DAA therapy and long-term hepatic function in advanced/decompensated cirrhosis: Real-world experience from HCV-TARGET cohort

Elizabeth C. Verna, Giuseppe Morelli, Norah A. Terrault, Anna S. Lok, Joseph K. Lim, Adrian M. Di Bisceglie, Stefan Zeuzem, Charles S. Landis, Paul Kwo, Mohamed Hassan, Michael P. Manns, Monika Vainorius, Lucy Akushevich, David R. Nelson, Michael W. Fried, K. Rajender Reddy

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Abstract

Background & Aims: Direct-acting antiviral (DAA) therapy is used in patients with HCV-related decompensated cirrhosis with the expectation of improving hepatic function. However, little is known about the long-term hepatic benefit of successful antiviral treatment. Methods: Patients with advanced/decompensated cirrhosis (model for end-stage liver disease [MELD] ≥10), in whom NS5A-containing DAA therapy was initiated prior to September 2018, were included (from the HCV-TARGET cohort). Treatment outcomes and the impact of treatment on short-term and long-term hepatic function were examined. Results: A total of 642 patients were analyzed. The mean age was 60 years, 68% were male. The median baseline MELD was 12 (range 10–39) and 64% had prior decompensation. Among patients with available virologic outcomes, 90.5% achieved a sustained virologic response at 12 weeks (SVR12). Eighty (24%) patients achieved a clinically significant decrease in MELD by ≥3 points during short-term follow-up (9–26 weeks after the end of treatment). However, in long-term follow-up (median of 4 years after treatment), mean changes in MELD (−0.30 points), total bilirubin (+0.23 mg/dl) and albumin (+0.36 g/dl) were marginal. Fifty-one patients died and 22 underwent liver transplant. In long-term follow-up, a clinically meaningful decrease in MELD of ≥3 occurred in 29% and a final MELD score of <10 was achieved in 25%. Conclusion: In a large real-world experience of patients with advanced/decompensated HCV-related cirrhosis treated with DAAs, there were only marginal improvements in MELD, total bilirubin, or albumin at long-term follow-up (after achieving SVR12). These patients may remain at high risk of decompensation and must continue to be closely monitored. ClinicalTrials.gov: NCT01474811. Lay summary: Hepatitis C virus infection can now be cured with medications, even in patients who have advanced scarring of the liver (cirrhosis). In this study, we evaluated whether liver function improves or deteriorates in the long-term, following successful treatment of hepatitis C in patients with cirrhosis. We found that overall liver function was relatively stable with only 29% of patients achieving a clinically meaningful improvement in liver function, and we therefore believe that these patients require ongoing monitoring.

Original languageEnglish (US)
Pages (from-to)540-548
Number of pages9
JournalJournal of Hepatology
Volume73
Issue number3
DOIs
StatePublished - Sep 2020

Keywords

  • Decompensated liver disease
  • HCV therapy
  • MELD score

PubMed: MeSH publication types

  • Journal Article

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    Verna, E. C., Morelli, G., Terrault, N. A., Lok, A. S., Lim, J. K., Di Bisceglie, A. M., Zeuzem, S., Landis, C. S., Kwo, P., Hassan, M., Manns, M. P., Vainorius, M., Akushevich, L., Nelson, D. R., Fried, M. W., & Reddy, K. R. (2020). DAA therapy and long-term hepatic function in advanced/decompensated cirrhosis: Real-world experience from HCV-TARGET cohort. Journal of Hepatology, 73(3), 540-548. https://doi.org/10.1016/j.jhep.2020.03.031