DAAs for chronic HCV reduce mortality, HCC risk
Patients with chronic hepatitis C virus (HCV) infection who are treated with direct-acting antivirals (DAAs) have a reduced risk of all-cause mortality and hepatocellular carcinoma (HCC), according to results of an observational French study.
“We saw a reduction of risk for complications related to the disease, and to mortality, and believe this treatment should be considered for all patients with chronic hepatitis C infection,” said study lead author Professor Fabrice Carrat of the Sorbonne Université, Paris, France.
The multicentre, prospective study involved 9,895 adults with chronic HCV infection (median age 56 years, 53 percent male), 7,344 of whom received treatment with DAAs during the 33.4-month follow-up period. Individuals previously treated with interferon-ribavirin, those with chronic hepatitis B, or with a history of decompensated cirrhosis, liver transplantation, or HCC were excluded. A total of 3,045 patients had cirrhosis at baseline.
Patients who received treatment with DAAs were more likely to have cirrhosis than those not treated with DAAs (42 percent vs 10 percent), as well as comorbidities such as diabetes (13 percent vs 8 percent) and arterial hypertension (30 percent vs 24 percent).
A total of 218 deaths – 73 of which were liver-related – occurred over the follow-up period (129 and 89 in treated and untreated patients, respectively), 258 incidences of HCC (187 and 71 in treated and untreated patients, respectively), and 106 cases of decompensated cirrhosis (74 and 32 in treated and untreated patients, respectively). Seventy-six percent of patients who initiated DAA treatment achieved sustained virological response (SVR).
The risk of all-cause mortality was reduced among patients who were treated with DAAs compared with those who were untreated (adjusted hazard ratio [adjHR], 0.48, 95 percent confidence interval [CI], 0.33–0.70; p=0.0001), be it liver-related (adjHR, 0.39, 95 percent CI, 0.21–0.71; p=0.0020) or non-liver-related mortality (adjHR, 0.60, 95 percent CI, 0.36–1.00; p=0.048). [Lancet 2019;doi:10.1016/S0140-6736(18)32111-1]
Patients who received treatment with DAAs also had a reduced risk of developing HCC compared with untreated patients (adjHR, 0.66, 95 percent CI, 0.46–0.93; p=0.018). There was no association between exposure to DAAs and the incidence of decompensated cirrhosis (adjHR, 1.14, 95 percent CI, 0.57–2.27; p=0.72).
Factors affecting HCC risk included, among others, older age (adjHR, 3.47 for age ≥64 vs <50 years), HCV genotype 3 (adjHR, 2.27) and 5, 6, or 7 (adjHR, 1.93 vs type 1), higher fibrosis score (adjHR, 15.3 for F4 vs F0, F1, or F2), and hypertension (adjHR, 1.44), while factors which increased the risk of all-cause mortality included older age (adjHR, 2.02 for age ≥64 vs <50 years), higher fibrosis score (adjHR, 3.69 for F4 vs F0, F1, or F2), hypertension (adjHR, 1.51), anaemia (adjHR, 2.45), and low BMI (adjHR, 2.57 for <18.5 vs ≥18.5 to <25 kg/m2).
Patients who achieved SVR following DAA treatment had lower risks for all-cause, liver-, and non-liver-related mortality, and HCC compared with untreated patients, while those who did not achieve SVR had an elevated risk of developing HCC (adjHR, 2.23, p=0.0012), though there was no risk for HCC while patients were on treatment (adjHR, 0.74; p=0.17).
Among patients with cirrhosis, DAA treatment was associated with reduced risks of all-cause mortality (adjHR, 0.34; p<0.0001), liver-related mortality (adjHR, 0.28; p=0.0001), non-liver-related mortality (adjHR, 0.40; p=0.015), and HCC (adjHR, 0.57; p=0.0016).
Despite the inability to establish cause and effect due to the observational study design, the researchers suggested that the SVR brought about by DAAs may have led to a decrease in liver damage and inflammation, and subsequently liver regeneration, which could have reduced the risks for liver-related complications including HCC. “Our results showing strikingly different risks for these liver-related events in patients with and without a SVR support these mechanisms,” they said.
“[This study] offers substantive evidence that cure of HCV delivered by all-oral DAA regimens is associated with clinical benefits,” said Drs Jacinta Holmes, Stephanie Rutledge, and Raymond Chung from Harvard Medical School, Boston, Massachusetts, US, in a commentary. [Lancet 2019;doi:10.1016/S0140-6736(18)32326-2]
“They also provide the best evidence to date to support guidance documents that recommend DAA treatment for all patients with chronic HCV infection,” they added.