Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.

Short-term effect of gluten-free diet on disease severity, quality of life, and inflammatory markers among patients with mild to moderate ulcerative colitis: A triple-blind randomized placebo-controlled trial.

BACKGROUND AND STUDY AIMS: Diet is an important underlying factor in ulcerative colitis (UC) disease. The present study aimed to investigate the effect of a gluten-free diet (GFD) on disease severity, quality of life, and inflammatory markers in patients with UC. PATIENTS AND METHODS: In this triple-blind randomized placebo-controlled clinical trial, we evaluated the effect of a GFD on the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, disease severity, and quality of life in patients with mild to moderate UC. Patients' quality of life and severity of symptoms were evaluated using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Simple Clinical Colitis Activity Index (SCCAI), respectively. Patients received this regimen for six weeks and were evaluated before and after the intervention. RESULTS: The mean age of patients (n = 26) was 39.31 years (standard deviation = 9.34). In both study groups, the mean ESR, CRP, IBDQ, and SCCAI showed no statistically significant improvement with the dietary intervention. Fecal calprotectin was increased in both groups without statistical significance. CONCLUSIONS: We could not find any significant effect of GFD on inflammatory markers, quality of life, and disease severity among patients with mild to moderate UC. It is too early to suggest the gluten-free diet as a safe and beneficial regimen for UC patients. There is a need for further investigations with larger sample sizes and longer follow-ups as clinical trials and cohort studies to obtain more reliable results.

Artificial intelligence in liver cancer research: a scientometrics analysis of trends and topics.

Background and aims: With the rapid growth of artificial intelligence (AI) applications in various fields, understanding its impact on liver cancer research is paramount. This scientometrics project aims to investigate publication trends and topics in AI-related publications in liver cancer. Materials and Methods: We employed a search strategy to identify AI-related publications in liver cancer using Scopus database. We analyzed the number of publications, author affiliations, and journals that publish AI-related publications in liver cancer. Finally, the publications were grouped based on intended application. Results: We identified 3950 eligible publications (2695 articles, 366 reviews, and 889 other document types) from 1968 to August 3, 2023. There was a 12.7-fold increase in AI-related publications from 2013 to 2022. By comparison, the number of total publications on liver cancer increased by 1.7-fold. Our analysis revealed a significant shift in trends of AI-related publications on liver cancer in 2019. We also found a statistically significant consistent increase in numbers of AI-related publications over time (tau = 0.756, p < 0.0001). Eight (53%) of the top 15 journals with the most publications were radiology journals. The largest number of publications were from China (n=1156), the US (n=719), and Germany (n=236). The three most common publication categories were "medical image analysis for diagnosis" (37%), "diagnostic or prognostic biomarkers modeling & bioinformatics" (19%), and "genomic or molecular analysis" (18%). Conclusion: Our study reveals increasing interest in AI for liver cancer research, evidenced by a 12.7-fold growth in related publications over the past decade. A common application of AI is in medical imaging analysis for various purposes. China, the US, and Germany are leading contributors.

A quantitative evaluation of the impact of vaccine roll-out rate and coverage on reducing deaths: insights from the first 2 years of COVID-19 epidemic in Iran.

BACKGROUND: Vaccination has played a pivotal role in reducing the burden of COVID-19. Despite numerous studies highlighting its benefits in reducing the risk of severe disease and death, we still lack a quantitative understanding of how varying vaccination roll-out rates influence COVID-19 mortality. METHODS: We developed a framework for estimating the number of avertable COVID-19 deaths (ACDs) by vaccination in Iran. To achieve this, we compared Iran's vaccination roll-out rates with those of eight model countries that predominantly used inactivated virus vaccines. We calculated net differences in the number of fully vaccinated individuals under counterfactual scenarios where Iran's per-capita roll-out rate was replaced with that of the model countries. This, in turn, enabled us to determine age specific ACDs for the Iranian population under counterfactual scenarios where number of COVID-19 deaths are estimated using all-cause mortality data. These estimates covered the period from the start of 2020 to 20 April 2022. RESULTS: We found that while Iran would have had an approximately similar number of fully vaccinated individuals under counterfactual roll-out rates based on Bangladesh, Nepal, Sri Lanka, and Turkey (~ 65-70%), adopting Turkey's roll-out rates could have averted 50,000 (95% confidence interval: 38,100-53,500) additional deaths, while following Bangladesh's rates may have resulted in 52,800 (17,400-189,500) more fatalities in Iran. Surprisingly, mimicking Argentina's slower roll-out led to only 12,600 (10,400-13,300) fewer deaths, despite a higher counterfactual percentage of fully vaccinated individuals (~ 79%). Emulating Montenegro or Bolivia, with faster per capita roll-out rates and approximately 50% counterfactual full vaccination, could have prevented more deaths in older age groups, especially during the early waves. Finally, replicating Bahrain's model as an upper-bound benchmark, Iran could have averted 75,300 (56,000-83,000) deaths, primarily in the > 50 age groups. CONCLUSIONS: Our analysis revealed that faster roll-outs were consistently associated with higher numbers of averted deaths, even in scenarios with lower overall coverage. This study offers valuable insights into future decision-making regarding infectious disease epidemic management through vaccination strategies. It accomplishes this by comparing various countries' relative performance in terms of timing, pace, and vaccination coverage, ultimately contributing to the prevention of COVID-19-related deaths.

Ethnic disparities in the epidemiology, treatment, and outcome of patients with hepatocellular carcinoma in the United States.

There are significant ethnic disparities in incidence, tumor stage, curative therapy receipt, and survival among patients with hepatocellular carcinoma (HCC) in the US. While previous models had predicted an increasing trend in the incidence rate of HCC until 2030 in the US, recent studies have shown that HCC incidence plateaued in 2013 and then started to decline in 2015. The decreasing trend has been observed in all ethnicities except for American Indians/Alaska Natives, whose incidence rates of HCC continue to rise. Current evidence shows that African-Americans and Hispanics are two groups that are more likely to be diagnosed with late-stage HCC, and this finding has been consistent in different socioeconomic statuses of the patients. These two ethnic minority groups are also among those who are less likely to have curative therapy for early-stage HCC. Finally, advances in early diagnosis and treatment approaches have led to an improvement in HCC survival for all ethnicities; however, African-Americans continue to have the worst survival. More studies to find the causes of these disparities and interventions to eliminate them are urgently needed.

Hepatitis E virus seroprevalence rate among Eastern Mediterranean and middle eastern countries; A systematic review and pooled analysis.

CONTEXT: Hepatitis E virus (HEV) as a hepatotropic virus is one of the major global health concerns. Autochthonous HEV transmitted by oral fecal-route in poor sanitation conditions as well as vertical and rarely blood transfusion. HEV occurrence is more common in developing countries and recently increased in developed countries too. Middle East (ME) and Eastern Mediterranean region (EMR) of WHO have been an endemic region for HEV infection. In this regard, we aimed to design a systematic review and pooled analysis to determine seroprevalence of anti-HEV antibody in ME and EMR countries. EVIDENCE ACQUISITION: By using PRISMA guideline, data were collected from papers identified through PubMed, Web of Science, Science Direct, Scopus and also from some national and regional databases from January 1990 to June 2016. Serum anti-HEV antibody (IgG) used for HEV prevalence estimation. HEV prevalence in the ME, WHO EMR countries, and in total, calculated by each country population size based on 2015 UN report. RESULTS: overall, 62 papers with a total sample size of 31,673 were fulfilled our eligibility criteria and included in our project. Considering anti-HEV antibody (IgG), prevalence of HEV infection in the countries of ME, WHO EMR and in total were 12.17% (95% CI: 11.79-12.57), 11.81% (95% CI: 11.43-12.21), and 11.87% (95% CI: 11.52-12.23) respectively. CONCLUSIONS: HEV seroprevalence in WHO EMR and ME countries has high rate and more considerations are needed for the prevention and control of this infection especially in high-risk groups such as pregnant women.

Glycosylated haemoglobin and coronary atherosclerosis in non-diabetic patients: is it a prognostic factor?

BACKGROUND: Some studies aimed to evaluate the relationship between HbA1c and coronary artery disease (CAD). However, it is well known that long-term glycometabolic disorders put the heart at risk for CAD. Considering the inconsistencies between previous studies, this study aimed to investigate the relationship between HbA1c and coronary artery atherosclerosis. METHODS: A cross-sectional study was conducted on 411 non-diabetic patients who underwent their first coronary angiography between November 2013 and December 2014 in Baqiyatallah Hospital. Blood samples were taken before angiography. Coronary angiograms were reported and reviewed by two cardiologists according to the Gensini score. They were not aware about the patients' HbA1c level. Severity of CAD was determined through ascertaining the prevalence of multi-vessel disease, extent of CAD (single-, two- or three-vessel disease or left main stem stenosis (>50%)). Data analysis was performed by using SPSS software. RESULTS: A total of 411 patients (252 men and 159 women) were evaluated. Angiography was normal in 67 patients (16.3%), 30.7% had single-vessel disease (SVD), and 29.1%, 20.7% and 3.2% had two-, three- and multivessel disease, respectively. Based on the ROC curve, the HbA1c was able to differentiate between patients with and without coronary atherosclerosis (p < .001, cut-off point = 5.45). The cut-off points for differentiation of severe CAD and patients with 75-100% stenosis of coronary artery were 5.55 (p < .001) and 5.65 (p < .001), respectively. CONCLUSIONS: The present study demonstrated that HbA1c might be an independent diagnostic factor in non-diabetic patients with severe coronary atherosclerosis.