Plasma TIMP-1 is a Useful Tool for Monitoring 24 Months Liver Fibrosis Improvement After Anti-HCV /DAA Therapy in HCV/HIV Mono/Coinfection

Long term liver fibrosis (LF) changes and their best -monitoring non-invasive tools after effective anti-HCV DAA therapy are little- known. Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs) are pivotal in liver inflammation repair .Their plasma levels might assess long term LF changes after therapy. Overall 374 HCV-infected adult patients, 214 HCV-HIV coinfected, were followed-up for 24 months after starting DAA. LF was assessed by transient elastometry (TE), biochemical indexes (APRI, Forns, FIB-4) and, in 61 individuals, by MMPs and TIMP-1 plasma levels. Several MMPs and TIMP-1 SNPs were genotyped in 319 patients.TE was better than biochemical indexes for early and long-term LF monitoring. MMPs-2,-8,-9 and-TIMP-1 levels and TE displayed parallel decreasing curves although only TIMP-1 correlated with TE (P=0.006) and biochemical indexes (P<0.02). HCV monoinfected had significantly higher baseline LF and TIMP-1 plasma levels, but lower MMPs levels than coinfected patients or between different DAA regimens. Only the MMP-2 (-1306 C/T) variant TT genotype associated with higher degrees of fibrosis LF regression extends 24 months after therapy. TE and TIMP1 are the most reliable LF-monitoring tools. LF courses were similar in mono- and coinfected patients, DAA regimens type did not influence fibrosis course.