By Lynda Williams
Profound suppression of the hepatitis C virus (HCV) reduces long-term hepatic inflammation and fibrosis even in patients who do not achieve a sustained virologic response (SVR), research demonstrates.
Among patients who did not respond to peginterferon/ribavirin therapy, the level of HCV RNA suppression achieved was associated with the likelihood of achieving a 2-point or greater improvement in Ishak hepatic activity index (HAI) scores for hepatic inflammation 1.5 (n=657) and 3.5 (n=516) years after treatment, report Chihiro Morishima (University of Washington, Seattle, USA) and co-authors.
For patients with Ishak 3‑4 fibrosis at baseline, improvement in HAI after 1.5 years was associated with significantly less fibrosis progression at this time point than those whose HAI did not change or declined.
Furthermore, patients whose HAI score improved at the 1.5-year checkup were significantly more likely to have achieved an improvement in average alanine transaminase (ALT) level.
Patients with HAI score or ALT improvements were significantly less likely to experience hepatic decompensation, hepatocellular carcinoma, or death over a median 6 years of follow up than those whose did not.
However, there was no significant difference in these outcomes among patients who did or did not receive maintenance peginterferon-alfa-2a during the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial, the researchers report in the American Journal of Gastroenterology.
In multivariate analysis, clinical outcomes in up to 8.5 years of follow up were significantly associated with maximal virologic suppression (4 log10) during initial treatment in patients who did and did not receive maintenance therapy (HR=0.37 and 0.50, respectively). When all patients were combined, both HAI improvement (HR=0.67) and virologic suppresssion (HR=0.57) were associated with clinical outcome.
Just 54 of the 274 patients who were randomly assigned to receive maintenance treatment achieved a HCV RNA load of 2 log10 or greater during both the initial and maintenance phases. But these patients were significantly more likely to achieve improvements in both HAI (74 vs 31%) and ALT (54 vs 34%) than patients with less viral suppression.
"The surprisingly durable beneficial effect of peginterferon/ribavirin (3.5 years later) on hepatic inflammation was also associated with a sustained improvement of ALT, despite viral recrudescence at the time of repeat biopsy and serum laboratory measurements," write Morishima et al.
"Of note, these results also suggest potential benefit for patients with advanced liver disease currently being treated with direct-acting antiviral agents in combination with peginterferon/ribavirin, regardless of whether they achieve SVR."
They conclude that "reduction of hepatic inflammation appears to be an important target for future therapeutic interventions to retard the progression of hepatitis C-related liver disease."
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