Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil–based lipid therapy should be implemented in order to successfully halt and reverse IFALD.     

Current management of the short bowel syndrome

Short bowel syndrome is a challenging clinical problem that benefits from a multidisciplinary approach. Much progress has recently been made in all aspects of management. Medical intestinal rehabilitation should be the initial treatment focus, and several new potential pharmacologic agents are being investigated. Surgical rehabilitation using nontransplant procedures in selected patients may further improve intestinal function. Intestinal lengthening procedures are particularly promising. Intestinal transplantation has increasingly been used with improving success in patients with life-threatening complications of intestinal failure.     

The gut microbiome in intravenous immunoglobulin-treated chronic inflammatory demyelinating polyneuropathy

Background and purpose

The gut microbiome is involved in autoimmunity. Data on its composition in chronic inflammatory demyelinating polyneuropathy (CIDP), the most common chronic autoimmune disorder of peripheral nerves, are currently lacking.

Methods

In this monocentric exploratory pilot study, stool samples were prospectively collected from 16 CIDP patients (mean age 58 ± 10 years, 25% female) before and 1 week after administration of intravenous immunoglobulin (IVIg). Gut microbiota were analyzed via bacterial 16S rRNA gene sequencing and compared to 15 age-matched healthy subjects (mean age 59 ± 15 years, 66% female).

Results

The gut microbiota of CIDP patients showed an increased alpha-diversity (p = 0.005) and enrichment of Firmicutes, such as Blautia (p = 0.0004), Eubacterium hallii (p = 0.0004), or Ruminococcus torques (p = 0.03), and of Actinobacteriota (p = 0.03) compared to healthy subjects. IVIg administration did not alter the gut microbiome composition in CIDP in this short-term observation (p = 0.95).

Conclusions

The gut microbiome in IVIg-treated CIDP shows distinct features, with increased bacterial diversity and enrichment of short-chain fatty acid producing Firmicutes. IVIg had no short-term impact on the gut microbiome in CIDP patients. As the main limitation of this exploratory pilot study was small cohort size, future studies also including therapy-naïve patients are warranted to verify our findings and to explore the impact of long-term IVIg treatment on the gut microbiome in CIDP.     

Cholecystectomy and Liver Disease in Short Bowel Syndrome

Background

Recently, an association has been proposed between cholecystectomy and various liver diseases. Our aim was to determine whether cholecystectomy in short bowel patients influences the risk of liver disease.

Methods

We reviewed 422 adults: 182 underwent cholecystectomy prior to short bowel, 102 after developing short bowel, and 138 patients still had the gallbladder in place.

Results

Compared to pre and post short bowel, gallbladder patients were significantly less likely to have obesity (18 % and 21 % vs 9 %), central line infections (59 % and 69 % vs 46 %), intestine <60 cm (30 % and 39 % vs 26 %), and require parenteral nutrition >1 year (72 % and 77 % vs 64 %). The incidence of fatty liver was similar (31, 26, and 25 %). Fibrosis/cirrhosis was less common in the gallbladder group (26 % and 36 % vs 16 %). Frequency of end-stage liver disease was similar (15, 22, and 11 %). On multivariate analysis, cholecystectomy, parenteral nutrition >1 year, line infection, and intestine <60 cm were predictors of fibrosis/cirrhosis. Parenteral nutrition >1 year, line infection, and intestine <60 cm were predictors of end-stage liver disease.

Conclusions

Cholecystectomy does not appear to increase the incidence of liver disease in short bowel patients overall. Fibrosis/cirrhosis occurs significantly less frequently in patients with an intact gallbladder.

     

High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages In Vitro

Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function in vitro. In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of Aspergillus fumigatus conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of Aspergillus species infection warrants control of the pathogen and preservation of tissue integrity at the same time.     

Pre-resection gastric bypass reduces post-resection body mass index but not liver disease in short bowel syndrome

Background

Obese patients developing short bowel syndrome (SBS) maintain a higher body mass index (BMI) and have increased risk of hepatobiliary complications. Our aim was to determine the effect of pre-resection gastric bypass (GBP) on SBS outcome.

Methods

We reviewed 136 adults with SBS: 69 patients with initial BMI < 35 were controls; 43 patients with BMI > 35 were the obese group; and 24 patients had undergone GBP before SBS.

Results

BMI at 1, 2, and 5 years was similar in control and GBP groups, whereas obese patients had a persistently increased BMI. Eight (33%) of the GBP patients had a pre-resection BMI > 35, but post-SBS BMI was similar to those <35. Obese patients were more likely to wean off PN (47% vs 20% control and 12% GBP, P < .05). Radiographic fatty liver tended to be higher in the GBP group (54% vs 19% control and 35% obese). End-stage liver disease occurred more frequently in obese and GBP patients (30% and 33% vs 13%, P < .05).

Conclusions

Pre-resection GBP prevents the nutritional benefits of obesity but does not eliminate the increased risk of hepatobiliary disease in obese SBS patients. This occurs independent of pre-SBS BMI suggesting the importance of GBP itself or history of obesity rather than weight loss.     

Impact of sarcopenia on mortality in patients undergoing liver re-transplantation

BACKGROUND Sarcopenia, which is a loss of skeletal muscle mass, has been reported to increase post-transplant mortality and morbidity in patients undergoing the first liver transplant. Cross-sectional imaging modalities typically determine sarcopenia in patients with cirrhosis by measuring core abdominal musculatures. However, there is limited evidence for sarcopenia related outcomes in patients undergoing liver re-transplantation(re-OLT).AIM To evaluate the risk of mortality in patients with pre-existing sarcopenia following liver re-OLT.METHODS This is a retrospective study of all adult patients who had undergone a liver reOLT at the University of Nebraska Medical Center from January 1, 2007 to January 1, 2017. We divided patients into sarcopenia and no sarcopenia groups. "TeraRecon AquariusNet 4.4.12.194" software was used to evaluate computed tomography or magnetic resonance imaging of the patients done within one year prior to their re-OLT, to calculate the Psoas muscle area at L3-L4 intervertebral disc. We defined cutoffs for sarcopenia as 1561 mm2 for males and 1464 mm2 for females. The primary outcome was to compare 90 d, one, and 5-year survival rates. We also compared complications after re-OLT, length of stay, and readmission within 30 d. Survival analysis was performed with Kaplan-Meier survival analysis. Continuous variables were evaluated with Wilcoxon rank-sum tests. Categorical variables were evaluated with Fisher's exact tests.RESULTS Fifty-seven patients were included, 32 males: 25 females, median age 50 years. Two patients were excluded due to incomplete information. Overall, 47%(26) of patients who underwent re-OLT had sarcopenia. Females were found to have significantly more sarcopenia than males(73% vs 17%, P 0.001). Median model for end stage liver disease at re-OLT was 28 in both sarcopenia and no sarcopenia groups. Patients in the no sarcopenia group had a trend of longer median time between the first and second transplant(36.5 mo vs 16.7 mo). Biological markers, outcome parameters, and survival at 90 d, 1 and 5 years, were similar between the two groups. Sarcopenia in re-OLT at our center was noted to be twice as common(47%) as historically reported in patients undergoing primary liver transplantation.CONCLUSION Overall survival and outcome parameters were no different in those with and without the evidence of sarcopenia after re-OLT.