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Summary: Background/Aims: Patients with hepatocellular cancer (HCC) are vulnerable to psychological distress given a new cancer diagnosis superimposed on pre‐existing chronic liver disease. We aimed to characterise the psychiatric burden in HCC, risk factors for incident diagnosis and treatment patterns over time. Methods: Using IQVIA PharMetrics® Plus for Academics—a nationally representative claims database of the commercially insured US population—we identified psychiatric diagnoses and treatment among patients with newly diagnosed HCC. Multivariable logistic regression modelling identified factors associated with psychiatric diagnosis and treatment. Results: Of 11,609 patients with HCC, 2166 (18.6%) had a psychiatric diagnosis after cancer diagnosis with depression (58.3%) and anxiety (53.0%) being most common. Women (aOR 1.33, 95% CI [1.19–1.49]), pre‐existing psychiatric diagnoses (aOR 9.12 [8.08–10.3]) and HCC treatment type (transplant: aOR 2.15 [1.66–2.77]; locoregional therapies: aOR 1.74 [1.52–1.99]; hospice: aOR 2.43 [1.79–3.29]) were significantly associated with psychiatric diagnosis. Female sex, ascites, higher comorbidity and treatment type were associated with incident psychiatric diagnosis. Pharmacotherapy was used in 1392 (64.3%) patients with a psychiatric diagnosis, with antidepressants (46.2%) and anxiolytics (32.8%) being most common. Psychiatric diagnoses increased from 14.8% in 2006–2009 to 21.1% in 2018–2021 (p < 0.001). In almost 20% of patients with pre‐existing psychiatric conditions, therapy was discontinued after HCC diagnosis. Conclusions: Nearly 2 of 10 patients with HCC were diagnosed with a psychiatric condition after cancer diagnosis with unique sociodemographic and clinical risk factors identified. This highlights a risk for increased psychological burden in need of early evaluation and treatment among patients with newly diagnosed HCC. [ABSTRACT FROM AUTHOR]

Background: Stage IV colorectal cancer (CRC) often requires multidisciplinary approach. However, multimodal treatment options (receipt of > 1 type of treatment) may not be uniformly delivered across health systems. We characterized the association between center-level cancer center designation and receipt of multimodal treatment and survival. Methods: The Texas Cancer Registry was used to identify patients diagnosed with stage IV CRC from 2004–2017. We identified those who received care at either: a National Cancer Institute-designated (NCI-D), an American College of Surgeons-Commission on Cancer-designated (ACS-D), or an undesignated facility. We used multivariable logistic regression and Cox regression for analysis to assess receipt of one or more treatment modality and 5-year overall survival. Results: Of 19,355 patients with stage IV CRC, 2955 (15%) received care at an NCI-D facility and 5871 (30%) received multimodal therapy. Both NCI-D (odds ratio [OR] 1.64; 95% confidence interval [CI] 1.49–1.81) and ACS-D (OR 1.37; 95% CI 1.27–1.48) were associated with increased likelihood of multimodal therapy compared with undesignated centers. NCI-D also was associated with significantly improved survival (hazard ratio [HR] 0.74; 95% CI 0.70–0.78), although ACS-D was associated with a modest improvement in survival (HR 0.95; 95% CI 0.92–0.99). Receipt of multimodal therapy was strongly associated with improved survival (HR 0.61; 95% CI 0.59–0.63). Conclusions: In patients with stage IV CRC, treatment at ACS-D and NCI-D facilities was associated with increased use of multimodality therapy and improved survival. However, only a small proportion of patients have access to these specialized centers, highlighting a need for expanded access to multimodal therapies at other centers. [ABSTRACT FROM AUTHOR]

Simple Summary: There is controversy over the optimal recommended screening practice for colorectal cancer. Between direct visualization methods, colonoscopy is more used more frequently, although randomized data suggest benefits from sigmoidoscopy rather than colonoscopy. We used the SEER database to assess the proportion of cancers that could be visualized with each screening strategy and found that 58% could be seen by sigmoidoscopy, including 73% of tumors for patients diagnosed younger than 50 years (early onset colorectal cancer). We recommend consideration of recommending flexible sigmoidoscopy as a population-based screening strategy for younger individuals who may be hesitant to undergo colonoscopy. Objectives: The effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy. Methods: Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000–2020). Tumors from the rectum to the descending colon were categorized as visible by sigmoidoscopy, whereas more proximal tumors required colonoscopy. Differential prognosis between tumor locations, stratified by age groups and stage, was assessed using the overall restricted mean survival time (RMST) at 2, 5, and 10 years. Results: Among 309,466 patients, 58% had tumors visible by sigmoidoscopy, including 73% of those under age 50 (OR 2.10, 95% CI 2.03–2.16 age < 45, OR 2.20, 95% CI 2.13–2.27 age 45–49 versus age ≥ 50). Male sex (OR 1.54, 95% CI 1.51–1.56) and Asian or Pacific Islander race (OR 1.60, 95% CI 1.56–1.64) were also positively associated with tumors visualizable by sigmoidoscopy. Across age groups, for local disease, RMST was comparable for tumors visible versus not visible on sigmoidoscopy. For regional and metastatic cancer, patients with tumors visible by sigmoidoscopy had improved RMST versus those with more proximal tumors. Conclusions: 58% of CRC arises in locations visible by flexible sigmoidoscopy. Flexible sigmoidoscopy should be considered as a viable option for CRC screening, particularly in younger patients unwilling or unable to undergo colonoscopy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: The two most common interventions used to treat painless jaundice from pancreatic cancer are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD). Our study aimed to characterize the geographic distribution of ERCP‐performing hospitals among patients with pancreatic cancer in the United States and the association between geographic accessibility to ERCP‐performing hospitals and biliary interventions patients receive. Methods: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database for pancreatic cancer from 2005 to 2013. Multilevel models were used to examine the association between accessibility to ERCP hospitals within a 30‐ and 45‐min drive from the patient's residential ZIP Code and the receipt of ERCP treatment. A two‐step floating catchment area model was used to calculate the measure of accessibility based on the distribution across SEER regions. Results: 7464 and 782 patients underwent ERCP and PTBD, respectively, over the study period. There were 808 hospitals in which 8246 patients diagnosed with pancreatic cancer in SEER regions from 2005 to 2013 received a procedure. Patients with high accessibility within both 30‐ and 45‐min drive to an ERCP‐performing hospital were more likely to receive an ERCP (30‐min adjusted odds ratio [aOR]: 1.53, 95% confidence interval [CI]: 1.17–2.01; 45‐min aOR: 1.31, 95% CI: 1.01–1.70). Furthermore, in the adjusted model, Black patients (vs. White) and patients with stage IV disease were less likely to receive ERCP than PTBD. Conclusions: Patients with pancreatic cancer and high accessibility to an ERCP‐performing hospital were more likely to receive ERCP. Disparities in the receipt of ERCP persisted for Black patients regardless of their access to ERCP‐performing hospitals. [ABSTRACT FROM AUTHOR]

Simple Summary: Atezolizumab plus bevacizumab (atezo + bev) is a preferred front-line treatment for unresectable hepatocellular carcinoma (HCC). However, there is limited real-world evidence regarding the use of atezo + bev and subsequent HCC therapies in clinical practice. This retrospective cohort study aimed to characterize the time to discontinuation of atezo + bev, sequencing of systemic therapy after atezo + bev, and time to next treatment. We identified 825 adults with HCC who were initiated on atezo + bev between June 2020 and June 2022. During a median follow-up of 15.3 months, most patients (72%) discontinued atezo + bev, with a median time to discontinuation of 3.5 months. Less than one in five (19%) received subsequent therapies (median time to subsequent treatment of 5.4 months); the most common subsequent agents were lenvatinib (6%), cabozantinib (4%), and nivolumab (4%). Further research is needed to identify those most likely to benefit from atezo + bev and evaluate optimal sequential HCC therapies to maximize overall survival. Real-world (RW) evidence is needed to evaluate atezolizumab plus bevacizumab (atezo + bev) utilization for hepatocellular carcinoma (HCC) in clinical practice. This retrospective cohort study used administrative claims databases to evaluate treatment patterns in individuals with HCC ≥18 years of age who were initiated on atezo + bev between June 2020 and June 2022. The endpoints of this study were the proportion of individuals who discontinued atezo + bev and received subsequent systemic therapies, time to discontinuation (TTD), and time to next treatment. Overall, 825 individuals were eligible (median age 67 years; 80% male). Over a median follow-up of 15.3 months, most (72%) discontinued atezo + bev, with a median TTD of 3.5 months. A minority (19%) received subsequent therapies, with the most common second-line agents being lenvatinib (6%), cabozantinib (4%), and nivolumab (4%). The median time from index to next treatment post-atezo + bev was 5.4 months. Further research is needed to identify the patients who are most likely to benefit from atezo + bev as well as later-line HCC therapies to optimize overall survival. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. Methods: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non‐BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing‐risk regression analysis, graft survival rates were compared using Kaplan–Meier time‐to‐event analysis and Cox proportional hazards modelling provided adjusted estimates. Results: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non‐BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living‐donor liver transplantations (LDLT) and 611 (27.7%) split deceased‐donor LTs. Five‐year graft survival was significantly higher among BA versus non‐BA cholestatic patients in the older group (88.3% vs. 79.5%, p <.01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03–3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87–6.2). Conclusion: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes. [ABSTRACT FROM AUTHOR]

Background Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. Methods The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. Results Of 18 751 liveborn offspring, about 15% (n  = 2635) were exposed in utero to antibiotics: 5.4% (n  = 1016) to tetracyclines, 4.9% (n  = 918) to penicillins, 4.2% (n  = 785) to short-acting sulfonamides and 1.5% (n  = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. Conclusion Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) infection invokes variable immune responses and poses a risk of post-acute sequelae SARS-CoV-2 infection (PASC) symptoms; however, most data on natural history are derived from patients with severe infection. Further data are needed among patients with mild infection, who comprise most cases. Methods: The Dallas Fort-Worth (DFW) COVID-19 Prevalence Study included 21,597 community-dwelling adults (ages 18–89) who underwent COVID-19 PCR and anti-nucleocapsid antibody testing between July 2020 and March 2021. We invited participants with positive COVID-19 results (cases) and a subset with negative results (controls), matched on age, sex, race/ethnicity, and ZIP code, to complete a follow-up questionnaire for PASC symptoms and repeat anti-nucleocapsid testing, and anti-spike antibody testing between July and December 2021. Results: Of 3,917 adults invited to participate, 2260 (57.7%) completed the questionnaire– 1150 cases and 1110 controls. Persistent symptoms were reported in 21.1% of cases, with the most common being shortness of breath, fatigue, and loss of taste or smell. Among 292 cases with asymptomatic infection, >15% reported new fatigue and 8–10% reported new loss of taste/smell, myalgias, or headache. Median anti-nucleocapsid levels in cases decreased from 3.5U to 0.7U over a median follow-up of 8.6 months. Anti-spike antibody levels at 6–7 months post-vaccination in cases were similar to that of controls. Conclusions: More than 1 in 5 patients with COVID-19 infection, including those with mild infection, reported persistent symptoms during follow-up. Both nucleocapsid and spike protein antibody levels decreased within six months following a COVID-19 infection and vaccination. [ABSTRACT FROM AUTHOR]

Patients at risk for hepatocellular carcinoma or liver cancer should undergo semiannual screening tests to facilitate early detection, effective treatment options at lower cost, better recovery prognosis, and higher life expectancy. Health care institutions invest in direct-to-patient outreach marketing to encourage regular screening. They ask the following questions: (1) Does the effectiveness of outreach vary among patients and over time?; (2) What is the return on outreach?; and (3) Can patient-level targeted outreach increase the return? The authors use a multiperiod, randomized field experiment involving 1,800 patients. Overall, relative to the usual-care condition, outreach alone (outreach with patient navigation) increases screening completion rates by 10–20 (13–24) percentage points. Causal forests demonstrate that patient-level treatment effects vary substantially across periods and by patients' demographics, health status, visit history, health system accessibility, and neighborhood socioeconomic status, thereby facilitating the implementation of the targeted outreach program. A simulation shows that the targeted outreach program improves the return on the randomized outreach program by 74%–96% or $1.6 million to $2 million. Thus, outreach marketing provides a substantial positive payoff to the health care system. [ABSTRACT FROM AUTHOR]

Death rates from primary liver cancer (hepatocellular carcinoma [HCC]) have continued to rise in the United States over the recent decades despite the availability of an increasing range of treatment modalities, including new systemic therapies. Prognosis is strongly associated with tumor stage at diagnosis; however, most cases of HCC are diagnosed beyond an early stage. This lack of early detection has contributed to low survival rates. Professional society guidelines recommend semiannual ultrasound-based HCC screening for at-risk populations, yet HCC surveillance continues to be underused in clinical practice. On April 28, 2022, the Hepatitis B Foundation convened a workshop to discuss the most pressing challenges and barriers to early HCC detection and the need to better leverage existing and emerging tools and technologies that could improve HCC screening and early detection. In this commentary, we summarize technical, patient-level, provider-level, and system-level challenges and opportunities to improve processes and outcomes across the HCC screening continuum. We highlight promising approaches to HCC risk stratification and screening, including new biomarkers, advanced imaging incorporating artificial intelligence, and algorithms for risk stratification. Workshop participants emphasized that action to improve early detection and reduce HCC mortality is urgently needed, noting concern that many of the challenges we face today are the same or similar to those faced a decade ago and that HCC mortality rates have not meaningfully improved. Increasing the uptake of HCC screening was identified as a short-term priority while developing and validating better screening tests and risk-appropriate surveillance strategies. [ABSTRACT FROM AUTHOR]

Background: Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC). Aims: The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound. Methods: We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1 cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively. Results: Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7 cm (interquartile range: 0.5-0.8 cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10 ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08). Conclusions: Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels. [ABSTRACT FROM AUTHOR]

Background: Polygenic risk scores (PRS) hold the promise to refine prognostication in hepatocellular cancer (HCC). The few available HCC PRS include germline risk variants identified among individuals of mostly European ancestry, but data are lacking on the transportability of these PRS in multiethnic U.S patients with cirrhosis from multiple etiologies. Methods: We used data from 1644 patients with cirrhosis enrolled in two prospective cohort studies in the U.S. Patients were followed until HCC diagnosis, death, liver transplantation, or last study visit through June 30, 2021. The high-risk variants in PNPLA3-MBOAT7-TM6SF2-GCKR were combined in a PRS and we evaluated its association with HCC. Discriminatory accuracy was assessed using the C-statistic. Results: During 4,759 person-years of follow-up, 93 patients developed HCC. Mean age was 59.8 years, 68.6% were male, 27.2% Hispanic, 25.1% non-Hispanic Black, 25.7% had NAFLD, 42.1% had heavy alcohol use, and 19.5% had active HCV. HCC risk increased by 134% per unit increase in PRS (HR = 2.30; 95% CI, 1.35–3.92). Compared to cirrhosis patients in the lowest tertile of the PRS, those in the highest tertile had 2-fold higher risk of HCC (HR = 2.05; 95% CI, 1.22–3.44). The PRS alone had modest discriminatory ability (C-statistic = 0.58; 95% CI, 0.52–0.63); however, adding PRS to a predictive model with traditional HCC risk factors had a C-statistic of 0.70 (95% CI, 0.64–0.76), increasing from 0.68 without the PRS (p = 0.0012). Conclusions: Our findings suggest that PRS may enhance risk prediction for HCC in contemporary U.S. cirrhosis patients. [ABSTRACT FROM AUTHOR]

Background: Transarterial radioembolization (TARE) is increasingly used as an alternative to transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). We aimed to perform an overall and individual patient data (IPD) meta‐analysis of studies comparing TACE and TARE. Methods: We performed a systematic literature search using pre‐specified keywords with the aid of an informationist for articles from inception to 3/2020. The primary endpoint was overall survival (OS), and the secondary endpoint was time to progression (TTP). Results: Seventeen studies met inclusion criteria with 2465 unique patients, with one randomized trial, 4 prospective studies and 12 retrospective studies. Barcelona Clinic Liver Cancer (BCLC) stage B (42.8%) was the most common stage followed by BCLC A (30.3%) and BCLC C (29.0%). There was no difference in OS between the two modalities (−0.55 months, 95% CI −1.95 to 3.05). In three studies with available TTP data, TARE resulted in a longer TTP than TACE (mean TTP 17.5 vs. 9.8 months; mean TTP difference 4.8 months, 95% CI 1.3–8.3 months). IPD‐level meta‐analysis of 311 patients from three studies showed no difference in overall OS between the two modalities including among subgroups stratified by tumor stage and liver function. Limitations of the current literature include inconsistent length of follow‐up, inconsistency in response criteria, and safety reporting. Conclusions: Current data suggest TARE provides significantly longer TTP than TACE, although the two treatments do not significantly differ in terms of OS. Given limitations of the current data, there is rationale for prospective studies comparing these modalities. [ABSTRACT FROM AUTHOR]

Background: Persons newly diagnosed with pancreas cancer and who have survived a previous cancer are often excluded from clinical trials, despite limited evidence about their prognosis. We examined the association between previous cancer and overall survival. Methods: This US population‐based cohort study included older adults (aged ≥66 years) diagnosed with pancreas cancer between 2005 and 2015 in the linked Surveillance, Epidemiology, and End Results‐Medicare data. We used Cox proportional hazards models to estimate stage‐specific effects of previous cancer on overall survival, adjusting for sociodemographic, treatment, and tumor characteristics. Results: Of 32,783 patients, 18.7% were previously diagnosed with another cancer. The most common previous cancers included prostate (29.0%), breast (18.9%), or colorectal (9.7%) cancer. More than half of previous cancers (53.9%) were diagnosed 5 or more years prior to pancreas cancer diagnosis or at an in situ or localized stage (47.8%). The proportions of patients surviving 1, 3, and 5 years after pancreas cancer were nearly identical for those with and without previous cancer. Median survival in months was as follows for those with and without previous cancer respectively: 7 versus 8 (Stage 0/I), 10 versus 10 (Stage II), 7 versus 7 (Stage III), and 3 versus 2 (Stage IV). Cox models indicated that patients with previous cancer had very similar or statistically equivalent survival to those with no previous cancer. Conclusions: Given nearly equivalent survival compared to those without previous cancer, cancer survivors newly diagnosed with pancreas cancer should be considered for inclusion in pancreas cancer clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and the incidence in the United States (USA) is increasing. Generally curative therapies are only possible for early-stage cancers, thus biomarkers that can be used to detect early-stage cancers are needed. Here, we describe the identification of a new biomarker that when used as a part of an algorithm can be used for the early detection of HCC with high accuracy. We have previously identified alterations in glycosylation on serum proteins from patients with HCC and developed plate-based assays using lectins to detect the change in glycosylation. However, heterophilic antibodies, which increase with non-malignant liver disease, compromised these assays. To address this, we developed a method of polyethylene glycol (PEG) precipitation that removed the contaminating IgG and IgM but allowed for the lectin detection of the relevant glycoprotein. We found that this PEG-precipitated material itself could differentiate between cirrhosis and HCC. In the analysis of three training cohorts and one validation cohort, consisting of 571 patients, PEG-IgG had AUC values that ranged from 0.713 to 0.810. In the validation cohort, which contained samples from patients at a time of 1–6 months prior to HCC detection or 7+ months prior to detection, the AUC of this marker remained consistent (0.813 and 0.846, respectively). When this marker was incorporated into a biomarker algorithm that also consisted of AFP and fucosylated kininogen, the AUROC increased to 0.816–0.883 in the training cohort and was 0.909 in the external validation cohort. Biomarker performance was also examined though the analysis of partial ROC curves, at false positive values less than 10% (90-ROC), ≤20% (80-ROC) or ≤30% (70-ROC), which highlighted the algorithm's improvement over the individual markers at clinically relevant specificity values. [ABSTRACT FROM AUTHOR]

Surveillance for hepatocellular carcinoma (HCC) is known to be underutilized; however, neither the variation of surveillance adherence by cirrhosis etiology nor the patient-side economic burden of surveillance are well understood. To identify potential barriers to HCC surveillance, we assessed utilization patterns and costs among US patients with cirrhosis monitored in routine clinical practice. We conducted a retrospective study of insured adult patients with cirrhosis using national administrative claims data from January 2013 through June 2019. Time up-to-date with recommended surveillance, correlates of surveillance receipt, and surveillance-associated costs were assessed during a ≥ 6-month follow-up. Among 15,543 patients with cirrhosis (mean [SD] age 64.0 [11.1] years, 50.7% male), 45.8% and 58.7% had received any abdominal imaging at 6 and 12 months, respectively. Patients were up-to-date with recommended surveillance for only 31% of a median 1.3-year follow-up. Those with viral hepatitis were more likely to receive surveillance than those with other etiologies (hazard ratio [HR] 1.55, 95% CI 1.11–2.17, p =.010 for patients without a baseline gastroenterologist [GI] visit and 2.69, 95% CI 1.77–4.09, p <.001 for patients with a GI visit, relative to those with nonalcoholic fatty liver disease and no GI visit). For all etiologies except NAFLD, the HR (95% CI) for surveillance receipt was higher among patients with vs without a baseline GI visit (alcohol-related, 1.164 [1.002–1.351] vs 0.880 [0.796–0.972]; viral hepatitis, 2.688 [1.765–4.093] vs 1.553 [1.111–2.171]; Other, 0.612 [0.519–0.722] vs 0.549 [0.470–0.641]). Mean total and patient-paid daily surveillance-related costs ranged from $540 and $113, respectively (ultrasound) to $1580 and $300, respectively (magnetic resonance imaging), and mean estimated patient productivity costs were $730–$2514 annually. HCC surveillance was underutilized and was lowest among patients with nonviral etiologies and those who had not seen a gastroenterologist. Surveillance-related out-of-pocket expenses and lost productivity were substantial. The development of surveillance strategies that reduce patient burden, such as those using blood-based biomarkers, may help improve surveillance adherence and effectiveness. [ABSTRACT FROM AUTHOR]

Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high‐risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow‐up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53–2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26–13.07, p < 0.001). Mean total and patient‐paid daily surveillance‐related costs ranged from $99 (ultrasound) to $334 (magnetic resonance imaging), and mean annual patient costs due to lost productivity for surveillance‐related outpatient visits ranged from $93 (using the federal minimum wage) to $321 (using the Bureau of Labor Statistics wage). Conclusion: Use of current HCC surveillance strategies was low across patients with HBV infection, and surveillance was associated with substantial patient financial burden. These data highlight an urgent need for accessible and easy‐to‐implement surveillance strategies with sufficient sensitivity and specificity for early HCC detection. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has resulted in over 1 million deaths in the U.S. as of June 2022, with continued surges after vaccine availability. Information on related attitudes and behaviors are needed to inform public health strategies. We aimed to estimate the prevalence of COVID-19, risk factors of infection, and related attitudes and behaviors in a racially, ethnically, and socioeconomically diverse urban population. Methods: The DFW COVID-19 Prevalence Study Protocol 1 was conducted from July 2020 to March 2021 on a randomly selected sample of adults aged 18–89 years, living in Dallas or Tarrant Counties, Texas. Participants were asked to complete a 15-minute questionnaire and COVID-19 PCR and antibody testing. COVID-19 prevalence estimates were calculated with survey-weighted data. Results: Of 2969 adults who completed the questionnaire (7.4% weighted response), 1772 (53.9% weighted) completed COVID-19 testing. Overall, 11.5% of adults had evidence of COVID-19 infection, with a higher prevalence among Hispanic and non-Hispanic Black persons, essential workers, those in low-income neighborhoods, and those with lower education attainment compared to their counterparts. We observed differences in attitudes and behaviors by race and ethnicity, with non-Hispanic White persons being less likely to believe in the importance of mask wearing, and racial and ethnic minorities more likely to attend social gatherings. Conclusion: Over 10% of an urban population was infected with COVID-19 early during the pandemic. Differences in attitudes and behaviors likely contribute to sociodemographic disparities in COVID-19 prevalence. [ABSTRACT FROM AUTHOR]