Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Entecavir vs. tenofovir disoproxil fumarate in the treatment of chronic hepatitis B patients with severe acute exacerbation.

BACKGROUND: The efficacy of different nucleos(t)ide analogs in the treatment of chronic hepatitis B virus (CHB) with severe acute exacerbation (SAE) remained unclear. Thus, this study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients having CHB with SAE. METHODS: We analyzed consecutive patients with treatment-naive CHB receiving TDF (n = 36) or ETV (n = 65) for SAE. The primary endpoint was overall mortality or receipt of liver transplantation (LT) by 24 weeks. The secondary endpoints are the comparison of ETV vs. TDF influences on renal function and virological and biochemical responses at 4, 12, 24, and 48 weeks. RESULTS: The baseline characteristics were comparable between the two groups. By 24 weeks, 8 (22%) patients in the TDF group and 10 (15%) patients in the ETV group had either died (n = 15) or received LT (n = 3) ( P  = 0.367). Cox-regression multivariate analysis revealed age ( P  = 0.003), baseline international normalized ratio of prothrombin time ( P  = 0.024), and early presence of hepatic encephalopathy ( P  = 0.003) as independent factors associated with mortality or LT. The two groups of patients achieved comparable biochemical and virological responses at 48 weeks. No significant difference was found in the estimated glomerular filtration rate (eGFR) between the TDF and the ETV groups. However, a significant reduction in the eGFR at 48 weeks, as compared with the baseline, was found in each group. CONCLUSION: TDF and ETV achieved similar short-term clinical outcomes and treatment responses in CHB patients with SAE.

The Motivation for COVID-19 Vaccination and Preventive Behavior.

COVID-19, a viral infection that emerged in late 2019, induces a severe acute respiratory syndrome marked by significant clinical symptoms, and the potential for progressive respiratory failure and death. People facing the threat of COVID-19 not only feared being infected, but were also worried about the side-effects of vaccination. This conflict affected their epidemic prevention behavior. To understand this issue, the present study explored whether infection anxiety affected the psychological avoidance or approach to getting vaccinated and the intention to take epidemic prevention measures. The study implemented a cross-sectional, web-based survey. We created questionnaires using Surveycake, an online e-form questionnaire platform. We used the snowball sampling method via a social media app to recruit participants. If individuals were willing to participate in the research, we emailed the e-form questionnaire link to them to collect data. After questionnaire collection, 288 questionnaires were returned, and 277 valid questionnaires were obtained for structural equation modeling analysis. According to the statistical results, it was found that infection anxiety was positively related to avoidance-avoidance conflict, and the power of infection anxiety on avoidance conflict was 23.0%. Infection anxiety was negatively related to approach-approach conflict regarding vaccination, and the power of infection anxiety on approach-approach conflict was 22.0%. Approach-approach conflict regarding vaccination was negatively related to prevention behavior, while avoidance-avoidance conflict regarding vaccination was positively related to prevention behavior. The two conflicts explained 12.5% of the total variance in prevention behavior. The study results highlight the long-term importance of achieving vaccine goals in order to prepare for future health emergencies similar to the recent COVID-19 pandemic.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

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<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. CONCLUSION: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Inhibition of Polyinosinic-Polycytidylic Acid-Induced Acute Pulmonary Inflammation and NF-κB Activation in Mice by a Banana Plant Extract.

NF-κB activation is pivotal for the excess inflammation causing the critical condition and mortality of respiratory viral infection patients. This study was aimed to evaluate the effect of a banana plant extract (BPE) on suppressing NF-κB activity and acute lung inflammatory responses in mice induced by a synthetic double-stranded RNA viral mimetic, polyinosinic-polycytidylic acid (poly (I:C)). The inflammatory responses were analyzed by immunohistochemistry and HE stains and ELISA. The NF-κB activities were detected by immunohistochemistry in vivo and immunofluorescence and Western blot in vitro. Results showed that BPE significantly decreased influx of immune cells (neutrophils, lymphocytes, and total WBC), markedly suppressed the elevation of pro-inflammatory cytokines and chemokines (IL-6, RANTES, IFN-γ, MCP-1, keratinocyte-derived chemokine, and IL-17), and restored the diminished anti-inflammatory IL-10 in the bronchoalveolar lavage fluid (BALF) of poly (I:C)-stimulated mice. Accordingly, HE staining revealed that BPE treatment alleviated poly (I:C)-induced inflammatory cell infiltration and histopathologic changes in mice lungs. Moreover, immunohistochemical analysis showed that BPE reduced the pulmonary IL-6, CD11b (macrophage marker), and nuclear NF-κB p65 staining intensities, whilst restored that of IL-10 in poly (I:C)-stimulated mice. In vitro, BPE antagonized poly(I:C)-induced elevation of IL-6, nitric oxide, reactive oxygen species, NF-κB p65 signaling, and transient activation of p38 MAPK in human lung epithelial-like A549 cells. Taken together, BPE ameliorated viral mimic poly(I:C)-induced acute pulmonary inflammation in mice, evidenced by reduced inflammatory cell infiltration and regulation of both pro- and anti-inflammatory cytokines. The mechanism of action might closely associate with NF-κB signaling inhibition.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

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. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy.

BACKGROUND: Hepatocellular carcinoma (HCC) with major portal vein invasion (MPVI) presents very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC. In this retrospective study, we compared the therapeutic outcomes of our "new" HAIC regimen with and without concurrent RT, before and after propensity score matching (PSM) in treating HCC patients with MPVI. METHODS: One hundred forty patients with MPVI received HAIC alone and 35 patients underwent concurrent HAIC and RT during a 16-year period. The left subclavian artery was adopted as the entry site for a temporary catheter placement for a 5-day chemoinfusion. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox regression model were used to assess hazard ratios. RESULTS: Of the 140 patients with Child-Pugh A liver function, the median OS was 17.0 months. In the initial cohort, higher ORR and PFS were found in the concurrent RT group than in the HAIC alone group (80% vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p = 0.039) was observed. After PSM, the OS was 10 and 15 months ( p = 0.012), respectively. Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, alpha fetal protein (AFP) level, and hepatic vein invasion. CONCLUSION: HAIC is an effective treatment for advanced HCC patients with MPVI. Concurrent HAIC and full-dose RT were associated with worse clinical outcomes.