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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

Purpose Snoring is closely related to obstructive sleep apnea in adults. The increasing abundance and availability of smartphone technology has facilitated the examination and monitoring of snoring at home through snoring apps. However, the accuracy of snoring detection by snoring apps is unclear. This study explored the snoring detection accuracy of Snore Clock—a paid snoring detection app for smartphones. Methods Snoring rates were detected by smartphones that had been installed with the paid app Snore Clock. The app provides information on the following variables: sleep duration, snoring duration, snoring loudness (in dB), maximum snoring loudness (in dB), and snoring duration rate (%). In brief, we first reviewed the snoring rates detected by Snore Clock; thereafter, an ear, nose, and throat specialist reviewed the actual snoring rates by using the playback of the app recordings. Results In total, the 201 snoring records of 11 patients were analyzed. Snoring rates measured by Snore Clock and those measured manually were closely correlated (r = 0.907). The mean snoring detection accuracy rate of Snore Clock was 95%, with a positive predictive value, negative predictive value, sensitivity, and specificity of 65% ± 35%, 97% ± 4%, 78% ± 25%, and 97% ± 4%, respectively. However, the higher the snoring rates, the higher were the false-negative rates for the app. Conclusion Snore Clock is compatible with various brands of smartphones and has a high predictive value for snoring. Based on the strong correlation between Snore Clock and manual approaches for snoring detection, these findings have validated that Snore Clock has the capacity for at-home snoring detection.

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

BackgroundCombined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups.MethodsWe prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis.ResultsIn the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM.ConclusionThe clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

Purpose To improve the three dimensional (3D) and two dimensional (2D) image correlation and differentiation of 3D endoluminal lesions in the traditional surface rendering (SR) computed tomographic endoscopy (CTE), a target gray level mapping (TGM) technique is developed and applied to computed tomographic colonography (CTC) in this study. Methods A study of sixty-two various endoluminal lesions from thirty patients (13 males, 17 females; age range 31–90 years) was approved by our institutional review board and evaluated retrospectively. The endoluminal lesions were segmented using gray level threshold. The marching cubes algorithm was used to detect isosurfaces in the segmented volumetric data sets. TGM allows users to interactively apply grey level mapping (GM) to region of interest (ROI) in the 3D CTC. Radiologists conducted the clinical evaluation and the resulting data were analyzed. Results TGM and GM are significantly superior to SR in terms of surface texture, 3D shape, the confidence of 3D to 2D, 2D to 3D image correlation, and clinical classification of endoluminal lesions (P

Background Acute gastric variceal hemorrhage (AGVH) is a serious complication of portal hypertension. Endoscopic cyanoacrylate glue injection is standard therapy for acute hemostasis; however, it may be associated with serious complications. The role of thrombin injection has not been confirmed. This study compared endoscopic thrombin and glue injections in the hemostasis of AGVH. Methods 68 eligible patients with AGVH were randomized to receive thrombin injection (33 patients) or glue injection (35 patients). The primary end point was injection-induced gastric ulcers. Secondary end points were acute hemostasis, rebleeding, and mortality within 42 days. Results Both groups had comparable baseline data. Hemostasis of active bleeding at endoscopy was 90.0 % (9/10) in the thrombin group and 90.9 % (10/11) in the glue group (P = 0.58), and 48-hour hemostasis was achieved in 93.9 % (31/33) and 97.1 % (34/35), respectively (P = 0.60). Treatment failure at 5 days occurred in two patients (6.1 %) in the thrombin group and two patients (5.7 %) in the glue group (P > 0.99). Gastric ulcers occurred in none of the thrombin group and 11/30 (36.7 %) of the glue group (P Conclusions Endoscopic thrombin injection was similar to glue injection in achieving successful hemostasis of AGVH. However, a higher incidence of complications may be associated with glue injection.

Background Patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are recommended to undergo transcatheter arterial chemoembolization (TACE). However, TACE in combination with radiofrequency ablation (RFA) is not inferior to surgical resection (SR), and the benefits of surgical resection (SR) for BCLC stage B HCC remain unclear. Hence, this study aims to compare the impact of SR, TACE+RFA, and TACE on analyzing overall survival (OS) in BCLC stage B HCC. Methods Overall, 428 HCC patients were included in BCLC stage B, and their clinical data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Results One hundred forty (32.7%) patients received SR, 57 (13.3%) received TACE+RFA, and 231 (53.9%) received TACE. The OS was significantly higher in the SR group than that in the TACE+RFA group [hazard ratio (HR): 1.78; 95% confidence incidence (CI): 1.15–2.75, p = 0.009]. The OS was significantly higher in the SR group than that in the TACE group (HR: 3.17; 95% CI: 2.31–4.36, p p = 0.004). The cumulative OS rates at 1, 3 and 5 years in the SR, TACE+RFA, and TACE groups were 89.2, 69.4 and 61.2%, 86.0, 57.9 and 38.2%, and 69.5, 37.0 and 15.2%, respectively. After propensity score matching, the SR group still had a higher OS than those of the TACE+RFA and TACE groups. The TACE+RFA group had a higher OS than that of the TACE group. Conclusion The SR group had higher OS than the TACE+RFA and TACE groups in BCLC stage B HCC. Furthermore, the TACE+RFA group had higher OS than the TACE group.

Background The detection rate of Barcelona Clinic Liver Cancer (BCLC) very-early-stage hepatocellular carcinoma (HCC) is increasing because of advances in surveillance and improved imaging technologies for high-risk populations. Surgical resection (SR) and radiofrequency ablation (RFA) are both first‐line treatments for very-early-stage HCC, but the differences in clinical outcomes between patients treated with SR and RFA remain unclear. This study investigated the prognosis of SR and RFA for very-early‐stage HCC patients with long‐term follow‐up. Methods This study was retrospectively collected data on the clinicopathological characteristics, overall survival (OS), and disease-free survival (DFS) of 188 very-early-stage HCC patients (≤ 2 cm single HCC). OS and DFS were analyzed using the Kaplan–Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. Results Of the 188 HCC patients, 103 received SR and 85 received RFA. The median follow‐up time was 56 months. The SR group had significantly higher OS than the RFA group (10-year cumulative OS: 55.2% and 31.3% in the SR and RFA groups, respectively). No statistically significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 45.9% and 32.6% in the SR and RFA groups, respectively). After PSM, the OS in the SR group remained significantly higher than that in the RFA group (10-year cumulative OS: 54.7% and 42.2% in the SR and RFA groups, respectively). No significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 43.0% and 35.4% in the SR and RFA groups, respectively). Furthermore, in the multivariate Cox regression analysis, treatment type (hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.31–0.95; P = 0.032) and total bilirubin (HR: 1.92; 95% CI: 1.09–3.41; P = 0.025) were highly associated with OS. In addition, age (HR: 2.14, 95% CI: 1.36–3.36; P = 0.001) and cirrhosis (HR: 1.79; 95% CI: 1.11–2.89; P = 0.018) were strongly associated with DFS. Conclusion For patients with very-early-stage HCC, SR was associated with significantly higher OS rates than RFA. However, no significant difference was observed in DFS between the SR and RFA groups.

Background Identifying prognostic factors and therapeutic strategies for single large hepatocellular carcinoma (HCC) is crucial. This retrospective study investigated prognostic factors in patients with single large HCC (≥5 cm) and Child–Pugh (CP) class A liver disease and recommended therapeutic strategies. Methods In total, 305 patients with single large HCC and CP class A liver disease but without distant metastasis or macrovascular invasion were included. Their clinicopathological data, overall survival (OS), and progression-free survival (PFS) were recorded. OS and PFS rates were analyzed using the Kaplan–Meier method and Cox regression analysis. Results In this study, 77.8% of the patients were men; the median age was 63 years. Approximately 34.1% of the patients had cirrhosis and 89.6% had CP class A5 disease. The most common initial treatment was resection (49.5%), followed by transarterial chemoembolization (TACE; 48.2%). OS and PFS rates 1, 5, and 10 years after initial treatment were 88.6%, 58.0%, and 46.8% and 73.6%, 48.2%, and 31.3%, respectively. OS and PRS rates were significantly higher in patients receiving surgical resection than in those receiving TACE. The 1-, 5-, and 10-year OS rates were 94.6%, 76.7%, and 66.7% after resection and 83.1%, 39.0%, and 26.6% after TACE. The 1-, 5-, and 10-year PRS rates were 82.5%, 55.7%, and 51.0% after resection and 64.3%, 40.5%, and 22.7% after TACE. In multivariate analysis, CP class A5/6 (A5 vs. A6; hazard ratio [HR]: 0.23; 95% confidence interval [CI]: 0.15–0.38, P < 0.001) and initial treatment (resection vs. TACE; HR: 0.22; 95% CI: 0.15–0.36, P < 0.001; resection vs. other treatments; HR: 0.37; 95% CI: 0.17–0.65, P = 0.016) were significantly associated with OS. In addition, CP class A5/6 (A5 vs. A6; HR: 0.32; 95% CI: 0.18–0.56, P < 0.001) and initial treatment (resection vs. TACE; HR: 0.30; 95% CI: 0.16–0.51, P < 0.001; resection vs. other treatments; HR: 0.51; 95% CI: 0.26–0.81, P = 0.042) were significantly associated with PFS. Conclusion Surgical resection achieved significantly higher OS and PRS rates than TACE. Surgical resection is an effective and safe therapy for single large HCC.

Background The role of Axl and LC3 as predictors of tumor recurrence and overall survival (OS) after hepatocellular carcinoma (HCC) resection remains unclear. Methods We retrospectively included 535 HCC patients who underwent hepatectomy from 2010 to 2014 in this study. Axl and the autophagy‐related marker LC3 were immunohistochemically assessed in tumors. Results Axl expression was significantly associated with advanced clinicopathological features, including cirrhosis, microvascular invasion, macrovascular invasion, tumor size, BCLC stage, recurrence, and mortality. HCC recurrence occurred in 245 patients, and 219 patients died. The 5‐year cumulative incidences of HCC recurrence and OS rate after HCC resection were 53.3% and 58.8%, respectively. In the Cox proportional analyses, high Axl expression and high LC3 expression were significantly associated with HCC recurrence (hazard ratio [HR]: 3.85, 95% confidence interval [CI]: 2.95‐5.02, P

Background Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. Conclusion High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Endoscopic variceal ligation (EVL) with vasoconstrictors has been recommended for acute esophageal variceal bleeding. However, the optimal duration of vasoconstrictors after EVL is controversial. This systematic review and meta-analysis was conducted to explore the efficacy of short-course vasoconstrictors (≤3 days) versus standard combination (3–5 days). A comprehensive literature review was conducted using the PubMed, Embase, and Cochrane library databases with subsequent meta-analysis. The primary outcomes were 5-day rebleeding, mortality, and treatment failure rates. A risk ratio (RR) with 95% confidence interval is used for outcome comparison. Nine randomized studies with 838 patients were included. The initial hemostasis (96.8% vs 97.4%, p = 0.919), 5-day rebleeding (11.2% vs 8.3%, RR = 1.05, 95% CI = 0.62–1.76), mortality (0 vs 1.3%, RR = 0.48, 95% CI = 0.10–2.39), and treatment failure (7.4% vs 5.9%, RR = 1.10, 95% CI = 0.48–2.49) were similar in both groups. Subgroup analysis suggested EVL alone had no significant difference of 5-day re-bleeding (15.9% vs 7.1%, RR = 2.25, 95% CI = 0.87–5.77), mortality (0 vs 0.7%, RR = 0.71, 95% CI = 0.08–6.03), treatment failure (9.6% vs 6.7%, RR = 1.43, 95% CI = 0.54–3.75) compared to standard combination. Clinical heterogeneity was found for the rebleeding rate for the subgroup during sensitivity analysis. EVL with short-course vasoconstrictors is highly efficacious for esophageal variceal bleeding. Further studies are required to determine the genuine need of subsequent vasoconstrictor after successful EVL.

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.

There is an ongoing debate as to whether patients with chronic hepatitis B (CHB) may discontinue nucleos(t)ide analogue (NA) therapy before seroclearance of hepatitis B surface antigen (HBsAg).1 Whereas treatment discontinuation may facilitate HBsAg seroclearance and avoid indefinite drug exposure,2 reactivation of viral replication almost always follows treatment cessation and frequently leads to clinical flares.3 In patients who encounter withdrawal flares, severe acute exacerbation (SAE) could occur with fatal consequences.4 Quantitative knowledge about the risk of SAE is imperative to inform the debate and also the practice.

Background: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7% and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2% and 74.6% in high LC3 expression patients and 0% and 0% in those with low LC3 expression. Conclusion: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Background The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages. Methods Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. Results In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0–96) months for the total cohort and was subdivided into 52 (8–96), 32 (1–96), 19 (0–84), and 12 (0–79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child–Pugh (C–P) class; (3) SR, hepatitis B virus (HBV) infection, and C–P class; and (4) SR, HBV infection, and C–P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values Conclusions SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy. We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n = 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n = 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n = 460). In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child–Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI] 32.2–53.7), 20.6 months (CI 14.1–25.9), 11.5 months (CI 8.02–14.1), 5.7 months (CI 4.02–5.98), and 3.2 months (CI 2.41–3.59), respectively, (p

Aim: The aim of this study was to investigate the long-term outcomes of endoscopic submucosal dissection (ESD) for superficial esophageal squamous cancer. Methods: A literature search was conducted using PubMed, ProQuest and Cochrane Library databases. Primary outcomes were overall survival, disease-specific survival and recurrence-free survival at 5 years. Secondary outcomes included adverse events, recurrence and metastasis. Hazard ratios were calculated based on time to events for survival analysis, and odds radios were used to compare discrete variables. Results: A total of 3796 patients in 21 retrospective studies, including 5 comparative studies for ESD and esophagectomy were enrolled. The invasion depth was 52.0% for M1–M2, 43.2% for M3–SM1 and 4.7% for SM2 or deeper. The 5-year survival rate was: overall survival 87.3%, disease-specific survival 97.7%, and recurrence-free survival 85.1%, respectively. Pooled local recurrence of ESD was 1.8% and metastasis was 3.3%. In terms of the comparison between ESD and esophagectomy, there was no difference in the overall survival (86.4% versus 81.8%, hazard ratio = 0.66, 95% CI = 0.39–1.11) as well as disease-specific and recurrence-free survival. In addition, ESD was associated with fewer adverse events (19.8 % versus 44.0%, odds ratio = 0.3, 95% CI = 0.23–0.39). Conclusions: For superficial esophageal squamous cancer, ESD may be considered as the primary treatment of for mucosal lesions, and additional treatment should be available for submucosal invasive cancers.

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.

Background The effectiveness of arthroscopic treatment for knee osteoarthritis (OA) has been subject to debate. This study presents an innovative concept of arthroscopic management for knee OA and investigates its clinical outcome.Methods An arthroscopic cartilage regeneration facilitating procedure (ACRFP) to eliminate medial abrasion phenomenon and decompress the patello-femoral joints was performed on 693 knees of 411 patients with knee OA, mean age 60 years (34-90). The Knee Society score (KSS) and the knee injury and osteoarthritis outcome score (KOOS) were used for subjective outcome study. Roentgenographic changes for all cases and magnetic resonance imaging (MRI) variations for twenty randomly selected cases were evaluated for objective outcomes. Results There were 634 knees in 369 patients (93.7%) available with more than 3 years of follow-ups (mean 40 months, SD 9). The overall subjective satisfactory rate was 91.1%. The KSS and all subscales of the KOOS improved statistically. Reversal of the degeneration process of cartilage was observed in 80.1% of the whole series (radiographic outcome) and in 72.2% of the 18 randomly selected cases (one-year MRI outcome study). Gender and OA severity were related to subjective outcomes. Age, body mass index (BMI), pre-operative hyaluronic acid injection, OA severity, and the type and severity of the medial plica are important predictors of radiographic outcomes. An analysis of failed cases reaffirmed the need for early ACRFP and skillful post-operative care. Conclusion ACRFP is an effective treatment for knee OA. If performed in time, it can satisfy most patients and might modify their degeneration process.

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.

Introduction and aim. In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB. Material and methods. We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA > 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated. Results. According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53-0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure. Conclusions. A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.

The remnant liver's ability to regenerate may affect post-hepatectomy immediate mortality. The promotion of autophagy post-hepatectomy could enhance liver regeneration and reduce mortality. This study aimed to identify predictive factors of immediate mortality after surgical resection for hepatocellular carcinoma (HCC). A total of 535 consecutive HCC patients who had undergone their first surgical resection in Taiwan were enrolled between 2010 and 2014. Clinicopathological data and immediate mortality, defined as all cause-mortality within three months after surgery, were analyzed. The expression of autophagy proteins (LC3, Beclin-1, and p62) in adjacent non-tumor tissues was scored by immunohistochemical staining. Approximately 5% of patients had immediate mortality after surgery. The absence of LC3, hypoalbuminemia (

BACKGROUND AND AIM Therapeutic duration of nucleos(t)ide analogues for chronic hepatitis B (CHB) is not indefinite in many parts of the world. Viral reactivation is common off therapy, but the risk of subsequent clinical outcome remains unclear and unpredictable. We aimed to quantify the incidence of and explore the predictors for clinical flare following virological relapse in CHB patients who discontinue entecavir therapy. METHODS This multicenter cohort study prospectively monitored 133 CHB patients who were HBeAg-negative and viral DNA-undetectable when discontinuing entecavir after at least 3 years on therapy. Following virological relapse (viral DNA >2,000 IU/mL) that occurred in 92 patients, the incidences of subsequent clinical flare and persistent (unremittent for 3 months) or severe hepatitis (with jaundice or coagulopathy) were determined, and risk factors were explored. Patients did not resume antiviral therapy until occurrence of persistent or severe hepatitis. RESULTS The cumulative incidence of clinical hepatitis 2 years after virological relapse was 61.0% (95% confidence interval [CI], 49.9-72.3%) and that of persistent or severe hepatitis was 53.0% (95% CI, 40.9-66.2%). Serum viral load at the virological relapse was associated with both clinical hepatitis (adjusted hazard ratio [HR], 1.31 per log IU/mL; 95% CI, 1.07-1.60) and persistent or severe hepatitis (adjusted HR, 1.63 per log IU/mL; 95% CI, 1.27-2.10), after adjustment for serum aminotransferase and alfa-fetoprotein levels in the multivariate analysis. Viral DNA >100 000 IU/mL predicted a nearly inevitable occurrence of clinical flare (P

BackgroundSeveral recent trials have suggested that the need for vasoconstrictors for preventing esophageal variceal bleeding may be considerably reduced after endoscopic variceal ligation (EVL). However, comprehensive systematic reviews on this topic are hardly available. MethodsA meticulous literature review and meta-analysis were conducted using the databases of PubMed, Embase, and the Cochrane Library. Primary outcomes were initial hemostasis, rebleeding, mortality, and treatment failure within 5 days, and secondary outcomes were 6-week mortality and adverse events. ResultsFive randomized trials with 423 participants were included in the meta-analysis. The results revealed that the following outcomes were similar in groups that received only EVL and a standard combination regimen: initial hemostasis (97.6% vs. 98.0%, risk ratio (RR) = 1.00, 95% confidence interval (CI) = 0.97–1.02), 5-day rebleeding (15.9% vs. 6.6%, RR = 2.25, 95% CI = 0.87–5.77), treatment failure (9.6% vs. 6.7%, RR = 1.43, 95% CI = 0.54––3.75), 5-day mortality rates (0 vs. 0.7%, RR = 0.81, 95% CI = 0.09–6.87), and 6-week mortality rates (2.9% vs. 3.0%, RR = 0.88, 95% CI = 0.25–3.13). By contrast, sensitivity analysis suggested obvious clinical heterogeneity in 5-day rebleeding although an outlier study was identified. ConclusionIn patients with acute esophageal variceal bleeding after EVL, 5-day and 6-week mortality rates were similar regardless of vasoconstrictor use. However, considering the controversial 5-day rebleeding rate, short course of vasoconstrictor use based on current evidence may be reasonable.

Hepatocellular carcinoma (HCC) accounts for 75–85% of primary liver cancers and is prevalent in the Asia-Pacific region. Till now, trans-arterial chemoembolization (TACE) is still one of common modalities in managing unresectable intermediate-stage HCC. However, post-TACE residual viable HCC is not uncommon, resulting in unsatisfied overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been suggested to manage HCC curatively. However, evidence from phase-III trials is largely lacking. Hence, the present phase III randomized trial is designed to compare clinical outcomes between SABR and re-TACE for unresectable HCC patients who had incomplete response after initial TACE. The present study is an open-label, parallel, randomized controlled trial. A total of 120 patients will be included into two study groups, i.e., SABR and re-TACE, with a 1:1 allocation rate. A 3-year allocating period is planned. Patients with incomplete response after initial TACE will be enrolled and randomized. The primary endpoint is 1-year freedom-form-local-progression rate. Secondary endpoints are disease-progression-free survival, overall survival, local control, response rate, toxicity, and duration of response of the treated tumor. SABR has been reported as an effective modality in managing intermediate-stage HCC patients, but evidence from phase-III randomized trials is largely lacking. As a result, conducting randomized trials to demarcate the role of SABR in these patients is warranted, especially in the Asia-Pacific region, where HBV- and HCV-related HCCs are prevalent. Before enrolling participants, the present study was registered prospectively on ClinicalTrials.gov (trial identifier, NCT02921139 ) on Sep. 29, 2016. This study is ongoing.

INTRODUCTION: The incidence of early-onset colorectal cancer is increasing. This study explored the feasibility of fecal immunochemical test (FIT) and risk factors for predicting colorectal neoplasm in younger adults. METHODS: This single-center study included 6,457 participants who underwent health examination from 2013 to 2016 including index colonoscopy (3,307 individuals aged 30–49 years as the younger adult group and 3,150 aged ≥50 years as the average-risk group). Primary outcomes were adenoma detection rate (ADR) and advanced ADR (AADR). Findings of younger participants were stratified by the results of FIT and clinical risk factors and were compared with those of the average-risk group. RESULTS: Among participants aged 30–49 years, a positive FIT was associated with significantly higher ADR (28.5% vs 15.5, P < 0.001) and AADR (14.5% vs 3.7%, P < 0.001) than a negative FIT. Moreover, a positive FIT was associated with higher AADR in younger participants than in average-risk counterparts (14.5% vs 9.8%, P = 0.028). Although no single risk factor predicted FIT positivity in younger participants, nonalcoholic fatty liver disease was independently associated with higher ADR (odds ratio = 2.60, 95% confidence interval = 1.27–5.34, P = 0.001), and metabolic syndrome was independently predictive of higher AADR in younger participants than in average-risk participants (odds ratio = 3.46, 95% confidence interval = 1.66–7.21, P = 0.001). DISCUSSION: A positive FIT in people aged 30–49 years implies a higher risk of colorectal neoplasm, particularly among patients with nonalcoholic fatty liver disease and metabolic syndrome.

There is controversy over the best therapeutic approach for T1 colorectal cancer. We performed a systematic review and meta-analysis of long-term outcomes of endoscopic resection (ER) vs those of primary or additional surgery.We performed a systematic review of the PubMed, Embase, and Cochrane databases through October 2019 for studies that reported outcomes (overall survival, disease-specific survival, recurrence-free survival at 5 years, recurrence, and metastasis) of ER vs surgery in patients with colorectal neoplasms. Hazard ratios (HR) were calculated based on time to events.In total, 17 published studies with 19,979 patients were included. The median follow-up time among the studies was 36 months. The meta-analysis found no significant differences between primary ER and primary surgery in overall survival (79.6% vs 82.1%, HR, 1.10; 95% CI, 0.84-1.45), recurrence-free survival (96.0% vs 96.7%, HR, 1.28; 95% CI, 0.87-1.88), or disease-specific survival (94.8% vs 96.5%; HR, 1.09; 95% CI, 0.67-1.78). Additional surgery and primary surgery did not produce significant differences in recurrence-free survival (HR, 1.27; 95% CI, 0.85-1.89). A significantly lower proportion of patients who underwent primary ER had procedure-related adverse events (2.3%) than patients who underwent primary surgery (10.9%) (P.001). Lymphovascular invasion and rectal cancer, but not depth of submucosal invasion, were independently associated with recurrence for all T1 colorectal cancers.In a systematic review and meta-analysis, we found that ER should be considered as the first-line treatment for endoscopically resectable T1 colorectal cancers. In cases of noncurative resection, additional surgery can have comparable outcomes to primary surgery.

Objective To date, few studies have examined end-of-life (EOL) care and healthcare costs for patients with ovarian cancer. We evaluated the effects of hospice care on the quality of EOL care and healthcare costs for patients with ovarian cancer in the final month of life. Materials and Methods We conducted a population-based study and analyzed data from Taiwan9s Longitudinal Health Insurance Database, which contains claims information for medical records of patients, healthcare costs, and insurance system exit dates: our proxy for death between 1997 and 2011. Results A total of 176 women who died of ovarian cancer were investigated. Of these patients, 32 (18.2%) had received hospice care. Univariate analysis revealed that the patients with hospice care (H group) had lower proportions of intensive care unit admission (0% vs 15.3%) and cardiopulmonary resuscitation (0% vs 18.1%). The mean health care cost per person during the final month of life for H group was approximately 5.5% significantly higher than patients without hospice care (non-H group) (US $3121 ± $376 vs $2957 ± $347). The effects of hospice care on intensive care unit admission, receipt of cardiopulmonary resuscitation, and more than 1 emergency room visit could not be assessed because no cases of these 3 occurrences were observed among the H group by the multivariate regression model. No significant difference was observed between the H and non-H groups in terms of chemotherapy during the final 2 weeks of life. The H group had higher probabilities for more than 1 hospitalization and death in acute hospitals after adjusting for confounders. Conclusions The aggressiveness of EOL cancer care and healthcare costs could not be offset in the final month of life among women with advanced ovarian cancer who received hospice care. The factors of more hospitalizations and dying in hospital warrant further investigation.

Background The predictive factors of overall survival after hepatectomy for HCC remain controversial and need to be investigated. Methods In total, 535 consecutive HCC patients undergoing resection were included and their clinicopathological data and overall survival were recorded. Both the tumor and adjacent non-tumor (ANT) tissues were subjected to immunohistochemistry analysis for the expression of autophagy-related markers. Results Death was observed for 219 patients, and the cumulative overall survival rates at 1, 3, 5 and 7 years were 91.0%, 72.3%, 58.8%, and 27.7%, respectively. In the multivariate analysis, mortality was significantly associated with the following: diminished LC3 expression in both the tumor and ANT tissues, in the HCC tissues alone and in the ANT tissues alone (hazard ratio/95% confidence interval: 6.74/2.052-22.19, 6.70/1.321-33.98 and 2.58/1.499-4.915, respectively); recurrent HCC (5.11/3.136-8.342); HBV infection (2.75/1.574-4.784); cirrhosis (1.78/1.059-2.974); and antiviral therapy (0.42/0.250-0.697). The 5-year overall survival rates were 70.2%, 57.3%, 49.6% and 10.7% for patients with positive LC3 expression in both tissue types, in the HCC tissues alone, in the ANT tissues alone, and in neither tissue type, respectively. The 5-year overall survival rates were 56.7%, 47.3%, 51.2% and 38.7% for patients with HBV-related HCC, cirrhosis, no antiviral therapy, and recurrent HCC, respectively, and these rates were significantly lower than those in their counterparts. Conclusions Patients with recurrent HCC, HBV-related HCC, cirrhosis, and the absence of antiviral therapy showed significantly lower overall survival rates. Furthermore, LC3 expression in both the tumor and liver microenvironments were significantly predictive of overall survival after resection for HCC.

Background The serum gradient of hepatitis B surface antigen (HBsAg) varies over time after cessation of nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB). The association between the time-varying HBsAg serum gradient and risk of relapse has not been elucidated. Methods This multicenter cohort study prospectively enrolled CHB patients who discontinued 3 year-NA treatment. Eligible patients were serologically negative for HBeAg and viral DNA at NA cessation. The participants (n = 140) were followed every 3 months through HBsAg quantification. Virological and clinical relapses were defined as viral DNA levels >2000 IU/mL and alanine aminotransferase (ALT) levels >80 U/mL, respectively. The association of time-varying HBsAg levels with relapses was assessed through a time-dependent Cox analysis. Results During a median follow-up of 19.9 (interquartile range [IQR], 10.6–25.3) months, virological and clinical relapses occurred in 94 and 49 patients, with a 2-year cumulative incidence of 79.2% (95% confidence interval [CI], 70.9%–86.4%) and 42.9% (95% CI, 34.1%–52.8%), respectively. The serum level of HBsAg was associated with virological (P

The accumulation of autophagosomes in the terminal step of the autophagic process has recently emerged as a potentially maladaptive process in the septic heart and lung. However, the role of autophagy in the septic liver has not been ascertained. This study was investigated by first examining the entire sequence of the autophagic process in the liver of septic mice. Second, a novel pharmacotherapeutic approach was utilized to treat sepsis with autophagy enhancer/inhibitor. Sepsis was induced by cecal ligation and puncture (CLP). C57BL/6 mice received autophagy enhancer carbamazepine (CBZ), autophagy inhibitor 3-methyladenine (inhibition of autophagosomal formation), or chloroquine (impairment of autophagosomal clearance). We found that the whole autophagic process was activated at 4 h after CLP; however, it did not proceed to completion during the 4- to 24-h time period, as indicated by accumulated autophagosomes and decreased autophagic flux. Carbamazepine, which induced complete activation of the autophagic process, improved CLP survival. This protective effect was also associated with decreased cell death, inflammatory responses, and hepatic injury. However, disruption of autophagosomal clearance with chloroquine abolished the above protective effects in CBZ-treated CLP mice. 3-Methyladenine, which resulted in inhibition of the autophagosomal formation, did not show any above beneficial effects in CLP mice. Impaired autophagosome-lysome fusion resulting in incomplete activation of autophagy may contribute to sepsis-induced liver injury. Treatment with CBZ may serve a protective role in the septic liver, possibly through the effect of complete activation of autophagic process.

The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies. We analyzed the treatment and OS of 401 patients with Barcelona clinic liver cancer stage C HCC between 2012 and 2017. Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the Kaplan–Meier method. The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1–80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥5 cm, serum alpha-fetoprotein ≥200, and serum albumin ≥3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multiple-line treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan–Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib alone. Sorafenib with concurrent multiple-line therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.

Taiwan has a high prevalence of hepatitis B viral (HBV) infection and hepatocellular carcinoma (HCC) with increasing consumption of alcohol. We investigated the impact of heavy alcohol consumption and HBV infection on HCC in cirrhotic patients.966 cirrhotic patients (132 with HBV infection and alcoholism, 632 with HBV infection, and 202 patients with alcoholism) were enrolled between 2000 and 2009 and followed until 2011. The primary end point was newly developed HCC.Within the three patient groups (cirrhotic patients with HBV infection and alcoholism, HBV infection alone, and alcoholism alone) 38 (28.8%), 100 (15.8%), and 21 (10.4%) showed newly developed HCC, respectively. The 10-year cumulative (52.8% vs. 39.8% vs. 25.6%, p0.001) and annual incidences (9.9%, 4.1%, and 2.1%) of HCC were significantly higher in cirrhotic patients with HBV infection and alcoholism than those in patients with HBV infection or alcoholism alone. For patients with HBV infection and alcoholism, baseline serum HBV DNA (OR=16.8, p=0.025), antiviral nucleos(t)ides analogues (NUCs) therapy (OR=0.01, p=0.035), and serum α-fetoprotein (OR=1.18, p=0.045) were risk predictors of HCC by multivariate logistic regression models. The cumulative incidence of HCC was higher in patients with higher baseline serum HBV DNA. Antiviral NUCs therapy reduced the incidence of HCC.Heavy alcohol consumption significantly increased the risk of HCC in HBV-related cirrhotic patients. Elevated baseline serum HBV DNA was a strong risk predictor of HCC and antiviral NUCs therapy reduced the incidence of HCC in cirrhotic patients with HBV infection and alcoholism.

In Taiwan, infants need to receive 3 doses of hepatitis B virus (HBV) vaccine under the public health policy from the government. However, there are many young adults who even though received complete HBV vaccination in their childhood would lose the positive response of anti-hepatitis B surface antibody (HBs) and need the booster dose of HBV vaccine. The aim of our study is to determine the powerful predictive factor for screening the candidates who need only 1 booster dose of HB vaccine then they can regain positive postbooster anti-HBs status (≧10 mIU/mL) or protective postbooster anti-HBs status (≧100 mIU/mL). We recruited 103 university freshmen who were born after July 1986 with complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels at their health examinations upon university entry. They received 1 booster dose of HB vaccine, and their anti-HBs titers were rechecked 4 weeks after the booster administration. Multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL, model 1) and protective postbooster anti-HBs status (≧100 mIU/mL, model 2) was done with predictive factors of prebooster anti-HBs level, body mass index, serum glutamate pyruvate transaminase level, and sex. Twenty-four students got positive postbooster anti-HBs status (10–100 mIU/mL) and 50 students got protective postbooster anti-HBs status (≧100 mIU/mL). In the model of multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL), prebooster anti-HBs level was the strongest predictive factor. The odds ratio was 218.645 and the P value was 0.001. Even in the model of multivariate analysis logistic regression for protective postbooster anti-HBs status (≧100 mIU/mL), prebooster anti-HBs level was still the strongest predictive factor, but the odds ratio of a protective booster effect was 2.143, with 95% confidence interval between 1.552 and 2.959, and the P value was less than 0.001. Prebooster anti-HBs level can be the powerful predictive factor for positive postbooster anti-HBs status (≧10 mIU/mL) and protective postbooster anti-HBs status (≧100 mIU/mL). According to the result of this study, if someone received complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels around 2 decades later, 1 booster dose of HBV vaccine could help him or her to regain positive postbooster anti-HBs status (≧10 mIU/mL) under the strong predictive factor of prebooster anti-HBs level higher than 1 mIU/mL. The other 2 HBV vaccines could be saved and the case could also save money and time.

Adipocytokines play an important role in adipose tissue homeostasis, especially in obesity-associated disorders such as non-alcoholic fatty liver and their complications including hepatocellular carcinoma (HCC). Although visfatin is an adipocytokine highly expressed in visceral fat that has been demonstrated to play a critical role in the progression of human malignancies, little is known about the role of visfatin in HCC associated with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. In this study, we investigated whether plasma visfatin levels were altered in patients with HCC and the association between plasma visfatin levels and pretreatment hematologic profiles. Plasma visfatin levels were measured by enzyme-linked immunosorbent assays in 193 patients with different stages of HBV or HCV infection, and 92 healthy control subjects. The patients with HCC and chronic HCV or HBV infection had higher levels of visfatin than patients with HBV, HCV, and cirrhosis. In multivariate logistic regression analysis, levels of alpha-fetoprotein (AFP) (OR: 1.13, p=0.003), and plasma visfatin (OR: 1.17, p=0.046) were independently associated with HCC. Multiple stepwise regression analysis showed that plasma visfatin level was positively associated with age, aspartate aminotransferase to platelet ratio index (APRI), and AFP. Trend analyses confirmed that plasma visfatin concentration was associated with AFP>8ng/mL, cirrhosis, HCC, tumor size>5cm, and Barcelona Clinic Liver Cancer-C stage. These results suggested that the plasma visfatin level is associated with the presence of HCC, and that a higher plasma visfatin level may be important in the pathogenesis of HCC. Visfatin may act as both a protective and pro-inflammatory factor. Plasma visfatin concentration may serve as an additional tool to identify patients with more advanced necroinflammation.

In this study, the ultrasound images of thyroid nodules were classified to facilitate clinical diagnosis and management. The hierarchical support vector machines (SVM) classification system was used to select the characteristic sonographic textural feature that represents the major histopathologic components of the thyroid nodules. Two ultrasound systems (LA39 and i12L mentioned in the Materials and Methods section) were used for comparison. Seventy-six thyroid nodular lesions and 157 regions-of-interest thyroid ultrasound image from each system were recruited in the study. The parameters affecting image acquisition were kept in the same condition for all lesions. Commonly used texture analysis methods were applied to characterize thyroid ultrasound images. Image features were classified according to the corresponding pathologic findings. To estimate their relevance and performance to classification, SVMs were used as a feature selector and a classifier. The thyroid nodules are first categorized as two main types, i.e., follicle base and fibrosis base nodule, by sum average. The follicle base nodules can be further and completely classified into follicles with few cells, follicles with follicular cells and follicles with papillary cancer cells by run length nonuniformity (RLNU). The fibrosis base nodules are further classified by sum square into fibrosis with few cells and fibrosis with dominant cells. The fibrosis base neoplasm with dominant cells can be separated into fibrosis with follicular cells and fibrosis with papillary cancer cells by entropy. The hierarchical SVM classification system achieves a diagnostic accuracy between 96.34% and 100%. Besides, the best sonographic textural feature can be selected by the system for the differentiation between the follicle and fibrosis base thyroid nodules or the cell types mixed in them. In follicle base thyroid nodules, papillary cancers show higher sonographic textural RLNU but less than follicular cells. In fibrosis base thyroid nodules, papillary cancers show increased sonographic textural variance and entropy.

Background The role of autophagy-related markers as the prognostic factor of post-operative hepatocellular carcinoma (HCC) recurrence remained controversial. Methods Overall, 535 consecutive HCC patients undergoing curative resection from 2010 to 2014 were followed and classified with early (ER

Doxycycline is the recommended antibiotic for acute Q fever, scrub typhus, and murine typhus and defervescence often occurs within 3 days of treatment. Patients with delayed defervescence (> 3 days) are troublesome for clinicians. To investigate the characteristics of such patients, 18 and 88 cases with and without delayed defervescence, respectively, were studied. By univariate analysis, absence of headache (P = 0.004), jaundice (P = 0.030), icteric sclera (P = 0.030), relative bradycardia (P = 0.003), and pulmonary involvement on chest x-ray (P = 0.028) were significant findings in patients with delayed defervescence. By multivariate analysis, absence of headache (odds ratio [OR] = 8.310; 95% confidence interval [CI] = 1.990-34.706, P = 0.004), jaundice (OR = 6.242; 95% CI = 1.374-28.365, P = 0.018), and relative bradycardia (OR = 10.449; 95% CI = 2.137-51.088, P = 0.004) were the independent characteristics of patients with delayed defervescence. In treating acute Q fever, scrub typhus, and murine typhus with doxycycline, clinicians should be aware that delayed defervescence may occur in patients presenting with jaundice, relative bradycardia, and absence of headache.

In this study, we propose a complete architecture based on digital watermarking techniques to solve the issue of copyright protection and authentication for digital contents. We apply visible and semi-fragile watermarks as dual watermarks where visible watermarking is used to establish the copyright protection and semi-fragile watermarking authenticates and verifies the integrity of the watermarked image. In order to get the best tradeoff between the embedding energy of watermark and the perceptual translucence for visible watermark, the composite coefficients using global and local characteristics of the host and watermark images in the discrete wavelet transform (DWT) domain is considered with Human Vision System (HVS) models. To achieve the optimum noise reduction of the visibility thresholds for HVS in DWT domain, the contrast-sensitive function (CSF) and noise visible function (NVF) of perceptual model is applied which characterizes the global and local image properties and identifies texture and edge regions to determine the optimal watermark locations and strength at the watermark embedding stage. In addition, the perceptual weights according to the basis function amplitudes of DWT coefficients is fine tuned for the best quality of perceptual translucence in the design of the proposed watermarking algorithm. Furthermore, the semi-fragile watermark can detect and localize malicious attack effectively yet tolerate mild modifications such as JPEG compression and channel additive white Gaussian noise (AWGN). From the experimental results, our proposed technique not only improves the PSNR values and visual quality than other algorithms but also preserves the visibility of the watermark visible under various signal processing and advanced image recovery attacks.

Acute Q fever is a worldwide zoonosis caused by Coxiella burnetii infection. In Taiwan, cases of acute Q fever increased during 3 y of observation, especially at Kaohsiung County and City in southern Taiwan. From 15 April 2004 to 15 April 2007, a total of 67 cases of acute Q fever were identified at E-Da hospital located at Kaohsiung County. 19 (28.4%) patients had a history of travel in rural areas and only 1 had been outside southern Taiwan. 21 (31.3%) patients had a history of animal contact. 20 (30.8%) of the 65 examined patients had underlying chronic hepatitis B or hepatitis C virus infection. Fever (98.5%), chills (79.1%), headache (79.1%), relative bradycardia (44.8%), elevated aminotransferases (100%), and thrombocytopenia (74.6%) were common manifestations. 12 (19.0%) cases had abnormal findings on chest X-ray. Fatty liver (50.0%) and hepatomegaly and/or splenomegaly (41.9%) were found by abdominal image examinations. 42 (76.4%) of 55 cases had defervescence within 3 d after treatment, whereas 4 (7.3%) had spontaneous remission. Acute Q fever is an endemic infectious disease with hepatitis rather than pneumonia as the major presentation in southern Taiwan and the emergence of Q fever is due to increased alertness for the disease by physicians.