J.A. Pons

Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C

BACKGROUND/AIMS To investigate the effect of sustained virological response (SVR) on impaired fasting glucose (IFG) and/or type 2 diabetes (T2DM); to assess the influence of glucose abnormalities on the SVR rate. METHODS 1059 patients with chronic HCV; normal glucose (< 100 mg/dl) in 734, IFG (between 100 and 125 mg/dl) in 218, and T2DM (126 mg/dl) in 107 cases, were treated with interferon plus ribavirin over 24 or 48 weeks, depending on viral genotype. RESULTS The SVR rate was lower in patients with IFG and/or T2DM than in patients with normal glucose concentrations [143/325 (44%) vs. 432/734 (58.8%); P=0.002]. In the follow-up, abnormal glucose concentrations were observed in 74 of 304 (24.3%) non-responders and in 49 of 430 (11.4%) sustained responders (log-rank: 13.8; P=0.00002). Reverse stepwise logistic regression analysis identified the independent variables predictive of IFG or T2DM development as: sustained response (OR: 0.44; 95%CI=0.20-0.97; P=0.004) and fibrosis stage (OR: 1.46; 95%CI=1.06-2.01;P=0.02). Family history of DM, steatosis, gender, HCV viral load, genotype, triglycerides, cholesterol and BMI did not enter the multivariate analysis equation. CONCLUSIONS SVR reduces the risk of IFG and/or T2DM development in patients with chronic hepatitis C while altered glucose metabolism impairs sustained response to viral treatment.

“Very Early” Intrahepatic Cholangiocarcinoma in Cirrhotic Patients: Should Liver Transplantation Be Reconsidered in These Patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm (“very early”) in which results after LT can be acceptable. Twenty‐nine patients comprised the study group, eight of whom had a “very early” iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the “very early” iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1‐, 3‐ and 5‐year actuarial survival of those in the “very early” iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5‐year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis.

AIM To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis. METHODS Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-naïve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up. RESULTS One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P ≤ 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively). CONCLUSION In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR.

Fine-mapping butyrophilin family genes revealed several polymorphisms influencing viral genotype selection in hepatitis C infection

Host–viral genetic interaction has a key role in hepatitis C infection (HCV) and maybe in the viral selection. In a preliminary GWAS analysis, we identified BTN3A2 rs9104 to be associated with HCV genotype 1. Therefore, our aim was to determine the influence of BTN family on the selection of HCV genotype. We performed a fine-mapping analysis of BTN gene region in a cohort of chronic HCV infection (N=841), validating significant results in another independent chronic HCV infection cohort (N=637), according to selection of viral genotype. BTN3A2 rs9104, BTN3A2 rs733528, BTN2A1 rs6929846, BTN2A1 rs7763910 and BTN3A3 rs13220495 were associated with viral genotype selection. Interestingly, BTN3A2 rs9104 GG genotype was closely related to genotype 1 infection (80.7% (394/488) compared with genotype 3 infection (53.5% (23/43); P=0.0001) in patients harboring IL28B-CT/TT genotype, although this effect was not observed in IL28B-CC genotype. Similarly, BTN3A3 rs13220495 CC genotype was linked to genotype 3 infection (100% (32/32)) compared to genotype 1 (87.3% (137/157); P=0.028) in patients harboring IL28B-CC genotype, but did not in IL28B-CT/TT genotype. Genetic variants in the butyrophilin family genes may alter susceptibility to infection, selecting HCV genotype and influencing disease progression. BTN3A2 rs9104 was strongly associated with genotype 1 infection and the haplotype BTN3A3 rs13220495 CC+IL28B genotype CC was universal in patients with hepatitis C genotype 3a.

P1200 EFFECTIVENESS OF TRIPLE THERAPY WITH BOCEPREVIR OR TELAPREVIR IN A MULTICENTRE CLINICAL PRACTICE COHORT OF HCV TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED HEPATIC FIBROSIS. SVR-12W AFTER TREATMENT

P1200 EFFECTIVENESS OF TRIPLE THERAPY WITH BOCEPREVIR OR TELAPREVIR IN A MULTICENTRE CLINICAL PRACTICE COHORT OF HCV TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED HEPATIC FIBROSIS. SVR-12W AFTER TREATMENT C. Fernandez, P. Munoz de Rueda, S. Alonso, M. Prieto, A. Martin-Alvarez, J. Pons, J. Pascasio, M. Serra, M. Romero, P. Conde, I. Carmona, M. Diago, M. Testillano, J. NavarroJarabo, J. Sanchez Ruano, J. Sousa, F. Nogueras, R. Granados, G. Sanchez Antolin, R. Andrade, H. Hallal, M. Marti Arribas, M. del Moral, J. Salmeron. Servicio de Aparato Digestivo, HU Fundacion de Alcorcon, Madrid, Unidad de Apoyo a la Investigacion, HU San Cecilio, Ciber de Enfermedades Hepaticas y Digestivas (CIBERehd), Granada, Unidad de Gestion Cĺinica de Enfermedades Digestivas, H La Fe, Valencia, Unidad de Hepatoloǵia, H Virgen de Arrixaca, Murcia, Unidad de Hepatoloǵia, H Virgen del Rocio, Sevilla, H Cĺinico de Valencia, Valencia, H Nuestra Senora de Valme, CIBERehd, Sevilla, H Virgen de la Concha, Zamora, Servicio de Aparato Digestivo, HU Virgen de la Macarena, Sevilla, H General de Valencia, Valencia, HU de CRUCES, Bilbao, Vizcaya, Unidad de Aparato Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Malaga, Servicio de Aparato Digestivo, Complejo Hospitalario de Toledo, Toledo, Servicio de Digestivo, HU Virgen de las Nieves, Granada, HU Gran Canaria Dr. Negŕin, Las Palmas de Gran Canaria, Unidad de Hepatologia, HU Ŕio Hortega, Valladolid, HU Virgen de la Victoria, Malaga, H Morales Meseguer, Murcia, HU Salamanca, Salamanca, Unidad de Gestion Cĺinica de Aparato Digestivo, HU San Cecilio, Ciber de Enfermedades Hepaticas y Digestivas (Ciberehd), Granada, Spain E-mail: fsalmero@ugr.es