Background:  Patients with co-infection (HIV/HCV) have a more rapid fibrosis progression rate and shortened time duration to development of cirrhosis. A beneficial effect on histology with Peg-IFN and RBV has been reported in HCV mono-infected patients. This study examined the effect on histology parameters (grade, stage, and fibrosis progression rate) on co-infected non responders to IFN or IFN-RBV combination when retreated with pegylated interferon-a-2a (Pegasys) and RBV.

Methods:  We randomized 76 patients (1:1) to receive Pegasys 180 mg weekly or Pegasys 180 mg weekly plus 800 mg RBV daily for 24 weeks. All responders (≥2 log HCV PCR decrease from baseline) at week 24, were continued in treatment for 24 additional weeks. Paired biopsies were obtained before baseline and 6 months after end of treatment (week 72). All liver biopsies were scored by a single hepato-pathologist using Ishak score (grade 0-18, stage 0-6); and blinded to treatment or response information. Fibrosis progression rate 1 (baseline) is defined as the ratio between fibrosis score (stage) and estimated duration of HCV infection. Fibrosis progression rate 2 (end of treatment) was calculated as the ratio of the subtraction of fibrosis progression rate at week 72 minus the fibrosis progression rate at baseline and the interval of time between both biopsies.

Results:  Patients that achieved a sustained viral response had improvement in grade; 2.83 (±2.64) from 6.4 (±4.25) p = 0.034, stage; 1.66 (±14.97) from 3.8 (±1.68) p = 0.023 and fibrosis progression rate 2; -1.38 (±1.16) from 0.36 (±0.43) p = 0.027. Non responders to treatment with Pegasys or Pegasys/RBV had a decrease from 0.42 (±0.41) to -0.42 (±1.15) p = 0.008 in the fibrosis progression rate 2. In all non-responders that received treatment either with Pegasys or Peg-RBV, for at least 24 weeks, there was a decrease in grade to 4.76 (±2.29) from 6.8 (±3.45) p = 0.012 and fibrosis progression rate 2 from 0.41 (±0.41) to -0.61 (±1.2) p = 0.000.

Conclusions:  As expected, sustained viral response have dramatic improvement in all parameters of liver histology. This study confirms that treatment with Pegasys/RBV is also beneficial for non responders. The demonstrated significant decrease in fibrosis progression rate 2 and grade for non-responders that received at least 24 weeks of treatment, is of particular importance. This benefit may result in clinical improvement, with deceleration of progression to end stage liver disease in patients that have failed all available therapeutic alternatives.

Keywords: Coinfection; Fibrosis; HCV