Introduction

Obesity is associated with gut dysbiosis, partially restored after a nutritional or surgical intervention. In the latter, the anatomical modification due to bariatric surgery, together with multiple antibiotic therapies, could be responsible for heterogeneous reported results. Endoscopic Sleeve Gastroplasty (ESG) is a new effective and minimally invasive treatment for patients with obesity (PWO).

Aims & Methods

This prospective observational study aimed to assess the effects of the ESG treatment on weight loss and gut microbiota.
Adult PWOs were consecutively enrolled and underwent ESG at the Endoscopy Unit of Fondazione Policlinico Campus Bio-medico of Rome. At the baseline (T0) and at four (T1) and eight (T2) months (T1) after ESG, anthropometric parameters (body weight, BMI, waist (WC), hip (HC), neck (NC) circumferences), blood pressure and heart rate measurement, and the food frequencies questionnaire (FFQ) were collected. Moreover, stool samples were collected at each visit, then analyzed using Next Generation Sequencing techniques (NGS). Significance was assessed for a p-value < 0.05.

Results

A total of 29 patients were enrolled in this study; at present, 15 patients completed the T1 and 10 the T2. No procedural complications were observed; none of the patients required antibiotic therapy after the endoscopic procedure. Body weight and BMI significantly decreased at T1 (p=0.0358 and p=0.0263, respectively) and T2 (p=0.0297 and p=0.0080, respectively) compared to the baseline. HC significantly decreased between T0 and T2 (p=0.0057) while WC and NC showed a decreasing trend. Maximum blood pressure decresed from T0 to T1 (p=0.0125). Regarding FFQ no statistical changes were observed in their food habits at each visit. After 4 months participants reduced the consumption of semi – skimmed milk, aged cheeses, red meat, eggs, vegetables, fruit, pasta, rice, bread and burger in the bun and increased the consumption of fresh cheeses, white meat, fish, coffee, alcoholic beverages, soft drinks and sugar. The consumption of semi – skimmed milk, fresh cheeses, red meat, eggs, pasta, rice, bread, vegetables and fruits and coffee increased again at t2. The consumption of fruit was almost of 1 fruit per day while the consumption of red meat after 8 months was 2 times/week, more than what is reported in nutritional recommendations. Regarding microbiota composition, the mean value of richness, biodiversity index and dysbiosis index at T0 were 167.13 ± 41.22, 8.71 ± 1.97 and 1.15 ± 1.83, respectively. After 4 and 8 months an increasing trend in richness (174.71 ± 38.56 and 207 ± 22.87, respectively) and biodiversity (8.93 ± 2.25 and 10.75 ± 2.1, respectively) was observed even if not statistically significant. Dysbiosis decreased significantly at T2 (0.027 ± 0.03) compared to baseline (p=0.0419).
No significant differences were found at phyla and family levels at each time compared to baseline: an interesting increasing trend of Akkermansia Muciniphila was observed at T1 (2.08 ± 6.62) compared to T0 (0.53 ± 1.1) values. This result was maintained until T2 without significant changes.

Conclusion

Preliminary results of the present study confirm the effectiveness of ESG in reducing body weight without significant post-operative complications. It seems to positively modulate the intestinal microbiota, partially increasing some beneficial species such as A. Muciniphila.

Introduction

Drug-induced liver injury (DILI) caused by metamizole has gained increasing attention in recent years^{1, 2}. However, causality assessment remains a challenge, in particular in patients with multiple drug intake.

Aims & Methods

We further characterized metamizole DILI cases with the goal to identify typical patterns that can help adjudication. To this end, the data of 88 patients with metamizole intake from our prospective study on acute liver injury with potential drug-related cause were analysed. DILI diagnosis and causality assessment was based on clinical, laboratory and histological features as well as expert adjudication³. Alternative causes of liver injury were identified or ruled out by a thorough hepatological work-up.

Results

DILI was associated with metamizole in 63 of 324 DILI patients from our cohort (prevalence 19.4%). Out of the remaining 25 patients with metamizole intake, nine patients suffered from non-metamizole DILI and 16 patients from an alternative cause for liver injury (mainly autoimmune hepatitis [n=10] and biliary obstruction [n=4]). A distinctive phenotype was observed in 45 of the 63 metamizole DILI cases, which was characterized by a relatively long latency from the start of drug intake until recognition of liver injury (median: 51 days), high transaminases at onset (aspartate aminotransferase [AST] 36.9xULN, alanine aminotransferase [ALT] 42.5xULN) and a delayed peak of bilirubin with a median of 7 days after DILI recognition. Patients with this phenotype had higher rates of jaundice (100.0% vs. 62.8%, p<0.001), coagulopathy (73.7% vs. 20.9%, p<0.001) and acute liver failure (40.0% vs. 7.0%, p<0.001) when compared to metamizole DILI cases without this clinical picture, non-metamizole DILI and non-DILI controls, however remission rates did not differ significantly when compared to the controls (71.1% vs. 76.7%, p=0.481) or to the recovery rates described in larger registry studies on DILI in general⁴. Overall, adverse outcome as defined by death or liver transplantation was observed in nine patients with metamizole DILI (14.3%). On multivariate analysis, AST and INR at DILI recognition were the only parameters independently associated with this endpoint. Regarding prediction of an adverse outcome INR had the highest discrimination (c-statistic 0.89, 95% confidence interval [CI]: 0.74-0.99) and with this performed better than Hy’s law, transaminases, bilirubin or the model for end-stage liver disease (MELD) score at baseline in terms of prognosis. INR at a cut-off of ≥1.95 showed a sensitivity and specificity as high as 77.8% and 93.5% for an adverse outcome.

Conclusion

Patients with DILI due to metamizole can present with a specific pattern which can help to identify metamizole as the causative agent and avoid erroneous association of liver injury with innocent bystander medication. Outcome, however, is not associated with this clinical picture and should rather be predicted by AST and especially INR at onset.

References

1 Sebode M, Reike-Kunze M, Weidemann S, et al. Metamizole: An underrated agent causing severe idiosyncratic drug-induced liver injury. Br J Clin Pharmacol. 2020;86(7):1406-15.
2 Weber S, Benesic A, Neumann J, et al. Liver injury associated with metamizole exposure: features of an underestimated adverse event. Drug Saf. 2021;44(6):669-80.
3 Bjornsson ES, Stephens C, Atallah E, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115-26.
4 Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology. 2015;148(7):1340-52 e7.

Disclosure

Sabine Weber and Alexander L. Gerbes received funding from TransBioLine (Translational Safety Biomarker Pipeline (TransBioLine): Enabling development and implementation of novel safety biomarkers in clinical trials and diagnosis of disease; Grant Agreement ID: 821283). The TransBioLine project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 821283. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.