A large nationwide cohort study in South Korea found that treatment with direct-acting antivirals may reduce disease burden and improved clinical outcomes in patients with chronic hepatitis C virus infections.
In the study, published in eClinicalMedicine, investigators analyzed the data from 11,725 patients across 29 tertiary institutions between 2007 and 2022. The retrospective cohort study included 8,464 dirtect-acting antiviral (DAA)-treated and 3,261 untreated patients with chronic hepatitis C virus (HCV) The primary outcome was disease burden measured by disability-adjusted life year (DALY), calculated using disability weights for HCV stages and fibrosis measures. Secondary outcomes included hepatocellular carcinoma (HCC), decompensation, mortality, and a composite endpoint.
Baseline characteristics of the study population included a median age of 59.8 years (Interquartile range (QR) = 51.1–69.2), with 44.2% (n = 5,182) male patients. Cirrhosis was present in 22.5% (n = 2,635) of patients, and 14.8% (n = 1,482) reported significant alcohol consumption. The median HCV RNA level was 966,000 IU/mL (IQR = 134,338–3.3 million). HCV genotype distribution was 53.0% genotype 1 and 45.0% genotype 2.
Fibrosis was assessed using APRI score, FIB-4 index, and liver stiffness by transient elastography. At baseline, the median APRI was 0.67 (IQR = 0.36–1.39), median FIB-4 was 2.49 (IQR = 1.49–4.57), and median liver stiffness was 7.5 kPa (IQR = 5.3–12.5). Fibrosis stage distribution varied depending on the assessment method used.
Multiple imputation was used to address missing data. Propensity score matching and competing risk analysis were performed as sensitivity analyses.
DAA treatment was associated with a lower DALY burden compared to no treatment (median DALY_basic 9.19 vs 10.29 years, P < .0001). DAA use independently reduced risks of HCC by 59% (hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.34–0.48), decompensation by 69% (HR = 0.31, 95% CI = 0.26–0.37), and mortality by 78% (HR = 0.22, 95% CI = 0.17–0.27). Fibrosis measures improved significantly after DAA treatment, including APRI score (median = 0.64 to 0.33, P < .0001) and FIB-4 index (median = 2.42 to 1.93, P < .0001). DALY reduction with DAAs was most pronounced in patients aged 40 to 60 years.
After a median follow-up of 27.5 months, DAA treatment was associated with significant reductions in HCC (2.9% vs 10.5%), decompensation (2.5% vs 11.4%), mortality (1.4% vs 10.8%), and the composite outcome (5.7% vs 22.4%) compared with no treatment (all P < .0001).
Cumulative incidence of HCC at 4 years was 4.44% with DAAs vs 9.99% without (P < .0001). For decompensation, 4-year cumulative incidence was 3.60% vs 10.86% (P < .0001).
Detailed clinical outcomes included 586 cases (5.0%) of HCC, 18 cases (0.2%) of liver transplantation, 42 cases (0.4%) of hepatic resection, 580 cases (4.9%) of decompensation, and 469 cases (4.0%) of mortality.
Multivariable analysis showed DAA use independently reduced DALY_basic scores based on APRI (coefficient –0.15, P < .0001), FIB-4 (–0.10, P < .0001), and liver stiffness (–0.07, P = .0026). Results were consistent in propensity-matched analysis of 896 pairs, which showed significant risk reductions for HCC (HR = 0.51, 95% CI = 0.34–0.75, P = .0008), decompensation (HR = 0.35, 95% CI = 0.24–0.51, P < .0001), and mortality (HR = 0.41, 95% CI = 0.26–0.64, P = .0001) with DAA treatment.
The SVR12 rate with DAA therapy was 95.8%. Fibrosis stage improvement was seen across all measures, with the proportion of APRI-defined cirrhosis decreasing from 14.8% to 1.8% following treatment.
Subgroup analysis in patients with advanced fibrosis (FIB-4 > 3.25) showed lower DALYs in the DAA group compared with the untreated group (DALY_basic = 12.19 vs 12.61 years, P = .001; DALY_weighted = 5.74 vs 5.87 years, P = .003).
Age-stratified analysis revealed that the DALY reduction with DAAs was most pronounced in the 40 to 60 years age group. In this subgroup, APRI-based DALY_basic was 11.14 vs 12.65 years (DAA vs untreated, P < .0001) and FIB-4-based DALY_basic was 13.21 vs 14.02 years (DAA vs untreated, P < .0001).
Competing risk analysis for liver-related mortality showed 211 liver-related deaths in the untreated group compared with 45 in the DAA group, whereas liver-unrelated deaths were 142 and 71, respectively.
Independent risk factors for HCC development included male sex (HR = 2.14, 95% CI = 1.80–2.55, P < .0001), age (HR = 1.04 per year, 95% CI = 1.03–1.05, P < .0001), diabetes mellitus (HR = 1.33, 95% CI = 1.12–1.58, P = .0014), significant alcohol consumption (HR = 1.54, 95% CI = 1.22–1.95, P = .0003), and cirrhosis (HR = 4.53, 95% CI = 3.82–5.37, P < .0001).
The study had limitations, including its retrospective design and use of noninvasive fibrosis measures. The investigators noted that ultrasound-based cirrhosis diagnosis may be inaccurate. Additionally, mortality data was limited to in-hospital deaths because privacy regulations.