Reduction in the incidence of hepatitis C-related decompensated cirrhosis associated with national scale-up of direct-acting antiviral therapies targeting patients with advanced liver fibrosis

In Pakistan, the burden of the hepatitis C virus (HCV) infection is the second highest in the world with the development of chronic hepatitis. Interferon-based combination therapy with ribavirin was the only available treatment until a few years back, with severe side-effects and high failure rates against different genotypes of HCV. Interferon-free all-oral direct-acting antiviral agents (DAAs) approved by the FDA have revolutionized the HCV therapeutic landscape due to their efficiency in targeting different genotypes in different categories of patients, including treatment naïve, treatment failure and relapsing patients, as well as patients with compensated and decompensated cirrhosis. The availability and use of these DAAs is limited in the developing world. Sofosbuvir (SOF), a uridine nucleotide analogue and inhibitor of HCV encoded NS5B polymerase, is now a widely available and in-use DAA in Pakistan; whereas daclatasvir was recently added in the list. According to the documented results, there is hope that this disease can be effectively cured in Pakistan, although a few concerns still remain. The aim of this article is to review the effectiveness of DAAs and the current status of this treatment against HCV genotype 3 infection in Pakistan; various factors associated with SVR; its limitations as an effective treatment regime; and future implications.

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Evaluation of liver fibrosis using hepatic extracellular volume fraction by contrast-enhanced computed tomography before and after direct-acting antiviral therapy in patients with chronic hepatitis C infection: comparison with serological liver fibrosis markers

British Journal of Radiology ◽

10.1259/bjr.20210045 ◽

2021 ◽

Author(s):

Akihiko Kanki ◽

Kiyoka Maeba ◽

Hidemitsu Sotozono ◽

Kazuya Yasokawa ◽

Atsushi Higaki ◽

...

Keyword(s):

Hepatitis C ◽

Liver Fibrosis ◽

Antiviral Therapy ◽

Volume Fraction ◽

Extracellular Volume ◽

Control Group ◽

Direct Acting Antiviral ◽

Contrast Enhanced ◽

Before And After ◽

Direct Acting

Objective: To evaluate time-dependent changes in hepatic extracellular volume (ECV) fraction using contrast-enhanced CT (CECT) and serological liver fibrosis markers, the fibrosis-4 (FIB-4) index and aspartate aminotransferase to platelet ratio index (APRI), before and after direct-acting antiviral therapy (DAA) for hepatitis C virus (HCV) infection. Methods: 41 HCV-infected patients who achieved sustained virological response (SVR) after DAA (SVR group) and 10 control patients (untreated or unresponsive to treatment) who underwent CECT and serum biochemical tests before or after the first examination/DAA (T1) and at intervals thereafter (T2:<6 months after T1, T3: at 6–12 months, T4: at 12–24 months, and T5:>24 months) were evaluated. Results: In the control group, ECV fractions remained relatively unchanged through the study, and significant differences in FIB-4 index comparisons and APRI comparisons were only seen between the T2 and T4 values (p = 0.046 and p = 0.028, respectively). In the SVR group, ECV fractions were significantly different between T1 and T4 and T1 and T5 (p = 0.046 and 0.022, respectively), and both FIB-4 index and APRI were significantly different between T1 and all other time points (p = 0.017 to p < 0.001 and p = 0.001 to p < 0.001, respectively). Conclusion: After DAA, ECV fraction decreased slowly, suggesting an improvement in hepatic fibrosis, while serological liver fibrosis markers decreased immediately, probably due to improvement in hepatic inflammation. Advances in knowledge: ECV fraction has the potential to be a non-invasive biomarker for the assessment of liver fibrosis after direct-acting antiviral therapy.

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