BACKGROUND: The utilization of liver transplantation (LT) is limited by the availability of suitable organs. This study aimed to assess the impact of the donor risk index (DRI) and other donor characteristics on fibrosis progression, graft, and patient survival in hepatitis C virus (HCV)-infected LT recipients.
METHODS: HCV-infected LT recipients who had at least 2 post-LT protocol liver biopsy specimens available were included. Hazard ratio for bivariate analysis was computed using Cox proportional hazard regression analysis.
RESULTS: Of 312 recipients, 26.6% died over a median follow-up of 58.5 months (95% CI: 46.5-67.3). Fourteen patients underwent re-transplantation. Mean time to graft failure was 84.3 months, median follow-up: 59 months, 95% CI (48.2, 68.3). DRI >1.5 was significantly associated with patient and graft survival (P = 0.04). Of the subset of 104 individuals who underwent histological analysis, 67.3% progressed to ≥F2. On multivariate analysis, significant donor-specific predictors of fibrosis progression were: donor age >50 years and DRI >1.7.
CONCLUSIONS: (1) Fibrosis progression in HCV-infected LT recipients is strongly associated with donor characteristics, specifically donor age and DRI. (2) DRI, an objective measure of donor quality, appears to correlate both with rate of histological progression and overall patient/graft survival.

Kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), are associated with inflammation. The mechanism that regulates inflammation in these renal injuries remains unclear. Here, we demonstrated that p300/CBP-associated factor (PCAF), a histone acetyltransferase, was overexpressed in the kidneys of db/db mice and lipopolysaccharide (LPS)-injected mice. Moreover, elevated histone acetylation, such as H3K18ac, and up-regulation of some inflammatory genes, such as ICAM-1, VCAM-1, and MCP-1, were found upon these renal injuries. Furthermore, increased H3K18ac was recruited to the promoters of ICAM-1, VCAM-1, and MCP-1 in the kidneys of LPS-injected mice. In vitro studies demonstrated that PCAF knockdown in human renal proximal tubule epithelial cells (HK-2) led to downregulation of inflammatory molecules, including VCAM-1, ICAM-1, p50 subunit of NF-κB (p50), and MCP-1 mRNA and protein levels, together with significantly decreased H3K18ac level. Consistent with these, overexpression of PCAF enhanced the expression of inflammatory molecules. Furthermore, PCAF deficiency reduced palmitate-induced recruitment of H3K18ac on the promoters of ICAM-1 and MCP-1, as well as inhibited palmitate-induced upregulation of these inflammatory molecules. In summary, the present work demonstrates that PCAF plays an essential role in the regulation of inflammatory molecules through H3K18ac, which provides a potential therapeutic target for inflammation-related renal diseases.