Age, Baseline Fibrosis Can Predict Fibrosis Regression with DAA Use

More than half of patients with hepatitis C virus (HCV) in a recent study experienced fibrosis regression after treatment with direct-acting antivirals (DAAs), with improvement linked to age and advanced fibrosis at baseline.

“The development of DAAs and transition to interferon-free oral treatment with high efficacy and a low rate of adverse events revolutionized the treatment of HCV,” wrote investigators.¹ “The updated literature has shown improvements in liver fibrosis after treatment with DAAs.”

An estimated 58 million people have chronic HCV globally, with about 1.5 million new infections occurring every year. According to the World Health Organization, DAAs can cure more than 95% of people with HCV.²

To assess changes in fibrosis after treatment with DAAs and determine factors associated with fibrosis regression, Naim Abu-Freha, MD, gastroenterologist at the Institute for Gastroenterology and Liver Diseases at Soroka University Medical Center in Israel, and a team of investigators collected retrospective data for 209 patients from Soroka University Medical Center diagnosed with HCV and treated with DAAs at least 3 years prior to the study. An updated assessment of liver fibrosis severity and stage was performed using Fibroscan vibration-controlled transient elastography and compared to data from the time of treatment onset. Investigators also collected Fibrosis-4 and Aspartate Transaminase to Platelet Ratio Index (APRI) scores at the time of treatment and compared them to the values calculated during the process of data collection.¹

Among the cohort, the average age was 58.02 (standard deviation [SD], 11.3) years and 56% of patients were male. Genotype 1 was most common, with 34 (16.3%) patients having genotype 1a and 121 (57.9%) patients having genotype 1b. Genotype 3 was present in 38 (18.2%) patients, while genotypes 2a and 4a had a low rate of prevalence (4% and 2%, respectively).¹

At the time of treatment, liver fibrosis severity was ≤ 7 kPa (F0–F1) in 25.4% of patients, > 7 kPa (F2) in 26.8% of patients, > 9.6 kPa (F3) in 18.2% of patients, and > 14.6 kPa (F4) in 29.7% of patients. In the updated liver fibrosis assessment, investigators found 69.9% of patients were F0–F1, 10.5% were F2, 7.7% were F3, and 12% were F4. No changes in liver fibrosis were observed for 35.9% of patients from the time of treatment to the updated assessment. Investigators pointed out liver fibrosis regression in 56.9% of patients, with improvement from F3/F4 at treatment to F2 or less during the study observed among 27.8% of participants. Fibrosis progression was seen among 7.1% of the cohort.¹

Significant improvements in liver enzymes were observed in the updated fibrosis assessment compared to the time of treatment. The mean alanine transaminase significantly decreased from 64.9 (SD, 47) at the time of treatment to 20.5 (SD, 12.2) at time of the study (P < .001), while aspartate transaminase decreased from 60.6 (SD, 39) to 29 (SD, 29) (P < .001), gamma-glutamyltransferase from 74 (SD, 71.4) to 35.6 (SD, 36.1) (P < .001), and alkaline phosphatase from 91.1 (SD, 31.7) to 79.3 (SD, 43.3) (P < .001). Investigators also noted improvement in the APRI score after HCV treatment, with an average decrease from 1.4 (SD, 1.7) to 0.93 (SD, 2.4) (P = .028).¹

In the univariate analysis, the following factors were associated with liver fibrosis regression:

• Age at the time of the study (odds ratio [OR], 1.027; 95% confidence interval [CI], 1.002–1.052; P = .038)
• Age at the time of treatment (OR, 1.029; 95% CI, 1.003–1.055; P = .031)
• Age at diagnosis (OR, 1.026; 95% CI, 1.003–1.051; P = .029
• Male gender (OR, 1.948; 95% CI, 1.116–3.399; P < .019)
• Fibrosis stage (OR, 2.209; 95% CI, 1.716–2.845; P < .001)

Of note, investigators pointed out only age at the time of treatment (OR, 1.359; 95% CI 1.055–1.751; P = .017) and fibrosis stage (OR, 2.555; 95% CI, 1.864–3.503; P < .001) remained statistically significant in multivariate analysis.¹

“Liver fibrosis regression was observed in most HCV patients treated with DAAs,” concluded investigators.¹ “Patients with HCV should be encouraged for treatment with DAA treatment.”

References:

1. Abu-Freha N, Abu-Kosh O, Yardeni D, et al. Liver Fibrosis Regression and Associated Factors in HCV Patients Treated with Direct-Acting Antiviral Agents. Life (Basel). 2023;13(9):1872. Published 2023 Sep 5. doi:10.3390/life13091872
2. World Health Organization. Hepatitis C. Newsroom. July 18, 2023. Accessed October 10, 2023. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c