Different Treatment Outcomes among Individuals Infected with the Same Strain of HCV  

A variety of viral and host factors contribute to liver disease progression and response to treatment in patients with chronic hepatitis C, often making it difficult to tease out which variables are most relevant.

As reported at the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007), researchers in Argentina have collected data resulting from an accidental “natural experiment” in which several people from the same town were infected with a single strain of HCV.

O'Brien is a small rural Argentinian town of 2200 inhabitants with a high prevalence of HCV infection: 102 of 1832 inhabitants overall (5.6%), 12.6% of those > 40 years, and 23.4% of those > 60 years.

All 83 individuals with detectable HCV were infected with genotype 1b strains with 90.4%-97.5% homology in NS5b nucleotide sequencing, indicating a very close relationship [Hepatology, 2002: 1660A]. The presumed common source of infection for all patients was the administration of unsafe injections some 35 years prior to diagnosis.

The investigators analyzed outcomes of combination pegylated interferon plus ribavirin treatment in 32 patients (half men, half women) with an average age of 51 years. At baseline, 21 subjects (75%) had high HCV viral load (>800000 IU/L; mean 6.4 log IU/L) and 9 (28%) had elevated ALT. Liver biopsies showed that 2 people had METAVIR stage F0 (absent) fibrosis, 5 had F1 (mild), 12 had F2 (significant), 6 had F3 (severe), and 5 had F4 (cirrhosis).

All 32 patients received 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day ribavirin according to body weight (> or < 75 kg) for 48 weeks.

Results

• 2 patients discontinued therapy prematurely (at weeks 2 and 8) due to adverse events, while the remaining 30 completed 48 weeks of treatment.
  
  
• 5 of these patients (17%) required pegylated interferon dose reductions and 8 (27%) needed ribavirin dose reductions.
  
  
• However, all participants fulfilled the 80%/80%/80% rule at all time points (at least 80% of the prescribed dose of both drug for 80% of the intended duration).
  
  
• 13 patients (43%) received G-CSF to manage neutropenia and 6 (20%) received erythropoietin to manage anemia.
  
  
• On an intention-to-treat basis, virological responses were as follows:
  
  
• 91% (29 of 32) at week 12 (early virological response);
• 91% at week 24;
• 91% at week 48 (end-of-treatment response);
• 59% (19 of 32) at week 72 (sustained virological response [SVR]).
  
  
• Predictors of SVR in a univariate analysis were:
  
  
• Age (48 vs 56 years; P=0.039);
• Significant alcohol consumption (>80 grams for men or >50 grams for women) (10.5% vs 45.5%; P=0.029);
• Low fibrosis stage (P=0.008);
• Presence of cirrhosis (0% vs 45.5%; P=0.001).
  
  
• Patients who achieved SVR were more likely to be female (63% vs 27%), to have a lower body mass index (25 vs 29), and to have a lower HCV viral load (42% vs 9%), but these differences were not statistically significant.
  
  
• In a multivariate analysis, fibrosis stage was the only independent predictor of SVR (OR 0.275; P=0.012).

Conclusion

The investigators concluded that treatment of patients from O'Brien with pegylated interferon plus ribavirin was associated with a SVR rate of 59%, despite the fact that a majority had elevated HCV viral load (75%) and a significant proportion (34%) had advanced disease with fibrosis stages 3 or 4.

“In this unique cohort of patients infected with the same strain of HCV genotype 1b, histological severity was the only independent predictor of SVR,” they added.

Liver Unit, Fundacion Favaloro, Buenos Aires, Argentina; Virology, InAV Lab, Buenos Aires, Argentina; Virco Lab.Inc., Raritan, NJ.

12/04/07

Reference