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New Hepatitis C Drugs Reduce Mortality Risk in First 18 Months After Treatment

For the first time, a large study has demonstrated that treatment with direct-acting antivirals (DAAs) significantly reduces mortality among people with hepatitis C virus (HCV) infection, according to a recent report in Clinical Infectious Diseases.

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The study matched people who received therapy with interferon-free all-DAA regimens with untreated control subjects. Mortality rates in the first 18 months after therapy were significantly lower among individuals who received DAAs. After controlling for other factors, treatment with DAAs was associated with a 57% reduction in the risk of death.

"To our knowledge, this is the first large-scale study to demonstrate the effect of newer DAA regimens upon survival," Adeel Butt and coauthors wrote. "Treatment with 2 commonly used DAA regimens…was associated with significant improvements in survival within the first 18 months of treatment, compared with demographically and clinically similar untreated HCV-infected controls."

DAAs have revolutionized the treatment of people with hepatitis C, with all-oral regimens achieving sustained virological response (SVR) -- or cure -- rates in excess of 90% in clinical trials. Successful treatment with DAAs in routine care has already been shown to be associated with a lower risk of liver fibrosis progression. However, the survival benefit from successful DAA therapy has never before been examined in a large study.

A recent Cochrane Collaboration systematic review concluded that, due to the lack of long-term follow-up studies, there was no evidence that DAAs prolonged life or reduced liver-related illness in people who achieved SVR with DAA treatment.

The Cochrane review has been strongly criticized by liver expert associations in the U.S. and Europe for ignoring the short-term nature of the DAA studies designed for regulatory registration and for ignoring previous evidence from the treatment of hepatitis C, which showed that achieving SVR with interferon-based treatment was associated with a reduction in the risk of death and liver disease.

Investigators used data from ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) to compared survival between people treated with one of two all-DAA regimens -- paritaprevir/ritonavir/ombitasvir/dasabuvir (Viekira) and sofosbuvir/ledipasvir (Harvoni) -- and matched untreated controls.

Individuals with HIV, hepatitis B virus, and liver cancer were excluded from the study, as were people without baseline HCV viral load measurements or FIB-4 measurements of liver disease.

The study populations consisted of 6970 people treated for at least 14 days (5497 of whom received sofosbuvir/ledipasvir) and an equal number of untreated HCV-infected controls.

Median age was approximately 61 years and approximately 96% of individuals were male. 94% of those treated with sofosbuvir/ledipasvir and 90% of those treated with the paritaprevir-based regimen achieved SVR.

There were some significant differences between the treated individuals and the controls. Those receiving DAAs were more likely to be obese and to have liver cirrhosis, but less likely to have serious kidney disease, drug or alcohol dependence, or anemia.

During the first 18 months of follow-up, mortality was significantly higher among the untreated controls (2.5%) compared to either treatment group (0.3% paritaprevir-based, 1.4% sofosbuvir/ledipasvir).

Treatment with either regimen was associated with a 57% reduction in mortality (hazard ratio [HR] 0.43%). Comparison between individuals who received therapy showed that attainment of SVR was associated with a 43% reduction in the risk of mortality (HR 0.57).

Between 17% and 20% of treated people had a history of drug or alcohol use disorders. This was not associated with lower chances of survival. "Our results suggest that a history of these conditions should not deter providers from initiating treatment," commented the investigators.

"Treatment for HCV with either [the paritaprevir-based regimen] or [sofosbuvir/ledipasvir] and attainment of SVR are associated with a significant reduction in mortality, a benefit that is seen within the first 18 months of treatment," the authors concluded. "“Benefits of treatment at a population level are expected to be substantial.”

8/17/17

Source

AA Butt et al. Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared with Untreated Hepatitis C Virus-Infected Persons: Results from ERCHIVES. Clinical Infectious Diseases. July 20, 2017 (online ahead of print).