Cholesterol Gallstones and Long-Term Use of Statins: Is Gut Microbiota Dysbiosis Bridging over Uncertainties?

A total of 300 research participants-200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (-)) and 100 healthy controls-were included in this observational study. The aim of the study was to deliver insights into the relationship between the long-term use of statins for dyslipidemia and gallstone disease (GSD), as well as insights into the background particularities of the gut microbiota. All study participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, and abdominal ultrasound/CT exams. Results: The research participants presented with similarities related to age, gender, and location. Patients displayed comparable heredity for GSs, metabolic issues, and related co-morbidities. Gut dysbiosis (DB) was present in 54% of the statin (-) patients vs. 35% of the statin (+) patients (p = 0.0070). GSs were present in 14% of patients in the statin (-) group vs. 5% of patients in the statin (+) group (p = 0.0304). Severe dysbiosis, with a significant reduction in biodiversity, an increase in LPS (+) bacteria, and a notable decrease in mucin-degrading bacteria, mucosa-protective bacteria, and butyrate-producing bacteria were observed in the statin (-) group. Strong positive correlations between GSD and diabetes/impaired glucose tolerance (r = 0.3368, p = 0.0006), obesity (r = 0.3923, p < 0.0001), nonalcoholic fatty liver disease (r = 0.3219, p = 0.0011), and DB (r = 0.7343, p < 0.0001), as well as significant negative correlations between GSD and alcohol use (r = -0.2305, p = 0.0211), were observed. The multiple regression equation demonstrated that only DB (95% CI: 0.3163 to 0.5670; p < 0.0001) and obesity (95% CI: 0.01431 to 0.2578; p = 0.0289) were independent risk factors predicting GSD in the group of patients treated with statins. Conclusion: The long-term use of statins in dyslipidemic patients was associated with a low risk of developing GSs. The gut microbiota associated with a long-term use of statins in dyslipidemic patients was characterized by a low risk of developing an imbalance of various functional bacteria and alterations in the metabolic microbiota. DB and obesity were found to be independent risk factors predicting GSD in statin (+) patients.

NASH/NAFLD-Related Hepatocellular Carcinoma: An Added Burden.

Hepatocellular carcinoma (HCC) is the most frequently found primary malignancy of the liver, showing an accelerated upward trend over the past few years and exhibiting an increasing relationship with metabolic syndrome, obesity, dyslipidemia and type 2 diabetes mellitus. The connection between these risk factors and the occurrence of HCC is represented by the occurrence of non-alcoholic fatty liver disease (NAFLD) which later, based on genetic predisposition and various triggers (including the presence of chronic inflammation and changes in the intestinal microbiome), may evolve into HCC. HCC in many cases is diagnosed at an advanced stage and can be an incidental finding. We present such a scenario in the case of a 41-year-old male patient who had mild obesity and mixed dyslipidemia, no family or personal records of digestive pathologies and who recently developed a history of progressive fatigue, dyspepsia and mild upper abdominal discomfort initially thought to be linked to post-COVID syndrome, as the patient had COVID-19 pneumonia a month prior. The abdominal ultrasound revealed a mild hepatomegaly with bright liver aspect of the right lobe (diffuse steatosis), a large zone of focal steatosis (segments IV, III and II) and a left lobe tumoral mass, highly suggestive of malignancy. Point shear wave elastography at the right lobe ruled out an end-stage chronic liver disease. Additional laboratory investigations, imaging studies (magnetic resonance imaging) and histopathological examination of liver fragments confirmed a highly aggressive HCC, with poorly differentiation-G3, (T4, N 1M 0) and stage IVA, associated with nonalcoholic steatohepatitis (NASH). A sorafenib course of treatment was attempted, but the patient discontinued it due to severe side effects. The subsequent evolution was extremely unfavorable, with rapid degradation, a few episodes of upper digestive bleeding, hepatic insufficiency and mortality in a couple of months. Conclusions: Diagnosis of NASH-related HCC is either an accidental finding or is diagnosed at an advanced stage. In order to earn time for a proper treatment, it becomes important to diagnose it at an early stage, for which regular check-ups should be performed in groups having the risk factors related to it. Patients suffering from obesity and mixed dyslipidemia should undergo periodic abdominal ultrasound examinations. This should be emphasized even more in the cases showing NASH. Complaints of any kind post-COVID-19 should be dealt with keenly as little is yet known about its virulence and its long-term side effects.

Dyspepsia and Gut Microbiota in Female Patients with Postcholecystectomy Syndrome.

BACKGROUND: Gallstone disease (GSD) represents one of the most frequent digestive disorders, highly reported in female gender. The purpose of the study was to explore the clinical and gut microbiota particularities of female patients with postcholecystectomy syndrome (PCS) and the possible relationship between gut dysbiosis (DB) and abdominal complaints. PATIENTS AND METHODS: In total, 129 female participants: 104 outpatients divided into two equal groups, 52 PCS (+), 52 PCS (-) and 25 healthy controls were consecutively enrolled in this observational study. Patients underwent clinical examination with assessment of pain, bloating, transit disturbances, abdominal ultrasound/computer tomography/magnetic resonance imaging/endoscopic retrograde cholangiopancreatography, upper and lower digestive endoscopies. Laboratory work-ups and stool microbiology assessments were performed for all study participants (patients and controls). Stool microorganisms were identified by matrix-assisted laser desorption ionization - time-of-flight- mass spectrometry and in patients with DB also by next-generation sequencing. RESULTS: Older age, complicated gallstones disease, associated conditions like diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome were significantly present in PCS (+) group, as well as sedentary lifestyle and diets characterized by a low fiber intake (p<0.0001). PCS (+) patients displayed significant differences related to the incidence and severity of overall gut microbiota DB, decreased H index of biodiversity and the unbalanced Firmicutes/Bacteroidetes (F/B) ratios by comparison to the PCS (-) group (p<0.0001). Strong positive correlations of the severity of overall DB with bloating and the intestinal habit disorders, as well as of F/B ratios to all abdominal symptoms were noted. CONCLUSION: PCS in female patients was associated with older age, sedentary lifestyle, specific dietary habits, history of complicated gallstone disease, diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome, as well as gut microbiota particularities. Overall DB and unbalanced F/B ratios were strongly correlated to abdominal complaints.

Influence of exercise training and eating behavior on arterial stiffness in young healthy students.

AIM: Increased arterial stiffness is an important risk factor for the development of cardiovascular disease. The aim of the present study was to compare arterial function and other anthropometric parameters in trained vs sedentary, healthy young students. Furthermore, the study explores the relationship between arterial stiffness and eating behavior in these students. METHODS: Two groups of healthy university students were recruited for this study. The first group consisted of 10 men and 8 women (mean age: 23.27 ± 3.2 years) with an athletic predisposition. Furthermore, over the course of 6 months this group participated in 60-min training sessions designed as interval training circuits with a frequency of three to five times a week. For comparison, a group of age-matched sedentary students (5 men and 13 women; 24.27 ± 2.6 years) were recruited from the same institution. Weight, height, body mass index (BMI), as well as neck and abdominal circumferences (ABs) were recorded. Arterial tension, heart rate, arterial stiffness measurements were simultaneously determined. Lastly, all students completed a 51-item "Eating Behavior Patterns Questionnaire". RESULTS: Age, weight, BMI, AB, and blood pressure were not significantly different between the two groups (p > 0.05). The moderately aerobic trained students showed a significantly lower heart rate, neck circumference, and arterial stiffness as compared with their untrained, sedentary counterparts. Additionally, pulse wave velocity (PWV) measurements were correlated to a lower weight, heart rate, blood pressure, AB, and neck circumference (p < 0.05) found in trained subjects at the end of the 6-month training period. Furthermore, the nutritional habit analysis showed that in the sedentary group, snacking, emotional eating, and cultural/lifestyle behaviors are positively correlated with PWV (p < 0.05). CONCLUSION: Healthy subjects with higher PWV may benefit from consistent aerobic exercise training to improve arterial stiffness. Our eating behavior study shows that healthy eating may improve vascular function and therefore can reduce the risk of cardiovascular diseases.

The association between arterial stiffness and carotid intima-media thickness in patients with known cardiovascular risk factors.

OBJECTIVES: The aim of this study was to evaluate the relationship between pulse wave velocity and carotid intima-media thickness (IMT) in patients with different cardiovascular risk factors. MATERIAL AND METHODS: This prospective study included 223 patients with at least 2 risk factors for atherosclerosis, divided based on the presence of coronary artery disease (CAD): 140 patients with angiographically documented CAD and 83 patients without CAD. The patients were compared with a control group of 74 healthy age-matched subjects (CON). We determined the following parameters: blood pressure, total cholesterol (TC), triglycerides (TG), LDL-cholesterol, HDL-cholesterol, fasting serum glucose and renal parameters: blood urea nitrogen, serum creatinine, and uric acid levels in all patients. Arterial stiffness was measured with non-invasive oscillometric Arteriograph device (Tensiomed Ltd., Budapest, Hungary) and carotid scan was performed with B-mode ultrasound. RESULTS: Patients with CAD had increased values of aortic PWV compared with patients without CAD and CON group (12.5±0.7 vs 10.9±0.6 vs 8.5±0.6 m/s, all p<0.001). The values of carotid IMT were significantly higher in CAD patients as compared to patients without CAD and CON group (1±0.05 versus 1.0±0.07 versus 0.7±0.08 mm, all p<0.001). The carotid IMT significantly correlated with aortic PWV (r=0.787, p<0.001). CONCLUSIONS: Carotid IMT and aortic PWV are useful non-invasive methods for atherosclerosis detection in patients with known cardiovascular risk factors. Both determinations in the same patient will increase the clinical relevance.