Screening for viral hepatitis B infection in cancer patients before receiving chemotherapy - A systematic review and meta-analysis.

AIM: We conducted a systematic review and meta-analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. METHODS: We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. RESULTS: The meta-analysis included 29 studies from various endemic regions (19 low-endemic, three lower intermediate-endemic, and seven higher intermediate-endemic). These studies encompassed hematologic malignancies (n = 10), solid-organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab-containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%-68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%-53%) in 2006-2010 to 68% (54%-80%) in 2011-2015 and 69% (48%-84%) in 2016-2020. Screening rates were highest at 89% (74%-96%) in high endemic countries, followed by 60% (45-73%) in lower-intermediate and 49% (34-64%) in low-endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%-74%) versus 37% (21%-57%), respectively. A screening rate was higher in patients receiving rituximab-containing chemotherapy than non-rituximab regimens, 68% (55%-79%) versus 45% (27%-65%). CONCLUSION: Despite existing guidelines, pre-chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines.

Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy.

Background and aims: Chronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in hepatitis B virus (HBV)-suppressed patients. Methods: We conducted a case-control study involving 120 noncirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and Fibrosis-4 (FIB-4)-matched controls. Clinical and laboratory data at viral suppression, including body mass index (BMI), comorbidities, pretreatment HBV viral load, HBe antigen status, hepatitis C virus (HCV) and HIV coinfections, liver chemistries, and AST to Platelets Ratio Index (APRI) values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. Results: Case and control groups had similar ages (51.4 ± 9.9 vs. 51.4 ± 10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, P = 0.01) and more diabetes prevalence (50.0% vs. 26.3%, P = 0.01), while other comorbidities and laboratory parameters were comparable (P > 0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46-6.13), 2.31 (1.23-4.36), and 2.71 (1.05-6.99), P = 0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, P = 0.006), while diabetes showed borderline significance (aHR: 1.99, P = 0.072). Conclusions: In HBV-infected patients achieving viral suppression with therapy, a BMI >23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.

Abbreviated MRI for Hepatocellular Carcinoma Surveillance - A Systematic Review and Meta-analysis.

BACKGROUND: Given the limited sensitivity of ultrasound in hepatocellular carcinoma (HCC) surveillance, this systematic review and meta-analysis were aimed to assess the diagnostic performance of non-contrast abbreviated MRI (NC-aMRI) compared to contrast-enhanced abbreviated MRI (CE-aMRI) for HCC surveillance, offering evidence-based guidance for clinical decision-making. METHODS: A comprehensive search was conducted across five databases, identifying studies on aMRI for HCC surveillance. The pooled sensitivity and specificity were estimated using a random effects model. Subgroup analyses and meta-regression were performed by study location, proportion of patients with cirrhosis and HCC, and underlying liver diseases. RESULTS: The meta-analysis included 27 studies (2009-2023), distributed between Western (n = 14) and Eastern (n = 13) countries. The pooled sensitivity and specificity (95%CI, I2) were 86% (83-88%, 63%) and 92% (90%-94%, 74%). The NC-aMRI protocols reported in 21 studies exhibited 83% (79-87%, 63%) sensitivity and 91% (88-93%, 67%) specificity, while the 15 studies on CE-aMRI protocols displayed 88% (84-91%, 64%) sensitivity and 94% (90-96%, 78%) specificity, with no statistically significant differences in sensitivity (p = 0.078) or specificity (p = 0.157). Subgroup analysis in NC-aMRI studies showed significant differences in sensitivity for high-prevalent chronic hepatitis B (87% vs. 78%, p = 0.003) and studies done in eastern countries (86% vs. 76%, p = 0.018). Additionally, specificity showed significant differences for high-prevalent chronic hepatitis C (94% vs. 90%, p = 0.009), with meta-regression identifying major sources of study heterogeneity as the inclusion of a majority of patients with chronic hepatitis B (p = 0.008) and the geographic regions where studies were conducted (p = 0.030). CONCLUSION: Surveillance aMRI protocols exhibit satisfactory performance for detecting HCC. NC-aMRI may be used effectively for HCC surveillance, especially in chronic hepatitis B prevalent settings.

Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis.

Background/Aims: Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Methods: Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. Results: aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Conclusions: Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.

ChAdOx1 nCoV-19 vaccine-associated thrombocytopenia: three cases of immune thrombocytopenia after 107 720 doses of ChAdOx1 vaccination in Thailand.

We reported three cases of immune thrombocytopenia (ITP) that developed within 6 weeks after ChAdOx1 nCoV-19 vaccination. Antiplatelet factor 4 antibodies were undetectable in all three cases. Therefore, vaccine-induced immune thrombotic thrombocytopenia was very unlikely. Other potential causes of thrombocytopenia were excluded. Their clinical presentations, severity of thrombocytopenia and outcomes were varied. Only one ITP case, an 80-year-old man, received ITP treatments and achieved complete response after 2 weeks of eltrombopag. An 84-year-old man had spontaneous complete remission, and a 55-year-old woman had partial platelet recovery without ITP treatments. Among 107 720 Thais administered the ChAdOx1 vaccine between 16 March and 10 May 2021, these three ITP cases resulted in an estimated risk of ITP of at least one per 36 000 doses, which was approximately similar to the risk of ITP after measles-mumps-rubella immunization. This raises the concern of an increased risk of ITP after ChAdOx1 vaccination.

Application of artificial intelligence for diagnosis of pancreatic ductal adenocarcinoma by EUS: A systematic review and meta-analysis.

EUS-guided tissue acquisition carries certain risks from unnecessary needle puncture in the low-likelihood lesions. Artificial intelligence (AI) system may enable us to resolve these limitations. We aimed to assess the performance of AI-assisted diagnosis of pancreatic ductal adenocarcinoma (PDAC) by off-line evaluating the EUS images from different modes. The databases PubMed, EMBASE, SCOPUS, ISI, IEEE, and Association for Computing Machinery were systematically searched for relevant studies. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curve were estimated using R software. Of 369 publications, 8 studies with a total of 870 PDAC patients were included. The pooled sensitivity and specificity of AI-assisted EUS were 0.91 (95% confidence interval [CI], 0.87-0.93) and 0.90 (95% CI, 0.79-0.96), respectively, with DOR of 81.6 (95% CI, 32.2-207.3), for diagnosis of PDAC. The area under the curve was 0.923. AI-assisted B-mode EUS had pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.91, 0.90, 0.94, and 0.84, respectively; while AI-assisted contrast-enhanced EUS and AI-assisted EUS elastography had sensitivity, specificity, PPV, and NPV of 0.95, 0.95, 0.97, and 0.90; and 0.88, 0.83, 0.96 and 0.57, respectively. AI-assisted EUS has a high accuracy rate and may potentially enhance the performance of EUS by aiding the endosonographers to distinguish PDAC from other solid lesions. Validation of these findings in other independent cohorts and improvement of AI function as a real-time diagnosis to guide for tissue acquisition are warranted.

Application of artificial intelligence in chronic liver diseases: a systematic review and meta-analysis.

BACKGROUND: The gold standard for the diagnosis of liver fibrosis and nonalcoholic fatty liver disease (NAFLD) is liver biopsy. Various noninvasive modalities, e.g., ultrasonography, elastography and clinical predictive scores, have been used as alternatives to liver biopsy, with limited performance. Recently, artificial intelligence (AI) models have been developed and integrated into noninvasive diagnostic tools to improve their performance. METHODS: We systematically searched for studies on AI-assisted diagnosis of liver fibrosis and NAFLD on MEDLINE, Scopus, Web of Science and Google Scholar. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic odds ratio (DOR) with their 95% confidence intervals (95% CIs) were calculated using a random effects model. A summary receiver operating characteristic curve and the area under the curve was generated to determine the diagnostic accuracy of the AI-assisted system. Subgroup analyses by diagnostic modalities, population and AI classifiers were performed. RESULTS: We included 19 studies reporting the performances of AI-assisted ultrasonography, elastrography, computed tomography, magnetic resonance imaging and clinical parameters for the diagnosis of liver fibrosis and steatosis. For the diagnosis of liver fibrosis, the pooled sensitivity, specificity, PPV, NPV and DOR were 0.78 (0.71-0.85), 0.89 (0.81-0.94), 0.72 (0.58-0.83), 0.92 (0.88-0.94) and 31.58 (11.84-84.25), respectively, for cirrhosis; 0.86 (0.80-0.90), 0.87 (0.80-0.92), 0.85 (0.75-0.91), 0.88 (0.82-0.92) and 37.79 (16.01-89.19), respectively; for advanced fibrosis; and 0.86 (0.78-0.92), 0.81 (0.77-0.84), 0.88 (0.80-0.93), 0.77 (0.58-0.89) and 26.79 (14.47-49.62), respectively, for significant fibrosis. Subgroup analyses showed significant differences in performance for the diagnosis of fibrosis among different modalities. The pooled sensitivity, specificity, PPV, NPV and DOR were 0.97 (0.76-1.00), 0.91 (0.78-0.97), 0.95 (0.87-0.98), 0.93 (0.80-0.98) and 191.52 (38.82-944.81), respectively, for the diagnosis of liver steatosis. CONCLUSIONS: AI-assisted systems have promising potential for the diagnosis of liver fibrosis and NAFLD. Validations of their performances are warranted before implementing these AI-assisted systems in clinical practice. TRIAL REGISTRATION: The protocol was registered with PROSPERO (CRD42020183295).

Application of artificial intelligence in non-alcoholic fatty liver disease and liver fibrosis: a systematic review and meta-analysis.

BACKGROUND: The global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise. Non-invasive diagnostic modalities including ultrasonography and clinical scoring systems have been proposed as alternatives to liver biopsy but with limited performance. Artificial intelligence (AI) is currently being integrated with conventional diagnostic methods in the hopes of performance improvements. We aimed to estimate the performance of AI-assisted systems for diagnosing NAFLD, non-alcoholic steatohepatitis (NASH), and liver fibrosis. METHODS: A systematic review was performed to identify studies integrating AI in the diagnosis of NAFLD, NASH, and liver fibrosis. Pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and summary receiver operating characteristic curves were calculated. RESULTS: Twenty-five studies were included in the systematic review. Meta-analysis of 13 studies showed that AI significantly improved the diagnosis of NAFLD, NASH and liver fibrosis. AI-assisted ultrasonography had excellent performance for diagnosing NAFLD, with a sensitivity, specificity, PPV, NPV of 0.97 (95% confidence interval (CI): 0.91-0.99), 0.98 (95% CI: 0.89-1.00), 0.98 (95% CI: 0.93-1.00), and 0.95 (95% CI: 0.88-0.98), respectively. The performance of AI-assisted ultrasonography was better than AI-assisted clinical data sets for the identification of NAFLD, which provided a sensitivity, specificity, PPV, NPV of 0.75 (95% CI: 0.66-0.82), 0.82 (95% CI: 0.74-0.88), 0.75 (95% CI: 0.60-0.86), and 0.82 (0.74-0.87), respectively. The area under the curves were 0.98 and 0.85 for AI-assisted ultrasonography and AI-assisted clinical data sets, respectively. AI-integrated clinical data sets had a pooled sensitivity, specificity of 0.80 (95%CI: 0.75-0.85), 0.69 (95%CI: 0.53-0.82) for identifying NASH, as well as 0.99-1.00 and 0.76-1.00 for diagnosing liver fibrosis stage F1-F4, respectively. CONCLUSION: AI-supported systems provide promising performance improvements for diagnosing NAFLD, NASH, and identifying liver fibrosis among NAFLD patients. Prospective trials with direct comparisons between AI-assisted modalities and conventional methods are warranted before real-world implementation. PROTOCOL REGISTRATION: PROSPERO (CRD42021230391).

High dose oral vitamin C and mesenchymal stem cells aid wound healing in a diabetic mouse model.

OBJECTIVE: This study sought to determine the effects of oral vitamin C (VitC) and mesenchymal stem cells (MSCs) on wound healing in diabetic nude mice. METHOD: Bilateral, full-skin thickness wounds were created as an in vivo wound model in BALB/C diabetic nude mice. The mice were separated into five groups: control (CON); diabetes mellitus (DM, from a streptozotocin injection); DM treated with MSCs (DM+MSCs); DM treated with VitC (DM+VitC), and DM treated with MSCs and VitC (DM+MSCs+VitC). After wounding, daily oral-feeding of high dose VitC (1.5g/l) was administered, and a single dose of MSCs (1x106 cells) was given topically using matrix gel application to the wounded area. RESULTS: At day seven, the lowest rate of wound healing, in terms of percentage of wound closure, appeared in the DM group, as compared with the CON and all other treatment groups (mean percentage of wound closure and standard deviation), CON=75.94±7.09%; DM=55.65±9.59%; DM+MSCs=78.57±6.46%; DM+VitC=77.52±3.31%; and DM+MSCs+VitC=84.61±2.87%, p≤0.05. At day 14 post-wounding, the combination of oral high dose VitC and MSCs accelerated wound healing (91.44±3.19%, p≤0.05). In addition, the highest capillary density in DM+MSCs+VitC was obtained at 14 days post-wounding (29.49±7.30%, p≤0.05). CONCLUSION: The findings of this study highlight the possibility of using oral high dose VitC in adjunct to MSCs to increase angiogenesis and accelerate diabetic wound healing in an animal model. This novel therapeutic approach should be studied further to test if it could be a useful adjunct of existing therapies to prevent infection and amputation in patients with diabetes.

Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits.

The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines and activity and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in mature DGCs increased survival of adult-born DGCs without affecting proliferation or DGC activity. Enhanced integration of adult-born DGCs transiently reorganized adult-born DGC local afferent connectivity and promoted global remapping in the DG. Rejuvenation of the DG by enhancing integration of adult-born DGCs in adulthood, middle age, and aging enhanced memory precision.