M.D. Giménez

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C

BACKGROUND & AIMS Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.

Applicability and accuracy improvement of transient elastography using the M and XL probes by experienced operators

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).

Drug-drug interactions of telaprevir and boceprevir in HCV-monoinfected and HIV/HCV-coinfected patients can modify the adherence.

The first generation protease inhibitors, boceprevir (BOC) and telaprevir (TVR), are both CYP3A4 inhibitors, which predispose drug–drug interactions (DDIs). The aim of this study was to evaluate the prevalence of potential DDIs, the management of outpatient medication and its impact on adherence and efficacy to antiviral treatment in hepatitis C virus (HCV)‐monoinfected and human immunodeficiency virus (HIV)/HCV‐coinfected patients receiving BOC and TVR.

Diagnostic Accuracy of the Enhanced Liver Fibrosis (ELF®) Score Using HCV-Infected Serum Samples Cryopreserved for up to 25 Years

Introduction & Aims Cryopreservation of serum samples is a standard procedure for biomedical research in tertiary centers. However, studies evaluating the long-term biological stability of direct liver fibrosis markers using cryopreserved samples are scarce. Methods We compared the stability of hyaluronic acid (HA), tissue inhibitor of metalloproteinases (TIMP-1) and amino-terminal propeptide of type III procollagen (PIIINP) in 225 frozen serum samples of HCV-infected patients with a paired liver biopsy for up to 25 years (1990–2014). Moreover, we assessed the diagnostic accuracy (AUROC) of the Enhanced Liver Fibrosis (ELF®) score to identify significant fibrosis (F2-4) and its predictive capacity to identify clinical events during follow-up. Results Seventy-six patients (39,8%) had mild fibrosis (F0-1) and 115 (60,2%) significant fibrosis (F2-4). HA, PIIINP and TIMP-1 values remained stable during the period from 1995 to 2014 while those of 1990–94 were slightly higher. We did not find significant differences in the median ELF® values during the 20-year period from 1995–2014 in patients with mild (from 8,4 to 8,7) and significant fibrosis (from 9,9 to 10,9) (p = ns between periods and fibrosis stages). The AUROCs of ELF® to identify significant fibrosis were high in all the periods (from 0,85 to 0,91). The ELF® score showed a good predictive capability to identify clinical events during follow-up. Conclusions The biological stability of direct serum markers (HA, PIIINP and TIMP-1) using HCV-infected samples cryopreserved for 20 years is good. Therefore, the diagnostic accuracy of the ELF® score to identify significant fibrosis and clinical events during follow-up is very high.

Quantification of HBsAg to predict low levels and seroclearance in HBeAg-negative patients receiving nucleos(t)ide analogues

Background HBeAg-negative chronic hepatitis B patients require long-term nucleos(t)ide analogues(NAs) because loss of surface antigen (HBsAg) is unusual. Low quantitative HBsAg (qHBsAg) levels can identify patients with higher probability of seroclearance. The aim of our study was to evaluate qHBsAg in HBeAg-negative patients receiving NAs to predict a reduction of HBsAg levels and seroclearance. Methods Retrospective analysis of qHBsAg in HBeAg-negative patients before and at years 1, 3, 5, 8 and over of NAs treatment. Results From 1999 to 2015, HBsAg was quantified in 358 serum samples from 95 HBeAg-negative patients. Low qHBsAg (<120 IU/mL) was identified at baseline or during follow-up in 14% of patients and HBsAg loss in 4%. No baseline variables predicted seroclearance and only treatment duration predicted low qHBsAg. The annual decline of qHBsAg was -0.102 log IU/mL and the median time to HBsAg loss was 6.04 years. The decline was greater in patients achieving low HBsAg levels (-0.257) than in those who did not (-0.057)(p<0.001). The diagnostic accuracy (ROC curve, 95%CI) of qHBsAg delta at year 3 was 0.89 (0.81–0.97), with cut-off >0.3 log IU/mL showing a positive and negative predictive value of 42% and 100% to identify patients achieving low levels of HBsAg. Conclusions Reduction of qHBsAg is slow in HBeAg-negative patients receiving NAs, although low levels or faster qHBsAg decline may occur in 14%. A qHBsAg reduction >0.3 log IU/mL at year 3 can identify patients with a higher probability of achieving low levels and HBsAg seroclearance.

261 INDIVIDUALIZED TREATMENT STRATEGIES AND MULTIDISCIPLINARY SUPPORT PROGRAMS (MSP) INCREASE THE EFFICACY OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C

261 INDIVIDUALIZED TREATMENT STRATEGIES AND MULTIDISCIPLINARY SUPPORT PROGRAMS (MSP) INCREASE THE EFFICACY OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C M. Garcia-Retortillo, I. Cirera, N. Canete, M.D. Gimenez, C. Marquez, P. Castellvi, R. Navines, J.R. Castano, O. Urbina, E. Salas, S. Coll, F. Bory, R. Martin-Santos, R. Sola. Liver Section, Hospital del Mar / IMIM / Universitat Autonoma de Barcelona, Department of Psychiatry and CIBERSAM, Institut Cĺinic de Neurociencies / Hospital Cĺinic / IDIBAPS, Psychiatry Service, Hospital del Mar, Pharmacy Service, Hospital del Mar / IMIM, Barcelona, Spain E-mail: 97235@imas.imim.es