Strength-ductility materials by engineering a coherent interface at incoherent precipitates.

In the quest for excellent light-structural materials that can withstand mechanical extremes for advanced applications, design and control of microstructures beyond current material design strategies have become paramount. Herein, we design a coherent shell at incoherent precipitates in the 2195 aluminum alloy with multi-step metastable phase transitions. A high local strain rate via a neoteric deformation-driven metallurgy method facilitated the diffusion of Li. The original T1 (Al2CuLi) phases were transformed into coherent-shell (Li-rich) irregular-coated incoherent-core (Al2Cu) precipitates. The ultimate tensile strength and elongation reached 620 ± 18 MPa and 22.3 ± 2.2%, exhibiting excellent strength-ductility synergy. Grain boundaries, dislocation, solid solution atoms, and precipitates all contributed to the yield strength of the materials, among which precipitates occupied a dominant position, contributing approximately 56.07%. A new "incoherent-coherent interact" strain-hardening mechanism was also clarified, which was believed to be promoted in other heat-treatable alloy systems, especially with multi-step metastable phase transitions.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

Supergravity-Steered Generic Manufacturing of Nanosheets-Embedded Nanocomposite Hydrogel with Highly Oriented, Heterogeneous Architecture.

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

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

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

The efficacy of multi-disciplinary lifestyle modifications in Taiwanese nonalcoholic steatohepatitis patients.

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.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis.

BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.

Phase 1 Trial of the Safety, Pharmacokinetics, and Antiviral Activity of EDP-514 in Untreated Viremic Chronic Hepatitis B Patients.

Background & Aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics (PK), and antiviral activity of three doses of EDP-514 in treatment naïve viremic patients with HBeAg-positive or -negative chronic HBV infection. Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were 2.9, 3.3, 3.5 and 0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was 2.9, 2.4, 2.0, and 0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events (TEAEs) of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions: In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Navigating the Diagnostic Journey in Pediatric Gastroenterology: Decoding Recurrent Vomiting and Epigastric Pain in a Child with Glutaric Aciduria Type II.

BACKGROUND: Glutaric aciduria type II (GA II), also known as multiple acyl-CoA dehydrogenase deficiency (MADD), is a rare autosomal recessive metabolic disorder with varied manifestations and onset ages. CASE REPORT: This study presents a distinctive case of a 10-year-old girl who experienced episodic, intermittent vomiting and epigastric pain, particularly aggravated by high-fat and sweet foods. Despite inconclusive physical examinations and routine laboratory tests, and an initial suspicion of cyclic vomiting syndrome, the persistence of recurrent symptoms and metabolic abnormalities (metabolic acidosis and hypoglycemia) during her third hospital admission necessitated further investigation. Advanced diagnostic tests, including urinary organic acid analysis and genetic testing, identified heterozygous pathogenic variants in the ETFDH gene, confirming a diagnosis of GA IIc. The patient showed a positive response to a custom low-protein, low-fat diet supplemented with carnitine and riboflavin. SIGNIFICANCE: This case emphasizes the diagnostic challenges associated with recurrent, nonspecific gastrointestinal symptoms in pediatric patients, particularly in differentiating between common gastrointestinal disorders and rare metabolic disorders like GA II. It highlights the importance of considering a broad differential diagnosis to enhance understanding and guide future medical approaches in similar cases.

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes.

INTRODUCTION: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD). METHODS: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC. RESULTS: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference. DISCUSSION: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study.

BACKGROUND AND AIM: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. METHODS: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF. RESULTS: The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups. CONCLUSIONS: Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.

Systematic integration of molecular and clinical approaches in HCV-induced hepatocellular carcinoma.

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.

Chronic Viral Hepatitis B and C Outweigh MASLD in the Associated Risk of Cirrhosis and HCC.

BACKGROUND & AIMS: The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known. METHODS: A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019. RESULTS: In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively. CONCLUSIONS: These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.

Effect of electroacupuncture on myocardial electrical remodeling in rats with acute myocardial infarction. / ç”µé’ˆå¯¹æ€¥æ€§å¿ƒè‚Œæ¢—æ­»å¤§é¼ å¿ƒè‚Œç”µé‡æž„çš„å½±å“åŠå ¶æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the mechanism of electroacupuncture (EA) at "Neiguan" (PC6) in impro-ving myocardial electrical remodeling in rats with acute myocardial infarction (AMI) by enhancing transient outward potassium current. METHODS: A total of 30 male SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The AMI model was established by subcutaneous injection with isoprenaline (ISO, 85 mg/kg). EA was applied to left PC6 for 20 min, once daily for 5 days. Electrocardiogram (ECG) was recorded after treatment. TTC staining was used to observe myocardial necrosis. HE staining was used to observe the pathological morphology of myocardial tissue and measure the cross-sectional area of myocardium. Potassium ion-related genes in myocardial tissue were detected by RNA sequencing. The mRNA and protein expressions of Kchip2 and Kv4.2 in myocardial tissue were detected by real-time fluorescence quantitative PCR and Western blot, respectively. RESULTS: Compared with the control group, cardiomyocyte cross-sectional area in the model group was significantly increased (P<0.01), the ST segment was significantly elevated (P<0.01), and QT, QTc, QTd and QTcd were all significantly increased (P<0.05, P<0.01). After EA treatment, cardiomyocyte cross-sectional area was significantly decreased (P<0.01), the ST segment was significantly reduced (P<0.01), and the QT, QTc, QTcd and QTd were significantly decreased (P<0.01, P<0.05). RNA sequencing results showed that a total of 20 potassium ion-related genes co-expressed by the 3 groups were identified. Among them, Kchip2 expression was up-regulated most notablely in the EA group. Compared with the control group, the mRNA and protein expressions of Kchip2 and Kv4.2 in the myocardial tissue of the model group were significantly decreased (P<0.01, P<0.05), while those were increased in the EA group (P<0.01, P<0.05). CONCLUSIONS: EA may improve myocardial electrical remodeling in rats with myocardial infarction, which may be related to its functions in up-regulating the expressions of Kchip2 and Kv4.2.

Poly(N,N-diethylacrylamide)-endowed spontaneous emulsification during the breath figure process and the formation of membranes with hierarchical pores.

The spontaneous emulsification for the formation of water-in-oil (W/O) or oil-in-water (O/W) emulsions needs the help of at least one kind of the third component (surfactant or cosolvent) to stabilize the oil-water interface. Herein, with the water/CS2-soluble polymer poly(N,N-diethylacrylamide) (PDEAM) as a surfactant, the spontaneous formation of water-in-PDEAM/CS2 emulsions is reported for the first time. The strong affinity between PDEAM and water or the increase of PDEAM concentration will accelerate the emulsification process with high dispersed phase content. It is demonstrated that the spontaneous emulsification of condensed water droplets into the PDEAM/CS2 solution occurs during the breath figure process, resulting in porous films with two levels of pore sizes (i.e., micron and submicron). The emulsification degree and the amounts of submicron-sized pores increase with PDEAM concentration and solidifying time of the solution. This work brings about incremental interest in spontaneous emulsification that may happen during the breath figure process. The combination of these two simultaneous processes provides us with an option to build hierarchically porous structures with condensed and emulsified water droplets as templates. Such porous membranes may have great potential in fields such as separation, cell culture, and biosensing.

Hepatitis C virus infection associated with coronary and thoracic aortic atherosclerosis.

BACKGROUND: Coronary and thoracic aortic calcification was associated with stroke, coronary heart, and peripheral vascular disease. Hepatitis C virus (HCV) infection is significantly associated with insulin resistance, diabetes mellitus and hepatic steatosis. We aimed to investigate the relationship between HCV infection and coronary, thoracic aortic atherosclerosis. METHODS: Calcification was detected by chest computed tomography and defined as any Agatston score greater than zero. Metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Fibrosis-4 (FIB-4) and AST-to-platelet ratio (APRI) was calculated. The anti-HCV signal-to-cutoff (S/CO) ratio was determined by the third generation ELISA kit. Atherosclerosis risk was estimated by using multiple logistic regression modeling. RESULTS: Being positive for both metabolic syndrome and HCV infection (OR= 2.65, 95% CI: 1.26-5.59, p= 0.007), negative for metabolic syndrome and positive for HCV infection (OR= 2.75, 95% CI: 1.48-5.30, p= 0.001), and positive for metabolic syndrome and negative for HCV infection (OR= 2.42, 95% CI: 1.92-3.07, p< 0.001) were associated with atherosclerosis compared with being negative for both metabolic syndrome and HCV infection (Ptrend< 0.001). HCV infection with liver fibrosis (HCVFIB4>1.4; OR= 2.16, 95% CI: 1.22-3.82, p= 0.008), or (HCVAPRI>0.5; OR = 3.40, 95% CI: 1.28-9.06, p = 0.014) and elevated anti-HCV S/CO ratio (anti-HCVS/CO>10.0; OR = 1.72, 95% CI: 1.01-2.93, p = 0.045) was associated with atherosclerosis. CONCLUSIONS: HCV infection with metabolic syndrome, liver fibrosis and elevated anti-HCV S/CO ratio was associated with atherosclerosis.

Third vaccine boosters and anti-S-IgG levels: A comparison of homologous and heterologous responses and poor immunogenicity in hepatocellular carcinoma.

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 < 0.001). Receiving the MMM booster regimen (OR = 10.67, 95% CI 5.20-21.91, p < 0.001) increased the odds of having significant antibody activity compared with the AZAZBNT booster regimen. Patients with active HCC had a reduced immune response to the third COVID-19 vaccine booster. These findings underscore the importance of booster vaccinations, especially in immunocompromised patients, with superior efficacy observed with the homologous mRNA-1273 regimen.

Performance of noninvasive seromarkers in predicting liver fibrosis among MAFLD patients with or without viral hepatitis.

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.

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.

Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients.

BACKGROUND/AIMS: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. METHODS: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. RESULTS: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1-2, and no linvencorvir-related serious adverse events were reported. CONCLUSION: 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.