Identifying and Linking Patients At Risk for MASLD with Advanced Fibrosis to Care in Primary Care.

BACKGROUND AND AIMS: Severity of fibrosis is the driver of liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD), and non-invasive testing such as fibrosis-4 (FIB-4) score is utilized for risk stratification. We aimed to determine if primary care patients at risk for MASLD and advanced fibrosis were evaluated with subsequent testing. A secondary aim was to determine if at-risk patients with normal aminotransferases had advanced fibrosis. METHODS: Primary care patients at increased risk for MASLD with advanced fibrosis (n = 91,914) were identified using previously established criteria. Patients with known alternative/concomitant etiology of liver disease or cirrhosis were excluded. The study cohort included patients with calculated FIB-4 score in 2020 (n = 52,006), and stratified into low, indeterminate, and high likelihood of advanced fibrosis. Among those at indeterminate/high risk, rates of subsequent testing were measured. RESULTS: Risk stratification with FIB-4 characterized 77% (n = 40,026) as low risk, 17% (n = 8847) as indeterminate, and 6% (n = 3133) as high risk. Among indeterminate/high-risk patients (n = 11,980), 78.7% (n = 9433) had aminotransferases within normal limits, 0.95% (n = 114) had elastography, and 8.2% (n = 984) were referred for subspecialty evaluation. CONCLUSION: In this cohort of primary care patients at risk for MASLD with fibrosis, the FIB-4 score identified a substantial proportion of indeterminate/high-risk patients, the majority of which had normal aminotransferase levels. Low rates of subsequent testing were observed. These data suggest that a majority of patients at increased risk for liver-related outcomes remain unrecognized and highlight opportunities to facilitate their identification.

Real-World Primary Care Data Comparing ALT and FIB-4 in Predicting Future Severe Liver Disease Outcomes.

BACKGROUND: Alanine aminotransferase (ALT) has long provided a cue for chronic liver disease (CLD) diagnostic evaluation, but the Fibrosis-4 Index (FIB-4), a serologic score used for predicting advanced fibrosis risk in CLD, may provide an alternative signal. OBJECTIVE: Compare the predictive performance of FIB-4 with ALT for severe liver disease (SLD) events while adjusting for potential confounders. DESIGN: Retrospective cohort study of primary care electronic health record data from 2012 to 2021. PATIENTS: Adult primary care patients with at least two sets of ALT and other lab values necessary for calculating two unique FIB-4 scores, excluding those patients with an SLD prior to their index FIB-4 value. MAIN MEASURES: The occurrence of an SLD event, a composite of cirrhosis, hepatocellular carcinoma, and liver transplantation, was the outcome of interest. Categories of ALT elevation and FIB-4 advanced fibrosis risk were the primary predictor variables. Multivariable logistic regression models were developed to evaluate the association of FIB-4 and ALT with SLD, and the areas under the curve (AUC) for each model were compared. KEY RESULTS: The cohort of 20,828 patients included 14% with an abnormal index ALT (≥40 IU/L) and 8% with a high-risk index FIB-4 (≥2.67). During the study period, 667 (3%) patients suffered an SLD event. Adjusted multivariable logistic regression models demonstrated an association between high-risk FIB-4 (OR 19.34; 95%CI 15.50-24.13), persistently high-risk FIB-4 (OR 23.85; 95%CI 18.24-31.17), abnormal ALT (OR 7.07; 95%CI 5.81-8.59), and persistently abnormal ALT (OR 7.58; 95%CI 5.97-9.62) with SLD outcomes. The AUC of the index FIB-4 (0.847, p < 0.001) and combined FIB-4 (0.849, p < 0.001) adjusted models exceeded the index ALT adjusted model (0.815). CONCLUSIONS: High-risk FIB-4 scores demonstrated superior performance compared to abnormal ALT in predicting future SLD outcomes.

FIB-4 and incident severe liver outcomes in patients with undiagnosed chronic liver disease: A Fine-Gray competing risk analysis.

BACKGROUND AND AIMS: The Fibrosis-4 index (FIB-4) can reliably assess fibrosis risk in patients with chronic liver disease, and advanced fibrosis is associated with severe liver disease (SLD) outcomes. However, CLD is underdiagnosed in primary care. We examined the association between FIB-4 risk strata and the incidence of SLD preceding a CLD diagnosis while considering incident CLD diagnoses as competing risks. METHODS: Using primary care clinic data between 2007 and 2018, we identified patients with two FIB-4 scores and no liver disease diagnoses preceding the index FIB-4. Patients were followed from index FIB-4 until an incident SLD (a composite of cirrhosis, hepatocellular carcinoma or liver transplantation), CLD or were censored. Hazard ratios were computed using a Fine-Gray competing risk model. RESULTS: Of 20 556 patients, there were 54.8% in the low, 34.8% in the indeterminate, 6.6% in the high and 3.8% in the persistently high-risk FIB-4 strata. During a mean 8.2 years of follow-up, 837 (4.1%) patients experienced an SLD outcome and 11.5% of the sample received a CLD diagnosis. Of patients with an SLD event, 49% received no preceding CLD diagnosis. In the adjusted Fine-Gray model, the indeterminate (HR 1.41, 95% CI 1.17-1.71), high (HR 4.65, 95% CI 3.76-5.76) and persistently high-risk (HR 7.60, 95% CI 6.04-9.57) FIB-4 risk strata were associated with a higher incidence of SLD compared to the low-risk stratum. CONCLUSIONS: FIB-4 scores with indeterminate- and high-risk values are associated with an increased incidence of SLD in primary care patients without known CLD.

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.

Identifying Patients at Risk for Fibrosis in a Primary Care NAFLD Cohort.

GOALS AND BACKGROUND: Using natural language processing to create a nonalcoholic fatty liver disease (NAFLD) cohort in primary care, we assessed advanced fibrosis risk with the Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Score (NFS) and evaluated risk score agreement. MATERIALS AND METHODS: In this retrospective study of adults with radiographic evidence of hepatic steatosis, we calculated patient-level FIB-4 and NFS scores and categorized them by fibrosis risk. Risk category and risk score agreement was analyzed using weighted κ, Pearson correlation, and Bland-Altman analysis. A multinomial logistic regression model evaluated associations between clinical variables and discrepant FIB-4 and NFS results. RESULTS: Of the 767 patient cohorts, 71% had a FIB-4 or NFS score in the indeterminate-risk or high-risk category for fibrosis. Risk categories disagreed in 43%, and scores would have resulted in different clinical decisions in 30% of the sample. The weighted κ statistic for risk category agreement was 0.41 [95% confidence interval (CI): 0.36-0.46] and the Pearson correlation coefficient for log FIB-4 and NFS was 0.66 (95% CI: 0.62-0.70). The multinomial logistic regression analysis identified black race (odds ratio=2.64, 95% CI: 1.84-3.78) and hemoglobin A1c (odds ratio=1.37, 95% CI: 1.23-1.52) with higher odds of having an NFS risk category exceeding FIB-4. CONCLUSIONS: In a primary care NAFLD cohort, many patients had elevated FIB-4 and NFS risk scores and these risk categories were often in disagreement. The choice between FIB-4 and NFS for fibrosis risk assessment can impact clinical decision-making and may contribute to disparities of care.

Gaps in Confirmatory Fibrosis Risk Assessment in Primary Care Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: As recommendations for non-invasive fibrosis risk assessment in nonalcoholic fatty liver disease (NAFLD) emerge, it is not known how often they are performed in primary care. AIMS: We investigated the completion of confirmatory fibrosis risk assessment in primary care patients with NAFLD and indeterminate-risk or greater Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Scores (NFS). METHODS: This retrospective cohort study of electronic health record data from a primary care clinic identified patients with diagnoses of NAFLD from 2012 through 2021. Patients with a diagnosis of a severe liver disease outcome during the study period were excluded. The most recent FIB-4 and NFS scores were calculated and categorized by advanced fibrosis risk. Charts were reviewed to identify the outcome of a confirmatory fibrosis risk assessment by liver elastography or liver biopsy for all patients with indeterminate-risk or higher FIB-4 (≥ 1.3) and NFS (≥ - 1.455) scores. RESULTS: The cohort included 604 patients diagnosed with NAFLD. Two-thirds of included patients (399) had a FIB-4 or NFS score greater than low-risk, 19% (113) had a high-risk FIB-4 (≥ 2.67) or NFS (≥ 0.676) score, and 7% (44) had high-risk FIB-4 and NFS values. Of these 399 patients with an indication for a confirmatory fibrosis test, 10% (41) underwent liver elastography (24) or liver biopsy (18) or both (1). CONCLUSIONS: Advanced fibrosis is a key indicator of future poor health outcomes in patients with NAFLD and a critical signal for referral to hepatology. Significant opportunities exist to improve confirmatory fibrosis risk assessment in patients with NAFLD.

"I'm Not Good with Money" and Other Lies Residents Tell Themselves about Personal Finance.

OBJECTIVES: Some physicians believe that they have difficulty managing their own personal finances, and many medical schools and residences do not have formal financial curricula embedded in education. Given that many medical students have >$200,000 in school loans, physicians are expected to navigate the complex financial world without guidance. METHODS: In this article, the authors developed a personal finance curriculum for Internal Medicine residents with the aim of evaluating the proportion of residents engaging in active personal finance activities, increasing their knowledge of financial literacy and their comfort with personal finance concepts using a pre- and postintervention survey. The content of the curriculum included four modules structured around different financial themes and delivered to trainees in 45-minute sessions. RESULTS: A majority of the residents were able to participate in workplace retirement, log into their retirement account, possessed a Roth individual retirement account, manage a budget, and check their credit score. An area prompting concern postintervention was the level of discomfort engaging with personal finance that disproportionally affected the female trainees more than their male counterparts. CONCLUSIONS: It is likely that an individual's comfort level managing finances stems from money beliefs, rather than actual ability given the requirements to graduate from medical school and the demands of an Internal Medicine residency.

The Association of Fibrosis-4 Index Scores with Severe Liver Outcomes in Primary Care.

BACKGROUND: The Fibrosis-4 Index (FIB-4)non-invasively assesses fibrosis risk in chronic liver disease (CLD), but underdiagnosis limits FIB-4's application in primary care. OBJECTIVE: To evaluate the association of FIB-4 risk with hazard of severe liver outcomes in primary care patients with and without diagnosed CLD. DESIGN: Retrospective cohort study of primary care data from 2007 to 2018. PARTICIPANTS: Adult patients with qualifying aminotransferase and platelet count results were included and a single FIB-4 score was calculated for each patient using the first of these values. Patients with a CLD diagnosis or outcome prior to their FIB-4 score were excluded. MEASURES: FIB-4 advanced fibrosis risk categorization (low, indeterminate, and high) was the primary predictor variable. Patients were followed from FIB-4 score to a severe liver outcome, a composite of cirrhosis, liver transplantation, and hepatocellular carcinoma. We analyzed the association of FIB-4 risk categories with hazard risk of a severe liver outcome using stratified Cox regression models, stratifying patients by known CLD. KEY RESULTS: A total of 20,556 patients were followed for a mean 2,978 days (SD 1,201 days), and 4% of patients experienced a severe liver outcome. Of patients with low-, indeterminate-, and high-risk FIB-4 scores, 2%, 4%, and 20% suffered a severe liver outcome, respectively. In the overall adjusted model, high-risk FIB-4 scores were associated with hazard of severe liver disease (HR 6.64; 95% CI 5.58-7.90). High-risk FIB-4 scores were associated with severe liver outcomes for patients with known NAFLD (HR 7.32; 95% CI 3.44-15.58), other liver disease (HR 11.39; 95% CI 8.53-15.20), and no known CLD (HR 4.05; 95% CI 3.10-5.28). CONCLUSIONS: High-risk FIB-4 scores were strongly associated with risk of severe liver outcomes in patients with and without known CLD. Comprehensive FIB-4 application in primary care may signal silently advancing liver fibrosis.

Advanced liver fibrosis and the metabolic syndrome in a primary care setting.

AIMS: The fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) are noninvasive and accessible methods for assessing advanced liver fibrosis risk in primary care. We evaluated the distribution of FIB-4 and NFS scores in primary care patients with clinical signals for nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This retrospective cohort study of electronic record data between 2007 and 2018 included adults with at least one abnormal aminotransferase and no known (non-NAFLD) liver disease. We calculated patient-level FIB-4 and NFS scores, the proportion of patients with mean values exceeding advanced fibrosis thresholds (indeterminate risk: FIB-4 > 1.3, NFS > -1.455; high-risk: FIB-4 > 2.67, NFS > 0.676), and the proportion of patients with a NAFLD International Classification of Diseases-9/10 code. Logistic regression models evaluated the associations of metabolic syndrome (MetS) components with elevated FIB-4 and NFS scores. RESULTS: The cohort included 6506 patients with a median of 6 (interquartile range: 3-13) FIB-4 and NFS scores per patient. Of these patients, 81% had at least two components of MetS, 29% had mean FIB-4 and NFS scores for indeterminate fibrosis risk, and 11% had either mean FIB-4 or NFS scores exceeding the high advanced fibrosis risk thresholds. Regression models identified associations of low high-density lipoprotein, hyperglycemia, Black race and male gender with high-risk FIB-4 and NFS values. Only 5% of patients had existing diagnoses for NAFLD identified. CONCLUSIONS: Many primary care patients have FIB-4 and NFS scores concerning for advanced fibrosis, but rarely a diagnosis of NAFLD. Elevated FIB-4 and NFS scores may provide signals for further clinical evaluation of liver disease in primary care settings.

A Multicenter Curricular Intervention to Address Resident Knowledge and Perceptions of Personal Finance.

OBJECTIVES: We evaluated internal medicine residents' confidence and knowledge of personal finance, perceptions of burnout, and relations between these issues before and after an educational intervention. METHODS: We surveyed internal medicine residents at two university-based training programs in 2018. We developed and implemented a curriculum at both sites, covering topics of budgeting, saving for retirement, investment options, and the costs of investing. Each site used the same content but different strategies for dissemination. One used a condensed-form lecture series (two 1-hour sessions) and the other used a microlecture series (four 30-minute sessions) series. Residents were resurveyed following the intervention for comparison. RESULTS: The preintervention survey response rate was 41.2% (122/296) and the postintervention response rate was 44.3% (120/271). Postintervention mean scores for personal finance knowledge improved for basic concepts (52.6% vs 39.4%, P < 0.001), mutual fund elements (30.8% vs 19.7%, P < 0.001), investment plans (68.5% vs. 49.2%, P < 0.001), and overall knowledge (50.1% vs 36.1%, P < 0.001). A significantly smaller proportion of residents reported feelings of burnout following the intervention (23.3% vs 36.9%, P = 0.022). CONCLUSIONS: Our findings show that residents want to learn about finances. Our brief educational intervention is a practical way to improve overall knowledge. Our intervention suggests that improving knowledge of finance may be associated with decreased feelings of burnout.

Population-based screening of hepatitis C virus in the United States.

PURPOSE OF REVIEW: This review summarized the recent evidence on the performance of population-based hepatitis C virus (HCV) screening, published and indexed to PubMed, in the Unite States during the 2-year window from 1 January 2017 to 31 December 2018. RECENT FINDINGS: A majority of the selected articles in this review focused on the birth cohort 1945-1965 because of the HCV screening recommendations released after August 2012. However, the articles for the high-risk population applied to all ages because the recommendations for this specific population have remained largely unchanged since 1998. The reported rates of HCV screening varied substantially not only across the three different populations (i.e. general, underserved, and high-risk) but also within each population. SUMMARY: More vigilant monitoring of HCV screening performance of younger birth cohorts is needed as these individuals have been experiencing a higher incidence of HCV infection than those in the birth cohort 1945-1965. In addition, to meet the goal of eliminating HCV infection as a US public health problem by 2030, significant improvement in more accurately and comprehensively reporting the trends in population-based HCV screening across different populations is warranted in the future.

Evaluation of abnormal liver tests in the adult asymptomatic patient.

PURPOSE OF REVIEW: Liver blood tests, including bilirubin, aminotransferases, and alkaline phosphatase, are among the most commonly encountered tests in medicine. With roles including the investigation of symptoms, medication monitoring, assessment of chronic disease, and routine assessment, these tests serve many purposes and result in abnormality in up to 40% of patients. RECENT FINDINGS: The toll of liver disease continues to rise and abnormal liver tests offer an opportunity to identify hepatic disease early, when treatment is most effective and before patients suffer the potential downstream consequences of cirrhosis, portal hypertension, and hepatocellular carcinoma. By utilizing diagnostic strategies including detailed history gathering, alcohol use assessment, recognition of metabolic syndrome, and identifying patterns of liver test abnormalities, clinicians can develop a systematic approach to address abnormal liver tests. For these reasons, developing an evidence-based, systematic approach to handling abnormal liver tests is critically important. SUMMARY: This review seeks to synthesize key elements of the best evidence, presently available guidelines, and expert opinion in drafting a strategy to aid clinicians and patients in the timely and accurate diagnosis of liver disease for the adult asymptomatic patient with abnormal liver tests.

Patterns of GI 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.

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.

EXPRESS: 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 exists 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 2012-2021, 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 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 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% vs. 64% (p=0.86), and the proportion with a decrease in HbA1c was 73% vs. 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.