Association Between Carpal Tunnel Syndrome and Subsequent Heart Failure Among Adults in Germany.

This cohort study investigates the association of carpal tunnel syndrome with heart failure among a large group of outpatients in Germany.

Non-Alcoholic Fatty Liver Disease (NAFLD) and risk of new-onset heart failure: a retrospective analysis of 173,966 patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease. Its high mortality and morbidity are mainly caused by non-hepatic comorbidities and their clinical complications. Accumulating evidence suggests an association between NAFLD and heart failure (HF), but large-scale data analyses from Germany are scarce. METHODS: Using the Disease Analyzer database (IQVIA), this analysis retrospectively evaluated two cohorts of outpatients with and without NAFLD with respect to the cumulative incidence of HF as the primary outcome between January 2005 and December 2020. Cohorts were propensity score matched for sex, age, index year, yearly consultation frequency, and known risk factors for HF. RESULTS: A total of 173,966 patients were included in the analysis. Within 10 years of the index date, 13.2% vs. 10.0% of patients with and without NAFLD were newly diagnosed with HF (p < 0.001). This finding was supported by univariate Cox regression analysis in which NAFLD was found to be significantly associated with subsequent HF (Hazard Ratio (HR) 1.34, 95% Confidence Interval (CI) 1.28-1.39, p < 0.001). The association between NAFLD and HF was observed across all analysed age groups and as comparable between both men (HR 1.30, 95% CI 1.23-1.38; p < 0.001) and women (HR: 1.37, 95% CI 1.29-1.45; p < 0.001). CONCLUSION: NAFLD is significantly associated with an increased cumulative incidence of HF, which, given its rapidly increasing global prevalence, could be crucial to further reduce its high mortality and morbidity. We recommend risk stratification within a multidisciplinary approach for NAFLD patients, including systematic prevention or early detection strategies for HF.

Prediction of heart transplant rejection from routine pathology slides with self-supervised deep learning.

Aims: One of the most important complications of heart transplantation is organ rejection, which is diagnosed on endomyocardial biopsies by pathologists. Computer-based systems could assist in the diagnostic process and potentially improve reproducibility. Here, we evaluated the feasibility of using deep learning in predicting the degree of cellular rejection from pathology slides as defined by the International Society for Heart and Lung Transplantation (ISHLT) grading system. Methods and results: We collected 1079 histopathology slides from 325 patients from three transplant centres in Germany. We trained an attention-based deep neural network to predict rejection in the primary cohort and evaluated its performance using cross-validation and by deploying it to three cohorts. For binary prediction (rejection yes/no), the mean area under the receiver operating curve (AUROC) was 0.849 in the cross-validated experiment and 0.734, 0.729, and 0.716 in external validation cohorts. For a prediction of the ISHLT grade (0R, 1R, 2/3R), AUROCs were 0.835, 0.633, and 0.905 in the cross-validated experiment and 0.764, 0.597, and 0.913; 0.631, 0.633, and 0.682; and 0.722, 0.601, and 0.805 in the validation cohorts, respectively. The predictions of the artificial intelligence model were interpretable by human experts and highlighted plausible morphological patterns. Conclusion: We conclude that artificial intelligence can detect patterns of cellular transplant rejection in routine pathology, even when trained on small cohorts.

Sublethal necroptosis signaling promotes inflammation and liver cancer.

It is currently not well known how necroptosis and necroptosis responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of necroptosis signaling in hepatocytes, fundamentally affecting immune responses and hepatocarcinogenesis. Concomitant necrosome and NF-κB activation in hepatocytes, which physiologically express low concentrations of receptor-interacting kinase 3 (RIPK3), did not lead to immediate cell death but forced them into a prolonged "sublethal" state with leaky membranes, functioning as secretory cells that released specific chemokines including CCL20 and MCP-1. This triggered hepatic cell proliferation as well as activation of procarcinogenic monocyte-derived macrophage cell clusters, contributing to hepatocarcinogenesis. In contrast, necrosome activation in hepatocytes with inactive NF-κB-signaling caused an accelerated execution of necroptosis, limiting alarmin release, and thereby preventing inflammation and hepatocarcinogenesis. Consistently, intratumoral NF-κB-necroptosis signatures were associated with poor prognosis in human hepatocarcinogenesis. Therefore, pharmacological reprogramming between these distinct forms of necroptosis may represent a promising strategy against hepatocellular carcinoma.

Association between gout and epilepsy in adults - a retrospective cohort study with 244,964 primary care outpatients.

BACKGROUND: Recently there has been a rising interest in the identification of possible risk factors for epilepsies. In the present study, we investigated the potential association between gout and epilepsy in an outpatient cohort in Germany. METHODS: Using the IQVIA Disease Analyzer database, we identified 112,482 patients with gout treated in outpatient departments. These were matched 1:1 to non-gout patients based on sex, age, yearly consultation frequency during the follow-up period, and diagnoses associated with an increased epilepsy risk documented prior to or on the index date. Cox regression models were used to evaluate the association between gout and epilepsy. RESULTS: Within 10 years after the index date, epilepsy had been diagnosed in 2.2% of gout and 1.6% of non-gout patients (log-rank p<0.001). In the regression analysis, we observed a significant association between gout and subsequent epilepsy (HR: 1.32; 95% CI: 1.21-1.44). The association was significant in all age groups, but strongest in the youngest age group (18-50) (HR: 1.86; 95% CI: 1.44-1.2.41). CONCLUSION: Our study demonstrates that gout is associated with an increased incidence of epilepsy. This finding could help us to understand the mechanisms of epilepsy and better protect affected individuals in the future.

Persistence with first-line antihypertensive therapy in Germany: A retrospective cohort study with 2,801,469 patients.

BACKGROUND: The goal of this retrospective cohort study was to investigate 3-year persistence with antihypertensive drug therapy and the association between antihypertensive drug classes and therapy discontinuation risk in Germany. MATERIALS AND METHODS: The present retrospective cohort study was based on the IQVIA longitudinal prescription database (LRx) and included adult outpatients (≥ 18 years) with an initial prescription of antihypertensive monotherapy alone including diuretics (DIU), ß-blockers (BB), calcium channel blockers (CCB), ACE inhibitors (ACEi), and angiotensin II receptor blockers (ARB) in Germany between January 2017 and December 2019 (index date). A Cox proportional hazards regression model was also used to assess the relationship between antihypertensive drug classes and non-persistence adjusted for age and sex. RESULTS: This study included 2,801,469 patients. Patients on ARB monotherapy exhibited the highest persistence within 1 year (39.4%) and 3 years (21.7%) after the index date. Patients on DIU monotherapy showed the lowest persistence (16.5% after 1 year, 6.2% 3 years after the index date). In the overall population, initial monotherapy with DIU (HR: 1.48) was positively associated with monotherapy discontinuation, whereas ARB monotherapy was (HR = 0.74) negatively associated with monotherapy discontinuation compared to BB. However, in the age group > 80, there was a slight negative association between DIU intake and monotherapy discontinuation (HR = 0.91). CONCLUSION: This large cohort study reveals significant differences in 3-year persistence with antihypertensives, which were strongest for ARB and weakest for DIU. However, the differences also depended on age, with much better DIU persistence in the elderly.

The Association between Antibiotic Use and the Incidence of Heart Failure: A Retrospective Case-Control Study of 162,188 Outpatients.

The pathogenesis of heart failure (HF) is multifactorial, and is characterized by structural, cellular, and molecular remodeling processes. Inflammatory signaling pathways may play a particularly understudied role in HF. Recent data suggest a possible impact of antibiotic use on HF risk. Therefore, the aim of this retrospective case-control study was to investigate the association between antibiotic use and the incidence of HF. Data from the Disease Analyzer (IQVIA) database for patients diagnosed with HF and matched non-HF controls from 983 general practices in Germany between 2000 and 2019 were analyzed. A multivariable conditional logistic regression model was performed. Regression models were calculated for all patients, as well as for data stratified for sex and four age groups. A total of 81,094 patients with HF and 81,094 patients without HF were included in the analyses. In the regression analysis, low, but not high, total antibiotic use was significantly associated with a slightly lower HF risk compared with non-antibiotic users (OR: 0.87; 95% CI: 0.85-0.90). A significantly lower HF incidence was observed for sulfonamides and trimethoprim (OR: 0.87, 95% CI: 0.81-0.93) and for macrolides (OR: 0.87, 95% CI: 0.84-0.91). High use of cephalosporins, however, was associated with an increased HF risk (OR: 1.16; 95% CI: 1.11-1.22). In conclusion, this study from a large real-world cohort from Germany provides evidence that the use of different antibiotics may be associated with HF risk in a dose-dependent manner, possibly due to involved inflammatory processes. Overall, this study should provide a basis for future research to offer new therapeutic strategies for HF patients to improve their limited prognosis.

Effects of percutaneous coronary intervention on dyspnea in stable coronary artery disease.

BACKGROUND: Dyspnea is a frequent symptom in patients with stable coronary artery disease (CAD) and is recognized as a possible angina equivalent. OBJECTIVES: This study was to assess the impact of percutaneous coronary intervention (PCI) on dyspnea, quality of life, and angina pectoris in patients with stable CAD. METHODS: The prospective, multi-center PLA-pCi-EBO-pilot trial included 144 patients with symptomatic stable CAD and successful PCI. The prespecified endpoints angina pectoris (Seattle Angina Questionnaire-SAQ) and dyspnea (NYHA scale) were assessed 6 months after PCI. Predictors for symptomatic improvement were assessed with uni- and multivariable logistic regression analyses. RESULTS: Patients with concomitant dyspnea had worse SAQ physical limitation scores at baseline (49.5 ± 21.0 vs 58.9 ± 22.0, p = 0.013) but showed no difference for angina frequency or quality of life. Overall, symptomatic burden of angina pectoris and dyspnea was alleviated by PCI. However, patients with concomitant dyspnea had markedly worse scores for physical limitation (78.9 ± 25.0 vs 94.3 ± 10.6, p < 0.001), angina frequency (77.9 ± 22.8 vs 91.1 ± 12.4, p < 0.001), and quality of life (69.4 ± 24.1 vs 82.5 ± 14.4, p < 0.001) after PCI. The prevalence of dyspnea (NYHA class ≥ 2) declined from 73% before PCI to 54%. Of 95 initially dyspneic patients, 57 (60%) improved at least one NYHA class 6 months after PCI. In a multivariable logistic regression analysis, "atypical angina pectoris" was associated with improved NYHA class, whereas "diabetes mellitus" had a negative association. CONCLUSION: PCI effectively reduced dyspnea, which is a frequent and demanding symptom in patients with CAD. The German Clinical Trials Register registration number is DRKS0001752 ( www.drks.de ).

Differential role of chronic liver diseases on the incidence of cancer: a longitudinal analysis among 248,224 outpatients in Germany.

BACKGROUND: Chronic liver diseases, especially chronic hepatitis, are a known risk factor for the development of liver cancer. However, the risk of total cancer development and malignant potential from these diseases is largely unknown. Systematic data on the risk of cancer development from these diseases are missing. Therefore, the goal of this study is to analyze the risk of total cancer development in chronic liver diseases. METHODS: A cohort of 15,706 patients with chronic hepatitis and 15,706 patients without hepatitis were matched by propensity scoring from outpatient practices in Germany over a period of 15 years. Cox regression models were conducted to study the association between alcoholic hepatitis, autoimmune hepatitis, hepatitis B, hepatitis C and cancer incidence, including liver, other digestive organs, skin, prostate, breast and lymphoid and hematopoietic tissue cancer. RESULTS: Within 10 years of the index date, 19.3% of patients with alcoholic hepatitis and 13.4% of non-hepatitis individuals were diagnosed with cancer (log-rank p = 0.035). These proportions were 15.0 vs. 9.9% (p = 0.078) for autoimmune hepatitis, 8.7 vs. 7.1% (p = 0.015) for hepatitis B, and 12.7 vs. 7.6% (p < 0.001) for hepatitis C. In regression analyses, only alcoholic hepatitis (HR: 1.84, 95% CI 1.32-2.54) and hepatitis C (HR: 2.10, 95% CI 1.77-2.50) were significantly associated with increased risk of cancer. There was a very strong positive association between hepatitis C and liver cancer (HR: 78.2 (95% CI 10.9-560.7). Furthermore, hepatitis C was associated with an increased risk of respiratory organ cancer (HR: 2.59, 95% CI 1.42-4.73). CONCLUSION: This study confirms the strong association between chronic hepatitis and liver cancer, but also with an overall elevated cancer risk, and especially of cancer in the respiratory tract in patients with chronic hepatitis C.

Antihypertensive Therapy and Incidence of Cancer.

Background: Antihypertensive pharmacological therapy includes diuretics, beta-blockers, ACE inhibitors, calcium channel blockers and angiotensin II receptor blockers. Besides their use in arterial hypertension, these drugs also play a major role in the therapy of portal hypertension, heart failure and coronary artery disease. Systematic analyses on the possible influence of these medications on cancer incidence are lacking. Methods: By utilizing the Disease Analyzer database (IQVIA), 349,210 patients with antihypertensive drug prescriptions between 2010 and 2020 without a diagnosis of cancer prior to or at the date of initial drug prescription were included. Propensity score matching was carried out by 1:1:1:1:1 according to the five antihypertensive treatments. Cox regression analyses were performed to investigate an association between antihypertensive drugs and the incidence of cancer. Results: Patients who were diagnosed with cancer were treated with diuretics in 19.9% of cases, calcium channel blockers in 16.9% of cases, and angiotensin II receptor blockers, ACE inhibitors, or beta-blockers in 13.9%, 13.2% and 12.8% of cases, respectively. Cox regression models revealed that diuretic use positively correlated with liver cancer incidence (HR: 1.31, 95%CI: 1.12-2.63) and lymphoid/haematopoietic tissue cancer incidence (HR: 1.27, 95%CI: 1.10-1.46). Use of diuretics negatively correlated with the incidence of prostate (HR: 0.64, 95%CI: 0.53-0.78) and skin cancer (HR: 0.81, 95%CI: 0.72-0.92). Finally, a positive association was found between angiotensin II receptor inhibitors and prostate cancer incidence (HR: 1.50, 95%CI: 1.28-1.65). Conclusions: These data suggest that diuretic use might be associated with liver cancer and lymphoid/haematopoetic tissue cancer development.

The Landscape of Outpatient Palliative Care in Germany: Results from a Retrospective Analysis of 14,792 Patients.

BACKGROUND: Palliative care comprises multiprofessional, integrated, person-centered healthcare services for patients and their families facing problems related to progressive or advanced diseases and limited life expectancy. Although non-oncology patients' needs are similar to those of tumor patients, they are often underestimated. The purpose of our study was to investigate the actual utilization of palliative care services in Germany, especially in the outpatient setting. METHODS: Using the IQVIA Disease Analyzer database, a total of 14,792 outpatients from 805 primary care practices in Germany with documented palliative care and related diagnosis between 2018 and 2021 were analyzed. Proportions of different diagnoses among patients receiving outpatient palliative care were stratified by gender and different age groups. RESULTS: The most common underlying diagnosis for outpatient palliative care was cancer (55%), followed by heart failure (16%) and dementia (8%), with age- and sex-specific differences found in the proportion of diagnoses for utilization. While the relative proportions of cancers decreased with age (87% in the 18- to 50-year-old age group versus 37% in the 80-plus age group), the proportion of palliative care related to heart failure increased in the older population (2% in the 18- to 50-year-old age group versus 25% in the 80-plus age group). CONCLUSIONS: This study provides an overview of the situation of outpatient palliative care in Germany and shows age- and gender-specific trends regarding the underlying medical diagnoses. Based on these data, palliative care should be adapted to current demographic developments.

The association between the body height and cardiovascular diseases: a retrospective analysis of 657,310 outpatients in Germany.

BACKGROUND: Cardiovascular disease (CVD) represents the leading cause of death worldwide. The identification of individuals at increased risk of CVD is essential to reduce its morbidity and mortality globally. Based on existing data on a potential association between the individual body height and the risk for CVD, we investigated this association in a large cohort of outpatients in Germany. METHODS: A total of 657,310 adult outpatients with available body height data from the Disease Analyzer (IQVIA) database were included in Germany between 2019 and 2021. The prevalence of common CVD diagnoses (hypertension, coronary heart disease, atrial fibrillation and flutter, heart failure, ischemic stroke, and venous thromboembolism) was evaluated as a function of the patients' body height stratified by age and sex. RESULTS: In both sexes, the prevalence of hypertension, coronary heart disease, heart failure, and ischemic stroke was higher among patients of smaller body height. In contrast, the prevalence of atrial fibrillation and venous thromboembolism was higher in taller patients. In age- and BMI-adjusted logistic regression analyses, an increased body height was negatively associated with coronary heart disease (OR = 0.91 in women and OR = 0.87 in men per 10-cm increase in height) and strongly positively associated with atrial fibrillation (OR = 1.25 in women and men) and venous thromboembolism (OR = 1.23 in women and OR = 1.24 in men). CONCLUSION: We present the first data from a large cohort of outpatients in Germany providing strong evidence for an association between the body height and common CVD. These data should stimulate a discussion as to how far the body height should be implemented as a parameter in stratification tools to assess CVD risk in order to further reduce cardiovascular morbidity and mortality in the future.

Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension.

Importance: Arterial hypertension is associated with an increased incidence of epilepsy. Results from animal studies suggest that angiotensin receptor blocker (ARB) therapy could inhibit epileptic seizures. However, there is a lack of clinical data to support the use of ARB therapy in humans. Objective: To assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension. Design, Setting, and Participants: This cohort study obtained data from the Disease Analyzer database (IQVIA) on patients aged 18 years or older who had hypertension and at least 1 antihypertensive drug prescription. Patients were treated at 1274 general practices between January 2010 and December 2020 in Germany. Data were available for 1 553 875 patients who had been prescribed at least 1 antihypertensive drug. Patients diagnosed with epilepsy before or up to 3 months after the index date were excluded. A total of 168 612 patients were included in propensity score matching. Patients treated with 1 of 4 antihypertensive drug classes (ß-blockers, ARBs, angiotensin-converting enzyme inhibitors, and calcium channel blockers [CCBs]) were matched to each other using propensity scores. Main Outcomes and Measures: The main outcome of the study was the incidence of epilepsy associated with ARB therapy compared with other antihypertensive drug classes. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group. Results: The study included a total of 168 612 patients, with 42 153 in each antihypertensive drug class. The mean [SD] age of patients was 62.3 [13.5] years, and 21 667 (51.4%) were women. The incidence of epilepsy within 5 years was lowest among patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years) and highest among patients receiving ß-blockers and CCBs (0.38% for both ß-blockers and CCBs at 1 year; 0.91% for ß-blockers and 0.93% for CCBs at 3 years; ß-blockers, 1.47%; and CCBs, 1.48% at 5 years). Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (hazard ratio, 0.77; 95% CI, 0.65-0.90) compared with the other drug classes as a group. Conclusions and Relevance: In this cohort study of patients with hypertension, ARB therapy was associated with a significantly decreased incidence of epilepsy. The findings suggest antihypertensive drugs could be used as a novel approach for preventing epilepsy in patients with arterial hypertension.

The Spectrum of Co-Diagnoses in Patients with Colorectal Cancer: A Retrospective Cohort Study of 17,824 Outpatients in Germany.

Background: The prognosis of colorectal cancer (CRC) patients is determined to a decisive extent by comorbidities. On the other hand, anti-cancer treatments for CRC are associated with relevant toxicities and may therefore cause additional comorbidities. Methods: This retrospective cohort study assessed the prevalence of various diseases in patients 12 months before and 12 months after an initial diagnosis of colorectal cancer (ICD-10: C18, C20) in 1274 general practices in Germany between January 2000 and December 2018. The study is based on the Disease Analyzer database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Patients with and without CRC were matched by sex, age, and index year. Results: We identified several diagnoses with a significantly higher prevalence among CRC patients 12 months prior to the index date compared to controls. These diagnoses included gastrointestinal hemorrhage, hemorrhoids, perianal venous thrombosis, and abdominal and pelvic pain, as well as functional intestinal disorders. In contrast, the prevalence of lipid metabolism disorder, depression, hypertension, coronary heart disease, or acute bronchitis was significantly lower in CRC cases. After diagnosis of CRC, we found a significantly higher prevalence of anemia, polyneuropathies, functional intestinal disorders, and chronic kidney disease among CRC patients compared to the control group, while the prevalence of acute upper respiratory infections of multiple and unspecified sites and acute bronchitis was significantly lower in CRC patients compared to non-CRC patients. Conclusions: In the present study, we identified a variety of diseases occurring at higher or lower frequencies in CRC patients compared to matched controls without CRC. This might help to select patients for early CRC screening and improve the clinical management of CRC patients.

Pulmonary hypertension is associated with an increased incidence of cancer diagnoses.

Pulmonary hypertension (PH) is a complex disease with increasing global incidence that eventually leads to right ventricular failure and is associated with a poor prognosis. The importance of noncardiac comorbidities in disease progression and prognosis has gained increasing recognition in recent years. In the present study, we investigated a potential association between PH and cancer in an outpatient cohort in Germany. Using the IQVIA Disease Analyzer database, we identified a total of 11,109 patients with PH and a propensity score matched cohort of equal size without PH who received medical treatment between 2005 and 2019. Logistic regression models were used to evaluate the potential association between PH and cancer. Within the 10-year observation period, the incidence of cancer was significantly higher in PH patients than non-PH patients (23.2% vs. 8.5%, log-rank p < 0.001). Importantly, this association was observed for both male (HR = 1.24, p = 0.002) and female (HR = 1.37, p < 0.001) patients, and was most pronounced in patients >80 years (HR = 1.50, p < 0.001). In terms of a specific tumor site, we found a significant association for respiratory organ cancer (HR = 1.60, p = 0.007) and skin cancer (HR = 1.48, p < 0.001). Our study provides strong evidence that PH is associated with an increased incidence of cancer. This finding should help raise awareness of this important comorbidity and could trigger specific screening programs in patients with PH.

Atrial fibrillation is associated with a subsequent epilepsy diagnosis independent of stroke: A retrospective matched administrative cohort study on 149,632 patients.

Recently there has been a rising interest in the identification and possible prevention of risk factors for epilepsies. In the present study, we investigated the potential association between atrial fibrillation (AF) and epilepsy in a German cohort of ambulatory patients aged ≥18 with an initial diagnosis of atrial fibrillation documented in 1274 general practices in Germany between January 2005 and December 2018. Using the IQVIA Disease Analyzer database, we identified 74,681 ambulatory patients with AF. These were matched 1:1 to patients without AF based on sex, age, index year, yearly consultation frequency, and defined co-diagnoses like stroke. Cox regression models were used to evaluate the association between AF and epilepsy. Within 10 years of the index date, 1.9% of individuals with AF and 1.5% of individuals without AF were diagnosed with epilepsy (log-rank p < 0.001). Atrial fibrillation was significantly associated with an increase in the incidence of epilepsy (Hazard Ratio (HR): 1.51, p < 0.001). The association was significant in all age groups, except in patients >80 years of age (HR: 1.29, p = 0.031). Our study demonstrates that AF is associated with an increased incidence of epilepsy. This finding could help understand the mechanisms of epilepsy in heart disease and to better protect affected individuals in the future.

An Elevated FIB-4 Score Is Associated with an Increased Incidence of Depression among Outpatients in Germany.

Background: Liver disease and depression are known to be closely associated. Non-invasive tests (NIT), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced fibrosis and to stratify the risk of liver-related outcomes in patients with chronic liver diseases. However, the predictive value of an elevated FIB-4 score regarding the development of depression and/or anxiety disorders among the general population is unknown. Methods: By using the Disease Analyzer database (IQVIA), which compiles diagnoses and laboratory values as well as basic medical and demographic data of patients followed in general practices in Germany, we identified 370,756 patients with available lab values for FIB-4 score calculation between 2005 and 2019. Patients with an FIB-4 score < 2 were matched 1:1 to patients with an FIB-4 index ≥ 2 by age, sex and yearly consultation frequency. Results: In regression analysis, the incidence rate ratio (IRR) of depression was significantly higher among patients with an FIB-4 score ≥ 2.0 compared to patients with a lower FIB-4 score <2.0 (IRR: 1.12, p < 0.001). This association was significant for both female (IRR: 1.10, p = 0.004) and male (IRR: 1.15, p < 0.001) patients and strongest in the age groups ≤50 years (IRR: 1.42, p < 0.001) and 51-60 years (IRR: 1.34, p < 0.001). There was no significant association between an elevated FIB-4 score ≥ 2.0 and the incidence of depression among patients aged 60 years and older. There was no significant increase in the IRR of anxiety disorders for patients with high or low FIB-4 scores. Conclusion: Our study suggests a previously unknown association between an elevated FIB-4 score and an increased incidence of depression. This finding suggests that the FIB-4 score is not only a valuable tool for the prediction of liver-specific endpoints but also may be of relevance for the prediction of extrahepatic comorbidities, which in turn may argue for clinical screening programs in patients with an elevated FIB-4.

An elevated FIB-4 score is associated with an increased incidence of liver cancer: A longitudinal analysis among 248,224 outpatients in Germany.

BACKGROUND: Non-invasive tests such as the FIB-4 index (calculated on the basis of patients' age, AST/ALT levels and platelet count) have been recommended by different guidelines to rule out advanced fibrosis and stratify the risk of liver-related outcomes in patients with chronic liver diseases. An elevated FIB-4 index ≥1.3 is an independent predictor for liver cancer development among patients with NAFLD. However, the predictive value of an elevated FIB-4 index regarding (liver) cancer development among the general population is unknown. METHODS: Using the Disease Analyzer database (IQVIA) which compiles diagnoses, laboratory values, and basic medical and demographic data for over 7.5 million patients followed in general practices in Germany, we identified 248,224 patients with available lab values for FIB-4 index calculation between 2005 and 2019. Patients with an average FIB-4 index of <1.3 were matched 1:1 to patients with a FIB-4 index of ≥1.3 by age and sex. RESULTS: Within 10 years of the index date, the cumulative incidence of liver cancer was significantly higher in patients with a FIB-4 index ≥1.3 (0.25% versus 0.04%, p < 0.001). In a multivariate Cox-regression analysis, this association was found to be higher in patients with pre-existing liver disease (hazard ratio, HR: 10.54 versus 3.79). The risk of liver cancer development was most pronounced among men (HR: 9.40, p < 0.001) and patients ≤50 years of age (HR: 16.36, p < 0.001). A persistently high or increasing FIB-4 index over time was a strong predictor for liver cancer. Notably, the cumulative incidence of cancer in general was comparable among patients with a low/high FIB-4 index (15.7% versus 16.6%; p = 0.060). CONCLUSION: Our data support the use of the FIB-4 index to estimate the risk of liver cancer development even in unselected patients without pre-existing liver disease. By contrast, the index does not appear to have any predictive value for other tumour sites.

An elevated FIB-4 score is not associated with cardiovascular events: a longitudinal analysis from 137 842 patients with and without chronic liver disease.

BACKGROUND: Liver diseases and cardiovascular diseases are closely associated. Noninvasive tests (NITs), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced fibrosis and estimate the risk of liver-related outcomes in patients with chronic liver diseases (CLDs). However, the association of an elevated FIB-4 score with the development of myocardial infarction and/or stroke/transient ischemic attack (TIA) is unknown. METHODS: By using the Disease Analyzer database (IQVIA), which compiles diagnoses, laboratory values as well as basic medical and demographic data of over 7.5 million patients followed in general practices in Germany, we identified 68 921 patients with available lab values for FIB-4 score calculation between 2005 and 2019. Patients with an FIB-4 score of less than 1.3 were matched 1:1 to patients with an FIB-4 score of at least 1.3 by age, sex and yearly consultation frequency. RESULTS: In regression analysis, the incidence rate ratio (IRR) of myocardial infarction was similar among patients with an FIB-4 score of at least 1.3 compared with patients with a low FIB-4 score of less than 1.3, regardless of whether patients with or without preexisting liver disease were analyzed. Moreover, there was no significant increase in the IRR of stroke/TIA between patients with a high or low FIB-4 score, both in the general population and patients with CLD. CONCLUSION: Our study suggests that the FIB-4 score is not associated with cardiovascular events both in the general population as well as in patients with CLD.