Diabetes mellitus - risk factor and potential future target for hepatic encephalopathy in patients with liver cirrhosis?

Hepatic encephalopathy (HE) is one of the major complications of cirrhosis, and its presence is associated with poor survival. Several risk factors for HE are well established, including age, history of HE, portosystemic shunts, or poorer liver function. In recent years, diabetes mellitus (DM) has emerged as another potential risk factor for the development of HE. This may be important for many patients, as the incidence of type 2 DM (T2DM) is increasing worldwide and, consequently, the incidence of NAFLD-related cirrhosis is rising simultaneously. In addition, DM is a critical factor in the progression of other liver diseases, such as alcohol-related liver disease. Thus, the number of patients with cirrhosis and comorbid T2DM will also increase. To date, the prevalence of DM already ranges between 22 - 40% in patients with cirrhosis. DM-associated factors that may influence the risk of HE include systemic inflammation, insulin resistance with increased muscle protein breakdown as well as autonomic dysfunction with prolonged intestinal transit time and small intestinal bacterial overgrowth. Currently, the evidence for an association between DM and both minimal and overt HE is weak and it seems likely that only poor glycemic control has an impact on HE risk. In addition, there are some early signs indicating that DM may impair the response of patients with HE to pharmacological therapies such as rifaximin. Thus, improvements in the management of glycemic control may be a candidate future target to reduce the risk of HE. In this concise review, we summarize the current evidence on the association between DM and HE and its potential future implications

Impact of thyroid disorders on the incidence of non-alcoholic fatty liver disease in Germany

Background Studies investigating a potential association between hypothyroidism and non-alcoholic fatty liver disease (NAFLD) showed conflicting results and large-scale population-based data from Germany on this topic are currently missing. Objective It was the aim of this analysis to investigate the impact of thyroid gland disorders on the prevalence of NAFLD in Germany. Methods In this case-control study, using the German disease Analyzer database (IQVIA), NAFLD patients were matched to patients without NAFLD by age, sex, index year, treating physician, diabetes mellitus type II, and obesity. The main outcome of the study was an association between thyroid gland disorders (hypothyroidism, hyperthyroidism and autoimmune thyroiditis) and incident NAFLD and was evaluated using logistic regression analyses. Results 57,483 patients with NAFLD were matched to 57,483 patients without liver disease. Mean age of the cohort was 60.3 years (±14.1) and 52.3% were men. In regression analyses, hypothyroidism (OR 1.17, 95% CI 1.10 - 1.24, p < 0.001) as well as autoimmune thyroiditis (OR 1.53, 95% CI 1.35–1.73, p < 0.001) were associated with a higher risk of NAFLD. In contrast, hyperthyroidism was associated with a lower risk of NAFLD (OR 0.85, 95% CI 0.77–0.94, p < 0.001). The effect of hypothyroidism on the prevalence of NAFLD remained significant across men (OR 1.31, 95% CI 1.15–1.48) as well as women (OR 1.12, 95% CI 1.05–1.21). Conclusion Hypothyroidism seems to be a risk factor for incident NAFLD

Incident dementia in elderly patients with nonalcoholic fatty liver disease in Germany

Dementia and NAFLD are two frequent conditions that share underlying risk factors mainly in the realm of metabolic disease. Additionally, an association between NAFLD and brain aging has been proposed. Therefore, we investigated the hypothesis if NAFLD is an independent risk factor for emerging dementia. In this population-based cohort study, elderly patients (≥ 65 years) with NAFLD diagnosed between 2000 and 2015 were matched 1:1 to a cohort without NAFLD based on ICD-10 coding in the Disease Analyzer database. Matching criteria were age, sex, physician, index year, and co-diagnoses associated with dementia. The primary outcomes of this study were all-cause dementia diagnoses, the incidence of vascular dementia, and antidementive drug prescription. A total of 22,317 patients with NAFLD were matched to 22,317 patients without NAFLD. Within 10 years of the index date, 16.0% of patients with NAFLD and 15.6% of the patients without NAFLD were diagnosed with dementia. On Cox regression analysis, there is no association between NAFLD and the incidence of all-cause dementia (HR 0.97, 95% CI 0.92–1.04), vascular dementia (HR 0.89, 95% CI 0.78–1.02), or the new prescription of antidementive therapy (HR 0.87, 95% CI 0.76–1.01). In sensitivity analyses, there was no association between NAFLD and dementia in different age-groups as well as men or women. In conclusion, in this database study of elderly patients coded with NAFLD no independent association with incident dementia was detected. Risk assessment regarding dementia in patients with NAFLD should be carried out in the same way as for metabolic burdened patients

Burden of depression and anxiety disorders per disease codes in patients with lymphoma in Germany

Purpose The aim of this study was to explore the incidence of depression and anxiety disorder diagnoses in a large German cohort of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) diagnoses in comparison to patients without cancer over a 10-year time frame. Methods Patients with HL (n=687) and NHL (n=4130) were matched to cohorts without a cancer diagnosis (n=687 and 4130) by age, sex, and yearly consultation frequency. The primary outcome of the study was the incidence of depression and anxiety disorders. The relationship between lymphoma, separated into HL and NHL, and both depression and anxiety disorders was investigated using Cox regression models. Results We compared 687 patients with HL with 687 matched non-cancer individuals and 4130 patients with NHL with 4130 matched non-cancer individuals. Within 10 years of the index date, 24.0% of patients with HL and 22.3% of patients with NHL were diagnosed with depression. Anxiety disorders were diagnosed in 6.7% and 5.3% of patients with HL and NHL, respectively. On regression analyses, HL (HR 2.30, 95% CI 1.65–3.21, p<0.001) and NHL (HR 2.09, 95% CI 1.81–2.41, p<0.001) were positively associated with incident depression. The HR for anxiety disorders was 1.64 (95% CI 1.24–2.16, p<0.001) in patients with NHL, while HL was not associated with incident anxiety disorders (HR 1.21, 95% CI 0.71–2.07, p<0.478). Conclusion Lymphoma constitutes a risk factor for emerging depression and anxiety disorders. Following the diagnosis of lymphoma, screening and strategies to prevent the occurrence of these diseases seem warranted

Proton pump inhibitor use and risk of hepatic encephalopathy : a multicentre study

Background & Aims: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE). Methods: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation. Results: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication. Conclusions: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication. Impact and implications: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis

Higher scores in the Clinical Frailty Scale are associated with covert and overt hepatic encephalopathy in patients with cirrhosis

Background: Frailty increases the vulnerability to internal and external stressors and may therefore be an indicator of a higher frequency of cirrhosis complications. We aimed to investigate the association of the Clinical Frailty Scale (CFS) with covert (CHE) and overt HE (OHE) development in patients with cirrhosis. Methods: This study analyzed data of 228 patients with cirrhosis. Frailty was assessed using CFS. Patients were examined for the presence of CHE (using PHES) at study inclusion and followed for OHE. Results: Median CFS was 3 and 26 (11 %) patients were at least pre-frail (CFS>3). In multivariable logistic regression analysis in patients without a history of OHE (n = 195), a higher CFS was associated with the presence of CHE at baseline (OR 1.6, p = 0.039). During follow-up, 42 (18 %) patients developed an episode of OHE. In multivariable competing risk regression analyses, a higher CFS was independently associated with the development of an OHE episode in the total cohort (sHR 1.97, p < 0.001) and in the subcohort of patients without a history of OHE (sHR 1.88, p = 0.008). Conclusion: CFS appears to be a reliable tool to identify patients at higher risk of HE in whom intensified monitoring and treatment may be justified

A higher FIB-4 index is associated with an increased incidence of renal failure in the general population

The Fibrosis-4 index (FIB-4) is a recommended noninvasive fibrosis test in patients at risk of liver fibrosis. Chronic liver diseases are often associated with kidney diseases. This study aimed to investigate the association between FIB-4 and the development of renal failure among the general population. For this study, we used the Disease Analyzer database, which includes diagnoses and basic medical and demographic data of patients followed in general practices in Germany. Using these data, we extensively matched patients with a FIB-4 index ≥ 1.3 (n = 66,084) to patients with a FIB-4 index < 1.3 (n = 66,084). The primary outcome was the incidence of renal failure or chronic renal failure during a 10-year period. Within 10 years of the index date, 9.2% of patients with a FIB-4 < 1.3 and 10.6% of patients with a FIB-4 ≥ 1.3 were diagnosed with renal failure (p = 0.007). The endpoint chronic renal failure was reached by 7.9% with a FIB-4 < 1.3 and 9.5% with a FIB-4 ≥ 1.3 (p < 0.001). A FIB-4 index ≥ 1.3 was associated with a slight increase in renal failure incidence (hazard ratio [HR]: 1.08, p = 0.009). There was an increasing association between an increase in FIB-4 index and the incidence of renal failure with the strongest association for a FIB-4 index ≥ 2.67 (HR: 1.34, p = 0.001). In sensitivity analyses, a significant association was found for the age group of 51–60 years (HR: 1.38, p < 0.001), patients with arterial hypertension (HR: 1.15, p < 0.001), obese patients (HR: 1.25, p = 0.005), and patients with lipid metabolism disorders (HR:1.22, p < 0.001). Conclusion: A higher FIB-4 index is associated with an increased incidence of renal failure. Therefore, the FIB-4 index may be useful in identifying patients who are at risk not only for liver-related events but also for renal disease

Impairment of health-related quality of life among people with type 2 diabetes and advanced liver fibrosis

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fbrosis. Their health-related quality of life (HRQL) is afected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fbrosis stage. The aim of this study was to investigate the efect size of advanced fbrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the fnal analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p< 0.001). Obesity (β: − 0.247; 95% CI − 0.419, − 0.077) and AF (β: − 0.222; 95% CI − 0.383, − 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively afect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specifc interventions may improve patientreported and liver-related outcomes in people with T2DM

GPs’ motivation for teaching medical students in a rural area—development of the Motivation for Medical Education Questionnaire (MoME-Q)

Background The establishment of a medical education program in the rural area of Siegen is planned to be the first step against a shortage of physicians in this region. General practitioners (GPs) will be extensively involved in this program as Family Medicine (Allgemeinmedizin) will become a core subject in the curriculum nationwide. Based on this situation we aim to figure out GPs motivation to participate in medical education. For this purpose, we had to construct and test a new questionnaire. Methods A survey was conducted among general practitioners (GPs) in the region of Siegen-Wittgenstein regarding their motivation to participate in medical education. For this purpose, the Motivation for Medical Education Questionnaire (MoME-Q), a 24-item questionnaire, was developed. Structural characteristics of GPs, the Maslach Burnout Inventory (MBI) and the Work Satisfaction Questionnaire (WSQ) were used for validation purposes. Results A representative number of GPs took part in the study (53.8%). Although the majority had no connection to a university (86%), 83% can imagine participating in the education of medical students. The items of the MoME-Q load on two factors (commitment and personal benefit). The confirmatory factor analysis shows a good model fit. Subscales of the MoME-Q were able to differentiate between physicians with and without authorization to train GP residents, between practices with and without a specialized practice nurse, and between physicians with and without previous experience in medical education. The MoME-Q subscale “commitment” correlated significantly with all three subscales of the MBI. Correlations were in the medium range around |.30|. Conclusion The MoME-Q seems to be an appropriate tool to assess motivation to participate in medical education of GPs. In our sample, a large number of GPs was motivated to participate in the education of medical students. Future studies with larger number of GPs should be carried out to validate and confirm our findings. Whether the MoME-Q is also appropriate for other specialties should also be shown in further empirical studies

Obesity and harmful alcohol consumption are predictors for advanced liver disease in the disease management program for type 2 diabetes

Background Type 2 diabetes mellitus (T2DM) is a major risk factor for advanced liver disease. The aim of this prospective cohort study was to assess the prevalence and associated risk factors of liver fibrosis and cirrhosis in primary care centers participating in the diabetes disease management program (DMP) in Germany. Methods A total of 175 participants with the diagnosis of T2DM were enrolled in two primary care centers. Steatotic liver disease (SLD; hepatic steatosis, ≥275 dB/m), fibrosis (≥8 kPa), and cirrhosis (≥15 kPa) were assessed non-invasively using vibration-controlled transient elastography. Multivariable logistic regression analysis was performed to identify clinical predictors of fibrosis and cirrhosis. The AUDIT questionnaire was used to screen for alcohol consumption, and a score ≥8 was considered harmful alcohol consumption. Results The majority of participants were male (62%), and the median age was 66 years (interquartile range 59; 71). The median body mass index was 31.1 kg/m2, with 58.9% of the participants being obese. Harmful alcohol consumption was prevalent in 8.0% and 20.0% of the entire cohort and in those with cirrhosis, respectively. The prevalence of SLD, fibrosis, and cirrhosis was 77.1%, 42.3%, and 12.0%, respectively. In multivariable logistic regression analysis, obesity, and harmful alcohol consumption were associated with the highest odds of fibrosis (odds ratio [OR] 5.198, 95% confidence interval [CI] 2.269–11.908) and cirrhosis (OR 5.615, 95% CI 1.274–24.756), respectively. Conclusion The prevalence of fibrosis and cirrhosis in patients seen in the diabetes DMP in Germany is high. Obesity and harmful alcohol consumption increase the risk of fibrosis and cirrhosis in people with T2DM. Screening for advanced liver disease and associated risk factors within the DMP program may reduce the liver disease burden in this high-risk population