1. www.ias2015.org Liver fibrosis regression after anti HCV therapy and the rate of death, liver-related death, liver- related complications, and hospital admissions in HIV / HCV coinfected patients with cirrhosis J.L. Casado, S. Bañon, C. Quereda, A. Moreno, M.J. Perez-Elías, S. Moreno Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain Session TUAB 02 HCV: The Good News Continues Abstract TUAB 0204

2. www.ias2015.org Introduction Cumulative evidence demonstrates that SVR is associated with a lower rate of death and liver related complications 1,2. However, in spite of a lower risk, patients with cirrhosis are not entirely protected against the development of liver complications or HCC after SVR 3,4. We and others have found an important rate of fibrosis regression (FR) during the follow-up of HIV/HCV-co-infected patients with SVR 5. In hypothesis, FR after SVR in patients with cirrhosis should be associated with even a lower risk of hepatic complications, and a prolonged survival. 1 Mira JA, et al. Clin Infect Dis 2013;56:1646-1653. 2 Berenguer J, et al. Hepatology. 2009;50:407-413 3 Merchante et al. Clin Infect Dis 2013;56:143-150; 4 Aleman S et al. Clin Infect Dis 2013;57:230-236. 5 Casado JL, et al. J Viral Hepat 2013;20:829-837.

3. www.ias2015.org Objective To determine the impact of FR and/or SVR on the clinical outcome of HIV/HCV co-infected patients with cirrhosis, in terms of: – Overall death, – Liver-related death, and – Liver-related complications

4. www.ias2015.org Methods (I) Observational cohort study at the Hospital Ramón y Cajal, in Madrid. Inclusion criteria: – All HIV/HCV coinfected patients who received therapy with pegylated interferon and ribavirin since 2004 – Baseline liver biopsy or transient elastography (TE) – Followed up by TE beginning in 2006. Fibrosis regression was defined as a confirmed reduction of at least one point in Fibrosis Metavir Score during the follow-up, without worsening in a successive TE, if available.

5. www.ias2015.org Methods (II) Primary end-points were death from any cause and liver- related death. – The time to the event was the length of time since the end of antiviral therapy until the primary endpoint. Secondary end-points were the development of a liver- related complication (ascites, encephalopathy, GI bleeding, HCC) and the number of hospital admissions. – Liver transplantation was considered as a liver-related endpoint. For patients who did not die or were not transplanted, the analysis was censored at July 2014.

6. www.ias2015.org Methods (III) Cumulative incidence curves of liver mortality and liver- related complications according to response and fibrosis regression were plotted using the Kaplan-Meier method. The differences between groups were assessed using log- rank tests. A multivariate Cox model was used to assess the independent effect of variables on the development of events during the follow-up.

7. www.ias2015.org Baseline characteristics 1 92 patients with baseline liver biopsy 2 41 patients with baseline TE

8. www.ias2015.org Fibrosis Regression according to SVR

9. www.ias2015.org SVR, Fibrosis Regression and Outcomes TE, transient elastography; L-R, liver related; IR, incidence rate

10. www.ias2015.org Overall Death and Liver-related Death according to SVR/FR Liver- related death Overall death

11. www.ias2015.org Overall Death and Liver-related Death according to SVR and FR Overall deathLiver- related death

12. www.ias2015.org Cox Regression Analysis Factors associated with Outcome

13. www.ias2015.org Conclusions Our study clarifies the risk of complications after therapy in HIV- infected patients with cirrhosis, showing a lower rate if fibrosis regression is attained in addition to SVR. Moreover, we demonstrate that the histological benefit is clearly associated with the lowest risk of any-cause death, liver-related death, and hospital admissions. Of clinical application, LSM is useful in demarcating cirrhotic patients at a high risk for complications after therapy, and who would require a more frequent check-up. Sequential LSM after therapy could be useful in the management of the patients, irrespective of achieving SVR.