215 Background: The decision to offer adjuvant chemotherapy (ACT) for patients with high-risk stage II and stage III colon cancer is fraught with challenges as most patients do not benefit from potentially toxic therapy. Histotype Px Colorectal stratifies patients into distinct risk groups by combining staging parameters with the DoMore v1 marker, a novel artificial intelligence-based digital biomarker that analyzes routine H&E-stained FFPE whole-slide images. The purpose of this study was to externally validate its prognostic performance and investigate its potential to predict adjuvant chemotherapy (ACT) benefit. Methods: This was a retrospective analysis of patients diagnosed with pathological stage II/III colon adenocarcinoma treated at Ohio State University in 2011-2024. Clinical parameters and outcome data were extracted from patient records. Blinded to clinical outcomes, anonymized digitized slides were analyzed by Histotype Px. Logrank test and Cox proportional hazards regression were used to analyze cancer-specific death (CSD). The multivariable models included age, sex, pN stage, pT stage, number of lymph nodes sampled, tumor perforation, lymphovascular invasion, perineural invasion, MSI status, and receipt of ACT. Competing risk analysis was used to calculate CSD rates. Results: Baseline characteristics of the 503 eligible patients included median age of 63 years (22-97), 54% male, 55% stage III, 61% right-sided tumors and 23% MSI, with 51% of patients receiving ACT and a median follow-up of 44 months. The DoMore v1 marker was statistically significant in both univariable (p<0.0001) and multivariable analysis with the clinicopathological markers (p=0.0010). Among the 298 patients in the Histotype Px low-risk group, 41.3% received ACT and their 5-year CSD rate was 6.1% (2.2%-12.8%) compared to 5.9% (2.7%-10.9%) for those that did not receive ACT. For the 123 Histotype Px intermediate-risk patients, 58.5% received ACT with a 5-year CSD rate of 17.5% (8.3%-29.5%) compared to 15.7% (6.2%-29.2%) without ACT. For the 81 Histotype Px high-risk patients, 76.5% received ACT with a 5-year CSD rate of 42.3% (21.9%-61.5%) compared to 58.3% (30.8%-78.1%) without ACT. In multivariable analyses, ACT benefit was observed in the high-risk group (HR 0.17, 95% CI 0.06-0.47; p=0.0007) but neither in the intermediate-risk (p=0.84) nor low-risk (p=0.16) group. Conclusions: Histotype Px Colorectal was able to improve risk stratification and showed promise as a predictive biomarker for ACT benefit in patients with stage II/III colon adenocarcinoma. Current standard-of-care ACT might not be sufficient for Histotype Px high-risk patients, while ACT might not be beneficial for Histotype Px low-risk patients.

3622 Background: According to current guidelines, most patients with high-risk stage II and stage III colon cancer should receive adjuvant chemotherapy (ACT). However, risk determination is controversial and most patients do not benefit from ACT. Histotype Px Colorectal is a novel artificial intelligence-based biomarker validated for R0 stage II-III colorectal adenocarcinoma that analyzes digitized routine H&E-stained FFPE tumor resections. Combined with clinical parameters, patients are stratified into distinct low, intermediate, and high-risk groups. This pilot study seeks to validate the applicability of Histotype Px Colorectal in an independent cohort from the United States. Methods: This was a retrospective analysis of patients diagnosed with pathological stage II-III colon adenocarcinoma at Ohio State University from 2016-2020. Anonymized slides were collected and digitized using the Aperio AT2 scanner. Clinical parameters and outcome data were extracted from patient records. Histotype Px Colorectal biomarker was blindly applied to each scan and subsequently linked to clinical outcomes. Statistical analysis was performed using Cox proportional hazards regression analysis. The pre-specified primary outcome was cancer-specific survival with a secondary outcome of time-to-recurrence. Results: Baseline characteristics of the 159 eligible patients included median age of 63 years (range 22-91), 52% female, 52% stage III, 64% right-sided tumors, and 31% MSI. 18% of stage II and 70% of stage III patients received ACT, respectively, with FOLFOX in 61%. Median follow-up for all patients was 54.2 months. For stage II patients, 21% were classified as intermediate-risk and 79% as low-risk. Only 6 (8%) of the 76 stage II patients had a cancer-related death with 3 of those patients classified as intermediate-risk. For stage III patients, 26% were classified as high-risk, 22% as intermediate-risk, and 52% as low-risk. 18 (22%) of the 83 stage III patients had a cancer-related death with 14 of those patients classified as high or intermediate-risk. Overall, Histotype Px Colorectal was a significant predictor of cancer-specific survival with HR=7.80 (95% CI 2.96-20.56, p<0.001) for high vs. low-risk patients and 2.81 (95% CI 0.98-8.04, p=0.05) for intermediate vs. low-risk patients. In addition, it was found to be a significant predictor for time-to-recurrence with HR=7.59 (3.56-16.20, p<0.001) for high vs. low-risk patients and 2.67 (1.20-5.96, p=0.02) for intermediate vs. low-risk patients. Conclusions: The findings from this study highlight the potential utility of this innovative biomarker in guiding clinical decisions regarding ACT. Further research involving a larger and more diverse patient cohort and subsequent clinical studies are planned to solidify these initial findings and to enable personalized treatment strategies based on individual risk assessments.

Over 70 million individuals are infected with hepatitis C virus (HCV) worldwide. Yet most prevalence data are in the adult population, with little focus on paediatrics, partially due to the scarcity of public data. The objective of this paper is to examine HCV prevalence in children by estimating prevalence rates among women, given the assumption that most cases are vertically transmitted. Between 2001 and 2017, maternal HCV infection affected ~ 0.24% of all births, with prevalence increasing by at least 261%. On average, approximately 0.01% of the total number of live births were infected with HCV, with a 245% increase in the number of children born with the infection. HCV epidemiology has evolved, with women of childbearing age representing a greater proportion of infected individuals in the United States, and infants born to infected mothers being at risk. We therefore recommend a greater public health focus of HCV on the paediatric population.

Introduction Liver transplant (LT) recipients have an increased risk of Clostridioides difficile infection (CDI) which associated with higher morbidity and mortality.CDI in LT has been argued to increase hospital costs, charges, and length of stay (LOS) in small studies.However, no recent nationwide analysis determines these outcomes.Methods Retrospective, observational study using the National Inpatient Sample 2016, the largest public inpatient database in the United States (US).All patients with ICD10CM diagnostic codes for CDI were included in the study.The cohort was stratified for the history of LT and LT index admission using respective ICD codes.The primary outcome was the odds of CDI in both patient cohorts to patients without OLT.Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, LOS, and total hospital costs and charges.Multivariate regression analyses were used to adjust for age, gender, Charlson Comorbidity Index, income in patient zip code, hospital region, location, size, and teaching status.Results A total of 360,364 patients with CDI were identified, out of which 1,665 had a history of LT and 155 had LT during that admission.The mean ages for patients with CDI and history of LT and LT index admission were 53.0 and 52.4,respectively, while 45.9 and 45.2% were female, respectively.For the primary outcome, patients with a history of LT had increased odds of CDI compared to patients with no history of LT (adjusted odds ratio (aOR): 2.78, p<0.01).Both cohorts that had associated CDI had greater odds of shock acute kidney injury (AKI), ICU stay, and organ failure compared to patients with LT history/index admission without CDI.Patients in the index admission for OLT with associated CDI had significantly higher colectomy odds.Both cohorts had significantly higher costs, charges and LOS compared to LT patients without CDI.All outcomes are shown in Table 1.Conclusion Patients with a history of LT increased odds of CDI, which may be a consequence of chronic immunosuppression in this subset of patients.In addition, patients with CDI that had associated history of LT and those in the index admission for LT had higher odds of morbidity and resource utilization compared to patients without CDI.For these reasons, it is important to promptly consider this pathogen in these patient populations that have symptoms suggestive of CDI to institute treatment in a timely fashion and avoid complications.

Purpose of review Alcoholic liver disease continues to be a major public health concern in the United States and around the world. Alcoholic liver disease remains the third most common indication for liver transplantation in the United States. Mortality has been reported in up to 30–50% of patients with severe alcoholic hepatitis. Liver transplantation can be lifesaving for patients with alcoholic hepatitis. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence. The majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. The purpose of this review is to provide an update from the most recent peer reviewed articles regarding early liver transplantation of alcoholic hepatitis. Recent findings This review shows that liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria is a key component for a successful transplant. No change in 1-year graft survival between patients who have 6 months sobriety vs. those transplanted prior to 6 months abstinence. Liver transplantation is limited by very narrow selection criteria and limited long-term data. Summary Liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria of patients has evolved and have become more permissive and the period of sobriety has become less important in the evaluation of process. However, long-term outcomes continue to lack in the literature. On the basis of previous studies, patients with longer pretransplant abstinence, disease process insight, older age at the time of transplant, the presence of social support that lives with the patient in the same dwelling place were noted to have lower rates of return to alcohol use after liver transplantation.

Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with cirrhosis. The impact of HE on the health care system is similarly profound. The number of hospital admissions for HE has increased in the last 10-year period. HE is a huge burden to the patients, care givers, and the health care system. HE represents a "revolving door" with readmission, severely affects care givers, and has effects on cognition that can persists after liver transplant. This article reviews the current literature to discuss the challenges and diagnostic and therapeutic approaches to HE.