Increase of serum amyloid A levels during the early phase of antiviral treatment predicts sustained virologic response in patients with chronic hepatitis C

Introduction: Serum amyloid A (SAA) is an acute phase protein, which is synthesized by the liver and induced by various inflammatory stimuli, including viral infections. SAA inhibits replication of hepatitis C virus (HCV) in vitro by blocking virus entry into hepatoyctes. We therefore hypothesized that SAA levels measured during the early phases of HCV-therapy predicts the success of antiviral treatment.

Material and Methods: The study population comprised 35 patients with chronic hepatitis C (m/f: 20/15; mean age±SD: 42.0±8.5, range: 23–61 years). Genotype (GT)-1 was the most prevalent one in this cohort (n=17), followed by GT-3 (n=9), GT-4 (n=7), and GT-2 (n=1). One patient was coinfected with GT-1 and GT-4. All patients received peginterferon plus ribavirin combination therapy for 24–72 weeks (depending on genotype and viral kinetics). Of the 35 patient, 71% achieved a sustained virologic response (SVR), 11% had relapses, 11% had a partial nonresponse, and 6% were nullresponders. The acute-phase response was mapped by measuring levels of selected acute-phase proteins (serum amyloid A [SAA], human interleukin-6 [IL-6], high-sensitivity C-reactive protein [hs-CRP], and fibronectin [FNC]) in the blood from these 35 patients. A significant increase of SAA during the early phase of treatment was defined as an increase of >1.5 from baseline levels to >10mg/l.

Results: In patients with SVR, SAA-levels increased significantly from 4.8±2.8mg/l at baseline to a peak concentration of 14.5±21.7mg/l between week 4 and week 12 (p<0.05), whereas SAA-levels in patients without SVR showed no significant change (15.1±18.6mg/l at baseline versus 7.1±5.9mg/l between week 4 and 12). In contrast, values of all other acute phase proteins remained within the limits of normal in all patients. Ten from 25 patients with SVR (40%, including 5 with GT-1, 4 with GT-3 and 1 with GT-4), but none of the patients without SVR had a significant increase of SAA between week 4 and week 12 (p<0.02). The positive predictive value (PPV) of a significant increase of SAA between week 4 and week 12 for SVR was 100%.

Discussion: The results of this pilot study contribute further evidence, that there is a clinically relevant interaction between SAA and replication of HCV. An increase of SAA during the early phases of antiviral treatment seems to predict SVR.