Missed and Delayed Diagnoses of Chronic Liver Disease in Primary Care Patients with Cirrhosis.

BACKGROUND: Chronic liver diseases (CLD), cirrhosis, and hepatocellular carcinoma (HCC) cause significant morbidity and mortality. Unfortunately, patients with CLD often go undiagnosed until progression to cirrhosis and HCC. We aimed to determine the proportion of primary care patients with severe liver disease outcomes that had missed or delayed CLD diagnoses. METHODS: This retrospective cohort study evaluated primary care patients with a diagnosis of cirrhosis, HCC, or other severe liver disease outcome between 2012 and 2021. The outcomes of interest were missed and delayed diagnoses of CLD, defined as the absence of a CLD diagnosis (missed) or first appearance of CLD on the same day as the cirrhosis diagnosis (delayed). Univariate analyses were performed to describe the cohort. Multivariable logistic regression models analyzed the association of aminotransferase elevations with the outcomes of interest. RESULTS: Of 667 patients with cirrhosis or HCC, 133 (20%) had a missed CLD diagnosis, and 243 (36%) had a delayed CLD diagnosis. Alcohol-related liver disease was the most common etiology among patients with missed/delayed diagnoses. A lower proportion of patients with missed/delayed diagnoses had an elevation in ALT or AST compared to patients with timely diagnoses (61% vs. 77%, p < 0.001). Elevated aminotransferase values were associated with lower odds of a missed/delayed diagnosis (OR 0.47; 95%CI 0.34-0.66). CONCLUSIONS: Most patients with cirrhosis or HCC had missed or delayed diagnoses of CLD in the context of probable overreliance on aminotransferase elevation for CLD detection. Enhanced screening for high prevalence CLD, especially alcohol, in primary care is needed.

Objective Measures of Cardiometabolic Risk and Advanced Fibrosis Risk Progression in Primary Care Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND: We examined the association of objective measures of cardiometabolic risk with progression to a high-risk for advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) at initially low- and indeterminate-risk for advanced fibrosis. METHODS: We performed a retrospective cohort study of primary care patients with MASLD between 2012 and 2021. We evaluated patients with MASLD and low- or indeterminate-risk Fibrosis-4 Index (FIB-4) scores and followed them until the outcome of a high-risk FIB-4 (≥2.67), or the end of the study period. Exposures of interest were body mass index, systolic blood pressure, hemoglobin A1c, cholesterol, estimated glomerular filtration rate, and smoking status. Variables were categorized by the threshold for primary care therapy intensification. Unadjusted and adjusted Cox regression models were developed for the outcome of time to a high-risk FIB-4 value. RESULTS: The cohort included 1347 patients with a mean follow-up of 3.6 years (SD 2.7). Of the cohort, 258 (19%) had a subsequent FIB-4 > 2.67. In the fully adjusted Cox regression models, mean systolic blood pressure ≥ 150 mm Hg (1.57; 95% confidence interval (CI) 1.02-2.41) and glomerular filtration rate ≤ 59 ml/min (hazard ratio 2.78; 95%CI 2.17-3.58) were associated with an increased hazard of a high-risk FIB-4, while receiving a statin prescription (hazard ratio 0.51; 95%CI 0.39-0.66) was associated with a lower risk. CONCLUSIONS: Nearly 1 in 5 primary care patients with MASLD transitioned to a high-risk FIB-4 score during 3.6 years of follow-up, and uncontrolled blood pressure and reduced kidney function were associated with an increased hazard of a FIB-4 at high-risk for advanced fibrosis.

Statin prescriptions and progression of advanced fibrosis risk in primary care patients with MASLD.

OBJECTIVE: We aimed to determine the association of statins with progression to a high risk for advanced fibrosis in primary care patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DESIGN: This retrospective cohort study of electronic health record data included patients with MASLD and an initial low or indeterminate risk for advanced fibrosis, determined by Fibrosis-4 Index (FIB-4) score (<2.67). Patients were followed from the index FIB-4 until the primary outcome of a high-risk FIB-4 (≥2.67) or the end of the study period. Prescription for a statin during follow-up was the primary exposure. We developed Cox regression models for the time to a high-risk FIB-4 score with statin therapy as the primary covariate and adjusting for baseline fibrosis risk, demographic and comorbidity variables. RESULTS: The cohort of 1238 patients with MASLD was followed for a mean of 3.3 years, with 47% of patients receiving a prescription for a statin, and 18% of patients progressing to a high-risk FIB-4. In the adjusted Cox model with statin prescription as the primary exposure, statins were associated with a lower risk (HR 0.60; 95% CI 0.45 to 0.80) of progressing to a FIB-4≥2.67. In the adjusted Cox models with statin prescription intensity as the exposure, moderate (HR 0.60; 95% CI 0.42 to 0.84) and high intensity (HR 0.61; 95% CI 0.42 to 0.88) statins were associated with a lower risk of progressing to a high-risk FIB-4. CONCLUSION: Statin prescriptions, and specifically moderate and high intensity statin prescriptions, demonstrate a protective association with fibrosis risk progression in primary care patients with MASLD.

Patterns of gastroenterology specialty referral for primary care patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: As metabolic dysfunction-associated steatotic liver disease (MASLD) management extends into primary care, little is known about patterns of specialty referral for affected patients. We determined the proportion of primary care patients with MASLD that received a gastroenterology (GI) consultation and compared advanced fibrosis risk between patients with and without a referral. METHODS: This retrospective study of electronic health record data from a primary care clinic included patients with MASLD, no competing chronic liver disease diagnoses, and no history of cirrhosis. Referral to GI for evaluation and management (E/M) any time after MASLD ascertainment was the outcome. Fibrosis-4 Index (FIB-4) scores were calculated, categorized by advanced fibrosis risk, and compared by receipt of a GI E/M referral. Logistic regression models were developed to determine the association of FIB-4 risk with receipt of a GI referral. RESULTS: The cohort included 652 patients of which 12% had FIB-4 scores (≥2.67) at high-risk for advanced fibrosis. Overall, 31% of cohort patients received a GI referral for E/M. There was no difference in the proportion of patients with high (12% vs. 12%, p=0.952) risk FIB-4 scores by receipt of a GI E/M referral. In adjusted logistic regression models, high-risk FIB-4 scores (OR 1.01; 95% CI 0.59 - 1.71) were not associated with receipt of a referral. CONCLUSIONS: Only 30% of patients in this primary care MASLD cohort received a GI E/M referral during the study period, and those patients with a referral did not differ by FIB-4 advanced fibrosis risk.

Glucagon-like peptide-1 receptor agonist therapy effects on glycemic control and weight in a primary care clinic population.

Glucagon-like peptide-1 receptor agonist (GLP-1a) medications have been shown in randomized controlled trials (RCTs) to have consistent and impressive effectiveness in lowering hemoglobin A1c (HbA1c) and weight, but limited data exist on the efficacy of GLP-1a medications in clinical practice. We studied the association between GLP-1a therapy and changes in weight and HbA1c in a real-world patient population. In this retrospective cohort study of patients seen in a primary care clinic between 2012 and 2021, we examined the change in weight and HbA1c over 12 months in a cohort of patients with at least one prescription for a GLP-1a. Within this cohort, treatment was defined as having ≥2 GLP-1a prescriptions at a therapeutic dosage separated by ≥10 months. The cohort included 693 patients of whom 393 (57%) were treated with GLP-1a therapy. The treatment group had a mean change in body mass index (BMI) of -0.83 kg/m2 (±2.88) compared to -0.70 kg/m2 (±2.99) in the without GLP-1a group (p = 0.57). Treated patients had a mean change in HbA1c of -1.00% (±2.07) compared to -0.83% (±1.92) in the without GLP-1a group (p = 0.27). For treated and without GLP-1a patients, respectively, the proportion of patients with a decrease in BMI was 65 versus 64% (p = 0.86), and the proportion with a decrease in HbA1c was 73 versus 69% (p = 0.28). In clinical practice, GLP-1a therapy was associated with more modest reductions in weight and HbA1c than shown in prior RCTs. As GLP-1a use continues to expand throughout primary care, the real-world impact of this pharmacotherapy will require further evaluation.

Hospitalization as an opportunity to improve lung cancer screening in high-risk patients.

BACKGROUND: Lung cancer screening with annual low-dose computed tomography (LDCT) in high-risk patients with exposure to smoking reduces lung cancer-related mortality, yet the screening rate of eligible adults is low. As hospitalization is an opportune moment to engage patients in their overall health, it may be an opportunity to improve rates of lung cancer screening. Prior to implementing a hospital-based lung cancer screening referral program, this study assesses the association between hospitalization and completion of lung cancer screening. METHODS: A retrospective cohort study of evaluated completion of at least one LDCT from 2014 to 2021 using electronic health record data using hospitalization as the primary exposure. Patients aged 55-80 who received care from a university-based internal medicine clinic and reported cigarette use were included. Univariate analysis and logistic regression evaluated the association of hospitalization and completion of LDCT. Cox proportional hazard model examined the time relationship between hospitalization and LDCT. RESULTS: Of the 1935 current smokers identified, 47% had at least one hospitalization, and 21% completed a LDCT during the study period. While a higher proportion of patients with a hospitalization had a LDCT (24%) compared to patients without a hospitalization (18%, p<0.001), there was no association between hospitalization and completion of a LDCT after adjusting for potentially confounding covariates (95%CI 0.680 - 1.149). There was an association between hospitalization time to event and LDCT completion, with hospitalized patients having a lower probability of competing LDCT compared to non-hospitalized patients (HR 0.747; 95% CI 0.611 - 0.914). CONCLUSIONS: In a cohort of patients at risk for lung cancer and established within a primary care clinic, only 1 in 4 patients who had been hospitalized completed lung cancer screening with LDCT. Hospitalization events were associated with a lower probability of LDCT completion. Hospitalization is a missed opportunity to refer at-risk patients to lung cancer screening.

Effect of Delirium on Interhospital Transfer Outcomes.

OBJECTIVES: Interhospital transfer (IHT) and in-hospital delirium are both independently associated with increased length of stay (LOS), mortality, and discharge to facility. Our objective was to investigate the joint effects between IHT and the presence of in-hospital delirium on the outcomes of LOS, discharge to a facility, and in-hospital mortality. METHODS: This was a single-center retrospective cohort study of 25,886 adult hospital admissions at a tertiary-care academic medical center. Staged multivariable logistic and linear regression models were used to evaluate the association between IHT status and the outcomes of discharge to a facility, LOS, and mortality while considering the joint impact of delirium. The joint effects of IHT status and delirium were evaluated by categorizing patients into one of four categories: emergency department (ED) admissions without delirium, ED admissions with delirium, IHT admissions without delirium, and IHT admissions with delirium. The primary outcomes were LOS, in-hospital mortality, and discharge disposition. RESULTS: The odds of discharge to a facility were 4.48 times higher in admissions through IHT with delirium when compared with ED admissions without delirium. IHT admissions with delirium had a 1.97-fold (95% confidence interval 1.88-2.06) longer LOS when compared with admission through the ED without delirium. Finally, admissions through IHT with delirium had 3.60 (95% confidence interval 2.36-5.49) times the odds of mortality when compared with admissions through the ED without delirium. CONCLUSIONS: The relationship between IHT and delirium is complex, and patients with IHT combined with in-hospital delirium are at high risk of longer LOS, discharge to a facility, and mortality.

Is hospitalization a missed opportunity to intervene on tobacco cessation?

BACKGROUND: Although tobacco use is associated with elevated morbidity and mortality, its use remains widespread among adults within the United States. Nicotine Replacement Therapy (NRT) products are effective aids that improve rates of tobacco cessation. Many smokers interact with the medical system, such as during hospitalization, without their tobacco use addressed. Hospitalization is a teachable moment for patients to make health-related changes, including tobacco cessation. METHODS: Retrospective cohort study of adult patients in a university-based patient-centered medical home from 2012 to 2021 evaluating the proportion of adults who smoke who received at least one prescription for NRT. Logistic regression models were used to analyze the association of being hospitalized and receipt of a NRT prescription. RESULTS: Of the 4,072 current smokers identified, 1,182 (29%) received at least one prescription for NRT during the study period. Hospitalization was associated with increased odds of receiving a NRT prescription (OR 1.68). Of 1,844 current smokers with a hospitalization during the study period, 1,078 (58%) never received a prescription for NRT at any point. Only 87 (5%) of the smokers received a prescription for NRT during hospitalization or at the time of hospital discharge. CONCLUSIONS: Despite hospitalization being associated with NRT prescribing, most patients who use tobacco and are hospitalized are not prescribed NRT. Hospitalization is an underutilized opportunity for both hospitalists and primary care physicians to intervene on smoking cessation through education and prescription of tobacco cessation aids.

FIB-4 as a Time-varying Covariate and Its Association With Severe Liver Disease in Primary Care: A Time-dependent Cox Regression Analysis.

BACKGROUND AND GOALS: The Fibrosis-4 Index (FIB-4) has demonstrated a strong association with severe liver disease (SLD) outcomes in primary care, but previous studies have only evaluated this relationship using 1 or 2 FIB-4 scores. In this study, we determined the association of FIB-4 as a time-varying covariate with SLD risk using time-dependent Cox regression models. STUDY: This retrospective cohort study included primary care patients with at least 2 FIB-4 scores between 2012 and 2021. The outcome was the occurrence of an SLD event, a composite of cirrhosis, complications of cirrhosis, hepatocellular carcinoma, and liver transplantation. The primary predictor was FIB-4 advanced fibrosis risk, categorized as low-(<1.3), indeterminate-(1.3≤FIB to 4<2.67), and high-risk (≥2.67). FIB-4 scores were calculated and the index, last, and maximum FIB-4s were identified. Time-dependent Cox regression models were used to estimate hazard ratios (HR) and their corresponding 95% CI with adjustment for potentially confounding covariates. RESULTS: In the cohort, 20,828 patients had a median of 5 (IQR: 3 to 11) FIB-4 scores each and 3% (n=667) suffered an SLD outcome during follow-up. Maximum FIB-4 scores were indeterminate-risk for 34% (7149) and high-risk for 24% (4971) of the sample, and 32% (6692) of patients had an increase in fibrosis risk category compared with their index value. The adjusted Cox regression model demonstrated an association between indeterminate- (hazard ratio 3.21; 95% CI 2.33-4.42) and high-risk (hazard ratio 20.36; 95% CI 15.03-27.57) FIB-4 scores with SLD outcomes. CONCLUSIONS: Multiple FIB-4 values per patient are accessible in primary care, FIB-4 fibrosis risk assessments change over time, and high-risk FIB-4 scores (≥2.67) are strongly associated with severe liver disease outcomes when accounting for FIB-4 as a time-varying variable.

Statin prescribing patterns in patient-centered medical home patients with NAFLD.

OBJECTIVES: Cardiovascular disease is the leading cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD), and statins play a pivotal role in the primary prevention of cardiovascular events. This study investigates statin prescribing in primary care patients with NAFLD to identify opportunities to address cardiovascular disease risk in this cohort. STUDY DESIGN: Retrospective cohort study of primary care electronic health record data from 2012-2018. METHODS: This cohort included 652 patients with radiographic evidence of hepatic steatosis and no evidence of competing chronic liver disease. A statin prescription identified at any time during the study period was the primary outcome. Univariate and multivariable analyses were performed to evaluate the association of clinical signals and comorbidities with statin prescribing. RESULTS: Of the 652 patients in the NAFLD cohort, 56% received a statin prescription during the study period. Elevations in aminotransferases were not associated with statin prescribing (adjusted odds ratio [AOR], 1.17; 95% CI, 0.78-1.76), whereas older patients (AOR, 1.06; 95% CI, 1.05-1.08) and those with diabetes (AOR, 2.61; 95% CI, 1.73-3.92), hypertension (AOR, 2.76; 95% CI, 1.70-4.48), and a BMI greater than or equal to 30 kg/m2 (AOR, 1.49; 95% CI, 1.01-2.22) had higher odds of having a statin prescribed. Of the 288 patients without a statin prescription, 49% had an indication for statin therapy by atherosclerotic cardiovascular disease risk. In total, 16% of included patients did not have lipid panel results during the study period. CONCLUSIONS: This study showed no association between NAFLD and statin prescribing, and the findings highlight opportunities to improve primary prevention of cardiovascular disease in these at-risk patients.