Impact of sleeve gastrectomy on renal function in patients with morbid obesity: a 1-year prospective cohort study.

PURPOSE: Obesity is an independent risk factor for renal injury. A more favorable metabolic environment following weight loss may theoretically lead to improved renal function. We aimed to evaluate the evolution of renal function one year after sleeve gastrectomy in a large prospective cohort of patients with morbid obesity and assess the influence of fat-free mass (FFM) changes. METHODS: We prospectively included obese patients admitted for sleeve gastrectomy between February 2014 and November 2016. We also included a historical observational cohort of patients undergoing sleeve gastrectomy between January 2013 and January 2014 who had FFM evaluation. Patients were systematically evaluated 1 year after surgery. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The FFM was estimated by analyzing computerized tomography (CT) scan sections from CT systematically performed 2 days and 1 year after sleeve gastrectomy to detect surgery complications. RESULTS: Five hundred sixty-three patients fulfilled the inclusion criteria. The mean age was 41.2 ± 0.5 years. The mean body mass index was 43.5 ± 0.3 kg/m2 and 20.4, 30.5, and 30.7% of the included patients had type 2 diabetes, hypertension, and dyslipidemia, respectively. One hundred fifteen patients were excluded and four hundred forty-eight patients were finally included in the analysis. The eGFR was significantly higher 1 year after sleeve gastrectomy than before surgery (87.8 ± 0.9 versus 86.1 ± 0.9, p < 0.01). There was no difference in terms of post-surgery FFM loss between patients with an improved eGFR and those without (6.7 ± 0.3 kg versus 6.8 ± 0.5 kg, p = 0.9). Furthermore, post-surgery changes in the eGFR did not correlate with the amount of FFM loss (r = 0.1, p = 0.18). CONCLUSION: Renal function assessed by eGFR is significantly improved at 1-year post-sleeve gastrectomy, independent of changes in skeletal muscle mass.

Computed tomography assessment of postoperative gastric vascular supply and staple-line leak development after sleeve gastrectomy.

BACKGROUND: Residual arterial supply of the gastric tube after sleeve gastrectomy (SG) can be damaged by surgery, which can reduce gastric tube perfusion and could promote postoperative leakage. OBJECTIVE: To compare the postoperative vascularization of the gastric tube using early computed tomography (CT) scanning after SG in patients with or without postoperative staple-line leak. SETTING: University hospital. METHODS: A retrospective analysis of a prospective database was performed in consecutive patients undergoing SG. Patients who presented with a staple-line leak were matched (1:3) with a control group of patients who underwent surgery without postoperative morbidity during the same period. Gastric tube vascularization was studied on a postoperative day 2 CT scan in both groups of patients. RESULTS: During the study period, 1826 patients underwent SG, including 42 patients (2.3%) who presented with a staple-line leak. Those 42 patients were successfully matched to 126 control patients. Global identification of residual gastric arterial supply in early postoperative CT scans was similar in patients with or without staple-line leak after SG. However, residual vascular supply of the gastroesophageal junction (i.e., terminal and anterior cardiotuberosity branches of the left gastric artery or left inferior phrenic artery) was more frequently interrupted by the staple line in the group of patients who developed a gastric leak. CONCLUSION: This study suggests a correlation between interruption of the main arteries supplying the gastroesophageal junction by the staple line on early postoperative CT scans and the development of gastric leak after SG. These results support the vascular theory as one of the causes of leak after SG.

Prevention of incisional hernia after single-port sleeve gastrectomy (PRISM): a prospective non-randomized controlled study.

BACKGROUND: SPSG carries a risk of incisional hernia, particularly in patients with high body mass index. Prophylactic mesh placement with either permanent or absorbable mesh could decrease the occurrence of incisional hernia, with uncertainty on other postoperative parietal complications. METHODS: This is a non-randomized monocentric single-blinded prospective study. High-risk patients (body mass index ≥ 45 kg/m2) underwent either 3 strategies of parietal closure (suture with or without permanent or absorbable mesh) during SPSG. The primary outcome was the occurrence of radiologically defined incisional hernia during the first postoperative year. Secondary outcomes included surgical site infection rates and postoperative pain. RESULTS: Between November 2018 and November 2019, 255 patients were included (85 in each group). All patients reached one-year postoperative follow-up. Significantly more incisional hernias were observed in the no mesh group in comparison with permanent and absorbable mesh groups, respectively (20% vs. 7.1% vs. 5.1%, P = 0.005). No difference was observed in mesh groups. No difference was observed regarding other parietal complications. One patient in the absorbable mesh group presented a superficial surgical site infection and required surgical drainage without mesh removal and one patient in the permanent mesh group presented a parietal hematoma and required surgical drainage with mesh removal. Twenty-six (92.8%) asymptomatic patients presented incisional hernia discovered on the one-year CT-scan. CONCLUSIONS: Prophylactic mesh placement during SPSG decreases the occurrence of postoperative incisional hernia. Routine permanent mesh placement could be proposed in high-risk patients.

Current strategies to induce liver remnant hypertrophy before major liver resection.

Hepatic resection is the gold standard for patients affected by primary or metastatic liver tumors but is hampered by the risk of post-hepatectomy liver failure. Despite recent improvements, liver surgery still requires excellent clinical judgement in selecting patients for surgery and, above all, efficient pre-operative strategies to provide adequate future liver remnant. The aim of this article is to review the literature on the rational, the preliminary assessment, the advantages as well as the limits of each existing technique for preparing the liver for major hepatectomy.

Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case-control study.

Background: The microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment. Methods: In this case-control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry. Results: The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment. Limitations: Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results. Conclusion: Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.

Computed Tomography Assessment of Fat Distribution and Staple-Line Leak Risk After Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) has become the most frequent bariatric procedure and staple-line leak represents its most feared complication. Visceral obesity, a core component of the metabolic syndrome, has been associated with worst postoperative outcomes after various abdominal surgical procedures, and can be estimated by computed tomography (CT). The aim of this study was to assess the impact of radiologically determined visceral obesity in the risk of staple-line leak after SG. MATERIAL AND METHODS: A retrospective analysis of a prospective database was performed in consecutive patients undergoing SG. Several anthropometric variables were measured on a preoperative CT scan. Multivariate analysis was performed to determine preoperative risk factors for staple-line leak. RESULTS: During the study period, 377 patients were included in the analysis. The median BMI was 39.7 kg/m2 (36.5-43.5) and 8 patients (2.1%) presented a gastric leak. After multivariate analysis, visceral obesity defined by visceral fat area (VFA)/body surface area (BSA) ≥ 85 cm2/m2 was the only independent predictive factor for gastric leak (OR = 5312). CONCLUSION: CT scan-assessed visceral obesity defined by a VFA/BSA ratio ≥ 85 cm2/m2 is associated with an increased risk of gastric leak after SG. Preoperatively radiological examination in patients suspected of visceral obesity would be useful to optimize preoperative management.

Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis.

BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING: The German Federal Ministry of Education and Research and Echosens.

Microbiota tryptophan metabolism induces aryl hydrocarbon receptor activation and improves alcohol-induced liver injury.

OBJECTIVE: Chronic alcohol consumption is an important cause of liver-related deaths. Specific intestinal microbiota profiles are associated with susceptibility or resistance to alcoholic liver disease in both mice and humans. We aimed to identify the mechanisms by which targeting intestinal microbiota can improve alcohol-induced liver lesions. DESIGN: We used human associated mice, a mouse model of alcoholic liver disease transplanted with the intestinal microbiota of alcoholic patients and used the prebiotic, pectin, to modulate the intestinal microbiota. Based on metabolomic analyses, we focused on microbiota tryptophan metabolites, which are ligands of the aryl hydrocarbon receptor (AhR). Involvement of the AhR pathway was assessed using both a pharmacological approach and AhR-deficient mice. RESULTS: Pectin treatment modified the microbiome and metabolome in human microbiota-associated alcohol-fed mice, leading to a specific faecal signature. High production of bacterial tryptophan metabolites was associated with an improvement of liver injury. The AhR agonist Ficz (6-formylindolo (3,2-b) carbazole) reduced liver lesions, similarly to prebiotic treatment. Conversely, inactivation of the ahr gene in alcohol-fed AhR knock-out mice abrogated the beneficial effects of the prebiotic. Importantly, patients with severe alcoholic hepatitis have low levels of bacterial tryptophan derivatives that are AhR agonists. CONCLUSIONS: Improvement of alcoholic liver disease by targeting the intestinal microbiota involves the AhR pathway, which should be considered as a new therapeutic target.

Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians.

BACKGROUND: Multikinase inhibitors (MKI) are targeted molecular agents that have revolutionized cancer management. However, there is a paucity of data concerning MKI-related liver injury risk and clinical guidelines for the management of liver toxicity in patients receiving MKI for cancer are scarce. DESIGN: We conducted a PubMed search of articles in English published from January 2000 to December 2018 related to hepatotoxicity of the 29 FDA-approved MKIs at doses used in clinical practice. The search terms were the international non-proprietary name of each agent cross-referenced with «hepatotoxicity¼, «hepatitis¼, «hepatic adverse event¼, or «liver failure¼, and «phase II clinical trial¼, «phase III clinical trial¼, or «case report¼. RESULTS: Following this search, 140 relevant studies and 99 case reports were considered. Although asymptomatic elevation of aminotransferase levels has been frequently observed in MKI clinical trials, clinically significant hepatotoxicity is a rare event. In most cases, the interval between treatment initiation and the onset of liver injury is between one week and two months. Liver toxicity is often hepatocellular and less frequently mixed. Life-threatening MKI-induced hepatic injury has been described, involving fulminant liver failure or death. Starting from existing data, a description of MKI-related liver events, grading of hepatotoxicity risk, and recommendations for management are also given for various MKI molecules. CONCLUSION: All MKIs can potentially cause liver injury, which is sometimes irreversible. As there is still no strategy available to prevent MKI-related hepatotoxicity, early detection remains crucial. The surveillance of liver function during treatment may help in the early detection of hepatotoxicity. Furthermore, the exclusion of potential causes of hepatic injury is essential to avoid unnecessary MKI withdrawal.

Laparoscopic sleeve gastrectomy for morbid obesity in renal transplantation candidates: a matched case-control study.

Obesity has become an important issue in patients with end-stage renal disease (ESRD). Since it is considered a relative contraindication for renal transplantation, bariatric surgery has been advocated to treat morbid obesity in transplant candidates, and laparoscopic sleeve gastrectomy (LSG) is the most reported procedure. However, comparative data regarding outcomes of LSG in patients with or without ESRD are scarce. Consecutive patients with ESRD (n = 29) undergoing LSG were compared with matched patients with normal renal function undergoing LSG in a 1:3 ratio using propensity score adjustment. Data were collected from a prospective database. Eligibility for transplantation was also studied. A lower weight loss (20 kg (16-30)) was observed in patients with ESRD within the first year as compared to matched patients (28 kg (21-34)) (P < 0.05). After a median follow-up of 30 (19-50) months in the ESRD group, contraindication due to morbid obesity was lifted in 20 patients. Twelve patients underwent transplantation. In patients with ESRD potentially eligible for transplantation, LSG allows similar weight loss in comparison with matched patients with normal renal function, enabling lifting contraindication for transplantation due to morbid obesity in the majority of patients within the first postoperative year.

Adaptation of controlled attenuation parameter (CAP) measurement depth in morbidly obese patients addressed for bariatric surgery.

BACKGROUND AND AIM: The controlled attenuation parameter (CAP) using FibroScan (Echosens, Paris, France) M or XL probe has been developed for liver steatosis assessment. However, CAP performs poorly in patients with high body mass index. The aim of our study was to assess whether CAP is overestimated using the standard XL probe in patients with morbid obesity, and in the case of an overestimation, to reprocess the data at a greater depth to obtain the appropriate CAP (CAPa). PATIENTS AND METHODS: We conducted an observational prospective cohort study on a total of 249 severely obese patients admitted to our institution to undergo sleeve gastrectomy. Patients had a liver biopsy performed during the surgery and a CAP measurement during the 15 days preceding biopsy. Patient files were reprocessed retrospectively by an algorithm, blinded to the patients' clinical data. The algorithm automatically assessed the probe-to-capsula distance (PCD) by analysing the echogenicity of ultrasound signals on the time-motion mode. In the case of a distance >35 mm, the algorithm automatically selected a deeper measurement for CAP (CAPa). When PCD was less than 35 mm, the measured CAP was considered as appropriated (CAPa) and no further reprocessing was performed. RESULTS: CAP recording was not performed at a sufficient depth in 130 patients. In these patients, the CAPa obtained at the adapted depth was significantly lower than CAP (298±3.9 versus 340±4.2 dB/m; p< 0.0001) measured at the standard depth (35 to 75 mm). Multiple linear regression analysis revealed that both body mass index and hepatic steatosis were independently correlated with CAP values. After reprocessing the CAP in patients with PCD > 35 mm, steatosis stage was the only parameter independently correlated with CAP values. For the diagnosis of steatosis (S≥1), moderate to severe steatosis (S≥2) and severe steatosis (S = 3), the AUROC curves of CAPa (measured CAP in patients with PCD<35 mm and reprocessed CAP in those with PCD>35 mm) were 0.86, 0.83 and 0.79, respectively. The Obuchowski measure for the diagnosis of steatosis was 0.90±0.013. CONCLUSION: CAP was overestimated in a half of morbidly obese patients using an XL probe, but CAP can be performed correctly in these patients after adapting the measurement depth.

Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis.

BACKGROUND: Intestinal microbiota plays an important role in bile acid homeostasis. AIM: To study the structure of the intestinal microbiota and its function in bile acid homeostasis in alcoholic patients based on the severity of alcoholic liver disease. METHODS: In this prospective study, we included four groups of active alcoholic patients (N = 108): two noncirrhotic, with (noCir_AH, n = 13) or without alcoholic hepatitis (noCir_noAH, n = 61), and two cirrhotic, with (Cir_sAH, n = 17) or without severe alcoholic hepatitis (Cir_noAH, n = 17). Plasma and faecal bile acid profiles and intestinal microbiota composition were assessed. RESULTS: Plasma levels of total bile acids (84.6 vs 6.8 µmol/L, P < 0.001) and total ursodeoxycholic acid (1.3 vs 0.3 µmol/L, P = 0.03) were higher in cirrhosis with severe alcoholic hepatitis (Cir_sAH) than Cir_noAH, whereas total faecal (2.4 vs 11.3, P = 0.01) and secondary bile acids (0.7 vs 10.7, P < 0.01) levels were lower. Cir_sAH patients had a different microbiota than Cir_noAH patients: at the phyla level, the abundance of Actinobacteria (9 vs 1%, P = 0.01) was higher and that of Bacteroidetes was lower (25 vs 40%, P = 0.04). Moreover, the microbiota of Cir_sAH patients showed changes in the abundance of genes involved in 15 metabolic pathways, including upregulation of glutathione metabolism, and downregulation of biotin metabolism. CONCLUSIONS: Patients with Cir_sAH show specific changes of the bile acid pool with a shift towards more hydrophobic and toxic species that may be responsible for the specific microbiota changes. Conversely, the microbiota may also alter the bile acid pool by transforming primary to secondary bile acids, leading to a vicious cycle.

Predictive score of sarcopenia occurrence one year after bariatric surgery in severely obese patients.

BACKGROUND AND AIM: Sarcopenic obesity is a risk factor of morbidity and mortality. The aim of this study was to generate a predictive score of sarcopenia occurrence one year after bariatric surgery. PATIENTS AND METHODS: We conducted an observational prospective cohort study on a total of 184 severely obese patients admitted to our institution to undergo sleeve gastrectomy. Skeletal muscle cross-sectional area at the third lumbar vertebrae (SMA, cm2) was measured from the routinely performed computed tomography. The skeletal muscle index (SMI) was calculated as follows: SMA/height2 (cm2/m2). Sarcopenia was defined as an SMI < 38.5 cm2/m2 for women and < 52.4 cm2/m2 for men. Measurements were performed at surgery and one year later. RESULTS: Most of the included patients were female (79%), with a mean age of 42±0.9 years and body mass index of 43.2±0.5 kg/m2. Fifteen patients (8%) had sarcopenia before surgery and 59 (32%) at the one-year follow-up. Male gender (p<0.0001), SMA before surgery (p<0.0001), and SMI before surgery (p<0.0001) significantly correlated with the occurrence of sarcopenia one year after surgery by multivariate analysis. Two predictive sarcopenia occurrence scores were constructed using SMA and gender (SS1 score) or SMI and gender (SS2 score). The area under receiver operating characteristic (AUROC) curve of the SS2 score was significantly greater than that of the SS1 score for the diagnosis of postoperative sarcopenia occurrence (0.95±0.02 versus 0.90±0.02; p<0.01). A cut-off value for the SS2 score of 0.53 had a sensitivity of 90%, a specificity of 91%, a positive predictive value of 83%, and a negative predictive value of 95%. In the group of patients without baseline sarcopenia, the SS2 score had still an excellent AUROC of 0.92±0.02. A cut-off of 0.55 predicted development of sarcopenia one year after sleeve gastrectomy in these patients with a sensitivity of 87%, a specificity of 88%, and negative predictive value of 95%. CONCLUSION: The SS2 score has excellent predictive value for the occurrence of sarcopenia one year after sleeve gastrectomy. This score can be used to target early intensification of nutritional and dietetic follow-up to the predicted high-risk population.

Characterization of intestinal microbiota in alcoholic patients with and without alcoholic hepatitis or chronic alcoholic pancreatitis.

Excessive alcohol consumption leads to severe alcoholic hepatitis (sAH) or chronic alcoholic pancreatitis (CAP) only in a subset of patients. We aimed to characterize the intestinal microbiota profiles of alcoholic patients according to the presence and nature of the complications observed: sAH or CAP. Eighty two alcoholic patients were included according to their complications: CAP (N = 24), sAH (N = 13) or no complications (alcoholic controls, AC, N = 45). We analyzed the intestinal microbiota by high-throughput sequencing. Bacterial diversity was lower in patients with CAP, who had a global intestinal microbiota composition different from that of AC. The intestinal microbiota composition of these two groups differed for 17 genera, eight of which were more frequent in patients with CAP (e.g. Klebsiella, Enterococcus and Sphingomonas). There was no significant difference in bacterial diversity between the sAH and CAP groups. However, 16 taxa were more frequent in sAH patients, and 10 were more frequent in CAP patients. After adjustment for confounding factors sAH patients were found to have higher levels of Haemophilus. For alcoholic patients, specific intestinal microbiota signatures are associated with different complications. Patients with CAP and sAH also display specific dysbiosis relative to AC.

Transient elastography alone and in combination with FibroTest® for the diagnosis of hepatic fibrosis in alcoholic liver disease.

BACKGROUND & AIMS: The reliability of transient elastography (TE) to assess liver fibrosis is insufficiently validated in alcoholic liver disease (ALD). We aimed to validate the diagnostic utility of TE for liver fibrosis in patients with excessive alcohol consumption and evaluate whether Fibrotest® adds diagnostic value relative to or in combination with TE. METHODS: We conducted a multicentre prospective study on a total of 217 heavy drinkers with high serum aminotransferase levels. Patients underwent liver biopsy, TE, Fibrotest® , PGAA, APRI, FIB-4 and FORNS. The overall diagnostic performance was evaluated by the area under the receiver operating characteristic (AUROC) curves and Obuchowski measures. RESULTS: TE values correlated with fibrosis stage (r=.73; P<.0001) and steatosis stage (r=.19; P<.01). Patients with alcoholic hepatitis had higher TE values than those without alcoholic hepatitis (P<.0001). In an multivariate analysis, fibrosis stage and the presence of alcoholic hepatitis were the only parameters that correlated with liver stiffness. For the diagnosis of advanced fibrosis (F≥3), the AUROC curves were 0.90, 0.85, 0.83, 0.91 and 0.90 for TE, Fibrotest® , PGAA and associations TE-Fibrotest® , TE-PGAA respectively. For the diagnosis of cirrhosis, the AUROC curves were 0.93, 0.88, 0.89, 0.94 and 0.95 respectively. The Obuchowski measures for the diagnosis of fibrosis were 0.94, 0.92, 0.91, 0.95 and 0.94 respectively. The performance of TE was not significantly different than those of Fibrotest® , PGAA and combinations TE-Fibrotest® , TE-PGAA. CONCLUSIONS: TE has excellent diagnostic value for liver fibrosis in alcoholic liver disease. The combined use of TE-Fibrotest® or TE-PGAA does not improve the performance of TE.

Aloe vera-induced acute liver injury: A case report and literature review.

Recent data suggest that herbal and dietary supplements are the second most common cause of liver injury. We herein report a case of acute liver injury in a 68-year old female caused by ingestion of Aloe vera. Upon discontinuation of the oral Aloe vera, liver function tests (LFT) returned to normal levels. Thus, it is crucial to consider the use of herbal products as causative agents of acute liver injury.

Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings.

BACKGROUND: Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. AIM: To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. METHODS: We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. RESULTS: An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. CONCLUSION: These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment.

Decreased expression of the glucocorticoid receptor-GILZ pathway in Kupffer cells promotes liver inflammation in obese mice.

BACKGROUND & AIMS: Kupffer cells (KC) play a key role in the onset of inflammation in non-alcoholic steatohepatitis (NASH). The glucocorticoid receptor (GR) induces glucocorticoid-induced leucine zipper (GILZ) expression in monocytes/macrophages and is involved in several inflammatory processes. We hypothesized that the GR-GILZ axis in KC may contribute to the pathophysiology of obesity-induced liver inflammation. METHODS: By using a combination of primary cell culture, pharmacological experiments, mice deficient for the Gr specifically in macrophages and transgenic mice overexpressing Gilz in macrophages, we explored the involvement of the Gr-Gilz axis in KC in the pathophysiology of obesity-induced liver inflammation. RESULTS: Obesity was associated with a downregulation of the Gr and Gilz, and an impairment of Gilz induction by lipopolysaccharide (LPS) and dexamethasone (DEX) in KC. Inhibition of Gilz expression in isolated KC transfected with Gilz siRNA demonstrated that Gilz downregulation was sufficient to sensitize KC to LPS. Conversely, liver inflammation was decreased in obese transgenic mice specifically overexpressing Gilz in macrophages. Pharmacological inhibition of the Gr showed that impairment of Gilz induction in KC by LPS and DEX in obesity was driven by a downregulation of the Gr. In mice specifically deficient for Gr in macrophages, Gilz expression was low, leading to an exacerbation of obesity-induced liver inflammation. CONCLUSIONS: Obesity is associated with a downregulation of the Gr-Gilz axis in KC, which promotes liver inflammation. The Gr-Gilz axis in KC is an important target for the regulation of liver inflammation in obesity.

Disseminated tuberculosis presenting as febrile seizures with fatal evolution in an infant.

Disseminated tuberculosis with the involvement of brain, liver and gut is a rare disease in immunocompetent infant. Early diagnostic and instauration of anti-tuberculosis therapy is capital because the outcome is poor. Here, we report the case of an 11-month-old boy with disseminated tuberculosis of brain, liver abdominal lymph nodes, small bowel and lung, which presented with fever, generalized tonic-clonic seizure, hemodynamic instability and a history of recurrent respiratory tract infections. His father was diagnosed with active pulmonary tuberculosis six month ago and family members completed an anti-tuberculosis chemoprophylaxis regimen.