Summary.  Among individuals with chronic hepatitis C virus (HCV) infection, approximately 30% of patients show persistently normal alanine aminotransferase (PNALT). Individuals with PNALT have been historically excluded from antiviral treatment. However, some studies have reported sudden worsening of disease in patients with PNALT, suggesting the need to treat such individuals. To evaluate this further, we compared fibrosis severity and response to treatment in patients with PNALT to patients with abnormal ALT. In addition, we investigated whether liver histology and schistosomiasis affect response to treatment differently in those with PNALT and abnormal ALT. A retrospective cohort study of 176 HCV‐Genotype 4 (HCV‐G4) patients treated with pegylated interferon (PEG‐IFN) and ribavirin. Of 176 cases studied, 53 (30.1%) had normal ALT. Prevalence of pretreatment severe fibrosis, sustained virological response (SVR) and relapse were not significantly different in patients with PNALT (26%, 66% and 5.7% respectively) compared to those with abnormal ALT (32.5%, 60.7%, and 6.6% respectively). Multivariable logistic regression revealed that pretreatment ALT, pretreatment viral load, inflammation and schistosomiasis were not significantly associated with SVR [OR (95% CI), 0.75 (0.34–1.65); 0.92 (0.61–1.37); 1.64 (0.64–4.18); 0.90 (0.44–1.84) respectively]. Severe fibrosis was the only significant predictor of SVR [OR (95% CI), 0.38 (0.14–0.99)]. PNALT does not reflect the degree of fibrotic changes or predict SVR. Furthermore, schistosomiasis is a predictor of neither fibrosis nor poor response in patients with PNALT. Severe fibrosis is a strong and independent predictor of response to treatment. Therefore, it is important to treat individuals with PNALT levels regardless of schistosomiasis.

AIM To evaluate pegylated interferon alpha2a (PegIFN-alpha2a) in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS A total of 73 naive patients (61 with history of bilharziasis) with compensated chronic HCV genotype 4 were enrolled into: group A (38 patients) who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B (35 patients) received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS Significant improvement in both end of treatment response (ETR) (P < 0.002) and sustained response (SR) (P < 0.05) was noted with pegylated interferon, where ETR was achieved in 29 (76.3%) and 14 patients (40%) in both groups respectively, and 25 patients in group A (65.8%) and 9 (25.7%) in group B could retain negative viraemia by the end of follow up period. Sustained virological response (SVR) showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR (P < 0.001), but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis (grade 3 and 4) with PegIFN-alpha2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect; both drugs were comparable. CONCLUSION PegIFN-alpha2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.