Outcome of Sustained Virological Responders (SVR) and Non-responders in the Hepatitis C Antiviral

Outcome of Sustained Virological Responders (SVR) and Non-responders in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial

Reported by Jules Levin
AASLD Oct 31-Nov 3 2009, Boston, MA

T. R. Morgan1, 2; M. G. Ghany6; H. Kim3; K. K. Snow3; K. Lindsay5; A. S. Lok4

1. VA Medical Center 11, Long Beach, CA, USA.

2. University of California, Irvine, CA, USA.

3. New England Research Institute, Boston, MA, USA.

4. University of Michigan, Ann Arbor, MI, USA.

5. University of Southern California, Los Angeles, CA, USA.

6. NIDDK/NIH, Bethesda, MD, USA.




Retrospective studies have suggested that subjects with chronic hepatitis C (CHC) and advanced fibrosis who achieve an SVR have a lower risk of developing hepatic decompensation and hepatocellular carcinoma (HCC). However, most of these studies had a short duration of follow up and none was performed in a US population. The HALT-C trial was a prospective study to determine whether low dose peginterferon could prevent liver disease progression in non-responders with CHC.

Aim: To compare the rate of clinical outcomes between patients who achieved an SVR during the lead-in phase of HALT-C and non-responders in the control arm of the randomized phase.

Methods: We attempted to determine liver-related outcomes (decompensation, HCC or death) on all SVR patients (n=180). Consenting SVR patients had a physical exam, blood tests and an ultrasound (US) or were interviewed by phone. Non-responders (n=309) were evaluated every 3 months for 3.5 years and then every 6 months.

Results: Data were obtained on 140 (78%) SVR patients (105 in-person, 32 by phone interview and 3 who had died). Median follow up for SVR patients was 85.8 months (range: 68.0 to 101.1), and for control patients 78.4 months (range: 11.7 to 102.8). At study entry, SVR patients were less likely to have cirrhosis or genotype 1 infection, and had higher platelet counts, ALT and albumin compared to non-responders. One SVR patient had relapse of viremia.

SVR patients had a significant improvement in platelet counts, albumin and ALT from baseline to last follow-up while non-responders had a significant decrease in platelet counts and albumin and an increase in bilirubin.

Four (2.9%) SVR patients developed 5 clinical outcomes (1 liver related death, 2 HCCs and 2 variceal hemorrhages) compared to 102 clinical outcomes (20 liver related deaths, 20 HCCs and 62 decompensation events) in 68 (22%) control patients.

By life-table analysis, the cumulative rate of the first clinical outcome in the SVR versus the control patients at 2.5, 5 and 7.5 years was 0%,1.4% and 3.7% vs. 4.6%, 15.2% and 27.7%, respectively (p < 0.0001).

The adjusted hazard ratio (HR) for time to development of the first clinical outcome was significantly higher in non-responder controls than SVR patients (HR = 7.09, 95% CI: 2.56-19.6).

Conclusion: Patients with advanced CHC who achieve an SVR remain at risk for development of hepatic decompensation and HCC, although this risk is markedly lower compared to non-responders. These results highlight the long-term clinical benefit of achieving an SVR but also underscore the importance of continued monitoring of persons with advanced CHC who achieve an SVR.