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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/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.

Hepatocellular carcinoma (HCC) is a relatively chemo-resistant tumor. Several multi-kinase inhibitors have been approved for treating advanced HCC. However, most HCC patients are highly refractory to these drugs. Therefore, the development of more effective therapies for advanced HCC patients is urgently needed. Stathmin 1 (STMN1) is an oncoprotein that destabilizes microtubules and promotes cancer cell migration and invasion. In this study, cancer genomics data mining identified STMN1 as a prognosis biomarker and a therapeutic target for HCC. Co-expressed gene analysis indicated that STMN1 expression was positively associated with cell-cycle-related gene expression. Chemical sensitivity profiling of HCC cell lines suggested that High-STMN1-expressing HCC cells were the most sensitive to MST-312 (a telomerase inhibitor). Drug–gene connectivity mapping supported that MST-312 reversed the STMN1-co-expressed gene signature (especially BUB1B, MCM2/5/6, and TTK genes). In vitro experiments validated that MST-312 inhibited HCC cell viability and related protein expression (STMN1, BUB1B, and MCM5). In addition, overexpression of STMN1 enhanced the anticancer activity of MST-312 in HCC cells. Therefore, MST-312 can be used for treating STMN1-high expression HCC.

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.

Introduction: Hepatitis C is one of the leading causes of chronic liver disease. The direct-acting-antivirals has revolutionized the chronic hepatitis C treatment. DAAs can achieve a sustained viro...

SummaryBackground and aimDistinguishing inactive hepatitis B surface antigen (HBsAg) carriers from hepatitis B e antigen-negative hepatitis remains difficult but is important because patients with active hepatitis may develop severe complications. Long-term follow-up data with stringent criteria are required for the identification of inactive HBsAg carriers. A single serum HBsAg level may be used to solve this difficult diagnostic issue; however, very few studies on its application in older patients have been published. This study was designed to evaluate the clinical significance of a single serum HBsAg level in older patients with chronic hepatitis B (CHB).Materials and methodsFrom January 2012 to December 2012, the clinical manifestations of 1749 HBsAg-positive patients were analyzed including 412 patients aged ≥ 60 years (mean age at enrollment, 68.6 ± 6.9 years; range, 60–90 years; 262 males and 150 females). We investigated the possibility of using a single serum HBsAg level to predict cirrhosis and hepatocellular carcinoma (HCC) in older patients with CHB.ResultsOf the 1749 HBsAg-positive patients, those aged ≥ 60 years tended to have lower serum HBsAg levels than the younger patients. In fact, all patients aged ≥ 60 years had a serum HBsAg level ≤ 10,000IU/mL. Of the 412 patients aged ≥ 60 years, 122 (29.6%) had cirrhosis and 59 (14.3%) developed HCC. When an HBsAg-titer < 100IU/mL was used to examine severe clinical outcomes (cirrhosis or HCC), the sensitivity, specificity, positive predictive value, and negative predictive value for being free of liver cirrhosis and HCC were 49.3% and 95.2%, 19.7% and 28.8%, 85.6% and 95.2%, and 40.0% and 71.2%, respectively.ConclusionA single serum HBsAg level < 100IU/mL might predict favorable clinical results in older patients with late-stage CHB virus infection.

Background Altered adiponectin levels are associated with metabolic abnormalities. The aim of this study was to explore the role of adiponectin in cholelithiasis. Methods A radioimmunoassay was used to determine serum adiponectin levels in 58 patients with cholesterol gallstones and 47 with pigment gallstones, and 101 healthy controls. The chemical composition of extracted gallstones was determined by Fourier transform infrared spectroscopy. Results The mean(s.d.) adiponectin level was decreased in patients with cholesterol gallstones (7·6(4·1) µg/ml; P < 0·001) but raised in patients with pigment gallstones (17·9(9·0) µg/ml; P < 0·001) in comparison with healthy controls (11·7(6·5) µg/ml). Decreased adiponectin levels (odds ratio (OR) 0·85 (95 per cent confidence interval (c.i.) 0·76 to 0·96); P = 0·008) and female sex (OR 6·06 (95 per cent c.i. 2·10 to 17·46); P = 0·001) were associated with cholesterol gallstone formation. Increased adiponectin levels (OR 1·11 (95 per cent c.i. 1·01 to 1·22); P = 0·025) and increased age (OR 1·06 (95 per cent c.i. 1·01 to 1·12); P = 0·029) were associated with pigment gallstone formation. Raised serum aspartate aminotransferase concentration was a risk factor for both cholesterol (OR 1·16 (95 per cent c.i. 1·03 to 1·30); P = 0·013) and pigment (OR 1·23 (95 per cent c.i. 1·10 to 1·38); P < 0·001) gallstones. Conclusion Gallstone formation is associated with altered serum adiponectin levels. Serum adiponectin might serve as a novel marker for cholesterol and pigment cholelithiasis.

To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography.One hundred and seventy-six patients with an episode of acute hepatitis flare (ALT value5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups (viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h (median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzedEnlarged lymph nodes (width ≥ 5mm) were noticeable in 110 (62.5%) patients, mostly in acute on chronic hepatitis B (54.5%). The viral group had a higher prevalence rate (89/110 = 80.9%) and larger nodal size (median, 7 mm) than those of the non-viral group (21/66 = 31.8%; median, 0 mm) (P0.001 for both). Meanwhile, there were significant differences in the nodal size between acute and chronic viral groups (P0.01), and between acute hepatitis A and non-hepatitis A viral groups (P0.001). In logistical regression analysis, the nodal width still showed strong significance in multivariate analysis (P0.0001) to stratify the two groups. The area under the curve of ROC was 0.805, with a sensitivity of 80.9%, a specificity of 68.2%, positive predictive value of 80.92%, negative predictive value of 68.18%, and an accuracy of 76.14%.Point-of-care ultrasonography to detect perihepatic nodal change is valuable for clarifying the etiologies in an episode of acute hepatitis flare.