INTRODUCTION: Patients with primary sclerosing cholangitis (PSC) are at increased risk of acute cholangitis. The epidemiological risks of cholangitis are poorly studied despite the high morbidity associated with this infection. The aim of this study was to understand the impact of statins on acute cholangitis in PSC. METHODS: This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with the development of cholangitis were identified using multivariable Cox regression. RESULTS: The patients were predominantly male (68.7%) with a median age at enrollment of 48 years (interquartile range [IQR]: 31.0-60.8). Fifty patients (17.0%) were prescribed statins. The median follow-up time was 6 years (IQR: 2.0-12.0), in which 29.6% (n = 87) developed cholangitis. In multivariable analysis, statins were associated with an 81% reduction in cholangitis (HR 0.19, 95% confidence interval 0.03-0.64). Statins were associated with a lower adjusted incidence of cholangitis at 36 months compared with patients not on statin therapy (incidence of 2.8% vs 12.2%, P < 0.001). Statins were also associated with increased time-to-stricture (P = 0.004), an outcome known to be associated with PSC complications. DISCUSSION: Statin therapy is associated with reduced risk of cholangitis in PSC, possibly by delaying the time to develop dominant or high-grade strictures. In patients with PSC, use of statin therapy may be a beneficial modality to prevent the development of cholangitis and warrants further investigation.

Inflammatory bowel disease (IBD) most commonly has onset between the second and fourth decades of life; however, about 10-20% of individuals develop late-onset disease, frequently defined as being diagnosed at age greater than 60. Late-onset Crohn’s disease (LOCD) is less well characterized compared to adult-onset Crohn’s disease (AOCD). We compared a cohort of patients with LOCD to those with AOCD at the time of diagnosis to identify differences in disease characteristics and potential risk factors for late-onset disease. This retrospective cohort study utilized our institution’s electronic medical record (EMR) database to identify LOCD patients (diagnosed at age ≥ 60) with complete data. AOCD patients (age 20–40) were selected using a random number generator in a 3:1 ratio. Factors recorded at the time of initial diagnosis included age, BMI, race/ethnicity, history of current or prior smoking, disease location based on endoscopy and/or imaging, family history of IBD, presence of extraintestinal manifestations, history of appendectomy or tonsillectomy, and history of diverticulitis. In descriptive analysis, the two groups were compared using the Wilcoxon rank sum test for continuous variables and the chi-square or Fisher’s exact test for categorical variables. A p-value of < 0.05 was considered statistically significant. A total of 40 LOCD patients (median age at diagnosis 64 years) and 120 AOCD patients (median age at diagnosis 28 years) were included in the analysis. The LOCD cohort had a higher percentage of white patients (80% vs. 55.8%, p=0.02), significantly higher BMI (median(IQR) 25(22-28.9) vs. 22.4(20.4-25), p< 0.01), and a greater proportion classified as obese or overweight (20% vs. 9.2% and 30% vs. 15.8%, respectively, p=0.03). There were statistically significant higher rates of prior diverticulitis and appendectomy/tonsillectomy in the LOCD cohort. A non-significant trend toward a higher proportion of isolated colonic disease was noted in the LOCD cohort (45% vs. 30%, p=0.10). Additionally, perianal disease was significantly less common in LOCD patients (5% vs. 22.5%, p=0.01). Our results suggest that higher BMI and classification as obese or overweight, may be risk factors for LOCD. Additionally, there was a higher prevalence of white patients in the LOCD cohort, suggesting a potential propensity for the condition in this group. Even though differences were noted in diverticulitis and surgical history, the low numbers and change in surgical practice patterns over time limit interpretation. We found a trend towards higher isolated colonic disease and significantly lower rates of perianal disease in the LOCD cohort. These differences in disease location at the time of diagnosis have potential implications for therapy response and risk of disease progression. Table 1: Late-Onset vs Adult-Onset Crohn’s Disease

INTRODUCTION:Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health threat, potentially leading to chronic liver disease and liver cancer. Current guidelines recommend using the Fibrosis-4 score for initial identification of subjects at risk of future complications. We formulate a novel population screening strategy based on the Steatosis-Associated Fibrosis Estimator (SAFE) score, recently developed for MASLD risk stratification in primary care. METHODS:We interrogated the National Health and Nutrition Examination Survey data, 2017-20, in which a sample of subjects representative of US civilian population underwent vibration-controlled transient elastography (VCTE). The current guideline and a new, SAFE-based proposal were applied to these data to project the number of subjects to be diagnosed with liver fibrosis gauged by liver stiffness measurement (LSM), including significant (LSM ≥8 kPa) and advanced (LSM ≥12 kPa) fibrosis, as well as the number of VCTEs to be performed. RESULTS:In the survey data, 2,691 subjects, projecting to 75.8 million US adults, were found to have MASLD, of whom 11% had LSM 8-12 kPa and 6% LSM ≥12 kPa. When the current guideline was applied, 18.1 million VCTEs would be needed to diagnose 3.5 million subjects with LSM ≥8 kPa and 1.7 million subjects with LSM ≥12 kPa. In comparison, a new approach based on the SAFE score would detect 4.9 million with LSM ≥8 kPa and 2.5 million subjects with LSM ≥12 kPa (37% and 45% improvement over the current guideline, respectively), while requiring 5.0 million fewer VCTEs (28% reduction). DISCUSSION:The proposed population risk stratification approach using the SAFE score is simpler and substantially more effective, yielding more subjects with liver fibrosis while requiring less resources compared with the currently recommended algorithm.

Background: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions.Methods: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated.Results: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years.Conclusions: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.