Despite increasing incidence of hepatocellular carcinoma (HCC) in vulnerable populations, accurate early detection tools are lacking. We aimed to investigate the associations between prediagnostic plasma metabolites and incident HCC in a diverse population. In a prospective, nested case-control study within the Southern Community Cohort Study, we conducted prediagnostic LC/MS metabolomic profiling in 150 incident HCC cases (median time to diagnosis, 7.9 years) and 100 controls with cirrhosis. Logistic regression assessed metabolite associations with HCC risk. Metabolite set enrichment analysis identified enriched pathways, and a random forest classifier was used for risk classification models. Candidate metabolites were validated in the UK Biobank (N = 12 incident HCC cases and 24 cirrhosis controls). In logistic regression analysis, seven metabolites were associated with incident HCC (MeffP < 0.0004), including N-acetylmethionine (OR = 0.46; 95% confidence interval, 0.31-0.66). Multiple pathways were enriched in HCC, including histidine and CoA metabolism (FDR P < 0.001). The random forest classifier identified 10 metabolites for inclusion in HCC risk classification models, which improved HCC risk classification compared with clinical covariates alone (AUC = 0.66 for covariates vs. 0.88 for 10 metabolites plus covariates; P < 0.0001). Findings were consistent in the UK Biobank (AUC = 0.72 for covariates vs. 0.88 for four analogous metabolites plus covariates; P = 0.04), assessed via nuclear magnetic resonance spectroscopy. Prediagnostic metabolites, primarily amino acid and sphingolipid derivatives, are associated with HCC risk and improve HCC risk classification beyond clinical covariates. These metabolite profiles, detectable years before diagnosis, could serve as early biomarkers for HCC detection and risk stratification if validated in larger studies. Prevention Relevance: Our findings support the need for larger prospective studies examining the role of prediagnostic plasma metabolomics for the preventive management of HCC in diverse patients across multiple etiologies of liver disease. This approach could improve HCC care by identifying metabolic changes years before diagnosis, potentially enhancing screening and early detection practices.

Background: Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction-associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by the free-text nature of pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score MASLD histology features. Methods: From the Mass General Brigham health care system electronic medical record, we identified all patients (1987-2021) with steatosis on index liver biopsy after excluding excess alcohol use and other etiologies of liver disease. An NLP algorithm was constructed in Python to detect steatosis, lobular inflammation, ballooning, and fibrosis stage from pathology free-text and manually validated in >1200 pathology reports. Patients were followed from the index biopsy to incident decompensated liver disease accounting for covariates. Results: The NLP algorithm demonstrated positive and negative predictive values from 93.5% to 100% for all histologic concepts. Among 3134 patients with biopsy-confirmed MASLD followed for 20,604 person-years, rates of the composite endpoint increased monotonically with worsening index fibrosis stage (p for linear trend <0.005). Compared to simple steatosis (incidence rate, 15.06/1000 person-years), the multivariable-adjusted HRs for cirrhosis were 1.04 (0.72-1.5) for metabolic dysfunction-associated steatohepatitis (MASH)/F0, 1.19 (0.92-1.54) for MASH/F1, 1.89 (1.41-2.52) for MASH/F2, and 4.21 (3.26-5.43) for MASH/F3. Conclusions: The NLP algorithm accurately scores histological features of MASLD from pathology free-text. This algorithm enabled the construction of a large and high-quality MASLD cohort across a multihospital health care system and disclosed an accelerating risk for cirrhosis based on the index MASLD fibrosis stage.

Background: Diet plays an important role in the pathogenesis of NAFLD. Inflammation is a potential mechanism linking diet to NAFLD development and its progression to cirrhosis. 1 We analyzed data from a large, prospective cohort of US women to examine the influence of dietary inflammatory potential on the long-term risk of developing NAFLD and cirrhosis. Methods: We prospectively followed 96,016 women in the Nurses’ Health Study II cohort (1995–2017) who were free of chronic liver disease, including NAFLD, at baseline. The inflammatory potential of the diet was ascertained using an established, food-based empirical dietary inflammatory pattern score. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% CIs for incident NAFLD and cirrhosis. Results: Over 2,085,947 person-years of follow-up, we documented 4389 cases of incident NAFLD and 102 cases of incident cirrhosis. Increasing cumulative average empirical dietary inflammatory pattern (EDIP) score was significantly and positively associated with incident NAFLD (multivariable-adjusted HR 1.31 per each 1-U increase in EDIP score, p-trend < 0.0001) and cirrhosis (p-trend of 0.034). Our findings also were consistent when examining recent diets using simple updated EDIP scores. In analyses of specific EDIP components, we observed an increased risk of incident NAFLD and cirrhosis with higher consumption of certain proinflammatory components of the EDIP score. Conclusions: Dietary patterns with a higher proinflammatory potential may be associated with a higher risk of developing both NAFLD and cirrhosis. Reducing the inflammatory potential of diet may potentially provide an effective strategy for preventing the development of NAFLD and progression to cirrhosis.

BACKGROUND:Therapies to prevent alcohol-associated liver disease (ALD) in high-risk patients are needed. AIMS:In this retrospective association study, we examined whether patients with alcohol use disorder (AUD) who reported greater exercise were less likely to develop liver disease. METHODS:In this retrospective cohort study, we used the Mass General Brigham Biobank to investigate the impact of both moderate-high and light-intensity exercise on the development of ALD in patients with AUD, using clinician-provided diagnostic International Classification of Diseases 10 codes. Exercise was evaluated using a questionnaire completed after an AUD diagnosis, and before evidence of liver disease. Cox regressions were used to generate hazard ratios (HRs) for the development of ALD. RESULTS:1987 patients met inclusion criteria. These patients were followed for an average of 10.7 years. In multivariable analyses, we found that patients that reported at least 2.5 h of moderate-high intensity exercise/week (confidence interval recommendation for exercise) were less likely to develop ALD compared to patients that did not exercise (HR: 0.26, 95%CI: 0.085-0.64, P = 0.007). Indeed, each hour of moderate-high intensity exercise was associated with progressively decreasing odds of developing ALD (HR: 0.76, 95%CI: 0.58-0.91, P = 0.02). Conversely, patients who did not engage in any moderate-high intensity exercise were more likely to develop ALD (HR: 2.76, 95%CI: 1.44-5.40, P = 0.003). CONCLUSIONS:In our cohort, patients with AUD who reported moderate-high intensity exercise showed a lower association with incidence of ALD development than patients who did not exercise.

Among All of Us participants, the prevalence of inflammatory bowel disease is similar to past estimates (around 1%) and is highest among White, non-Hispanic, college-educated participants. Medication treatment patterns differ significantly based on ethnicity, education, and income status.

Summary Aim To examine the relationship between periodontal disease and tooth loss and risk of inflammatory bowel disease (IBD). Methods We conducted a prospective cohort study of 86,602 women from the Nurses' Health Study (1992–2016) and 50,349 men from the Health Professionals Follow‐up Study (1986–2016) with available data on periodontal disease and tooth loss. Cases of IBD were initially reported by participants and then confirmed by medical record review. We used Cox proportional hazards modelling to estimate multivariable‐adjusted hazard ratios (aHRs) and 95% CIs. Results Through the end of follow‐up, we documented 175 cases of Crohn's disease (CD) and 209 cases of ulcerative colitis (UC). After adjustment for potential risk factors, there was no association between periodontal disease and risk of CD (pooled aHR: 0.99, 95% CI: 0.65–1.52, p = 0.970) or UC (aHR: 0.99, 95% CI: 0.68–1.45, p = 0.971). Similarly, we did not observe an association between tooth loss and risk of CD (aHR: 0.72, 95% CI: 0.43–1.21, p = 0.218) or UC (aHR: 0.89, 95% CI: 0.58–1.36, p = 0.581) in the pooled analysis. The associations were not modified by sex, age, body mass index (BMI), smoking status or NSAID use (all p interaction > 0.87). Conclusion In two large prospective cohort studies, we did not observe an association between periodontal disease and tooth loss and risk of CD or UC.

Microscopic colitis is a chronic inflammatory disease that most commonly affects post-menopausal women. Exogenous hormone use has recently been linked with increased risk of microscopic colitis. Yet, it is unclear whether levels of endogenous sex hormones are also associated with risk of microscopic colitis. To evaluate the association between prediagnostic plasma androgens and subsequent risk of microscopic colitis. We conducted a case–control study nested within prospective cohort studies of the Nurses' Health Study (NHS) and NHSII. Cases of microscopic colitis were each matched to two controls according to age, cohort, menopause status, fasting status, and season of plasma collection. Prediagnosis plasma levels of androgens including dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of microscopic colitis using conditional logistic regression models. Our study included 96 cases of microscopic colitis matched to 190 controls. Plasma levels of testosterone were not associated with risk of microscopic colitis (Ptrend = 0.70). Compared to participants in the lowest quartile of plasma testosterone levels, the aOR of microscopic colitis for women in the highest quartile was 0.88, 95

Catheter ablation has become an important and widely used treatment modality for patients with symptomatic atrial fibrillation. The superior efficacy of catheter ablation over antiarrhythmic therapy has been well established. The understanding of the pathophysiology of atrial fibrillation has led to the development of catheter-based ablation techniques. The development of techniques for catheter ablation of atrial fibrillation has rapidly progressed over the last 15 years. As our knowledge of this arrhythmia expands the strategies for ablation treatment continue to evolve. New technologies aim to improve the safety, efficacy, and speed of catheter ablation for atrial fibrillation.