clinic Liver Cancer (BCLC) classification stage C. The exclusion criteria: those of BCLC classification stage A or B, with the absence or co-infection of hepatitis B (HBV) and hepatitis C (HCV). The presence of HBV, HCV, macoscopic vascular invasion (MVI) or extrahepatic spread (EHS) was recorded for each patient. Time-to-progression (TTP) and overall survival (OS) were analyzed. Among a total of 90 HCC patients, 48 (53.3%) had HBV infection, 42 (46.7%) had HCV infection, 51 (56.7%) had MVI, and 39 (43.3%) had EHS. Patients with HCV infection showed better TTP and OS than those with HBV infection. Patients with EHS had a longer TTP and OS than those with MVI. For patients with HBV infection, those with EHS had a longer TTP (mean 4.60 vs 2.64 months, P = .002) and OS (mean 6.65 vs 4.53 months, P = .045) compared to those with MVI. Among those with MVI, patients with HBV infection had a poorer TTP (mean 2.64 vs 4.74 months, P = .019) and shorter OS (mean 4.53 vs 7.00 months, P = .059) compared to those with HCV infection. HCC patients with HCV infection or with the presence of EHS showed better sorafenib efficacy.

AIM Longitudinal data of the reactivation of hepatitis B virus (rHBV) and serial serological markers or HBV-DNA has been limited. This study aimed to investigate the temporal course of rHBV development in rheumatoid arthritis (RA) patients undergoing long-term rituximab therapy. METHODS The occurrence of rHBV was examined in 157 RA patients during rituximab therapy. Serum levels of HBV surface antigen (HBsAg), HBV core antibody (HBcAb), and HBsAb were determined by electrochemiluminescence immunoassays, and viral loads by real-time polymerase chain reaction assay. RESULTS Among 157 patients undergoing rituximab therapy, 103 (65.6%) were HBsAg-negative and HBcAb-positive. Before rituximab therapy, 20 (19.4%) of these 103 patients were HBsAb-negative, while 83 (80.1%) were HBsAb-positive. Five (20%) HBsAb-negative patients developed rHBV after rituximab therapy. Among 83 HBsAb-positive patients, 4 (4.8%) developed rHBV. Among 9 patients with rHBV, 7 (77.7%) exhibited HBsAg seroreversion. Significant decline of HBsAb titers (mean ± SD, 296.0 ± 417.3 mIU/mL at baseline vs 187.0 ± 332.5 mIU/mL after rituximab therapy, P

Transcatheter arterial chemoembolization (TACE) is a standard treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the tumor radiological characteristics associated with prognosis of patients with early-staged HCC receiving TACE. Patients with BCLC stage A HCC were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. According to mRECIST criteria, patients with or without complete response (CR) were assigned to either the CR group or the non-CR group. Clinical and radiological characteristics were compared between the two groups. In 40 enrolled patients, 24 (60%) were in the CR group, and 16 (40%) in the non-CR group. Clinical parameters were similar between the 2 groups. Radiological characteristics including complete lipidol retention and the absence of residual tumor blush were significantly correlated with achievement of CR in the patients with small-sized HCC. Patients with CR after TACE had a significantly longer overall survival than those without (31.29 vs 22.63 months, P = .021). Complete lipidol retention and the absence of residual tumor blush were correlated with the radiological complete tumor response of these patients with small-sized early-stage HCC receiving TACE.

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.

Real-world data regarding the effectiveness and safety of generic sofosbuvir (SOF)-based interferon-free direct acting antiviral agents (DAAs) for patients with chronic hepatitis C virus (HCV) infection remain limited. A total of 517 chronic HCV-infected patients receiving 12 or 24 weeks of SOF-based therapies were retrospectively enrolled in 4 academic centers in Taiwan. The rate of sustained virologic response at week 12 off-therapy (SVR12) and that of treatment completion were assessed. The baseline characteristics and on-treatment HCV viral kinetics to predict SVR12 were analyzed. By evaluable population (EP) analysis, the SVR12 rate was 95.4% (95% confidence interval [CI]: 93.2–96.9%). The SVR12 was achieved in 29 of 34 patients (85.3%, 95% CI: 69.6–93.6%), 130 of 139 patients (93.5%, 95% CI: 88.2–96.6%), 119 of 124 patients (96.0%, 95% CI: 90.9–98.3%) and 215 of 220 patients (97.7%, 95% CI: 94.8–99.0%) who received SOF in combination with ribavirin (RBV), ledipasvir (LDV), daclatasvir (DCV) and velpatasvir (VEL), respectively. Of 517 patients, 514 (99.4%) completed the scheduled treatment. All 15 patients with true virologic failures were relapsers. Two decompensated cirrhotic patients had on-treatment deaths which were not related to DAAs. All 7 patients who were lost to follow-up had undetectable HCV RNA level at the last visit. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment. In conclusion, generic SOF-based regimens are well tolerated and provide high SVR12 rates in patients with chronic HCV infection.

The treatment of chronic hepatitis C is revolutionizing rapidly. The aim of this study is to review the efficacy and safety of daclatasvir (DCV)-containing all-oral regimens in clinical studies for chronic hepatitis C treatment. Using PubMed and search terms of 'DCV,' 'hepatitis C virus (HCV) treatment,' and 'HCV NS5A inhibitors,' literature on the clinical development of DCV, as well as abstracts presented at the April 2015 annual meeting of the European Association for the Study of the Liver (EASL) and November 2014 annual meeting of the American Association for the Study of Liver Diseases were reviewed. The final search was undertaken on 14 July 2015. With its potent antiviral activity to all HCV genotypes (GT) demonstrated in preclinical, phases 1-3 studies, DCV has been acting as a very competent team player in clinical trials of all-oral regimens. It is generally safe and well tolerated with a low genetic barrier to resistance and low potential for drug-drug interaction. Administered with a non-structural protein 3 (NS3) protease inhibitor (asunaprevir, ASV) with or without a non-nucleoside NS5B polymerase inhibitor (beclabuvir, BCV), or a nucleotide NS5B polymerase inhibitor (sofosbuvir, SOF), DCV is able to achieve greater than a 90-% HCV eradication rate in both treatment-naïve and treatment-experienced patients with GT 1. A triple combination regimen with DCV/ASV/BCV results in 100% sustained virologic response (SVR) rates in HCV GT 4 treatment-naïve subjects. DCV/SOF combination also had demonstrated up to 90-% SVR rates in GT 3-infected non-cirrhotic patients. The efficacy and safety of DCV-containing all-oral regimens highlight a new era of interferon-free therapy for chronic hepatitis C.

A subgroup analysis of a GLOBE study identified subgroups of chronic hepatitis B (CHB) patients with excellent outcomes to telbivudine (LdT) treatment. The aim of this study was to validate this concept using a real-world clinical population. This prospective, retrospective, and multicenter study examined both HBeAg-positive and HBeAg-negative CHB patients treated with LdT for 2 years. A total of 116 CHB patients were recruited. Of the 64 HBeAg-positive patients, 35 had favorable baseline characteristics [hepatitis B virus (HBV) DNA ≤ 9 log10 copies/mL and alanine aminotransferase ≥ 2× the upper limit of normal (ULN)], but only 40 % (14/35) achieved polymerase chain reaction (PCR) negativity at week 24. Among the 14 patients with favorable baseline characteristics and on-treatment response, the rates of virologic, biochemical, and serologic response and genotypic resistance were 78.6 % (11/14), 64.3 % (9/14), 50 % (7/14), and 7.1 % (1/14), respectively, at week 104 of therapy. Of the 52 HBeAg-negative patients, 34 met the criteria of a baseline serum HBV-DNA level less than 7 log10 copies/mL, and 29 (85.3 %) achieved PCR negativity at week 24. Among the 29 patients with favorable baseline characteristics and on-treatment response, the rates of virologic and biochemical response and genotypic resistance were 96.6 % (28/29), 72.4 % (21/29), and 6.9 % (2/29), respectively. In addition, the PCR negativity at week 24 was the only factor associated with the virologic response and genotypic resistance to LdT treatment. The efficacy and resistance to LdT treatment in CHB patients with favorable predictors were comparable between a real-world clinical population and the GLOBE study. In addition, PCR negativity at week 24 could predict virologic response and genotypic resistance to LdT treatment.

Background/Purpose Interferon (IFN) is able to induce significant psychiatric side effects in chronic hepatitis C (CHC) patients, whereas the risk of nonpsychotic mental disorder (NPMD) development in antiviral-treated mentally healthy CHC patients remains obscure. We used a population-based study to assess the risk of NPMD development in patients who had undergone antiviral treatment compared with untreated chronic hepatitis C virus (HCV)-infected and nonalcoholic fatty liver disease (NAFLD) patients. Methods Data were retrieved from Taiwan's National Health Insurance Research Database cohort consisting of 1 million individuals for a longitudinal analysis. A total of 313 mentally healthy CHC patients who received IFN-based antiviral therapy were recruited and compared with those without antiviral therapy and NAFLD patients. The Chi-square test was used to obtain the hazard ratio and 95% confidence interval. Results Among the 313 CHC patients receiving pegylated interferon/ribavirin therapy, 62 patients (19.8%) were associated with NPMD. In the comparison cohort, composed of 313 age- and sex-matched CHC patients not receiving antiviral therapy, 70 patients (22.4%) were associated with NPMD. The Chi-square analysis revealed that antiviral therapy was not significantly associated with NPMD. The diagnosis of HCV-infected hepatitis was independently associated with NPMD when compared with NAFLD. The hazard ratio was 1.67 (95% confidence interval, 1.11–2.52; p = 0.018). Furthermore, generalized anxiety disorder was specifically higher in HCV-infected patients than those with NAFLD. Conclusion Patients with HCV infection are at high risk of developing NPMD with or without IFN-based therapy.

It is estimated that more than two billion people around the world have been infected by Hepatitis B virus (HBV). Reactivation of HBV (rHBV) is a potentially fatal complication after biological therapy. With the increasing use of biologics and targeted therapy in rheumatoid arthritis (RA) patients who are refractory to conventional synthetic disease-modifying anti-rheumatic drugs, rHBV in those with past infection has become increasingly problematic, especially in HBV-endemic regions. Among those receiving biological therapy, the risk of rHBV varies according to the status of HBV infection and the degree of biologic-related immunosuppression. As rHBV is largely preventable, it is imperative that the risk status of rHBV in RA patients receiving biological and targeted therapy be stratified. Therefore, the aim of this review was to summarize the reported data on rHBV, and propose management strategies for RA patients with different risks of rHBV based on evidence presented in the current literature. Keywords: Biologics, Targeted therapy, Hepatitis B, HBV reactivation, Rheumatoid arthritis

Objective We aimed to investigate risk of hepatitis B virus reactivation in systemic lupus erythematosus patients with different hepatitis B virus infection statuses receiving immunosuppressive therapy. Methods We retrospectively analyzed systemic lupus erythematosus patients with positive hepatitis B surface antigen or anti-hepatitis B core IgG antibody who underwent immunosuppressive therapies from January 2001 to December 2012 at a medical center in Taiwan for evidence of hepatitis B virus reactivation. Results During this period, 906 out of 3125 patients who were diagnosed with systemic lupus erythematosus received screening tests for hepatitis B virus. Thirty-eight patients were identified as hepatitis B surface antigen-positive. Fifteen of 38 (39.5%) hepatitis B surface antigen-positive patients developed hepatitis B virus reactivation, and 53.3% of these patients experienced severe hepatitis flare. Three of 157 hepatitis B surface antigen-negative/anti-hepatitis B core IgG antibody-positive patients (1.9%) experienced hepatitis B surface antigen seroreversion after immunosuppressive therapy. Five patients received prophylactic or preemptive antiviral therapy and none of them developed hepatitis B virus flares. A daily dose of prednisolone greater than 5 mg was a risk factor for hepatitis B reactivation by multivariate logistic analysis. Conclusions The risk of hepatitis B virus reactivation is high in lupus patients receiving immunosuppressive therapy. Antiviral prophylaxis or preemption can effectively reduce the incidence of hepatitis B virus reactivation in lupus patients.

Background The frequency and risks of hepatitis B reactivation in patients receiving glucocorticoid pulse therapy has not been reported. Objective The aim of our study was to investigate the possibility of glucocorticoid pulse therapy related hepatitis B flare. Setting A Taiwanese tertiary hospital. Methods Chronic hepatitis B patients underwent glucocorticoid pulse therapy were retrospectively collected. The prevalence of hepatitis B flare was counted, and the statistic analysis with logistic regression was adapted to assess the associated risk factors. Main outcome measure The prevalence and associated risk factors of the individuals with hepatitis B flare after glucocorticoid pulse therapy were collected and analyzed. Results A total of 112 patients were identified. Forty patients had received prophylactic antiviral therapy and none of them developed hepatitis B flare. Among the 72 patients who had not received antiviral prophylaxis, 11 of them (15.3%) experienced hepatitis B flares. Those individuals with hepatitis B flares, comparing to those without, were younger (37.4 ± 13.3 vs. 46.0 ± 11.1, p = 0.038), had higher ratio of HBeAg positivity (50 vs. 15.9%, p = 0.017), higher percentage of high hepatitis B viral load (81.8 vs. 8.3%, p = 0.002), higher maintenance glucocorticoid dose (prednisone or equivalent 22.7 ± 14.9 vs. 10.7 ± 12.4 mg, p = 0.003) and higher ratio of cyclophosphamide use (27.3 vs. 1.6%, p = 0.010). After multivariate analysis, only higher dose of maintenance glucocorticoid was related to hepatitis B flare (odds ratio, 1.08; 95% CI, 1.01–1.16). Conclusion A higher maintenance glucocorticoid dosage is associated with the risk of hepatitis B flare after glucocorticoid pulse therapy. No hepatitis B flare occurred in patients receiving prophylactic antiviral therapy before glucocorticoid pulse therapy.

Background: Hepatitis B e antigen (HBeAg) status is associated with clinical outcomes, and seroconversion of HBeAg is one of the treatment goals. In this study, we determined the association of on-treatment serum hepatitis B virus (HBV) DNA levels in HBeAg-positive chronic hepatitis B patients who were receiving entecavir (ETV) treatment. Methods: A retrospective cohort study was conducted involving 135 (78 male and 57 female; mean age, 42.3 ± 13 years) patients with HBeAg-positive chronic hepatitis B (CHB). Between August 2008 and March 2014, each patient was treated with ETV for at least 96 weeks, and their HBV DNA levels were evaluated every 3–6 months. HBeAg seroclearance at the 96th week was defined as an absence of serum HBeAg within 96 weeks after ETV treatment. Univariate and multivariate logistic regression analysis was used to identify the predictors of 96th week HBeAg seroclearance, and a multivariable model was constructed. Results: Among the 135 ETV-treated HBeAg-positive CHB patients, 37 patients achieved HBeAg seroclearance (Group 1), whereas 98 patients had persistent HBeAg-positive status (Group 2) at the 96th week check-up. The baseline laboratory data was not significantly different between both the two groups. At the 24th and 48th weeks, there were significant differences between Group 1 and Group 2 in the percentage of patients with HBV DNA levels < 20 IU/mL [17/77 (22.1%) and 11/23 (47.8%), p = 0.032; 45/89 (50.6%) and 26/35 (74.3%), p = 0.028, respectively). Conclusion: Our study demonstrated that HBV DNA levels < 20 IU/mL at the 24th and 48th weeks could predict serum HBeAg loss in ETV-treated HBeAg-positive patients with CHB.

Objective: The aim of this study was to investigate the effect of gender on symptom presentation and quality of life of patients with erosive esophagitis (EE) and nonerosive reflux disorder (NERD). Subjects and Methods: Medical records from patients with gastroesophageal reflux disease (GERD) between January and December 2009 were reviewed. The patients were assigned to either the EE or the NERD group. The general demographic data, the modified Chinese GERDQ scores and the Short Form (SF)-36 life quality questionnaire scores of the two groups of patients were compared. Results: Of the 261 patients, 87 (33.3%), 86 (33.0%) and 88 (33.7%) patients were classified into the EE, the NERD and the control groups, respectively. The patients in the EE group were significantly older (48.94 ± 17.38 vs. 43.34 ± 12.67 years), were predominately male (58.6 vs. 39.5%), had more frequently hiatal hernia (34.5 vs 17.4%), had a higher body weight (67.57 ± 15.13 vs. 61.06 ± 11.08 kg) and a higher body mass index (24.09 ± 4.61 vs. 22.68 ± 3.12) than those in the NERD group. The GERD-specific symptom scores and the general life quality scores of the EE and the NERD groups were similar, and both groups had lower life quality scores than the control group did. The female patients with NERD had a higher frequency of GERD symptoms and lower quality of life scores. Gender had no effect on symptom scores or life quality scores in the EE group. Conclusion: The GERD-specific symptom severity and general quality of life scores of the EE and the NERD patients were similar. Gender had a great influence on symptom presentation and quality of life in patients with NERD, but not in those with EE.

Background & aimsTo evaluate virological breakthrough (VBT) and the risk of hepatocellular carcinoma (HCC) in HBeAg-positive chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment.MethodsA retrospective cohort study was conducted in a tertiary referral hospital and a total of 228 HBeAg-positive CHB patients treated with ETV for more than 48 weeks were enrolled. Clinical outcome measures included HBeAg seroclearance, maintained virological response and the development of HCC.ResultsDuring a median follow-up period of 197 weeks, VBT developed in 26 (11.4%) patients (VBT group), and the other 202 patients without VBT (non-VBT group). The overall cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group were 23.1% and 23.8%, 27.1% and 37.9%, 27.1% and 55.1%, 27.1% and 74.1%, 27.1% and 76.7% from week 48 to 240, respectively(p = 0.013). The cumulative probability of maintained virological responses from week 48 to 240 were 7.69% and 21.78%, 7.69% in the VBT groups and 36.85%, 7.69% and 51.68%, 7.69% and 64.97%, 7.69% and 72.1% in the non-VBT groups, respectively (pConclusionsVBT was associated with adverse clinical outcomes, including a low probability of HBeAg seroclearance, failure to achieve maintained virological responses, and a risk of developing HCC. Patients, particularly with cirrhosis, who had experienced VBT during ETV treatment, more likely developed HCC.

To better assess the usefulness of miniature ultrasound probe (MUP) sonography in the evaluation of the adequacy of gastric variceal injection with cyanoacrylate to decrease the risk of post injection rebleeding.Sixty-nine patients with bleeding gastric varices were included in this study. Endoscopic cyanoacrylate injection was performed in the acute phase for variceal hemostasis. After injection, patients (n = 34) included in the MUP group prospectively received endoscopic ultrasonography (EUS) with MUP during each scheduled endoscopic follow-up session. Patients (n = 35) in the control group who were included historically were followed up with the same interval with endoscopy only.Four (11.4%) patients in the control group received reinjection, and there were 10 episodes of rebleeding in 7 (20.0%) patients. Nine (26.5%) patients received reinjection due to inadequate obturation as judged by EUS. There were six episodes of rebleeding in three (8.8%) patients in the MUP group. The free-of-rebleeding rate for the MUP group was significantly higher than that for the control group (p0.05). The cumulative survival for the MUP group was slightly better than that for the control group but was not statistically significant. The patients' compliance in both groups was similar. The endosonographers considered the performance of MUP sonography to be convenient.MUP sonography is useful for the evaluation of the adequacy of tissue adhesive obturation of gastric varices that may reduce the probability of rebleeding.

Background Patient education is crucial in improving the health-related quality of life (HRQOL) of patients. At the same, understanding the concerns and needs of patients is essential in providing appropriate education. This study assessed the educational needs and HRQOL experienced by chronic hepatitis patients. Methods We developed structured questionnaires with satisfactory validity and reliability to assess the educational needs of patients. HROQL was measured using a generic Short Form 36 (SF-36) and a liver disease-specific Chronic Liver Disease Questionnaire (CLDQ). Descriptive statistic measures and Pearson’s correlation analysis were applied for data analysis. Results A total of 135 subjects were recruited from two regional teaching hospitals in Taiwan. “Disease characteristics and management” exhibited the highest mean score (3.17) among all the subscales of educational needs. In comparison with those without antiviral therapy, chronic hepatitis patients undergoing antiviral treatment scored significantly higher on all subscales of educational needs, especially on “side effects of antiviral treatment” (p

Objectives To compare the efficacy and safety of ultrasound (US) and computed tomography (CT) in the guidance of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Materials and Methods We retrospectively analyzed consecutive treatment-naive patients who received curative RFA for HCC from January 2008 to July 2013. Patients were divided into the US group or the CT group according to their RFA guidance instruments. Patients who were only suitable for US- or CT-guided RFA were excluded. Cumulative incidences of and hazard ratios for HCC recurrence were analyzed after adjusting for competing mortality risk. Results We recruited a total of 101 patients in the US group and 51 patients in the CT group. The baseline demographic characteristics were not significantly different in both groups. Initial response rates were similar between the two groups (US vs. CT: 89.1% vs. 92.2%, p = 0.54), and complete tumor ablation was finally achieved for all patients. However, more ablations per session were performed in US group (median 2.0 [1.0–3.0] vs. 1.0 [1.0–2.0]; p

Background Non-alcoholic fatty liver disease (NAFLD) occurs not only in obese individuals but also in non-obese ones. The aim of this study was to focus on the association between NAFLD and metabolic events in a non-obese or obese Chinese population. Methods Data collected from subjects registered at Taichung Veterans General Hospital from January to December 2009 were analyzed. The exclusion criteria were alcoholics, chronic hepatitis B or C. Patients included in analyses were assigned to four groups according to sonography of their liver (normal or NAFLD), and body mass index (BMI) levels (non-obese if BMI Results There were 745, 208, 770 and 285 patients enrolled in four groups labeled non-obese normal liver (group A), non-obese NAFLD (group B), obese normal liver (group C) and obese NAFLD (group D), respectively. The highest ratio of metabolic syndrome existed in the group B (26.9%), followed by group A (11.7%), group D (10.9%) and finally the group C (5.2%). The positive association with NAFLD in non-obese individuals was significant in triglyceride (OR = 1.01; 95% CI: 1.01–1.02) and glucose (OR = 1.02; 95% CI: 1.01–1.03), while the positive association with NAFLD in obese subjects was only significant in triglyceride (OR = 1.01; 95% CI: 1.01–1.02). The positive association was most significant in all cases (adjusted OR = 2.41; 95% CI: 1.78–3.24), especially in non-obese individuals (OR = 2.81; 95% CI: 1.92–4.12). Conclusions Non-obese NAFLD subjects displayed a higher proportion of metabolic abnormality. Hyperlipidemia and hyperglycemia had the most positive strength association with NAFLD.

Background Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear. Methods Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 ( n=168) or 72 ( n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration. Results Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75–88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91–100% versus 13–44%; P=0.001). Conclusions Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.

Background Interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and viral factors can predict sustained virological response (SVR) in HCV genotype-1 (HCV-1) patients receiving 48 weeks of pegylated interferon and ribavirin. Whether these factors would identify those patients who can benefit from a shorter duration of therapy remains unclear. Methods Treatment-naive HCV-1 patients ( n=662) receiving 24 or 48 weeks of combination therapy were enrolled. Baseline demographic data, HCV viral load, IL28B SNP genotypes (rs8099917), duration of therapy and rapid virological response (RVR) were evaluated to predict SVR. The SVR rates were further stratified by the independent factors and compared. Results The IL28B rs8099917 TT genotype, low baseline viral load (HCV RNA≤600,000 IU/ml), RVR and 48-week therapy independently predicted SVR. In RVR patients with the IL28B rs8099917 TT genotype, the SVR rate of 24-week therapy was comparable to 48-week therapy (95% versus 99%; P=0.21) at low baseline viral load, but was inferior to 48-week therapy (70% versus 97%; PConclusions HCV-1 patients simultaneously bearing the IL28B rs8099917 TT genotype, low baseline viral load and RVR can benefit from a shorter duration of combination therapy.

ObjectiveTo investigate the kinetics of hepatitis B virus (HBV) viral loads and HBV reactivation in rheumatoid arthritis (RA) patients undergoing therapy with tumour necrosis factor alpha (TNFα) inhibitors.MethodsThe authors investigated the virological, serological and biochemical evidence of HBV reactivation in 88 RA patients receiving anti-TNFα therapy. Levels of HBV surface (HBs) antigen (Ag), anti-HBV core (HBc)-IgG and anti-HBs antibody (Ab) were detected by electrochemiluminescence immunoassay, and viral loads were determined by real-time PCR assay.ResultsIn a total of 88 HBcAb-positive patients, 18 (20.5%) patients were HBsAg-positive, 12 (13.6%) patients were HBsAg-negative/HBsAb-negative and 58 (65.9%) patients were HBsAg-negative/HBsAb-positive before starting anti-TNFα therapy. Among HBsAg-positive patients receiving anti-TNFα therapy, HBV reactivation was documented in none of 10 patients who received lamivudine pre-emptive therapy and serum viral loads significantly decreased (mean±SEM, 153 860±80 120 IU/ml at baseline vs 313±235 IU/ml after 12 months antiviral therapy, pConclusionHBV reactivation can occur in both HBsAg-positive and HBsAg-negative/HBcAb-positive patients with detectable HBV DNA, so-called occult HBV infection, during anti-TNFα therapy. Antiviral prophylaxis may effectively reduce HBV reactivation in HBsAg-positive RA patients undergoing anti-TNFα therapy.

Background and Aim: Prompt treatments for acute calculous cholecystitis can reduce both mortality and morbidity. The aim of this retrospective study was to assess the impact of the Tokyo guidelines on management of patients with acute cholecystitis. Methods: The records of patients admitted due to acute calculous cholecystitis were collected between January 2007 and June 2008. Exclusion criteria included acalculous, hepatobiliary malignancy, younger than 18 years old and mortality unrelated to cholecystitis. These 235 patients were classified into three groups; grade I, grade II and grade III, according to the severity grading in the Tokyo guidelines for acute cholecystitis. They were further classified into two subgroups; those compatible with and incompatible with managements suggested in the Tokyo guidelines, for comparison. Results: Lower levels of platelets, lower blood pressure, higher levels of C-reactive protein, blood urine nitrogen, prothrombin time, bilirubin, alkaline phosphatase, and more incidences of positive microorganisms cultured in bile or blood, were found in patients as the severity of disease progressed. Shorter mean length of hospital stay was compatible with the Tokyo guidelines, but no significant differences in outcomes, including incidences of survival, post-surgery complications and mortality, were found between the two subgroups. Conclusion: No significant benefit of the application of the Tokyo guidelines in the management of patients was found between the two subgroups except for reduced mean length of hospital stay. The application of the Tokyo guidelines for improving the outcomes of patients with acute cholecystitis needs further investigation and evaluation.

Background Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts. Methods Data on 1958 patients with hepatocellular carcinoma who were aged 6 – 29 years at diagnosis in Taiwan between 1983 and 2004 were collected from two national hepatocellular carcinoma registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analyzed by using Poisson regression models. All statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination program were compared for HBV immunization characteristics during infancy and prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) serostatus. Results Hepatocellular carcinoma incidence was statistically significantly lower among children aged 6 – 19 years in vaccinated compared with unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709 304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person-years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for persons vaccinated at birth). The risk of developing hepatocellular carcinoma for vaccinated cohorts was statistically significantly associated with incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with prenatal maternal HBeAg seropositivity (with administration of hepatitis B immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR = 9.43, 95% CI = 3.54 to 25.11). Conclusion The prevention of hepatocellular carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure to prevent hepatocellular carcinoma results mostly from unsuccessful control of HBV infection by highly infectious mothers.

BACKGROUND AND STUDY AIMS: Rebleeding can occur after endoscopic injection of gastric varices with tissue adhesive. The aim of this study was to evaluate whether adjuvant hypertonic glucose solution injections enhance the effects of Histoacryl after successful initial variceal obliteration. PATIENTS AND METHODS: A total of 67 patients (37 men, 30 women; mean age ± standard deviation [SD] 60 ± 17 years) with initially successful Histoacryl obliteration of bleeding gastric varices were included in the study and randomly divided into two groups: a ”combined” group of patients who had adjuvant injection of hypertonic glucose solutions in cases of residual gastric varices (F1 or less) and a ”control” group of patients who did not receive such therapy. End points were either variceal recurrence/progression (F2 or more) requiring Histoacryl reinjection or rebleeding. RESULTS: Residual small varices were found in 56 % of patients in the combined group and in 60 % of patients in the control group. Adjuvant therapy was only performed in the combined group. During the follow-up period (mean duration ± SD 37.9 ± 18.5 months, range 19 - 56 months), two patients in the combined group showed gastric variceal progression, compared with nine patients showing progression in the control group, with two cases of rebleeding, both occurring in the control group. Two years after the first Histoacryl injection, the cumulative proportion of patients who did not have gastric variceal progression was significantly higher in the combined group than it was in the control group (92.8 % vs. 71.4 %, P = 0.029). There was no significant difference between the two groups with respect to their survival curves ( P = 0.12). No marked immediate or delayed symptoms or complications were observed in the patients given hypertonic glucose injections. CONCLUSIONS: Adjuvant treatment with hypertonic glucose solution for residual small gastric varices is a safe and simple method. It helps reduce the recurrence or progression of gastric varices after tissue adhesive injections and can therefore reduce the risk of rebleeding.