Retained NK Cell Phenotype and Functionality in Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), and the progressive stage non-alcoholic steatohepatitis (NASH), is the predominant cause of chronic liver disease globally. As part of the complex pathogenesis, natural killer (NK) cells have been implicated in the development of liver inflammation in experimental murine models of NASH. However, there is a lack of knowledge on how NK cells are affected in humans with this disease. Here, we explored the presence of disease-specific changes within circulating and tissue-resident NK cell populations, as well as within other major immune cell subsets, in patients with liver biopsy-confirmed NAFLD. Using 18-color-flow cytometry, substantial changes were observed in certain myeloid populations in patients as compared to controls. NK cell numbers, on the other hand, were not altered. Furthermore, only minor differences in expression of activating and inhibitory NK cell receptors were noted, with the exception of an increased expression of NKG2D on NK cells from patients with NASH. NK cell differentiation remained constant, and NK cells from these patients retain their ability to respond adequately upon stimulation. Instead, considerable alterations were observed between liver, adipose tissue, and peripheral blood NK cells, independently of disease status. Taken together, these results increase our understanding of the importance of the local microenvironment in shaping the NK cell compartment and stress the need for further studies exploring how NASH affects intrahepatic NK cells in humans.

1000 consecutive ablation sessions in the era of computer assisted image guidance - Lessons learned.

BACKGROUND: Ablation therapies for tumours are becoming more used as ablation modalities evolve and targeting solutions are getting better. There is an increasing body of long-term results challenging resection and proving lower morbidities and costs. The aim of this paper is to share the experiences from a high-volume centre in introducing computer assisted targeting solutions and efficient ablation modalities like microwave generators and irreversible electroporation. MATERIAL AND METHODS: One thousand consecutive treatments in one high-volume centre were evaluated retrospectively from prospectively collected data. RESULTS: The purpose of this paper is to present the benefits of going into computer assisted targeting techniques and microwave technology; pitfalls and overview of outcomes. The main target organ was the liver and the main indications were ablation of hepatocellular carcinomas and colorectal liver metastases. With the assistance of computer assisted targeting the local recurrence rate within 6 months has dropped from 30 to near 10%. The survival of patients with hepatocellular carcinoma and colorectal liver metastases is not worse if the tumour can be retreated after a local recurrence. Multiple colorectal liver metastases can be treated successfully. DISCUSSION: The incorporation of computer assisted targeting technologies for ultrasound-, ct guided- and laparoscopic tumour ablation has been very successful and without a noticeable learning curve. The same is true for switching from radiofrequency energies to microwave generators and irreversible electroporation. CONCLUSION: It is well worthwhile upgrading ablation and targeting technologies to achieve excellent and reproducible results and minimizing operator dependency.

The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function.

BACKGROUND: Previous studies have shown that liver function is inhomogeneously distributed in diseased livers, and this uneven distribution cannot be compensated for if a global liver function test is used for the prediction of post-operative remnant liver function. Dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) can assess segmental liver function, thus offering the possibility to overcome this problem. METHODS: In 10 patients with liver cirrhosis and 10 normal volunteers, the contribution of individual liver segments to total liver function and volume was calculated using dynamic Gd-EOB-DTPA-enhanced MRI. Remnant liver function predictions using a segmental method and global assessment were compared for a simulated left hemihepatectomy. For the prediction based on segmental functional MRI assessment, the estimated function of the remnant liver segments was added. RESULTS: Global liver function assessment overestimated the remnant liver function in 9 out of 10 patients by as much as 9.3% [median -3.5% (-9.3-3.5%)]. In the normal volunteers there was a slight underestimation of remnant function in 9 out of 10 cases [median 1.07% (-0.7-2.5%)]. DISCUSSION: The present study underlines the necessity of a segmental liver function test able to compensate for the non-homogeneous nature of liver function, if the prediction of post-operative remnant liver function is to be improved.