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DAA therapy for HCV patients without serious liver disease has significant survival benefits

Michael Carter
26 July 2018

Successful HCV treatment with direct-acting antivirals (DAAs) significantly reduces the risk of death for people who do not have advanced liver disease, investigators report in Hepatology. A sustained virologic response (SVR) reduced mortality risk by up to two-thirds. The observational study involved over 40,000 US military veterans.

“This study provides the strongest and most direct evidence yet that treatment of HCV infection in patients without advanced liver disease results in significant clinical benefits,” comment the authors. “We provide impetus to lift existing restrictions imposed by private and other public payers that restrict treatment to those with more advanced liver disease.”

The development of DAAs has revolutionised the treatment of HCV. However, their high cost has resulted in many healthcare providers limiting access according to clinical needs, prioritising people with advanced fibrosis or cirrhosis.

Investigators from the US Department of Veterans Affairs (VA) – the largest provider of HCV care in the US – wanted to see if providing DAA therapy to people without significant liver damage had benefits in terms of a reduction in the risk of all-cause mortality.

The VA treats all people with HCV, regardless of the stage of liver disease, and there has been a rapid uptake of DAAs by VA healthcare providers and patients.

The study population consisted of approximately 40,000 people with HCV without significant liver disease who were treated with DAAs between early 2014 and March 2017. An untreated comparison group comprised approximately 63,000 people with HCV who likewise did not have any evidence of serious liver disease.

All the participants had mono-infection and carried HCV genotypes 1, 2 or 3. The absence of severe liver disease was defined as FIB-4 <3.25, no cirrhosis, no history of decompensated liver disease and no liver transplantation.

Of the DAA-treated people, a little below 97% attained an SVR; the other 3% did not attain SVR.

Mortality rates during follow-up were 1.6% for SVR patients, 3.6% for non-SVR patients and 5% for the untreated controls.

The mortality rate (per 100 person-years of follow-up) for SVR patients of 1.18 was significantly lower than the 2.84 observed in non-SVR patients and the 3.84 seen in the untreated comparison group (both comparisons, p < 0.001).

The survival benefit of SVR was also apparent when mortality risk was compared according to baseline cirrhosis. SVR patients with FIB-4 < 1.45 and 1.45-3.25 had 46% (p = 0.036) and 63% (p < 0.001) reductions in mortality rates, respectively, compared to non-SVR patients. The benefits were even more pronounced when compared to patients who did not receive DAAs, the mortality risk reduced by 67% for FIB-4 > 1.45 (p < 0.001) and 71% for FIB-4 < 1.45 (p < 0.001), respectively.

A final analysis took into account baseline demographics, clinical characteristics and the presence of co-morbidities. This showed that SVR reduced mortality risk by 66% (HR = 0.44; 95% CI, 0.32-0.59, p < 0.001) compared to non-SVR and by 68% (HR = 0.32; 95% CI, 0.29-0.36, p < 0.001) compared to no treatment. Non-SVR patients also had a significantly lower mortality risk than patients who did not receive treatment (HR = 0.74; 95% CI, 0.55-0.99, p = 0.049).

“Successfully treating HCV before the development of clinically apparent advanced liver disease translates into a significant mortality benefit,” conclude the authors. “Increasing access to DAAs for all HCV-infected individuals should result in fewer deaths.”

The author of an accompanying editorial notes that the study did not include information on the causes of death. She also highlights unexplained SVR-associated survival benefits in females compared to males and in black people compared to white people. However, she concludes that the study has important public health benefits, making a strong case for the provision of DAA therapy for people with HCV who do not have significant liver disease.  


Backus LI et al. Direct-acting antiviral sustained virologic response: impact on mortality in patients without advanced liver disease. Hepatology, online edition, 10.1002/hep.29811, 2018.

Serper, M. Direct acting antivirals for patients without advanced liver disease: all for treatment and treatment for all. Hepatology, online edition, 10.1002/hep.29873, 2018.