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Abstract Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct‐acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost‐effective identification of high‐risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high‐throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non‐linear data and identify hidden patterns within real‐world datasets. The combination of AI and multi‐omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non‐invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision‐making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases.

Background/Aims Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, P

Conflict of interest: Yes, Gilead-sponsored research Introduction and Objectives: A previous real-world data (RWD) analysis demonstrated high effectiveness of sofosbuvir/velpatasvir (SOF/VEL) without ribavirin in > 6,000 HCV patients from 12 clinical cohorts across Australia, Canada, Europe & USA. Expand this research initiative with the ongoing SVR10K study, to include even more patients from additional geographical areas, which will allow to show SOF/VEL effectiveness across multiple diverse populations, including Latin-American (LATAM) region. Patients / Materials and Methods: This RWD analysis includes patients ≥ 18 years treated with SOF/VEL without RBV for 12 weeks, as decided by the treating HCP, from 13 sites across Brazil, Colombia, Hong Kong, Mexico, Singapore, Sweden, Spain, Taiwan, and the United Arab Emirates. Age, sex, treatment experienced (TE), cirrhosis stage (no decompensated included), genotype, coinfections, time to treatment initiation (TTI) from HCV diagnosis, and SVR were analyzed for LATAM region. Results and Discussion: Overall, 7,027 patients have been included up to now, 13% (n=890) of them from four sites in the LATAM region (Table). There, median age was 54.5 [IQR 43.2-63.5], where males 51%, and age > 50 years in 62%. Genotype 3 was present in 14%, cirrhotic (CC) 34%, TE 8%, while HIV, HBV and HDV coinfection was reported in 7.2%, 0.3%, and 0.0%, respectively. The TTI was available in 94%, with 28% having ≤30 days (In Brazil 57%). In terms of effectiveness, SVR was achieved in 99.6% of the treated population (n=788); being 98.2% in GT3 patients (n=112), 99.6% in CC patients (n=279), and 97.4% in GT3 CC patients (n=38). Conclusions: Results on treatment effectiveness in LATAM region did not differ from RWD studies of patients in the North-Western countries, reinforcing that HCV treatment guidelines are globally applicable, and supporting the efficacy of panfibrotic, pangenotypic, and pangeographic DAA therapy. Although with positive signs, there is still a significant room for improvement in the time to treatment initiation in the LATAM region.

Abstract Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk.

Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.

Background/Aims Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P

Abstract Lifestyle modification is the standard of care for nonalcoholic fatty liver disease (NAFLD) patients. We aimed to investigate the efficacy of a short‐term lifestyle modification program in the disease course of Taiwanese nonalcoholic steatohepatitis (NASH) patients with paired biopsies. All patients received a 6‐month, strict multidisciplinary program of lifestyle modifications led by physicians, dieticians, and nursing staff. The histopathological and clinical features were assessed. The endpoints were normalization of transaminase levels, metabolic parameters, a decrease in the NAFLD activity score (NAS) ≥1, and a decrease in the fibrosis stage ≥1. We also aimed to elucidate the predictors associated with disease progression. A total of 37 patients with biopsy‐proven NASH were enrolled. The normalization of transaminase levels increased from 0% to 13.5%. There were also significantly increased proportions of patients with normal total cholesterol, triglyceride, and hemoglobin A1c levels. Fifteen (40.5%) patients had an increased NAS ≥1, whereas 10 (27.0%) patients had NAS regression. Twelve (32.4%) patients had increased fibrosis ≥1 stage. Only 2 (5.4%) patients experienced fibrosis regression. A high fasting plasma glucose (FPG) level was associated with NAS progression. Older age and higher transaminase and FPG levels were factors associated with fibrosis progression. Seven (18.9%) patients achieved a body weight reduction >3%, and 4 (57.1%) of them experienced NAS regression. No significant effect of weight reduction on the progression of fibrosis was observed. The short‐term lifestyle modification program significantly decreased liver enzymes and metabolic parameters in NASH patients. A more precise or intensive program may be needed for fibrosis improvement.

Abstract The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID‐19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA‐1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti‐S‐IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti‐S‐IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti‐S‐IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non‐decompensation and 91.3% non‐liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non‐active HCC and 94.7% non‐HCC, p

Abstract The accuracy of noninvasive seromarkers in predicting liver fibrosis in metabolic dysfunction‐associated fatty liver disease (MAFLD) patients with or without viral hepatitis is elusive. The AST to platelet ratio index (APRI), fibrosis‐4 index (FIB‐4), and NAFLD fibrosis score (NFS) were assessed in 871 MAFLD patients who received elastography in a viral hepatitis‐endemic area. The area under the receiver operating characteristic (AUROC) curve increased substantially with increasing fibrotic stage across the three biomarkers. APRI (AUROC range 0.73–0.80) and FIB‐4 (AUROC range 0.66–0.82) performed better than NFS (AUROC range 0.63–0.75). When patients were divided into viral and non‐viral MAFLD groups, a better AUROC of APRI (range 0.76–0.80) and FIB‐4 (range 0.68–0.78) than NFS (range 0.62–70) existed only in viral MALFD but not in non‐viral MAFLD. Regarding the NFS, the AUROC was higher in non‐viral MAFLD (range 0.69–0.86) and outperformed viral MAFLD at all fibrotic stages. The accuracy in predicting liver fibrosis increased with the advancement of liver disease for the three biomarkers. NFS exerted better diagnostic accuracy in non‐viral than in viral MAFLD patients across different fibrotic stages. The best accuracy was 91.1% using the cutoff value of −9.98 for the NFS in predicting liver cirrhosis in non‐viral MAFLD patients. The APRI and FIB‐4 performed better than the NFS in predicting liver fibrosis in MAFLD as a whole. The suboptimal performance and accuracy of the NFS existed only in viral MAFLD patients. Caution should be taken when assessing the NFS in MAFLD patients with viral hepatitis.

Abstract Introduction Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). Methods The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. Results A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. Conclusion Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Abstract We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti‐HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 μm in diameter [PM2.5], nitrogen dioxide [NO2], ozone [O3] and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.05–4.77; p

Abstract Background MicroRNAs (miRNAs) play a crucial role in gene expression and regulation, with dysregulation of miRNA function linked to various diseases, including hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). There is still a gap in understanding the regulatory relationship between miRNAs and mRNAs in HCV-HCC. This study aimed to investigate the function and effects of persistent HCV-induced miRNA expression on gene regulation in HCC. Methods MiRNA array data were used to identify differentially expressed miRNAs and their targets, and miRNAs were analyzed via DIANA for KEGG pathways, gene ontology (GO) functional enrichment, and Ingenuity Pathways Analysis (IPA) for hepatotoxicity, canonical pathways, associated network functions, and interactive networks. Results Seventeen miRNAs in L-HCV and 9 miRNAs in S-HCV were differentially expressed, and 5 miRNAs in L-HCV and 5 miRNAs in S-HCV were significantly expressed in liver hepatocellular carcinoma (LIHC) tumors. Grouped miRNA survival analysis showed that L-HCV miRNAs were associated with survival in LIHC, and miRNA‒mRNA targets regulated viral carcinogenesis and cell cycle alteration through cancer pathways in LIHC. MiRNA-regulated RCN1 was suppressed through miRNA-oncogene interactions, and suppression of RCN1 inhibited invasion and migration in HCC. Conclusion Persistent HCV infection induced the expression of miRNAs that act as tumor suppressors by inhibiting oncogenes in HCC. RCN1 was suppressed while miRNAs were upregulated, demonstrating an inverse relationship. Therefore, hsa-miR-215-5p, hsa-miR-10b-5p, hsa-let-7a-5p and their target RCN1 may be ideal biomarkers for monitoring HCV-HCC progression. Graphical Abstract

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p

Abstract Elevated serum gamma‐glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)‐related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month‐6) after initiating NAs were measured to explore their association with all‐cause, liver‐related, and non‐liver‐related mortality. The annual incidence of all‐cause mortality was 0.9/100 person‐years over a follow‐up period of 17,436.3 person‐years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month‐6‐GGT levels (62.1 vs. 38.4 U/L, p 75 percentile of pretreatment GGT levels was observed with respect to the all‐cause mortality (trend p

Abstract With the introduction of direct‐acting antivirals, elimination of hepatitis C virus (HCV) infection is becoming possible. People who inject drugs (PWID) represent a population with a high risk for HCV infection, which has been reported as high as 90% in Taiwanese PWID. To reach the goal of HCV elimination, PWID is a key population deserving special attention. Barriers in HCV care cascade still exist in PWID, and interventions to promote access to HCV diagnosis, link‐to‐care, treatment, and prevention for PWID are warranted. Although HCV micro‐elimination can be achieved in some prisons and opioid substitution therapy (OST) centers by a multidisciplinary team and integrated care in Taiwan, there are still several unmet needs for HCV elimination in PWID. Continuous efforts, such as the participation of OST specialists and the continuum of care for HCV among PWID, are needed to achieve HCV elimination in Taiwan. In addition, the combination of harm reduction services, treatment as prevention and regular posttreatment HCV surveillance is critical to substantially reduce HCV transmission and prevalence in PWID.

Background/Aims Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Abstract Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti‐HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post‐treatment follow‐up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy‐three (4.9%) individuals were seropositive for anti‐HCV antibodies. Of the 73 anti‐HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty‐three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post‐treatment follow‐up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient‐centered and integrated outreach program facilitated HCV care in this marginalized population.

Background: The Fibrosis-4 (FIB-4) index is widely recommended as a first-tier method for screening advanced hepatic fibrosis; however, its diagnostic performance is known to be suboptimal in patients with Type 2 diabetes mellitus (T2DM). We aim to propose a modified FIB-4, using the parameters of the existing FIB-4, tailored specifically for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A total of 1503 patients who underwent liver biopsy were divided into T2DM (n = 517) and non-T2DM (n = 986) groups. The model was developed using multiple regression analysis in the derivation cohort and validated in the validation cohort. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic (AUC) curves. Results: Among the 1503 individuals, those with T2DM were older, more likely to be male, and had a higher prevalence of advanced hepatic fibrosis (≥F3) compared to non-T2DM individuals. Independent risk factors for advanced fibrosis in T2DM included age, AST, AST/ALT ratio, albumin, triglycerides, and platelet count. The optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index) demonstrated superior diagnostic accuracy (AUC 0.771) compared to the FIB-4 (AUC 0.735, p = 0.012). The model showed a higher negative predictive value than the original FIB-4 across all age groups in the diabetic group. Conclusions: The newly optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index), incorporating a non-linear predictive model, improves diagnostic performance (AUC) and the negative predictive value in MASLD with T2DM.

Abstract Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV‐related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV‐related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety‐one (23%) of the HBV‐aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, impacting almost one-third of the global population. MAFLD constitutes a primary cause of end-stage liver disease, liver cancer and the need for liver transplantation. Moreover, it has a strong association with increased mortality rates due to various extrahepatic complications, notably cardiometabolic diseases. While MAFLD is typically correlated with obesity, not all individuals with obesity develop the disease and a significant percentage of MAFLD occurs in patients without obesity, termed lean MAFLD. The clinical features, progression and underlying physiological mechanisms of patients with lean MAFLD remain inadequately characterized. The present review aims to provide a comprehensive summary of current knowledge on lean MAFLD and offer a perspective on defining MAFLD in individuals with normal weight. Key to this process is the concept of metabolic health and flexibility, which links states of dysmetabolism to the development of lean MAFLD. This perspective offers a more nuanced understanding of MAFLD and its underlying mechanisms and highlights the importance of considering the broader metabolic context in which the disease occurs. It also bridges the knowledge gap and offers insights that can inform clinical practice.

Introduction: Taiwan has several hepatitis C virus (HCV) hyper-endemic areas. We aimed to evaluate the effectiveness and safety of a collaborative HCV care system with an outreach decentralized strategy among the resource-constrained rural/remote areas of Taiwan. Methods: The pilot study was conducted in four high HCV-endemic townships in the rural/remote areas of Taoyuan, Alishan, Zhuoxi and Xiulin. Registered residents who worked or lived in the four areas and were aged 30–75 years were invited to participate in this program. Multidisciplinary HCV care teams provided outreach decentralized services of anti-HCV screening, link-to-diagnosis, and link-to-treatment with direct-acting antiviral agents (DAA). The primary end-point was sustained virological response (SVR). Results: Of 8291 registered residents who were invited as the target population, 7807 (94.2%) subjects received anti-HCV screening, with the average anti-HCV prevalence rate of 14.2% (1108/7807) (range among four areas: 11.8%–16.7%). The rate of link-to-diagnosis was 94.4% (1046/1108) of anti-HCV-positive subjects (range: 90.9%–100%) with an average HCV-viremic rate of 55.1% (576/1046) (range: 50.0%–64.3%). The link-to-treat rate was 94.4% (544/576) in HCV-viremic subjects (range from 92.7% to 97.2%). Overall, 523 (96.1%) patients achieved an SVR (range: 94.7%–97.6%). Eventually, the overall effectiveness was 80.7% (range: 74.6%–93.1%). The presence of hepatocellular carcinoma at baseline was the only factor associated with DAA failure. The DAA regimens were well-tolerated. Conclusion: The outreach decentralized community-based care system with DAA therapy was highly effective and safe in the achievement of HCV micro-elimination in the resource-constrained rural and remote regions, which could help us to tackle the disparity.

Objectives: Gaps in linkage-to-care remain the barriers toward hepatitis C virus (HCV) elimination in the directly-acting-antivirals (DAA) era, especially during SARS Co–V2 pandemics. We established an outreach project to target HCV micro-elimination in HCV-hyperendemic villages. Methods: The COMPACT provided “door-by-door” screening by an “outreach HCV-checkpoint team” and an “outreach HCV-care team” for HCV diagnosis, assessment and DAA therapy in Chidong/Chikan villages between 2019 and 2021. Participants from neighboring villages served as Control group. Results: A total of 5731 adult residents participated in the project. Anti-HCV prevalence rate was 24.0% (886/3684) in Target Group and 9.5% (194/2047) in Control group (P

Abstract Background/Aims Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. Methods Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. Results A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0–1, 2–3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ–AZ–Moderna (39.2%), followed by Moderna–Moderna–Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34–0.72, P

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.

Background & Aims: Hepatocellular carcinoma (HCC) is a model of a diverse spectrum of cancers because it is induced by well-known etiologies, mainly hepatitis C virus (HCV) and hepatitis B virus. Here, we aimed to identify HCV-specific mutational signatures and explored the link between the HCV-related regional variation in mutations rates and HCV-induced alterations in genome-wide chromatin organization. Methods: To identify an HCV-specific mutational signature in HCC, we performed high-resolution targeted sequencing to detect passenger mutations on 64 HCC samples from 3 etiology groups: hepatitis B virus, HCV, or other. To explore the link between the genomic signature and genome-wide chromatin organization we performed chromatin immunoprecipitation sequencing for the transcriptionally permissive H3K4Me3, H3K9Ac, and suppressive H3K9Me3 modifications after HCV infection. Results: Regional variation in mutation rate analysis showed significant etiology-dependent regional mutation rates in 12 genes: LRP2, KRT84, TMEM132B, DOCK2, DMD, INADL, JAK2, DNAH6, MTMR9, ATM, SLX4, and ARSD. We found an enrichment of C->T transversion mutations in the HCV-associated HCC cases. Furthermore, these cases showed regional variation in mutation rates associated with genomic intervals in which HCV infection dictated epigenetic alterations. This signature may be related to the HCV-induced decreased expression of genes encoding key enzymes in the base excision repair pathway. Conclusions: We identified novel distinct HCV etiology-dependent mutation signatures in HCC associated with HCV-induced alterations in histone modification. This study presents a link between cancer-causing mutagenesis and the increased predisposition to liver cancer in chronic HCV-infected individuals, and unveils novel etiology-specific mechanisms leading to HCC and cancer in general.

Abstract Hepatocellular carcinoma (HCC) is a highly invasive malignancy. Recently, GATOR1 (Gap Activity TOward Rags 1) complexes have been shown to play an important role in regulating tumor growth. NPRL2 is a critical component of the GATOR1 complex. Therefore, this study used NPRL2 knockdown to investigate how GATORC1 regulates the prognosis and development of HCC via the mammalian target of rapamycin (mTOR) and autophagy signaling pathways. We established HepG2 cells with NPRL2 knockdown using small interfering RNA (siRNA) and short hairpin RNA (shRNA) systems. The siRNA‐mediated and shRNA‐mediated NPRL2 down‐regulation significantly reduced the expression of NPRL2 and two other GATPOR1 complex components, NPRL3 and DEPDC5, in HepG2 cells; furthermore, the efficient down‐regulation of NPRL2 protein expression by both the shRNA and siRNA systems enhanced the proliferation, migration, and colony formation in vitro. Additionally, the NPRL2 down‐regulation significantly increased HCC growth in the subcutaneous and orthotopic xenograft mouse models. The NPRL2 down‐regulation increased the Rag GTPases and mTOR activation and inhibited autophagy in vitro and in vivo. Moreover, the NPRL2 level in the tumors was significantly associated with mortality, recurrence, the serum alpha fetoprotein level, the tumor size, the American Joint Committee on Cancer stage, and the Barcelona Clinic Liver Cancer stage. Low NPRL2, NPRL3, DEPDC5, and LC3, and high p62 and mTOR protein expression in the tumors was significantly associated with disease‐free survival and overall survival in 300 patients with HCC after surgical resection. Conclusion: The efficient down‐regulation of NPRL2 significantly increased HCC proliferation, migration, and colony formation in vitro, and increased HCC growth in vivo. Low NPRL2 protein expression in the tumors was closely correlated with poorer clinical outcomes in patients with HCC. These results provide a mechanistic understanding of HCC and aid the development of treatments for HCC.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus emerged in late 2019 leading to the COVID‐19 disease pandemic that triggered socioeconomic turmoil worldwide. A precise, prompt, and affordable diagnostic assay is essential for the detection of SARS‐CoV‐2 as well as its variants. Antibody against SARS‐CoV‐2 spike (S) protein was reported as a suitable strategy for therapy and diagnosis of COVID‐19. We, therefore, developed a quick and precise phase‐sensitive surface plasmon resonance (PS‐SPR) biosensor integrated with a novel generated anti‐S monoclonal antibody (S‐mAb). Our results indicated that the newly generated S‐mAb could detect the original SARS‐CoV‐2 strain along with its variants. In addition, a SARS‐CoV‐2 pseudovirus, which could be processed in BSL‐2 facility was generated for evaluation of sensitivity and specificity of the assays including PS‐SPR, homemade target‐captured ELISA, spike rapid antigen test (SRAT), and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Experimentally, PS‐SPR exerted high sensitivity to detect SARS‐CoV‐2 pseudovirus at 589 copies/ml, with 7‐fold and 70‐fold increase in sensitivity when compared with the two conventional immunoassays, including homemade target‐captured ELISA (4 × 103 copies/ml) and SRAT (4 × 104 copies/ml), using the identical antibody. Moreover, the PS‐SPR was applied in the measurement of mimic clinical samples containing the SARS‐CoV‐2 pseudovirus mixed with nasal mucosa. The detection limit of PS‐SPR is calculated to be 1725 copies/ml, which has higher accuracy than homemade target‐captured ELISA (4 × 104 copies/ml) and SRAT (4 × 105 copies/ml) and is comparable with qRT‐PCR (1250 copies/ml). Finally, the ability of PS‐SPR to detect SARS‐CoV‐2 in real clinical specimens was further demonstrated, and the assay time was less than 10 min. Taken together, our results indicate that this novel S‐mAb integrated into PS‐SPR biosensor demonstrates high sensitivity and is time‐saving in SARS‐CoV‐2 virus detection. This study suggests that incorporation of a high specific recognizer in SPR biosensor is an alternative strategy that could be applied in developing other emerging or re‐emerging pathogenic detection platforms.

Abstract Hepatitis C virus (HCV) eradication through antivirals ameliorates metabolic profiles. The changes in 2‐h plasma glucose (2HPG) levels by oral glucose tolerance test (OGTT), in chronic hepatitis C (CHC) patients who receive directly acting antivirals (DAAs) was elusive. Five hundred and thirty‐three CHC patients who achieved sustained virological response (SVR, undetectable HCV RNA throughout 3 months after the end‐of‐treatment) by DAAs were consecutively enrolled. Pre‐ and posttreatment 2HPG levels and glucose status were compared. The proportion of patients with improved, worsened, and stable 2HPG was 14.4% (n = 77), 18.6% (n = 99), and 67.0% (n = 357), respectively. Compared with patients with worsening 2HPG, those with improved 2HPG had a higher proportion of cirrhosis (45.5% vs. 24.2%, p = 0.004) and higher pretreatment 2HPG levels (175.3 vs. 129.5 mg/dl, p

Background: An outbreak of SARS-CoV-2 Delta variant infection occurred in Pingtung, Taiwan, in June 2021. In this study, we aimed to elucidate the clinical characteristics of the Delta-variant SARS-CoV-2 infection and the treatment outcome of antiviral agents in patients from Pingtung County in Southern Taiwan. Methods: A total of 11 patients with Delta-variant COVID-19 were consecutively admitted to a governmental hospital in June 2021. Baseline characteristics and treatment outcome were evaluated. Results: All patients were symptomatic. The most common symptoms were cough (72.7%), followed by fever (54.5%), headache (18.2%) and dysosmia/dysgeusia (18.2%). Two patients developed pneumonia without mechanical ventilation requirement. Compared to patients without pneumonia, those with pneumonia had higher aspartate aminotransferase (AST) (21.0 vs. 126.0 IU/L, P = 0.03) and lactate dehydrogenase (LDH) (143.1 vs. 409.0 IU/mL, P = 0.03), and ferritin (0.2 vs. 2.0 mg/L, P = 0.046) levels. Pneumonia improved after 2-week treatment, and no mortality occurred after 30 days of diagnosis. The median duration of viral shedding duration of viral shedding was 16.5 days (range 11–42 days) (defined by time to repeated negative real-time reverse transcriptase polymerase chain reaction (RT-PCR) or a cycle threshold (CT) value ≥ 30). Conclusion: We demonstrated the clinical characteristics of Delta-variant COVID-19 and treatment outcome of antiviral agents. The risk factors attributed to pneumonia were higher serum AST, ferritin, and LDH levels.

ABSTRACT: Objectives: Monkeypox has recently been detected outside African countries. This study aimed to report and analyze the first case of monkeypox virus infection in Taiwan. Methods: The global epidemiological information was collected from the World Health Organization (WHO) and US Centers for Disease Control and Prevention (CDC). The data from the first confirmed Taiwanese monkeypox case was obtained from Taiwan Centers for Disease Control. Monkeypox diagnosis and prevention strategies were obtained from WHO guidelines on monkeypox. Phylogenetic tree analysis and sequence alignment and comparison were used to identify the phylogeny and single nucleotide polymorphism (SNP) characterization. Results: Epidemiological data indicated that since 2013, monkeypox has caused outbreaks outside African countries through contact with infected animals and international travels. Recently, two confirmed monkeypox cases were reported in Singapore and South Korea. On June 24, 2022, Taiwan CDC reported the first confirmed case of monkeypox virus infection in a 20-year-old man who returned from Germany, from January to June 2022. This is the third confirmed case of an imported monkeypox infection in Asia. Phylogenetic analysis demonstrated that this imported monkeypox virus belonged to the West African clade and is clustered with the 2022 European outbreak monkeypox isolates. Full-length sequence analysis indicates that this virus contains 51 SNPs, and has five variant SNPs compared with the recent outbreak strains. Conclusion: This study suggests that active surveillance, enhancing border control, and the development of vaccines and antiviral drugs are urgently required to prevent and control the burden of monkeypox disease.

Objective Hepatitis C is an important risk factor for cirrhosis and liver cancer in the Taiwanese population. Domestic prisons reported a higher rate of hepatitis C infection than the national average. Efficient and effective treatment of patients with hepatitis C in prisons is required to decrease the number of infections. This study analysed the effectiveness of hepatitis C treatment and its side effects in prison patients.Design This retrospective analysis included adult patients with hepatitis C who received direct-acting antiviral agents between 2018 and 2021.Setting The special hepatitis C clinics in the two prisons were run by a medium-sized hepatitis C treatment hospital in Southern Taiwan. Three direct-acting antiviral agents, sofosbuvir/ledipasvir for 12 weeks, glecaprevir/pibrentasvir for 8 or 12 weeks and sofosbuvir/velpatasvir for 12 weeks, were adopted based on patient characteristics.Participants 470 patients were included.Outcome measure The sustained virological response at 12 weeks after the end of treatment was compared between the different groups.Results Most of the patients were men (70.0%) with a median age of 44 years. The most prevalent hepatitis C virus genotype was genotype 1 (44.26%). A total of 240 patients (51.06%) had a history of injectable drug use; 44 (9.36%) and 71 (15.11%) patients were coinfected with hepatitis B virus and HIV, respectively. Only 51 patients (10.85%) had liver cirrhosis. Most patients (98.30%) had normal renal function or no history of kidney disease. The patients had a sustained virological response achievement rate of 99.2%. The average incidence of adverse reactions during treatment was approximately 10%. Many of the adverse reactions were mild and resolved spontaneously.Conclusion Direct-acting antiviral agents are effective for treating hepatitis C in Taiwanese prisoners. These therapeutics were well-tolerated by the patient population.

Background/purpose: 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. Methods: 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). Results: 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 were >98%, 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

Background/Purpose: Switching to a tenofovir alafenamide (TAF)-containing regimen has been reported to be associated with body weight gain in human immunodeficiency virus-infected subjects. We aimed to investigate the body weight change and virological, hepatic, and renal outcomes of TAF switching among chronic hepatitis B (CHB) patients. Methods: This retrospective study included 121 CHB patients who were switched to TAF after >12 months of treatment with another nucleot(s)ide analog (NUC). All patients were monitored for 12 months. Results: The cohort was mostly Asian (96.7%) with a mean age of 55 years, 72% male, 14% cirrhosis, 21% HBeAg positive, and 75% with prior use of tenofovir disoproxil fumarate. At 12 months after TAF switching, their body weight significantly increased from 66.4 ± 11.8 to 67.8 ± 12.3 kg (p

Abstract Chronic hepatitis B (CHB) patients with low disease activity are at risk of liver fibrosis. The age‐adjusted fibrosis‐4 index (FIB4‐AA), developed in our previous publication, and was implemented to evaluate the tendency of liver fibrosis in these patients. We aimed to investigate the rate of liver fibrosis in CHB patients with low disease activity. Resuming our previous study, the FIB‐4 changes of 244 antiviral treatment‐naïve CHB patients, with a total of 1243.48 person‐years, were reviewed. Among the cohort, patients were categorized as FIB4‐AA positive or negative according to the results of their last FIB4‐AA minus their initial FIB‐4 during at least 18 months of observation time. The compound annual growth rate (CAGR) of FIB‐4 was calculated for the FIB4‐AA positive and negative groups. The assumed healthy controls had an FIB‐4 CAGR calculated to be 2.34% for both men and women, while the FIB‐4 CAGR of the whole study cohort was 2.84% ± 6.01%. FIB4‐AA positive effectively identifies CHB patients with higher mean FIB‐4 CAGR (7.11% ± 3.88% vs. −2.36% ± 3.52%, p

Abstract Understanding the barriers and tackling the hurdles of hepatitis C virus (HCV) care cascades is key to HCV elimination. The current study aimed to investigate the rates of disease awareness, link‐to‐care, and treatment uptake of HCV in a hyperendemic area in Taiwan. Tzukuan residents from 2000 to 2018 were invited to participate in the questionnaire‐based interviews for HCV. The rates of disease awareness, accessibility, and anti‐HCV therapy were evaluated in anti‐HCV‐seropositive participants. Among 10,348 residents, 1789 (17.3%) were anti‐HCV seropositive. Of these 1789 anti‐HCV‐seropositive participants, data of 594 participants from questionnaire‐based interviews in 2005–2018 were analyzed for HCV care cascades. Overall, 24.9% of anti‐HCV‐seropositive HCV participants had disease awareness, 53.9% of aware participants had accessibility, and 79.8% of assessed participants had received HCV treatment, with a community effectiveness of 10.7%. HCV prevalence decreased over time, from 21.2% in the early cohort to 9.3% in the recent cohort. Disease awareness increased over time, from 15.6% to 41.7%, with the community effectiveness increasing from 1.3% to 28.8%. Lower education levels and normal liver biochemistry were associated with a lower rate of disease awareness. Notably, 68% of participants with abnormal liver biochemistry and 69% of those with advanced fibrosis (FIB‐4 > 3.25) were unaware of their HCV disease. We demonstrated huge gaps in disease awareness, link‐to‐care, and treatment uptake in the HCV care cascade in an HCV‐hyperendemic area, even in the initial era of direct‐acting antiviral agents. There is an urgent need to overcome these hurdles to achieve HCV elimination.

Abstract The role of Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) in the prediction of disease severity in nonalcoholic fatty liver disease (NAFLD) remains elusive. This study evaluated the performance of WFA+‐M2BP in predicting fibrosis in patients with NAFLD. A total of 80 patients with biopsy‐proven nonalcoholic steatohepatitis (NASH) were enrolled. Serum WFA+‐M2BP levels were measured using standard methods. The fibrosis‐4 (FIB‐4) index was also measured. The mean values of WFA+‐M2BP were 1.0, 1.0, 0.8, and 2.2 in Metavir fibrosis stage F0, F1, F2, and F3‐4, respectively (linear trend p = 0.005). The optimal cut‐off value of WFA+‐M2BP in predicting advanced fibrosis (F3‐4) was 1.37 cut‐off index (COI), yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of 75.0, 79.4, 39.1, 94.7, and 78.7%, respectively (p

Abstract Cancer stem cell is considered as an important cause to exacerbate the prognosis. NANOG and POU5F1 are markers for cancer stem cells. The associations between NANOG and POU5F1 expressions with the sorafenib anticancer effects in primary cultured hepatocellular carcinoma (HCC) cells were investigated. Eight primary cultured HCC parent cell lines and 13 subgroups established by flow cytometric sorting using NANOG and POU5F1 as targets were investigated with clinically achievable sorafenib plasma concentrations (5 and 10 μg/mL). Sorafenib showed obvious downregulation of RAF/MEK/ERK signaling pathways and dose‐dependent anti‐proliferative effects only on s003 parent cell line, which showed the lowest expression of NANOG among all tested cell lines except one downregulated NANOG with upregulated POU5F1 s020 subgroup. Sorafenib also inhibited proliferation in this s020 subgroup but promoted proliferation in its parent cell line. For the only one downregulated NANOG alone s015 subgroup, sorafenib which had no influence on its parent cell line inhibited proliferation in this subgroup. Only the above three cell lines could demonstrate sorafenib antiproliferative effects. On the contrary, sorafenib promoted proliferation in three (s003, s015, s071) out of four upregulated NANOG alone subgroups. On the other hand, Sorafenib showed diverse influence on proliferation among four upregulated POU5F1 alone subgroups. In conclusion, NANOG rather than POU5F1 expression is a critical marker for the anticancer effects of sorafenib on HCC. The sorafenib anticancer effects on HCC cells with high NANOG expression were limited. Sorafenib should be combined with other drug able to target cancer cells with high NANOG expression.

Abstract Background and Aims Regorafenib has demonstrated its survival benefit for unresectable hepatocellular carcinoma (uHCC) patients in a phase III clinical trial. We aimed to assess the efficacy and tolerability of regorafenib and the predictors of treatment outcomes in Taiwanese patients. Methods We analyzed the survival, best overall response, predictors of treatment outcomes, and safety for uHCC patients who had tumor progression on sorafenib therapy and received regorafenib as salvage therapy between March 2018 and November 2020. Results Eighty‐six patients with uHCC were enrolled (median age, 66.5 years; 76.7% male). The median regorafenib treatment duration was 4.0 months (95% confidence interval [CI], 3.6–4.6). The most frequently reported adverse events were hand‐foot skin reaction (44.2%), diarrhea (36.0%), and fatigue (29.1%). No unpredictable toxicity was observed during treatment. The median overall survival (OS) with regorafenib was 12.4 months (95% CI, 7.8–17.0) and the median progression‐free survival (PFS) was 4.2 months (95% CI, 3.7–4.7). Of 82 patients with regorafenib responses assessable, 4 patients (4.9%) achieved a partial response, and 33 (40.2%) had stable disease, leading to a disease control rate (DCR) of 45.1% (n = 37). Patients possessing baseline AFP 10% reduction at 4 weeks or >20% reduction at 8 weeks after regorafenib administration) exhibited comparable treatment outcomes to those with baseline AFP

Abstract 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.

Background & aims: Treatment of hepatitis C virus (HCV) by elbasvir/grazoprevir (EBR/GZR) was found to be efficacious and well tolerated in clinical trials. This study aimed to evaluate the effectiveness and tolerability of EBR/GZR in the treatment of HCV genotype 1-infected Taiwanese patients. Methods: Chronic hepatitis C patients infected with GT1b or 1a without resistance-associated substitution, and treated with 12-week EBR/GZR were enrolled from 10 hospitals in Taiwan between August 2017 and December 2018. All clinical and virologic data were collected at each participating center. Primary efficacy endpoint was sustained virologic response at week 12 (SVR12) after end of the EBR/GZR therapy, assessed in the per-protocol population, which excluded patients with important deviations from the protocol. Analysis was also performed based on the modified full analysis set, which included all allocated patients receiving at least 4-week medication. Virologic failure was recorded as breakthrough, nonresponse, or relapse. Safety was assessed through collection of adverse events, physical examination, vital signs, and standard laboratory evaluations. Results: Per protocol SVR12 rates were 99.5% (1169/1175) for all HCV genotype 1 patients. Among patients with stage 4 or 5 chronic kidney diseases, 100% (107/107) achieved SVR12. In univariate analyses, variables associated with SVR12 were treatment termination (P

Abstract Previous in vitro and in vivo experiments had demonstrated dose‐dependent anti‐cancer effects of clinical plasma colchicine concentrations on hepatocellular carcinoma (HCC) cells. This phase IIa trial was to evaluate the potential efficiency and safety of our novel colchicine dosage schedule for the palliative treatment of advanced HCC. The dosage schedule started from oral intake of 1 mg colchicine three times per day for 4 days and discontinuation in the following 3 days (one cycle). The treatment cycle was repeated and the dosage was adjusted ranging from 3 to 1.5 mg/day according to the condition of the participant. The control group was originated from chart review of 86 HCC patients treated by sorafenib for more than 2 months. Fifteen participants signed the inform consent. Two participants were excluded due to screening failure in one and less than four treatment cycles in another. For severe adverse events, the colchicine group demonstrated higher incidence of biliary tract obstruction (p = 0.0184) than the sorafenib group. Comparison grade 1 or 2 adverse events between two groups, the colchicine group had higher incidence of diarrhea (p = 0) and the sorafenib group had higher incidence of palmar‐plantar erythrodysesthesia syndrome (p = 0.0045). There was no significant difference in mortality, median survival, and overall survival between two groups (all p > 0.2). In conclusion, our novel colchicine dosage schedule is clinically feasible and has the potential to be applied in the palliative treatment of advanced HCC especially based on the cost‐effectiveness consideration.