Abstract
Long term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) 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 declining curves although only TIMP-1 correlated with TE (P = 0.006) and biochemical indexes (P < 0.02). HCV monoinfected had significantly higher baseline NILFM and TIMP-1 plasma values, but lower MMPs levels than coinfected patients. No differences in NILFM course were observed between mono-and coinfected or between different DAA regimens. Only the MMP-2 (-1306 C/T) variant TT genotype associated with higher values of NILFM NILFM decline extends 24 months after therapy. TE and TIMP1 are reliable LF-monitoring tools. NILFM courses were similar in mono-and coinfected patients, DAA regimens type did not influence NILFM course.
Highlights
Long term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) after effective anti-Hepatitis C virus (HCV) Direct-acting antiviral agents (DAA) therapy are little- known
Among HIV/HCV co-infected patients the HIV viral load was undetectable in 74.6% of the patients at baseline and HIV undetectability increased to 88.3% at the 24th month measurement
Our study showed that non-invasive liver fibrosis markers (NILFM) decline is a continuous process lasting for at least the 24 months of follow-up after starting DAA therapy
Summary
Long term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) after effective anti-HCV DAA therapy are little- known. Matrix-metalloproteases (MMPs) and their tissueinhibitors (TIMPs) are pivotal in liver inflammation repair Their plasma levels might assess longterm LF changes after therapy. HCV monoinfected had significantly higher baseline NILFM and TIMP-1 plasma values, but lower MMPs levels than coinfected patients. Some authors consider TE the best tool for monitoring fibrosis regression following cure in DAA-treated HCV-HIV infected patients[19,20]. The routine use of non-invasive scores and liver stiffness measurements (LSM) by TE and other elastography methods following antiviral therapy in HCV-infected patients is currently not recommended to detect fibrosis by the European Association for the Study of the Liver (EASL) Clinical Practice Guidelines[21]. New tools to assess LF at long term after DAA therapy are needed, if linked to the pathogenic mechanisms underlying LF generation and regression
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