The histological response rate was significantly higher in HIV-HCV-co-infected patients who received pegIFNalpha-2a (40KD) plus ribavirin than in those receiving pegIFNalpha-2a (40KD) plus placebo or IFNalpha-2a plus ribavirin. Histological response was correlated with virological response, although a substantial proportion of patients who did not achieve an SVR experienced histological improvement.

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Transient elastography (TE) is the reference method to obtain liver stiffness measurements (LSM), but no results are obtained in 3.1% and unreliable in 15.8%. We assessed the applicability and diagnostic accuracy of TE re-evaluation using M and XL probes. From March 2011 to April 2012 868 LSM were performed with the M probe by trained operators (50-500 studies) (LSM1). Measurements were categorized as inadequate (no values or ratio <60% and/or IQR/LSM >30%) or adequate. Inadequate LSM1 were re-evaluated by experienced operators (>500 explorations) (LSM2) and inadequate LSM2 using XL probe (LSMXL). Inadequate LSM1 were obtained in 187 (21.5%) patients, IQR/LSM >30% in 97 (51%), ratio <60% in 24 (13%) and TE failed to obtain a measurement in 67 (36%). LSM2 achieved adequate registers in 123 (70%) of 175 registers previously considered as inadequate. Independent variables (OR, 95%CI) related to inadequate LSM1 were body mass index (1.11, 1.04-1.18), abdominal circumference (1.03, 1.01-1.06) and age (1.03, 1.01-1.04) and to inadequate LSM2 were skin-capsule distance (1.21, 1.09-1.34) and abdominal circumference (1.05, 1.01-1.10). The diagnostic accuracy (AUROC) to identify significant fibrosis improved from 0.89 (LSM1) to 0.91 (LSM2) (P = 0.046) in 334 patients with liver biopsy or clinically significant portal hypertension. A third evaluation (LSMXL) obtained adequate registers in 41 (93%) of 44 patients with inadequate LSM2. Operator experience increases the applicability and diagnostic accuracy of TE. The XL probe may be recommended for patients with inadequate values obtained by experienced operators using the M probe. http://clinicaltrials.gov (NCT01900808).

Minority drug-resistant hepatitis C virus (HCV) variants may go undetected yet be clinically important. NS3/4A protease resistance substitutions V36A and A156S/T/V were selected in patients treated with protease inhibitors. The aim of this study was to investigate whether these substitutions pre-existed in HCV infected patients. An allele-specific PCR protocol that detected the NS3/4A protease resistance substitutions V36A and A156S/T/V was used to determine the prevalence of naturally occurring variants in 45 patients. All patient samples were infected with HCV of genotype 1b and were naïve for pegIFNα/ribavirin treatment. Thirty samples (67%) had at least one HCV PI-resistant variant. A156T (23, 51%) was detected more frequently than A156V (13, 29%) or A156S (1, 2%). V36A was detected in 12 samples (27%). These results demonstrate the high prevalence of minority drug-resistant NS3/4 protease resistance substitutions. Our results also demonstrate that allele-specific PCR can be used to detect minor HCV NS3 protease resistant variants in pretreatment samples and to study in detail the evolution of mutant viruses during targeted antiviral therapy.

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