DAA Treatment Improves Liver-Related Outcomes, Reduces Fibrosis Burden in HCV

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Findings from a recent study suggest treatment with direct-acting antivirals (DAAs) may be associated with improvements in liver-related outcomes and a reduction of fibrosis-based disease burden in patients with hepatitis C virus (HCV) infection.¹

The study recruited patients from 29 tertiary institutions in South Korea and found that along with improved fibrotic burden, DAA treatment was independently associated with a decreased risk of hepatocellular carcinoma (HCC), decompensation, and mortality, underscoring the importance of early detection and treatment for reducing fibrosis-based disease burden and improving clinical outcomes.¹

“Early detection and effective treatment would mean fewer complications, better health outcomes, and enhanced quality of life,” Seungbong Han, PhD, an associate professor in the department of biostatistics at Korea University, said in a press release.¹ “Successful strategies could serve as models for other countries with high hepatitis C prevalence, leading to global improvement in hepatitis C management.”

According to the World Health Organization, globally, an estimated 50 million people have chronic HCV infection, with about 1 million new infections occurring per year. Although there is no effective vaccine against HCV, DAAs can cure more than 95% of persons with infection.³ Previous research has shown the use of DAAs is associated with a reduced risk of liver-related events, but little is known whether DAA treatment improves disease burden.¹

To investigate the effect of DAA treatment on disease burden in patients with HCV infection, investigators conducted a nationwide, multicenter, retrospective cohort study of patients with chronic HCV at 29 tertiary academic institutes in South Korea between January 1, 2007, and February 17, 2022. The study included untreated patients and DAA-treated patients but excluded those with a history of interferon-based treatments. Since DAAs were introduced in South Korea in December 2014, patients in the DAA group were recruited between January 1, 2015, and February 17, 2022, whereas those in the untreated group were recruited between January 1, 2007, and February 17, 2022.¹

Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using aspartate aminotransferase to platelet ratio index (APRI), FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were HCC, decompensation, and mortality.¹

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 analyzed. Among the cohort, the median age was 59.8 (IQR, 51.1–69.2) years and 44.2% of patients were male.¹

Investigators noted patients in the untreated group were older than those in the DAA group (60.6 vs 59.5; P = .027) and more likely to be male (47.1% vs 43.1%; P <.0001). The median APRI (0.76 vs 0.64; P <.0001), FIB-4 index (2.66 vs 2.42; P <.0001), and LS (7.9 vs 7.4 kPa; P = .012) were greater in the untreated group than in the DAA group.¹

In total, 95.8% of patients with chronic HCV in the DAA group achieved SVR12, defined as undetectable HCV RNA 12 weeks after the end of treatment. Investigators pointed out DAA treatment significantly improved APRI- (median 0.64–0.33; P <.0001), FIB-4- (median 2.42–1.93; P <.0001), and LS-based fibrosis (median 7.4 –6.2 kPa; P <.0001).¹

During a median follow-up of 27.5 (interquartile range [IQR], 10.6–52.4) months, 469 (4.0%) patients died, 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. Investigators noted the proportion of patients who experienced liver-related events, except for liver transplantation, during follow-up was significantly lower in the DAA group than in the untreated group.¹

Results showed the APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs 5.14 years; P <.0001), as was the FIB-4-based DALY estimate (median 5.43 vs 5.79 years; P <.0001).¹

Multivariable analysis showed male sex (hazard ratio [HR], 2.14, 95% CI, 1.80–2.55), older age (HR, 1.04; 95% CI, 1.03–1.05), diabetes mellitus (HR, 1.33; 95% CI, 1.12–1.58), significant alcohol consumption (HR, 1.54; 95% CI, 1.22–1.95), and cirrhosis (HR, 4.53; 95% CI, 3.82–5.37) were independently associated with an increased risk of HCC development, whereas DAA use was independently associated with a decreased risk (HR, 0.41; 95% CI, 0.34–0.48) (all P <.0001). Similarly, investigators noted the use of DAAs was independently associated with a decreased risk of decompensation (HR, 0.31; 95% CI, 0.26–0.37), mortality (HR, 0.22; 95% CI, 0.17–0.27), and the composite outcome (HR, 0.34; 95% CI, 0.30–0.38) (all P <.0001).¹

Investigators acknowledged the lack of histological information; limited transient elastography data; and the retrospective nature of the study as potential limitations to these findings.¹

“Our study can help improve public health, healthcare systems, and individual lives by encouraging the development of early intervention and effective treatment strategies for HCV infection,” Han concluded.²

References

1. ^{Sohn W, Park SU, Lee TH, et al. 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. eClinicalMedicine. doi:https://doi.org/10.1016/j.eclinm.2024.102671}
2. ^{Korea University. Korea University Offers New Breakthrough for Hepatitis C to Improve Life Expectancy. Accessed August 20, 2024. https://medicine.korea.ac.kr/en/news/research/list.do}
3. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed August 20, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}