Changes in the epidemiology and distribution of the hepatitis C virus genotypes in North-Eastern Spain over the last 35 years.

BACKGROUND: Genotypic distribution and epidemiology of HCV infection in Western Europe countries has changed over the last decades. AIM: To establish the local genotypic profile and characterize the associated demographic variables. MATERIAL AND METHOD: All the genotyping from 1988 to 2015 were considered. Associated demographic variables were included in logistic regression models. Genotyping was carried out with updated commercial kits. RESULTS: Genotype 1b was the most prevalent (42.4%) followed by 1a (22.5%), 3 (18.6%), 4 (10.6%) and 2 (4.6%). The prevalence of 1a was higher in males, in patients younger than 45 and in intravenous drug users (IDU). 1b was more frequent in older than 45, with transfusion-associated and parenteral/nosocomial infections and in immigrants from Eastern Europe. Genotype 2 was highly prevalent in the postransfusional route (54.9%). Genotype 3 prevalence was high in males, in patients younger than 45, in IDU (69.3%) and in Asian and Eastern European immigrants. Genotype 4 was high in males, in patients younger than 45, and in IDU (63.5%). 1a, 3, 4 were the most prevalent genotypes in HIV-coinfected patients. There was a significant decline in genotype 1b and an increase in genotypes 3 and 4 over time. CONCLUSIONS: There has been a decline of genotype 1b, associated with transfusion or parenteral/nosocomial infections, and increases in the prevalence of genotypes 1a, 3 and 4 associated with male gender and IDU, now the most prevalent infection route. Immigration contributed with genotype 2 infections from Africa and genotype 1b and 3 infections from Eastern Europe and Asia.

Predictive variables of sustained virological response after early discontinuation of triple therapy with telaprevir for genotype-1 HCV infection.

BACKGROUND: Pivotal phase studies of telaprevir (TLV) and boceprevir (BOV) showed 10-56% rates of early treatment interruption. However, there have been no reports on the sustained virological response (SVR) rates of these patients. AIM: To assess the SVR rate in a large cohort of patients who discontinued triple therapy with TLV or BOV for reasons other than stopping rules and to identify variables predicting SVR. MATERIAL AND METHOD: A survey was sent to 15 hospitals in Catalonia asking them to report all TLV/BOV treatments finished by 31 May 2014. Demographic, clinical, laboratory, liver fibrosis and therapeutic data were recorded for treatments with early discontinuation. Logistic regression analysis, ROC curves and prognostic assessment of the variables identified were calculated. RESULTS: Twelve hospitals responded to the survey, representing 467 treatments and 121 (21.2%) early discontinuations, 76 (62.8%) due to stopping rules and 45 (37.2%) for other reasons. Early discontinuation was more frequent with BOV [38.2% (50/131) versus 21.1% (71/336) p<0.005], mainly due to stopping rules [78% (39/50) versus 52.1% (37/71); p=0.004]. SVR was achieved in 21/121 patients (17.4%), 19/71 (26.8%) treated with TLV and 2/50 (4.0%) treated with BOV. In patients discontinuing treatment for reasons other than stopping rules, SVR was achieved in 19/37 (55.9%) treated with TLV and in 2/11 (18.2%) treated with BOV. The SVR rate in patients treated with TLV who discontinued due to a severe adverse event was 61.5% (16/26). A logistic regression analysis was performed only with triple therapy with TLV and early discontinuation. The predictive variables of SVR were undetectable HCV-RNA at treatment week 4 and treatment length longer than 11 weeks. Treatment duration longer than 11 weeks showed the best accuracy (0.794), with a positive predictive value of 0.928. CONCLUSIONS: Early discontinuation of TLV-based triple therapy due to reasons other than stopping rules still have a significant SVR rate (55.9%). Undetectable HVC-RNA at week 4 of treatment and treatment duration longer than 11 weeks are predictive of SVR in this subset of patients.

[To consider negative viral loads below the limit of quantification can lead to errors in the diagnosis and treatment of hepatitis C virus infection]. / Considerar negativa una carga viral expresada como menor del límite inferior de cuantificación puede inducir a error en el diagnóstico y manejo terapéutico de la hepatitis C.

INTRODUCTION: For years many clinical laboratories have routinely classified undetectable and unquantifiable levels of hepatitis C virus RNA (HCV-RNA) determined by RT-PCR as below limit of quantification (BLOQ). This practice might result in erroneous clinical decisions. AIM: To assess the frequency and clinical relevance of assuming that samples that are BLOQ are negative. MATERIAL AND METHOD: We performed a retrospective analysis of RNA determinations performed between 2009 and 2011 (Cobas/Taqman, lower LOQ: 15 IU/ml). We distinguished between samples classified as «undetectable¼ and those classified as «<1.50E+01IU/mL¼ (BLOQ). RESULTS: We analyzed 2.432 HCV-RNA measurements in 1.371 patients. RNA was BLOQ in 26 samples (1.07%) from 23 patients (1.68%). BLOQ results were highly prevalent among patients receiving Peg-Riba: 23 of 216 samples (10.6%) from 20 of 88 patients receiving treatment (22.7%). The clinical impact of BLOQ RNA samples was as follows: a) 2 patients initially considered to have negative results subsequently showed quantifiable RNA; b) 8 of 9 patients (88.9%) with BLOQ RNA at week 4 of treatment later showed sustained viral response; c) 3 patients with BLOQ RNA at weeks 12 and 48 of treatment relapsed; d) 4 patients with BLOQ RNA at week 24 and/or later had partial or breakthrough treatment responses, and e) in 5 patients the impact were null or could not be ascertained. CONCLUSIONS: This study suggests that BLOQ HCV-RNA indicates viremia and that equating a BLOQ result with a negative result can lead to treatment errors. BLOQ results are highly prevalent in on-treatment patients. The results of HCV-RNA quantification should be classified clearly, distinguishing between undetectable levels and levels that are BLOQ.