Effectiveness of direct-acting agents for chronic hepatitis C treatment in South America: a systematic review and meta-analysis.

The effectiveness of direct-acting agents (DAAs) for hepatitis C treatment in limited-resource settings remains unclear. We estimated the pooled sustained virological response rates of DAA therapy in South America. We searched online databases for studies that reported 12-weeks sustained virological response (SVR12) to hepatitis C virus (HCV) treatment in individuals living in South America. Pooled SVR12 in intention-to-treat (ITT) and per-protocol were estimated. Additionally, using all studies with available data, the pooled relative risk (RR) of SVR12 using a random-effects model (DerSimonian-Laird) was estimated to compare effectiveness of DAAs in patients with or without cirrhosis, HIV co-infection or previous HCV therapy. Heterogeneity was assessed using the I2 statistics. We identified 20 studies [14 manuscripts and 6 conference abstracts] comprising 7,393 individuals from five countries [Brazil (n=11), Argentina (n=4), Chile (n=1), Colombia (n=1) and Peru (n=1)] and two South-American collaborations. The pooled overall SVR12 rates [95% confidence interval (CI)] were 92.6% [90.2-94.7] and 95.5% [94.3-96.6] by ITT (11 studies; n=4,153; I2 =84.2%) and per-protocol analysis (15 studies; n=4,833; I2 =64.5%), respectively. The RR of SVR12 was similar in patients with or without HIV co-infection [4 studies; RR=1.03(0.99-1.07)] and those naive compared to treatment experimented-individuals [9 studies; RR=1.01(1.00-1.03)], but significantly higher in patients without cirrhosis compared to those with cirrhosis [11 studies; RR=1.04(1.02-1.05), p<0.001]. DAAs are highly effective for HCV treatment in South America. The use of DAAs should be considered in limited-resource settings to decrease the burden of liver disease in HCV-infected patients. PROSPERO[CRD 42019134603].