Influence Of Liver Transplantation Research Articles

The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia.

Biliary atresia (BA) causes neonatal cholestasis and rapidly progresses into cirrhosis if left untreated. Kasai portoenterostomy may delay cirrhosis. BA remains among the most common indications for liver transplantation (LT) during childhood. Liver function and gut microbiome are interconnected. Disturbed liver function and enterohepatic signaling influence microbial diversity. We, herein, investigate the impact of LT and reestablishment of bile flow on gut microbiome-bile acid homeostasis in children with BA before (pre, n = 10), 3 months (post3m, n = 12), 12 months (post12m, n = 9), and more than 24 months (post24 + m, n = 12) after LT. We analyzed the intestinal microbiome of BA patients before and after LT by 16S-rRNA-sequencing and bioinformatics analyses, and serum primary and secondary bile acid levels. The gut microbiome in BA patients exhibits a markedly reduced alpha diversity in pre (p = 0.015) and post3m group (p = 0.044), and approximated healthy control groups at later timepoints post12m (p = 1.0) and post24 + m (p = 0.74). Beta diversity analysis showed overall community structure similarities of pre and post3m (p = 0.675), but both differed from the post24 + m (p < 0.001). Longitudinal analysis of the composition of the gut microbiome revealed the Klebsiella genus to show increased abundance in the post24 + m group compared with an age-matched control (p = 0.029). Secondary bile acid production increased 2+ years after LT (p = 0.03). Multivariable associations of microbial communities and clinical metadata reveal several significant associations of microbial genera with tacrolimus and mycophenolate mofetil-based immunosuppressive regimens. In children with BA, the gut microbiome shows strongly reduced diversity before and shortly after LT, and approximates healthy controls at later timepoints. Changes in diversity correlate with altered secondary bile acid synthesis at 2+ years and with the selection of different immunosuppressants.

Cognitive impairment and electroencephalographic alterations before and after liver transplantation: what is reversible?

The influence of liver transplantation (LT) on mental performance is debated, as is the role of pretransplant overt hepatic encephalopathy (OHE). The aim of this study was to evaluate the time course of the neuropsychological and electroencephalogram (EEG) features of patients with cirrhosis before and after LT with respect to prior OHE. The study population included 65 patients with cirrhosis on the transplant waiting list; 23 had a history of OHE. Each patient underwent an extensive psychometric assessment (10 tests, including paper and pencil tests and a computerized test) and an EEG before and 9 to 12 months after LT. For a subgroup of 11 patients, the assessment was also performed 3 and 6 months after LT. EEGs were analyzed spectrally, and the mean dominant frequencies were obtained. Both psychometric tests and EEGs improved 9 to 12 months after LT. Patients with a history of OHE before LT had worse cognitive performances (P < 0.001) and EEG performances in comparison with their counterparts with a negative history. They also showed greater cognitive improvement after LT (P < 0.01); however, their global cognitive performance remained slightly impaired (P < 0.01). After LT, EEGs normalized for 98% of the patients (P < 0.01), regardless of any history of OHE. In the subgroup of patients evaluated every 3 months, psychometric and EEG findings showed deterioration at 3 months and subsequently steady improvements from 6 months onward. In conclusion, both neuropsychological and EEG performances had significantly improved 1 year after LT. Patients with a history of OHE showed greater improvements after LT than patients with a negative history, but their global cognitive function remained slightly worse; in contrast, EEGs normalized in both groups.

Pharmacokinetics of Rocuronium During the Three Stages of Liver Transplantation

FISHER, DENNIS M.; RAMSAY, MICHAEL A.E.; TILLMANN HEIN, H. A.; MARCEL, RANDY J.; SHARMA, MANOHAR; RAMSAY, KIRSTEN J.; MILLER, RONALD D. Author Information

Intravenous nicardipine does not alter hepatic blood flow after orthotopic liver transplant

To evaluate the effects of nicardipine on hepatic blood flow in patients with recent liver transplants. Secondly, to evaluate the liver extraction of nicardipine in order to determine the influence of liver transplantation on its disposition. Prospective self-controlled clinical study. University hospital intensive care unit. Eight patients in the early postoperative period of orthotopic liver transplantation. Patients were given 5 mg of i.v. nicardipine. Systemic and splanchnic haemodynamic and metabolic parameters were measured before nicardipine administration (T0) and at 5 min (T1), 30 min (T2), and 120 min (T3) after administration. A catheter was inserted into a hepatic vein to determine the total hepatic blood flow (HBF) and the hepatic extraction coefficient of nicardipine. Nicardipine caused no significant changes in HBF, oxygen delivery, oxygen uptake, hepatic venous oxygen saturation, or the hepatic venous partial pressure of oxygen. Likewise, neither blood lactate concentrations nor arterial and hepatic venous lactate-pyruvate ratios were modified by nicardipine. The hepatic extraction coefficient of nicardipine was approximately 0.70 in the first 3 min after complete infusion, then decreased and remained stable at approximately 0.50, showing a non-linear first-pass metabolism pattern. Nicardipine administration after liver transplantation appears to have no deleterious effects on HBF. Nicardipine can be classified as a drug of intermediate hepatic extraction coefficient, whose elimination partly depends on hepatic enzyme activity.

Influence of liver transplantation and cyclosporin on bile secretion – an experimental study in the rat

Abstract Bile secretion is reduced after liver transplantation. It has been suggested that this is due either to the effect of cyclosporin or to the damage to the liver graft during preservation and reperfusion. The aim of this study was to explore the influence of cyclosporin as well as of liver transplantation on bile secretion. Bile flow was studied in an experimental model in the rat. In syngeneic liver-transplanted animals, the bile flow was increased compared to the bile flow in the control group (1.29 ± 0.09 ml/h vs 0.66 ± 0.03 ml/h; P < 0.01), mainly due to an increased bile acid-independent flow (0.76 ml/h vs 0.50 ml/h; P < 0.01). The findings in the liver-transplanted rats contrasted with those in a group of nontransplanted animals treated with cyclosporin. Cyclosporin treatment resulted in a reduced bile acid-independent fraction (0.37 ml/h vs 0.50 ml/h, P < 0.05) of the bile flow, although no biochemical signs of hepatotoxicity were present. This reduction in the bile acid-independent fraction could, however, not be demonstrated when cyclosporin was given to a group of liver-transplanted rats, although a reduced total bile flow was recorded in the 1st hour measurements. In contrast to previous studies, we found that the cyclosporin vehicle (Cremophor EL), when administered chronically, induced a higher bile flow than that in the control rats. This effect was not seen in the transplanted rats. Our findings in this experimental rat model indicate that cyclosporin will influence and reduce bile secretion and bile acid secretion even if no other signs of liver dysfunction are present. On the other hand, the preservation and reperfusion in this model resulted in an increased bile flow, while bile acid secretion remained constant.

Influence of liver transplantation and cyclosporin on bile secretion--an experimental study in the rat.

Bile secretion is reduced after liver transplantation. It has been suggested that this is due either to the effect of cyclosporin or to the damage to the liver graft during preservation and reperfusion. The aim of this study was to explore the influence of cyclosporin as well as of liver transplantation on bile secretion. Bile flow was studied in an experimental model in the rat. In syngeneic liver-transplanted animals, the bile flow was increased compared to the bile flow in the control group (1.29 +/- 0.09 ml/h vs 0.66 +/- 0.03 ml/h; P < 0.01), mainly due to an increased bile acid-independent flow (0.76 ml/h vs 0.50 ml/h; P < 0.01). The findings in the liver-transplanted rats contrasted with those in a group of nontransplanted animals treated with cyclosporin. Cyclosporin treatment resulted in a reduced bile acid-independent fraction (0.37 ml/h vs 0.50 ml/h, P < 0.05) of the bile flow, although no biochemical signs of hepatotoxicity were present. This reduction in the bile acid-independent fraction could, however, not be demonstrated when cyclosporin was given to a group of liver-transplanted rats, although a reduced total bile flow was recorded in the 1st hour measurements. In contrast to previous studies, we found that the cyclosporin vehicle (Cremophor EL), when administered chronically, induced a higher bile flow than that in the control rats. This effect was not seen in the transplanted rats. Our findings in this experimental rat model indicate that cyclosporin will influence and reduce bile secretion and bile acid secretion even if no other signs of liver dysfunction are present. On the other hand, the preservation and reperfusion in this model resulted in an increased bile flow, while bile acid secretion remained constant.