Predictive Factors for Sustained Virological Response after Treatment with Pegylated Interferon α-2a and Ribavirin in Patients Infected with HCV Genotypes 2 and 3

<div><p>Background</p><p>Previous trials have often defined genotype 2 and 3 patients as an “easy to treat” group and guidelines recommend similar management.</p><p>Aims</p><p>The present study looks for differences between the two genotypes and analyzes predictive factors for SVR.</p><p>Methods</p><p>Prospective, community-based cohort study involving 421 physicians throughout Germany. The analysis includes 2,347 patients with untreated chronic HCV genotype 2 (n = 391) and 3 (n = 1,956) infection treated with PEG-IFN α-2a plus ribavirin between August 2007 and July 2012.</p><p>Results</p><p>When compared with genotype 2 patients, those with genotype 3 were younger, had a shorter duration of infection, lower values of total cholesterol, LDL cholesterol and BMI, a higher frequency of drug use as infection mode and male gender (p<0.0001, respectively), and a higher APRI score (p<0.005). SVR was higher in genotype 2 when compared with genotype 3 (64.7% vs. 56.9%, p = 0.004). By multivariate analysis of genotype 2 patients, low baseline γ -GT and RVR predicted SVR. In genotype 3 age ≤45 years, cholesterol>130 mg/dl, a low APRI score, and a γ-GT ≥3-times ULN, RVR, and RBV starting dose were associated with SVR by multivariate analysis.</p><p>Conclusions</p><p>The present study corroborates that liver fibrosis is more pronounced in genotype 3 vs. 2. SVR is higher in genotype 2 versus genotype 3 partly because of follow-up problems in genotype 3 patients, in particular in those infected by drug use. Thus, subgroups of genotype 3 patients have adherence problems and need special attention also because they often have significant liver fibrosis.</p><p>Trial Registration</p><p>Verband Forschender Arzneimittelhersteller e.V., Berlin, Germany <a href="http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb" target="_blank">ML21645</a> ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT02106156" target="_blank">NCT02106156</a></p></div

Main characteristics of patients infected with GT2 and GT3.

<p># alcohol abuse was assessed by judgement of the physician.</p><p>* only patients who were treated at least for 4 weeks and in whom RVR was correctly determined (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107592#s2" target="_blank">Methods</a> for further details).</p><p>** only patients who were treated at least for 12 weeks and in whom EVR was correctly determined (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107592#s2" target="_blank">Methods</a> for further details).</p><p>Main characteristics of patients infected with GT2 and GT3.</p

SVR versus mode of infection in GT2 and GT3 patients.

<p>(multiple answers allowed; differences between modes of infections in GT2 versus GT3 were tested for significance by Fisher's exact χ²-test without correcting for multiple testing).</p><p>SVR versus mode of infection in GT2 and GT3 patients.</p

BMI and baseline cholesterol versus gender.

<p>BMI and baseline cholesterol versus gender.</p

Univariate analysis of variables for prediction of SVR in GT2 and GT3.

<p>* OR  =  Odds Ratio; CI  =  Confidence interval.</p><p>** With a planned treatment end or with treatment discontinuation for virological failure or adverse events.</p><p># By univariate analysis baseline thrombocytes and GOT were also significant in GT3 in predicting SVR; in GT2 these variables were not significant. Since the APRI score which combines these two variables had a higher predictive value when compared with the two single variables only the APRI score was used for further analyses.</p><p>Univariate analysis of variables for prediction of SVR in GT2 and GT3.</p

Main characteristics of patients infected with GT2 and GT3 (Mean).

<p>Main characteristics of patients infected with GT2 and GT3 (Mean).</p

CONSORT flowchart for the OPTEX trial.

<p>CONSORT flowchart for the OPTEX trial.</p

SF-36 Physical and Mental Health.

<p>SF-36 Physical and Mental Health.</p

Baseline characteristics of all randomized patients at study initiation.

<p>* In Delgard et al., 400.000IU/mL was used as cut-off for high and low viral load</p><p>Baseline characteristics of all randomized patients at study initiation.</p

Results of SF-36 questionnaires analysing quality of life during the study period.

<p>Results of SF-36 questionnaires analysing quality of life during the study period.</p