Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study

초록

Background It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon -based treatments. Disease burden was the primary outcome, as represented by disability -adjusted life years (DALYs). Improvement in fi brosis after DAA treatment was assessed using APRI, FIB -4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment signi fi cantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35 - 1.31] - 0.33 [0.23 - 0.52], p < 0.0001), FIB -4(median 2.42 [IQR, 1.48 - 4.40] - 1.93 [1.31 - 2.97], p < 0.0001), and liver LS -based fi brosis (median 7.4 [IQR, 5.3 - 12.3] - 6.2 [4.6 - 10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6 - 52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was signi fi cantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB -4based DALY estimate (median 5.43 [IQR, 3.00 - 6.44] vs. 5.79 [3.85 - 8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40 - 60 years. In multivariable analyses, the DAA group had a signi fi cantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% con fi dence interval (CI), 0.34 - 0.48], 0.31 [95% CI, 0.30 - 0.38], and 0.22 [95% CI, 0.17 - 0.27], respectively; p < 0.0001). Interpretation Our fi ndings suggest that DAA treatment is associated with the improvement of liver -related outcomes and a reduction of liver fi brosis -based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fi brosis -based disease burden beyond noninvasive tests.

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