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AASLD 2014: Sustained Response to HCV Treatment Reduces Mortality, Liver Cancer, Liver Transplants

People who achieve sustained virological response (SVR) when treated with interferon-based therapy for hepatitis C have a lower risk of death, are less likely to develop liver cancer, and need fewer liver transplants than those who were treated but not cured, according to results from a meta-analysis of more than 34,000 patients presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting this week in Boston.

While more research is needed to confirm these findings, benefits are likely to be even greater for hepatitis C patients treated with interferon-free direct-acting antivirals (DAAs), which produce higher cure rates generally above 90%.

Previous studies have shown that SVR -- or continued undetectable HCV viral load after completion of treatment -- reduces the risk of hepatocellular carcinoma (HCC), liver transplantation, liver-related death, and all-cause mortality, but findings have been inconsistent and many of these studies have been small.

To learn more about how SVR affects long-term outcomes, Andrew Hill from the University of Liverpool and colleagues performed a meta-analysis of data from 34,563 people treated for chronic hepatitis C. Combined data were used to calculate 5-year risk of all-cause mortality, HCC, and liver transplantation. They also looked at rates of HCV reinfection after treatment.

The cost-effectiveness of hepatitis C treatment depends not on achieving undetectable HCV RNA per se -- although this would reduce the risk of onward transmission -- but rather on reducing the occurrence of liver cancer, need for liver transplantation and all-cause mortality.

The researchers searched the MEDLINE and EMBASE databases for studies comparing outcomes among treated hepatitis C patients with SVR at 24 weeks post-treatment (SVR24) versus those who were not cured. Typically, the regimen used was pegylated interferon plus ribavirin -- the old standard of care before the advent of direct-acting antivirals. (SVR12 is now considered to be a cure in studies of DAAs.)

The investigators looked at people with HCV monoinfection overall, HCV monoinfected patients with liver cirrhosis, and HIV/HCV coinfected individuals. Although they attempted to compare results from univariate and multivariate analysis to control for confounding factors, multivariate data often were not available.

Results

• Looking at a subset of all-cause mortality studies with multivariate and univariate data:

o   Risk of death due to any cause fell by 71% for HCV monoinfected people who achieved SVR in univariate analyses, or 62% in multivariate analyses, relative to those without SVR;

o   Among HCV monoinfected patients with cirrhosis, all-cause mortality dropped by 73% in univariate analyses and by 84% in multivariate analyses;

o   Among HIV/HCV coinfected people, all-cause mortality risk reductions were 75% and 73%, respectively.

• The 5-year all-cause mortality risk analysis included 18 studies of HCV monoinfected people (29,269 total participants, average follow-up 4.6 years), 9 studies of HCV monoinfected patients with cirrhosis (2734 participants, average follow-up 6.6 years), and 5 studies of HIV/HCV coinfected people (2560 participants, average follow-up 5.1 years):

o   All-cause death rates were 4.5% among all HCV monoinfected people who achieved SVR, compared to 10.5% among those without SVR;

o   Death rates were 3.6% among HCV monoinfected patients with cirrhosis who achieved SVR versus 11.3% without SVR;

o   Death rates were 1.3% with SVR versus 10.0% without SVR among HIV/HCV coinfected people.

• The 5-year liver cancer risk analysis included 21 studies of HCV monoinfected people (12,496 total participants, average follow-up 6.1 years), 18 studies of HCV monoinfected people with cirrhosis (4987 participants, average follow-up of 6.6 years), and 3 HIV/HCV coinfection studies (2085 participants, average follow-up 4.7 years):

o   The risk of developing HCC was 2.9% among all HCV monoinfected people who achieved SVR, compared to 9.3% among those without SVR;

o   HCC rates were 5.3% among cirrhotic HCV monoinfected patients with SVR versus 13.9% without SVR;

o   HCC rates were 0.9% with SVR versus 10.0% without SVR among HIV/HCV coinfected patients.

• The 5-year liver transplant risk analysis included just 1 study of HCV monoinfected people (108 participants, average follow-up 4.2 years), 2 studies of HCV monoinfected cirrhotic people (1046 participants, average follow-up 7.7 years), and 2 HIV/HCV coinfection studies (2039 participants, follow-up 4.9 years):

o   None of the HCV monoinfected people with SVR needed a liver transplant, compared with 2.2% of those who were not cured;

o   Transplant rates were 0.2% among HCV monoinfected cirrhotics with SVR, rising to 7.3% without SVR;

o   Transplant rates were 0.6% with SVR and 2.7% without SVR among coinfected patients.

• Turning to reinfection after achieving SVR, there was a "marked difference" across the 3 populations analysed:

o   Reinfection was rare, at 0.9%, among people considered low-risk (24 studies, 6046 participants, 4.1 years average follow-up);

o   The reinfection rate rose to 8.2% in a higher-risk group of prisoners and people who inject drugs (16 studies, 1203 participants, 5.0 years average follow-up);

o   The reinfection rate was much higher, at 23.6%, among HIV/HCV coinfected people (10 studies, 1106 participants, 3.1 years average follow-up).

Hill noted that many of the coinfected patients were men who have sex with men. Starting around the year 2000, outbreaks of apparently sexually transmitted HCV infection have been widely reported among HIV-positive gay and bisexual men in cities in Europe, the U.S. and Australia. He said this analysis could not provide details about specific risk factors, but the highest reinfection rate was seen among coinfected people who also injected drugs.

With regard to the limitations of this meta-analysis, Hill noted that people with SVR and those who are not cured may differ in baseline characteristics, so more multivariate data are needed. He also stressed that these findings are from studies of interferon-based treatment, and long-term outcome data are not yet available for people treated with direct-acting antivirals.

In this analysis of data from 34,563 patients treated for hepatitis C, achieving SVR was associated with 62%-84% reductions in all-cause mortality, 68%-79% reductions in the risk of developing HCC, and a 90% reduction in liver transplantation, the researchers summarized.

However, they added, "there was a significant risk of subsequent re-infection after SVR in some studies, which could reverse these benefits of treatment."

11/10/14

Reference

A Hill, J Saleem, KA Heath, et al. Effects of Sustained virological response (SVR) on the risk of liver transplant, hepatocellular carcinoma, death and re-infection: meta-analysis of 129 studies in 23,309 patients with Hepatitis C infection. American Association for the Study of Liver Diseases (AASLD) Liver Meeting. Boston, November 7-11, 2014. Abstract 44.