Orphan nuclear receptor estrogen-related receptor γ (ERRγ) stimulates bile acid production; however, the role and the regulatory mechanism of ERRγ in cholestatic liver disease are largely unknown. This study identifies that Sirt6 is a deacetylase of ERRγ and suggests a potentially novel mechanism by which Sirt6 activation alleviates cholestatic liver damage and fibrosis through regulating ERRγ. We observed that hepatic expression of Sirt6 is repressed, whereas hepatic expression of ERRγ is upregulated in murine cholestasis models. Hepatocyte-specific Sirt6-KO mice were more severely injured after a bile duct ligation (BDL) than WT mice, and adenoviral reexpression of Sirt6 reversed liver damage and fibrosis as demonstrated by biochemical and histological analyses. Mechanistically, Sirt6 deacetylated ERRγ, thereby destabilizing ERRγ and inhibiting its transcriptional activity. Elimination of hepatic ERRγ using Ad-shERRγ abolished the deleterious effects of Sirt6 deficiency, whereas ERRγ overexpression aggravated cholestatic liver injury. Administration of a Sirt6 deacetylase activator prevented BDL-induced liver damage and fibrosis. In patients with cholestasis, Sirt6 expression was decreased, whereas total ERRγ and acetylated ERRγ levels were increased, confirming negative regulation of ERRγ by Sirt6. Thus, Sirt6 activation represents a potentially novel therapeutic strategy for treating cholestatic liver injury.

This study evaluated the safety and effectiveness of minimally invasive living donor hepatectomy in comparison with the open procedure, using Korean Organ Transplantation Registry data. We reviewed the prospectively collected data of all 1,694 living liver donors (1,071 men, 623 women) who underwent donor hepatectomy between April 2014 and December 2017. The donors were grouped on the basis of procedure type to the minimally invasive procedure group (n = 304) or to the open procedure group (n = 1,390) and analyzed the relationships between clinical data and complications. No donors died after the procedure. The overall complication rates after operation in the minimally invasive procedure group and the open procedure group were 6.2% and 3.5%, respectively. Biliary complications were the most frequent events in both groups (minimally invasive procedure group, 2.4%; open procedure group, 1.6%). The majority of complications occurred within 7 days after surgery in both groups. The duration of hospitalization was shorter in the minimally invasive procedure group than in the open procedure group (9.04 ± 3.78 days versus 10.29 ± 4.01 days; P < .05). Based on its similar outcomes in our study, minimally invasive donor hepatectomy cannot be an alternative option compared with the open procedure method. To overcome this, we need to ensure better surgical safety, such as lower complication rate and shorter duration of hospitalization.

Sang-Hoon Kim, Shin Hwang, Gi-Won Song, Dong-Hwan Jung, Deok-Bog Moon, Jae Do Yang, Hee Chul Yu. Ann Hepatobiliary Pancreat Surg 2022;26:58-68. https://doi.org/10.14701/ahbps.21-108

This study aimed at developing a fully automatic technique for right lobe graft weight estimation using deep learning algorithms. The proposed method consists of segmentation of the full liver region from computed tomography (CT) images, classification of the entire liver region into the right and left lobes, and estimation of the right lobe graft weight from the CT-measured right lobe graft volume using a volume-to-weight conversion formula. The first two steps were performed with a transformer-based deep learning model. To train and evaluate the model, a total of 248 CT datasets (188 for training, 40 for validation, and 20 for testing and clinical evaluation) were used. The Dice similarity coefficient (DSC), mean surface distance (MSD), and the 95th percentile Hausdorff distance (HD95) were used for evaluating the segmentation accuracy of the full liver region and the right liver lobe. The correlation coefficient (CC), percentage error (PE), and percentage absolute error (PAE) were used for the clinical evaluation of the estimated right lobe graft weight. The proposed method achieved high accuracy in segmentation for DSC, MSD, and HD95 (95.9% ± 1.0%, 1.2 ± 0.4 mm, and 5.2 ± 1.9 mm for the entire liver region; 92.4% ± 2.7%, 2.0 ± 0.7 mm, and 8.8 ± 2.9 mm for the right lobe) and in clinical evaluation for CC, PE, and PAE (0.859, − 1.8% ± 9.6%, and 8.6% ± 4.7%). For the right lobe graft weight estimation, the present study underestimated the graft weight by − 1.8% on average. A mean difference of − 21.3 g (95% confidence interval: − 55.7 to 13.1, p = 0.211) between the estimated graft weight and the actual graft weight was achieved in this study. The proposed method is effective for clinical application.

Jae Seung Kang, Lydia Mok, Jin Seok Heo, In Woong Han, Sang Hyun Shin, Yoo-Seok Yoon, Ho-Seong Han, Dae Wook Hwang, Jae Hoon Lee, Woo Jung Lee, Sang Jae Park, Joon Seong Park, Yonghoon Kim, Huisong Lee, Young-Dong Yu, Jae Do Yang, Seung Eun Lee, Il Young Park, Chi-Young Jeong, Younghoon Roh, Seong-Ryong Kim, Ju Ik Moon, Sang Kuon Lee, Hee Joon Kim, Seungyeoun Lee, Hongbeom Kim, Wooil Kwon, Chang-Sup Lim, Jin-Young Jang, and Taesung Park. Gut and Liver 2021;15:912-21. https://doi.org/10.5009/gnl20306